BR112018073061B1 - 5,6,7,8- TETRAHYDRO[1,2,4]TRIAZOLO[4,3-A]PYRIDIN-3(2H)-ONES AND 2,5,6,7-TETRAHYDRO-3H-PYRROL[2 ,1-C][1,2,4]TRIAZOLE-3-ONES, ITS USES AND ITS PREPARATION PROCESS, AND MEDICATION - Google Patents

Abstract

5,6,7,8-TETRAHYDRO[1,2,4]TRIAZOLO[4,3-A]PYRIDIN-3(2H)-ONES AND 2,5,6,7-TETRA-HYDRO-3H-PYRROLE [2,1-C][1,2,4]TRIAZOLE-3-ONES AND ITS USE. The present application relates to 5,6,7,8-tetrahydro [1,2,4] triazolo[4,3-a]pyridin-3(2H)-ones and 2,5,6,7-tetra -hydro-3H-pyrrole [2,1-c] [1,2,4] triazol-3-ones, to processes for their preparation, their use, alone or in combinations, for the treatment and/or prophylaxis of diseases and for use in the production of medicines for the treatment and/or prophylaxis of diseases, especially for the treatment and/or prophylaxis of pulmonary inflammation disorders

Description

[001] The present application refers to 5,6,7,8-tetrahydro [1,2,4] triazolo[4,3-a]pyridin-3(2H)-ones and 2,5,6, 7-tetrahydro-3H-pyrrole [2,1-c] [1,2,4] triazol-3-ones, processes for their preparation, their use, alone or in combinations, for treatment and/or prophylaxis of diseases and the use for the production of medicines for the treatment and/or prophylaxis of diseases, especially for the treatment and/or prophylaxis of pulmonary inflammation disorders.

[002] The enzyme prolyla endopeptidase (PREP, prolyla oligopetidase, PE, POP) is a serine protease that cleaves peptides up to a length of 30 amino acids in addition to the amino acid proline [Moriyama et al., J. Biochem. 1988, 104:112-117]. PREP is constitutively expressed and secreted in all organs and tissues by cells, including leukocytes and epithelial cells. Release increases with contact with irritating and inflammatory substances [Szul et al., Am. J. Respir. Cell Mol. Biol. 2016, 54:359-369]. While PREP in the central nervous system is involved in the degradation of peptide neurotransmitters, PREP throughout the periphery, including in the lung, is an enzyme that cleaves collagen degradation products, inter alia, in degenerative and inflammatory processes. Due to the high content of proline and glycine in the collagen amino acid sequence, tripeptides with the sequence proline-glycine-proline (PGP) are formed by the degradation of collagen fragments [Weathington et al., Nat. Med. 2006, 12: 317-323]. Significantly elevated PGP concentrations have been described in sputum in patients with chronic inflammatory lung disorders such as chronic obstructive pulmonary disease (COPD) or cystic fibrosis (mucoviscidosis, CF) [O’Reilly et al., Respir. Res. 2009, 10:38 doi:10.1186/1465-9921-10-38; Gaggar et al., J. Immunol. 2008, 180:5662-5669]. PGP, which is produced by PREP, is a chemokine for neutrophil granulocytes (neutrophils for short), meaning that PGP leads to the migration of neutrophils into tissues with elevated concentrations of PGP. There are indicators that the mechanism of this neutrophil attraction is based on direct stimulation of neutrophils through PGP-sensitive receptors on the neutrophil cell membrane (e.g., CXCR1, CXCR2) or indirectly through the release of other chemokines, e.g., interleukins. (e.g. interleukin-8, CXCL8), by other cell types (e.g. macrophages, epithelial cells). The chemokine effect of PGP on neutrophils has been repeatedly demonstrated in vitro and in vivo [Weathington et al., Nat. Med. 2006, 12:317-323; De Kruijf et al., Eur. J. Pharmacol. 2010, 643:29-33; Overbeek et al., Eur. J. Pharmacol. 2011, 668:428-434; Braber et al., Eur. J. Pharmacol. 2011, 668:443-449]. In an animal experiment, the effect of PGP was eliminated by the addition of a complementary tripeptide (threonine-arginine-threonine, RTR) and administration of a CXCR2 receptor blocker. It has been shown that repeated application of PGP to the lungs of mice can trigger pulmonary emphysema. Furthermore, cigarette smoke increases the concentration of PGP in the lungs of mice exposed to cigarette smoke. Simultaneous administration of PGP-neutralizing RTR can eliminate the aforementioned cigarette smoke-induced effects [Braber et al., Eur J. Pharmacol. 2011, 668:443-449; Braber et al., Am. J. Physiol. Lung Cell Mol. Pysiol. 2011, 300:L255-L265].

[003] Chronic obstructive pulmonary disease (COPD) is a lung disease associated with chronic bronchitis, shortness of breath, cough and sputum, and the decline of lung tissue (emphysema). Lung function is increasingly restricted due to obstructive change in the bronchi and as a result of loss of functional lung tissue as the disease progresses. Lung hyperinflation is a common consequence of obstructed exhalation.

[004] The most common cause of COPD is chronic inhalation of cigarette smoke. Furthermore, on a global scale, with regional differences, 10% to 40% of patients develop COPD, which is not attributable to cigarette smoke but likely to exposure to environmental poisons such as coal, wood or exhaust fumes. diesel. [Salvi, Clin. Chest Med. 2014, 35:17-27].

[005] Currently, only the treatment of COPD symptoms is possible. COPD patients are mainly given medications that dilate the bronchi, which makes breathing easier. The use of inflammation-inhibiting medications has been limited to date.

[006] Just like the chronic symptoms described, COPD patients often suffer from an acute onset of time-limited deteriorations in their health status, which is impaired in any case, and this requires additional treatment [Ewig, Klinikarzt 2013, 42 :182-187]. Treatment of these disease episodes, referred to as acute exacerbations, is currently restricted to the administration of oxygen and systemically administered corticosteroids.

[007] In a COPD clinical study, it was demonstrated that roflumilast (an anti-inflammatory PDE4 inhibitor) leads to a decrease in the concentration of PGP in the sputum and serum of treated COPD patients [Wells et al., Am. J . Breathe. Crit. Care Med. 2015, 192:934-942].

[008] Elevated pro-inflammatory concentrations of PGP have additionally been described, inter alia, in shock lung (acute respiratory syndrome, ARDS) and in corneal injury of the eye [Hahn et al., Sci. Adv. 2015, 1: e1500175; Pfister et al., Invest. Ophthalmol. View. Sci. 1998, 39:1744-1750]. Here too, a pro-inflammatory effect of PGP is formulated, which leads firstly to increased permeability of the vessels and secondly, as already described above, to increased recruitment of neutrophils (neutrophilia) and therefore to increased inflammation. As PGP formation in inflammatory processes is directly linked to tissue destruction, and PGP in turn promotes inflammation, the involvement of PGP in self-sustaining chronic inflammation processes is likely. Mention should be made here of COPD and acute exacerbations of COPD (AS-COPD), which are based on chronic inflammation. [Russell et al., Curr Opin Pilm Med. 2016, 22:91-99; Anzueto, Eur. Breathe. Rev. 2010, 19:113-118]. But there are also other chronic disorders of inflammation and wound healing disorders in the lung and other tissues and organs, for example the skin, eye, blood vessels, connective tissue, skeleton and musculature, that could also benefit. of the reduction in PGP concentration as a result of PREP inhibition.

[009] Potential fields of use for PREP inhibitors are acute and chronic pathological processes involving PREP or PREP substrates and products. As this anti-inflammatory effect of PREP inhibitors is unlikely to directly interfere with immune system function and therefore possibly no immunosuppressive effects are expected, an advantage of PREP inhibition could be that fewer side effects could occur in this regard in treated patients. than with conventional immunomodulatory principles of action. As PGP is formed from collagen fragments through the enzyme PREP which is constitutively expressed, that is, it is constantly present, and the production of PGP is not controlled or regulated by the immune system, it is expected that the anti-inflammatory effect -inflammatory also occurs in patients and the effectiveness in relation to corticosteroids is reduced, for example, due to resistance. Resistance to corticosteroids has been described, particularly in patients with COPD, in stable phases, outside of acute exacerbations. Furthermore, an additive or synergistic efficacy of the combination with corticosteroids is also to be expected if the corticosteroids are fully effective and if their effects are limited or very low. A combination with any other inflammatory mechanisms of action is also possible.

[010] As PGP, whose formation is prevented by PREP inhibition, probably plays a preponderant role in the inflammation process in all disorders with inflammatory components and the involvement of collagen or fragments thereof, PREP inhibition may have positive effects in many disorders such as autoimmune disorders, chronic inflammation disorders such as rheumatoid disorders, infection events, degenerative processes (skin, organs, bones, muscles).

[011] The problem addressed by the present invention was to identify and provide new low molecular weight compounds that act as potent inhibitors of the enzyme prolyl endopeptidase (PREP, prolyl oligopeptidase, PE, POP), and, in the case of pathological degeneration processes acute or chronic inflammation, by reducing PREP-dependent PGP production, particularly reduces the recruitment of neutrophil granulocytes in organs, especially in the lung.

[012] WO2006052962A2 describes bicyclic triazoles for controlling disorders that occur via integrin inhibition. 1,2-dihydro-3H-indazol-3-ones as NOX inhibitors for controlling diseases such as COPD, Alzheimer's, inflammatory or fibrotic diseases are known in document WO2011062864A2.

[013] The present invention provides the compounds of General Formula (I) in which

[014] A is (C1-C4)-alkylene or CD2, where (C1-C4)-alkylene can be substituted by hydroxyl and (C1-C4)-alkoxy and even pentassubstituted by fluorine, or is a group of the Formula in which

[015] n is 0 or 1,

[016] p is 0 or 1,

[017] q is 1 or 2, with #1 marking the bond to the nitrogen atom of the 5-oxo-4,5-dihydro-1H-1,2,4-triazol-1-yl ring,

[018] * marks the connection to R1,

[019] of the CR4R5- group, with ** marking the bond to the carbon atom of the 5-oxo-4,5-dihydro-1H-1,2,4-triazol-1-yl ring, with

[020] R6 is hydrogen, fluorine, (C1-C4)-alkyl, (C1-C4)-alkoxy, trifluoromethoxy, hydroxyl, mono-(C1-C4)-alkylamino or di-(C1-C4)-alkylamino, being that (C1-C4)-alkyl can be substituted by (C1-C4)-alkoxy, hydroxyl, mono-(C1-C4)-alkylamino or di-(C1-C4)-alkylamino and even pentassubstituted by fluorine,

[021] R7 is hydrogen, fluorine or (C1-C4)-alkyl, and (C1-C4)-alkyl can even be pentassubstituted by fluorine or

[022] R6 and R7 together with the carbon atom to which they are attached form a carbonyl group, or

[023] R6 and R7 together with the carbon atom to which they are attached form a cyclopropyl ring, cyclobutyl ring or cyclopentyl ring, or

[024] R6 and R4 together with the carbon atom to which they are attached form a cyclopropyl ring, cyclobutyl ring or cyclopentyl ring,

[025] R8 is hydrogen, (C1-C4)-alkyl, (C1-C4)-alkoxy, fluorine, hydroxyl, mono-(C1-C4)-alkylamino or di-(C1-C4)-alkylamino, where ( C1-C4)-alkyl can be substituted by (C1-C4)-alkoxy, hydroxyl, mono-(C1-C4)-alkylamino or di-(C1-C4)-alkylamino and even pentassubstituted by fluorine,

[026] R9 is hydrogen, fluorine or (C1-C4)-alkyl, and (C1-C4)-alkyl can even be pentassubstituted by fluorine or

[027] R8 and R9 together with the carbon atom to which they are attached form a cyclopropyl ring, cyclobutyl ring or cyclopentyl ring, or

[028] R7 and R9 together with the carbon atoms to which they are linked form a cyclopropyl ring, cyclobutyl ring or cyclopentyl ring,

[029] R10 is hydrogen, (C1-C4)-alkyl, (C1-C4)-alkoxy, fluorine, hydroxyl, mono-(C1-C4)-alkylamino or di-(C1-C4)-alkylamino, where ( C1-C4)-alkyl can be substituted by (C1-C4)-alkoxy, hydroxyl, mono-(C1-C4)-alkylamino or di-(C1-C4)-alkylamino and even pentassubstituted by fluorine,

[030] R11 is hydrogen, fluorine or (C1-C4)-alkyl, and (C1-C4)-alkyl can even be pentassubstituted by fluorine or

[031] R10 and R11 together with the carbon atom to which they are attached form a cyclopropyl ring, cyclobutyl ring or cyclopentyl ring,

[032] R1 is (C3-C7)-cycloalkyl, phenyl or heteroaryl with 5 to 10 members, where (C3-C7)-cycloalkyl can be replaced by 1 to 3 substituents independently selected from the halgen, cyano, trifluoromethyl, C1 group -C4)-alkyl and (C1-C4)-alkoxy, where (C1-C4)-alkyl can be even pentasubstituted by fluorine, with phenyl being substituted by 1 to 4 substituents independently selected from the halgen group, cyano, (C1 -C4)-alkyl, (C3-C6)-cycloalkyl, trifluoromethyl, (C1-C4)-alkoxy, (C3-C5)-cycloalkoxy, monofluoromethoxy, difluoromethoxy, trifluoromethoxy, hydroxycarbonyl, (C1-C4)-alkoxycarbonyl, aminocarbonyl, mono-(C1-C4)-alkylaminocarbonyl, di-(C1-C4)-alkylaminocarbonyl, (C3-C5)-cycloalkylaminocarbonyl, (C1-C4)-alkylsulfanyl, (C1-C4)-alkylsulfonyl, (C1-C4)- alkylsulfonimidoyl, (C1-C4)-cycloalkylsulfonyl, aminosulfonyl, mono-(C1-C4)-alkylaminosulfonyl, di-(C1-C4)-alkylaminosulfonyl, (C1-C4)-alkylsulfinyl, amino, mono-(C1-C4)- alkylamino or di-(C1-C4)-alkylamino, or where phenyl can be fused to (C3-C7)-cycloalkyl, (C3-C7)-heterocyclyl or heteroaryl with 5 to 6 members, with phenyl being substituted by methyl, ethyl, chlorine, fluorine or methoxy, and (C3-C7)-cycloalkyl, (C3-C7)-heterocyclyl and heteroaryl with 5 to 6 members can be substituted by 1 or 2 substituents (C1-C4)-alkyl , and (C1-C4)-alkyl can be substituted by (C1-C4)-alkoxy, hydroxyl, mono-(C1-C4)-alkylamino or di-(C1-C4)-alkylamino and even pentassubstituted by fluorine, or whereby 5 to 10 membered heteroaryl may be substituted by 1 to 4 substituents independently selected from the group halgen, cyano, (C1-C4)-alkyl, (C3-C6)-cycloalkyl, trifluoromethyl, (C1-C4)-alkoxy, (C3-C5)-cycloalkoxy, difluoromethoxy, trifluoromethoxy, 2,2,2-trifluoroethoxy, phenyl, hydroxycarbonyl, (C1-C4)-alkoxycarbonyl, aminocarbonyl, mono-(C1-C4)-alkylaminocarbonyl, di-(C1-C4 )-alkylaminocarbonyl, (C3-C5)-cycloalkylaminocarbonyl, (C1-C4)-alkylsulfanyl, (C1-C4)-alkylsulfonyl, (C1-C4)-alkylsulfonimidoyl, (C1-C4)-cycloalkylsulfonyl, aminosulfonyl, mono-(C1 -C4)-alkylaminosulfonyl, di-(C1-C4)-alkylaminosulfonyl, (C1-C4)-alkylsulfinyl, amino, mono-(C1-C4)-alkylamino or di-(C1-C4)-alkylamino, with phenyl can be replaced by methyl, ethyl, chlorine, fluorine or methoxy, or the heteroaryl with 5 to 10 members can be fused to (C3-C7)-cycloalkyl or (C3-C7)-heterocyclyl, with the heteroaryl with 5 the 10-membered can be substituted by methyl, ethyl, chlorine, fluorine or methoxy, and (C3-C7)-cycloalkyl and (C3-C7)- heterocyclyl can be substituted by 1 or 2 substituents (C1-C4)- alkyl, where (C1-C4)-alkyl can be substituted by (C1-C4)-alkoxy, hydroxyl, mono-(C1-C4)-alkylamino or di-(C1-C4)-alkylamino and even pentassubstituted by fluorine,

[033] R2 is a group of the Formula in which

[034] #3 marks the bond to the carbonyl carbon atom,

[035] r is 0 or 1,

[036] Z is O, NR18, S, SO, SO2 or CR14AR14B, where

[037] R14A is hydrogen, halgen, cyano, (C1-C4)-alkyl, (C3-C6)-cycloalkyl, trifluoromethyl, difluoromethyl, fluoromethyl, hydroxyl, (C1-C4)-alkoxy, (C3-C5)-cycloalkoxy , difluoromethoxy, trifluoromethoxy or 2,2,2-trifluoroethoxy, where (C1-C4)-alkyl can be replaced by hydroxyl, amino, mono-(C1-C4)-alkylamino or di-(C1-C4)-alkylamino,

[038] R14B is hydrogen, fluorine or (C1-C4)-alkyl, and (C1-C4)-alkyl can even be pentassubstituted by fluorine or

[039] R14A and R14B together with the carbon atom to which they are attached form a carbonyl group,

[040] R18 is hydrogen or methyl,

[041] R12 is hydrogen, cyano, (C1-C4)-alkyl, acetyl or formyl, where (C1-C4)-alkyl can be replaced by hydroxyl or even pentassubstituted by fluorine, with acetyl can be replaced by hydroxyl or even trisubstituted by fluorine,

[042] R13 is hydrogen, fluorine or (C1-C4)-alkyl, or

[043] R12 and R13 together with the carbon atoms to which they are linked form a cyclopropyl or cyclobutyl ring, and the cyclopropyl or cyclobutyl ring can even be disubstituted by fluorine, or

[044] R13 and R14A together with the carbon atoms to which they are linked form a cyclopropyl or cyclobutyl ring, and the cyclopropyl or cyclobutyl ring can even be disubstituted by fluorine, or

[045] R14A and R14B together with the carbon atom to which they are linked form a cyclopropyl or cyclobutyl ring, and the cyclopropyl or cyclobutyl ring can even be disubstituted by fluorine, with R13, R14A and R14B being hydrogen when R12 is not hydrogen, where R12 is hydrogen when one of the substituents R13, R14A and R14B is not hydrogen, or is a group of the Formula in which

[046] #4 marks the bond to the carbonyl carbon atom,

[047] Y is NR15, CR16AR16B, oxygen or sulfur, where

[048] R15 is hydrogen or methyl,

[049] R16A is hydrogen or methyl,

[050] R 16B is hydrogen or methyl,

[051] R3 is hydrogen or (C1-C4)-alkyl,

[052] R4 is hydrogen, (C1-C4)-alkyl, (C1-C4)-alkoxy, fluorine, hydroxyl, mono-(C1-C4)-alkylamino or di-(C1-C4)-alkylamino, where ( C1-C4)-alkyl can be substituted by (C1-C4)-alkoxy, hydroxyl, mono-(C1-C4)-alkylamino or di-(C1-C4)-alkylamino and even pentassubstituted by fluorine,

[053] R5 is hydrogen or (C1-C4)-alkyl, and (C1-C4)-alkyl can even be pentassubstituted by fluorine or

[054] R4 and R5 together with the carbon atom to which they are attached form a carbonyl group, or

[055] R4 and R5 together with the carbon atom to which they are attached form a cyclopropyl ring, cyclobutyl ring or cyclopentyl ring, and the salts, solvates and solvates of the salts of the compounds of Formula (I).

[056] The inventive compounds are the compounds of Formula (I) and the salts, solvates and solvates of their salts, the compounds that are covered by Formula (I) and are part of the Formulas mentioned below and the salts, solvates and solvates of their salts and the compounds which are covered by Formula (I) and which are mentioned below and their salts, solvates and solvates of their salts, if the compounds which are covered by Formula (I) and which are mentioned below are not already salts, solvates and salt solvates.

[057] Preferred salts in the context of the present invention are physiologically acceptable salts of the compounds of the invention. Also included are salts that are not suitable for pharmaceutical applications, but that can be used, for example, for isolation or purification of the compounds of the invention.

[058] Physiologically acceptable salts of the compounds of the invention include acid addition salts of mineral acids, carboxylic acids and sulfonic acids, for example, salts of hydrochloric acid, hydrobromic acid, sulfuric acid, phosphoric acid, methanesulfonic acid, ethanesulfonic acid, toluenesulfonic acid, benzenesulfonic acid, naphthalenedisulfonic acid, formic acid, acetic acid, trifluoroacetic acid, propionic acid, lactic acid, tartaric acid, malic acid, citric acid, fumaric acid, maleic acid and benzoic acid.

[059] Physiologically acceptable salts of the compounds of the invention also include salts of conventional bases, for example and preferably, alkali metal salts (e.g., sodium and potassium salts), alkaline earth metal salts (e.g., salts calcium and magnesium) and ammonium salts derived from ammonia and organic amines, having 1 to 6 carbon atoms, for example and preferably, ethylamine, diethylamine, triethylamine, ethyldiisopropylamine, monoethanolamine, diethanolamine, triethanolamine, dicyclohexylamine, dimethylamino - ethanol, procaine, dibenzylamine, N-methylmorpholine, arginine, lysine, ethylenediamine and N-methylpiperidine.

[060] Solvates in the context of the invention are described as forms of the compounds of the invention that form a complex in the solid or liquid state by coordination with solvent molecules. Hydrates are a specific form of solvates in which coordination is carried out with water. Preferred solvates in the context of the present invention are hydrates.

[061] Compounds may, depending on their structure, exist in different stereoisomeric forms, that is, in the form of configurational isomers or another, if appropriate, with conformative isomers (enantiomers and/or diastereomers, including those in the case of atropisomers) . Therefore, the present invention includes enantiomers and diastereomers and their respective mixtures. Stereoisomerically homogeneous constituents can be isolated in a known manner from this type of mixtures of enantiomers and/or diastereomers; Preference is given to the use of chromatographic methods for this purpose, especially HPLC chromatography in an achiral or chiral phase. In the case of carboxylic acids as intermediates or end products, separation is also alternatively also possible via diastereomeric salts using chiral amine bases.

[062] If the compounds of the invention can occur in tautomeric forms, the present invention will include all tautomeric forms.

[063] The compounds of General Formula (I) can take the form of isotopic variants. Therefore, the invention encompasses one or more isotopic variants of the compounds of General Formula (I), especially deuterium-containing compounds of General Formula (I).

[064] The expression "isotopic variant" of a compound or reagent is defined as a compound with an unnatural proportion of one or more isotopes from which the compound is constituted.

[065] The expression "isotopic variant of the compound of General Formula (I)" is defined as a compound of General Formula (I) with an unnatural proportion of one or more isotopes from which that compound is constituted.

[066] The expression "unnatural proportion" means a proportion of that isotope greater than its natural frequency. “The natural frequencies of isotopes to be used in this connection can be found in Isotopic Compositions of the Elements 1997", Pure Appl. Chem., 70(1), 217-235, 1998.

[067] Examples of these isotopes are the stable and radioactive isotopes of hydrogen, carbon, nitrogen, oxygen, phosphorus, sulfur, fluorine, chlorine, bromine and iodine, such as 2H (deuterium), 3H (tritium), 11C, 13C, 14C, 15N, 17O, 18O, 32P, 33P, 33S, 34S, 35S, 36S, 18F, 36Cl, 82Br, 123I, 124I 125I 129I and 131I.

[068] In relation to the treatment and/or prophylaxis of the diseases specified herein, the isotopic variant(s) of the compounds of General Formula (I) preferably contain deuterium ("deuterium-containing compounds of the General Formula (I)"). Isotopic variants of compounds of General Formula (I) where one or more radioactive isotopes such as 3H or 14C have been incorporated are beneficial, for example, in tissue distribution studies of drugs and/or substrates. Due to their easy incorporation and detectability, these isotopes are particularly preferred. It is possible to incorporate positron-emitting isotopes such as 18F or 11C into a compound of General Formula (I). These isotopic variants of the compounds of General Formula (I) are suitable for use in in vivo imaging applications. Deuterium-containing and 13C-containing compounds of General Formula (I) can be used in preclinical or clinical studies in mass spectrometry analyses.

[069] Isotopic variants of the compounds of General Formula (I) can be prepared by processes known to those skilled in the art, as described in the schemes and/or examples described herein, replacing a reagent with an isotopic variant of the reagent, preferably , a deuterium-containing reagent. Depending on the desired deuteration sites, in some cases, the deuterium from D2O can be incorporated directly into compounds or into reagents that can be used for the synthesis of these compounds. Another useful reagent for incorporating deuterium into molecules is deuterium gas. A rapid route for deuterium incorporation is the catalytic deuteration of olefinic bonds and acetylenic bonds. For direct exchange of hydrogen for deuterium in hydrocarbons containing functional groups, it is also possible to use metal catalysts (i.e. Pd, Pt and Rh) in the presence of deuterium gas. Various deuterated reagents and synthesis units are commercially available from companies such as, for example, C/D/N Isotopes, Quebec, Canada; Cambridge Isotope Laboratories Inc., Andover, MA, USA; and CombiPhos Catalysts, Inc., Princeton, NJ, USA.

[070] The term "deuterium-containing compound of General Formula (I)" is defined as a compound of General Formula (I) in which one or more hydrogen atoms have been replaced by one or more deuterium atoms and where the frequency of deuterium at each deuterated position in the compound of the general Formula (I) is greater than the natural frequency of deuterium, which is about 0.015%. More particularly, in a deuterium-containing compound of General Formula (I), the frequency of deuterium at all deuterated positions in the compound of General Formula (I) is greater than 10%, 20%, 30%, 40%, 50%, 60%, 70% or 80%, preferably greater than 90%, 95%, 96% or 97%, even more preferably greater than 98% or 99%, in this position(s). It will be evident that the frequency of deuterium in all deuterated positions is independent of the frequency of deuterium in other deuterated positions.

[071] By selectively incorporating one or more deuterium atoms into a compound in accordance with General Formula (I), it is possible to change the physicochemical properties (for example, acidity). [W. L. Perrin, et al., J. Am. Chem. Soc., 2007, 129, 4490], basicity [C. L. Perrin et al., J. Am. Chem. Soc., 2005, 127, 9641], lipophilicity [B. Testa et al., Int. J. Pharm., 1984, 19(3), 271]) and/or the metabolic profile of the molecule and cause changes in the proportion of the original compound in relation to the metabolites or the amounts of metabolites formed. These changes may lead to specific therapeutic benefits and are therefore preferable under particular circumstances. Reduced rates of metabolism and metabolic exchange, with the proportion of metabolites being altered, have been reported (A. E. Mutlib et al., Toxicol. Appl. Pharmacol., 2000, 169, 102). These changes in exposure to the original drug and metabolites can have important consequences in relation to pharmacodynamics, tolerability and efficacy of a deuterium-containing compound of General Formula (I). In some cases, deuterium substitution reduces or eliminates the formation of an unwanted or toxic metabolite and increases the formation of a desired metabolite (e.g., Nevirapine: A. M. Sharma et al., Chem. Res. Toxicol., 2013, 26, 410; Efavirenz: A. E. Mutlib et al., Toxicol., 2000, 169, 102). In other cases, the main effect of deuteration is to reduce the rate of systemic clearance. As a result, the biological half-life of the compound is increased. Potential clinical benefits would include the ability to maintain similar systemic exposure with decreased peak levels and increased trough levels. This may result in fewer side effects and greater efficacy, depending on the pharmacokinetic/pharmacodynamic relationship of the compound in question. Examples of this deuterium effect are ML-337 (C. J. Wenthur et al., J. Med. Chem., 2013, 56, 5208) and odanacatib (K. Kassahun et al., WO2012/112363). Other cases have also been reported in which reduced rates of metabolism result in increased exposure of the drug without altering the rate of systemic clearance (e.g., Rofecoxib: F. Schneider et al., Arzneim. Forsch. Drug. Res., 2006, 56, 295; Telaprevir: F. Maltais et al., J. Med. Chem., 2009, 52, 7993). Deuterated drugs that exhibit this effect may have reduced dosage requirements (e.g., fewer doses or lower dosage to achieve the desired effect) and/or may produce lower metabolic burdens.

[072] A compound of General Formula (I) can have several potential attack sites for metabolism. To optimize the previously described effects on physicochemical properties and metabolic profile, deuterium-containing compounds of General Formula (I) with a certain pattern of one or more hydrogen-deuterium exchanges can be selected. Particularly, the deuterium atom(s) of the deuterium-containing compound(s) of General Formula (I) is/are bonded to a carbon atom and/or is/are located at the positions of the compound of Formula General (I), which are attack sites for metabolizing enzymes, such as cytochrome P450.

[073] The present invention also includes prodrugs of the compounds according to the invention. The term "prodrugs" in this context refers to compounds that may be biologically active or inactive, but that have reacted (e.g., metabolically or hydrolytically) to produce the compounds of the invention during their residence time in the body.

[074] In the context of the present invention, unless otherwise specified, substituents are defined as follows:

[075] Alkyl, in the context of the invention, is a branched or straight-chain alkyl radical having a particular number of specified carbon atoms. Preferred examples include: methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, 1-methylpropyl, tert-butyl, n-pentyl, isopentyl, 1-ethylpropyl, 1-methylbutyl, 2-methylbutyl, 3-methylbutyl, n-hexyl, 1-methylpentyl, 2-methylpentyl, 3-methylpentyl, 4-methylpentyl, 3,3-dimethylbutyl, 1-ethylbutyl, 2-ethylbutyl, 1,4-dimethylpentyl, 4,4-dimethylpentyl and 1,4, 4-trimethylpentyl.

[076] Alkylcarbonyl in the context of the invention is a straight or branched chain alkyl radical that has the specified particular number of carbon atoms and a carbonyl group attached to the carbon atom. Preferred examples include: methylcarbonyl, ethylcarbonyl, n-propylcarbonyl, isopropylcarbonyl and tert-butylcarbonyl.

[077] Alkoxy, in the context of the invention, is a branched or straight-chain alkoxy radical having a particular number of specified carbon atoms. Preferred examples include: methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy and tert-butoxy.

[078] Cycloalkoxy in the context of the invention is a monocyclic saturated alkyl radical that has the particular number of carbon atoms of the specified ring and is joined by means of an oxygen atom. Preferred examples include: cyclopropyloxy, cyclobutyloxy, cyclopentyloxy and cyclohexyloxy.

[079] Cycloalkyl or carbocycle in the context of the invention is a monocyclic saturated alkyl radical with the particular number of carbon atoms of the specified ring. Preferred examples include: cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl and cycloheptyl.

[080] Cycloalkylcarbonyl in the context of the invention is a monocyclic saturated alkyl radical having the particular number of carbon atoms of the specified ring and a carbonyl group attached to the carbon atom. Preferred examples include: cyclopropylcarbonyl, cyclobutylcarbonyl, cyclopentylcarbonyl, cyclohexylcarbonyl and cycloheptylcarbonyl.

[081] Alkoxycarbonyl, in the context of the invention, is a straight or branched chain alkoxy radical having a particular number of specified carbon atoms and a carbonyl group attached to the oxygen atom. Preferred examples include: methoxycarbonyl, ethoxycarbonyl, n-propoxycarbonyl, isopropoxycarbonyl and tert-butoxycarbonyl.

[082] Heterocycle or heterocyclic in the context of the invention is a saturated monocyclic or bicyclic heterocycle that has the particular number of ring atoms specified, contains one or two heteroatoms in the ring of the group N, O, S, SO and SO2 and is joined via ring carbon atom or, optionally, a ring nitrogen atom. Preferred examples include: azetidinyl, oxetanyl, pyrrolidinyl, pyrazolidinyl, tetrahydrofuranyl, thiolanyl, piperidinyl, piperazinyl, tetrahydropyranyl, tetrahydrothiopyranyl, morpholinyl, thiomorpholinyl, hexahydroazepinyl and hexahydro-1,4-diazepinyl. Preference is given to azetidinyl, oxetanyl, pyrrolidinyl, tetrahydrofuranyl, piperidinyl, piperazinyl, tetrahydropyranyl and morpholinil.

[083] Azaheterocyclyl in the context of the invention is a monocyclic or bicyclic, saturated or partially unsaturated heterocycle that has the particular number of atoms specified, contains a nitrogen atom and may also contain one or two other heteroatom(s) of the N group ring , O, S, SO and/or SO2, and is linked through a ring nitrogen atom. Preferred examples include: pyrrolidinyl, pyrazolidinyl, piperidinyl, piperazinyl, morpholinyl, thiomorpholinyl, 1,1-dioxothiomorpholinyl, hexahydroazepinyl, hexahydro-1,4-diazepinyl, 1,2,3,4-tetrahydroisoquinolinyl, 1, 2,3,4-tetrahydroquinolinyl, indolinyl, 8-azabicyclo[3.2.1]octanyl, 9-azabicyclo[3.3.1]nonanyl, 3-azabicyclo[4.1.0]heptanyl and quinuclidinyl.

[084] Heteroaryl in the context of the invention is a monocyclic or bicyclic (heteroaromatic) aromatic heterocycle that has the particular number of ring atoms specified, contains up to four ring heteroatoms identical or different from the group N, O and S and is joined via from a ring carbon atom or, optionally, through a ring nitrogen atom. Preferred examples include: furyl, pyrrolyl, thienyl, pyrazolyl, imidazolyl, quinolinyl, thiazolyl, oxazolyl, isoxazolyl, isothiazolyl, triazolyl, oxadiazolyl, thiadiazolyl, tetrazolyl, pyridyl, pyrimidinyl, pyridazinyl, pyrazinyl and triazinyl.

[085] Monoalkylaminocarbonyl in the context of the invention is an amino group that is linked through a carbonyl group and has a straight or branched chain alkyl substituent having the specified particular number of carbon atoms. Preferred examples include: methylaminocarbonyl, ethylaminocarbonyl, n-propylaminocarbonyl, isopropylaminocarbonyl, n-butylaminocarbonyl, tert-butylaminocarbonyl, n-pentylaminocarbonyl and n-hexylaminocarbonyl.

[086] Dialkylaminocarbonyl in the context of the invention is an amino group that is linked through a carbonyl group and has two equal or different alkyl substituents, straight or branched chain, each having the particular number of carbon atoms specified. Preferred examples include: N,N-dimethylaminocarbonyl, N,N-diethylaminocarbonyl, N-ethyl-N-methylaminocarbonyl, N-methyl-N-n-propylaminocarbonyl, N-n-butyl-N-methylaminocarbonyl, N-tert-butyl-N-methylaminocarbonyl, N-n-pentyl-N-methylaminocarbonyl and N-n-hexyl-N-methylaminocarbonyl.

[087] Monoalkylaminosulfonyl in the context of the invention is an amino group that is linked through a sulfonyl group and has a straight or branched chain alkyl substituent having the specified particular number of carbon atoms. Preferred examples include: methylaminosulfonyl, ethylaminosulfonyl, n-propylaminosulfonyl, isopropylaminosulfonyl, n-butylaminosulfonyl, tert-butylaminosulfonyl, n-pentylaminosulfonyl and n-hexylaminosulfonyl.

[088] Dialkylaminocarbonyl in the context of the invention is an amino group that is linked through a sulfonyl group and has two equal or different alkyl substituents, straight or branched chain, each having the particular number of carbon atoms specified. Preferred examples include: N,N-dimethylaminosulfonyl, N,N-diethylaminosulfonyl, N-ethyl-N-methylaminosulfonyl, N-methyl-N-n-propylaminosulfonyl, N-n-butyl-N-methylaminosulfonyl, N-tert-butyl-N-methylaminosulfonyl, N-n-pentyl-N-methylaminosulfonyl and N-n-hexyl-N-methylaminosulfonyl.

[089] Monoalkylamino in the context of the invention is an amino group that has a linear or branched alkyl substituent having the specified particular number of carbon atoms. Preferred examples include: methylamino, ethylamino, n-propylamino, isopropylamino, n-butylamino, tert-butylamino, n-pentylamino and n-hexylamino.

[090] Dialkylamino in the context of the invention is an amino group with two equal or different alkyl substituents, straight or branched chain, each having the particular number of carbon atoms specified. Preferred examples include: N,N-dimethylamino, N,N-diethylamino, N-ethyl-N-methylamino, N-methyl-N-n-propylamino, N-n-butyl-N-methylamino, N-tert-butyl-N-methylamino, N-n-pentyl-N-methylamino and N-n-hexyl-N-methylamino.

[091] In the context of the invention, halgen includes fluorine, chlorine, bromine and iodine. Preference is given to chlorine or fluorine.

[092] An oxo group in the context of the invention is an oxygen atom linked to a carbon atom through a double bond.

[093] In the Formulas of the group where A, X and R2 can represent, the end point of the line marked by a symbol #1 or #2 or #3 or #4 or #5 or * or ** or *** does not represents a carbon atom or a CH2 group, but is part of the bond to the respective atom to which A, X and R2 are bonded.

[094] When the radicals in the compounds of the invention are substituted, the radicals can be mono- or polysubstituted, unless otherwise specified. In the context of the present invention, all radicals that occur more than once are defined independently of each other. Substitution with one or two identical or different substituents is preferred. Very particular preference is given to substitution by a substituent.

[095] In the context of the present invention, the term "treatment" or "treat" includes inhibition, delay, check, relief, attenuation, restriction, reduction, suppression, repellence or cure of a disease, a condition, a disorder, an injury or a health problem or the development, course or progression of such conditions and/or symptoms of such conditions. The term "therapy" is understood as synonymous with the term "treatment".

[096] The terms "prevention", "prophylaxis" and "prevention" are used synonymously in the context of the present invention and refer to the avoidance or reduction of the risk of contracting, feeling, suffering from or having a disease, a condition, a disorder, an injury or a health problem or a development or advancement of these states and/or the symptoms of these states.

[097] The treatment or prevention of a disease, a condition, a disorder, an injury or a health problem can be partial or complete.

[098] Preference is given in the context of the present invention to compounds of General Formula (I) in which

[099] A is (C1-C4)-alkylene, where (C1-C4)-alkylene can be substituted by hydroxyl and methoxy and can even be trisubstituted by fluorine, or is a group of the Formula in which

[0100] n is 1,

[0101] p is 0,

[0102] q is 1, where

[0103] #1 marks the bond to the nitrogen atom of the 5-oxo-4,5-dihydro-1H-1,2,4-triazol-1-yl ring,

[0104] * marks the connection to R1,

[0105] oxo-4,5-dihydro-1H- 1,2,4-triazol-1-yl, where

[0106] R6 is hydrogen, fluorine, methyl, ethyl, methoxy, ethoxy, trifluoromethoxy, hydroxyl, mono-(C1-C4)-alkylamino or di-(C1-C4)-alkylamino, and methyl and ethyl can even be trisubstituted by fluorine,

[0107] R7 is hydrogen, fluorine or methyl, and methyl can even be trisubstituted by fluorine, or

[0108] R6 and R7 together with the carbon atom to which they are attached form a carbonyl group, or

[0109] R6 and R7 together with the carbon atom to which they are attached form a cyclopropyl or cyclobutyl ring, or

[0110] R6 and R4 together with the carbon atoms to which they are attached form a cyclopropyl or cyclobutyl ring,

[0111] R8 is hydrogen, fluorine, methyl, ethyl, methoxy, ethoxy, trifluoromethoxy, hydroxyl, mono-(C1-C4)-alkylamino or di-(C1-C4)-alkylamino, and methyl and ethyl can even be trisubstituted by fluorine,

[0112] R9 is hydrogen, fluorine or methyl, and methyl can even be trisubstituted by fluorine, or

[0113] R8 and R9 together with the carbon atom to which they are attached form a cyclopropyl or cyclobutyl ring,

[0114] R1 is (C5-C6)-cycloalkyl, phenyl or heteroaryl with 5 to 10 members, where (C5-C6)-cycloalkyl can be replaced by 1 to 3 substituents independently selected from the group consisting of fluorine, cyano, trifluoromethyl , methyl, ethyl, methoxy and ethoxy, and methyl and ethyl can even be trisubstituted by fluorine, with phenyl being substituted by 1 to 4 substituents independently selected from the halgen group, cyano, (C1-C4)-alkyl, (C3- C6)- cycloalkyl, trifluoromethyl, (C1-C4)-alkoxy, (C3-C5)-cycloalkoxy, monofluoromethoxy, difluoromethoxy, trifluoromethoxy, hydroxycarbonyl, (C1-C4)-alkoxycarbonyl, aminocarbonyl, mono-(C1-C4)-alkylaminocarbonyl , di-(C1-C4)-alkylaminocarbonyl, (C1-C4)-alkylsulfanyl, (C1-C4)-alkylsulfonyl, (C1-C4)-alkylsulfonimidoyl, aminosulfonyl, mono-(C1-C4)-alkylaminosulfonyl, di-( C1-C4)-alkylaminosulfonyl, (C1-C4)-alkylsulfinyl, amino, mono-(C1-C4)-alkylamino or di-(C1-C4)-alkylamino, or where phenyl can be fused to cyclopentyl, cyclo- hexyl, 5- to 6-membered heterocyclyl or 5 to 6-membered heteroaryl, with phenyl being substituted by methyl, ethyl, chlorine, fluorine or methoxy, with cyclopentyl, cyclohexyl, 5- to 6-membered heterocyclyl and heteroaryl with 5 to 6 members can be substituted by 1 or 2 methyl or ethyl substituents, with methyl and ethyl being substituted by methoxy, hydroxyl, monomethylamino or diethylamino and even trisubstituted by fluorine, or the 5 to 10 membered heteroaryl can be be substituted by 1 to 4 substituents independently selected from the group halgen, cyano, (C1-C4)-alkyl, (C3-C6)-cycloalkyl, trifluoromethyl, (C1-C4)-alkoxy, (C3-C5)-cycloalkoxy, difluoromethoxy , trifluoromethoxy, 2,2,2-trifluoroethoxy, hydroxycarbonyl, (C1-C4)-alkoxycarbonyl, aminocarbonyl, mono-(C1-C4)-alkylaminocarbonyl, di-(C1-C4)-alkylaminocarbonyl, (C1-C4)-alkylsulfanyl , (C1-C4)-alkylsulfonyl, (C1-C4)-alkylsulfonimidoyl, aminosulfonyl, mono-(C1-C4)-alkylaminosulfonyl, di-(C1-C4)-alkylaminosulfonyl, (C1-C4)-alkylsulfinyl, amino, mono -(C1-C4)-alkylamino or di-(C1-C4)-alkylamino, or where the heteroaryl with 5 to 10 members can be fused to cyclopentyl, cyclohexyl or heterocyclyl with 5 to 6 members, with the heteroaryl having 5 The 10-membered group can be substituted by methyl, ethyl, chlorine, fluorine or methoxy, and cyclopentyl, cyclohexyl and heterocyclyl with 5 to 6 members can be substituted by 1 or 2 (C1-C4)-alkyl substituents, where ( C1-C4)-alkyl can be substituted by (C1-C4)-alkoxy, hydroxyl, mono-(C1-C4)-alkylamino or di-(C1-C4)-alkylamino and even pentassubstituted by fluorine,

[0115] R2 is a group of the Formula in which

[0116] #3 marks the bond to the carbonyl carbon atom,

[0117] r is 0 or 1,

[0118] Z is S, SO, SO2 or CR14AR14B, where

[0119] R14A is hydrogen, halgen, cyano, (C1-C4)-alkyl, cyclopropyl, trifluoromethyl, difluoromethyl, fluoromethyl, hydroxyl, methoxy, ethoxy, cyclopropoxy, difluoromethoxy, trifluoromethoxy, 2,2,2-trifluoroethoxy, hydroxycarbonyl, aminocarbonyl or amino, where (C1-C4)-alkyl can be replaced by hydroxyl, amino, mono-(C1-C4)-alkylamino or di-(C1-C4)-alkylamino,

[0120] R14B is hydrogen, fluorine, methyl or trifluoromethyl, or

[0121] R14A and R14B together with the carbon atom to which they are attached form a carbonyl group,

[0122] R12 is hydrogen, cyano, methyl, ethyl, acetyl or formyl, where methyl can be replaced by hydroxyl or even pentassubstituted by fluorine, with acetyl being replaced by hydroxyl or even trisubstituted by fluorine,

[0123] R13 is hydrogen, fluorine or methyl, or

[0124] R12 and R13 together with the carbon atoms to which they are attached form a cyclopropyl ring, and the cyclopropyl ring can even be disubstituted by fluorine, or

[0125] R13 and R14A together with the carbon atoms to which they are attached form a cyclopropyl or cyclobutyl ring, and the cyclopropyl or cyclobutyl ring can even be disubstituted by fluorine, or

[0126] R14A and R14B together with the carbon atom to which they are linked form a cyclopropyl or cyclobutyl ring, and the cyclopropyl or cyclobutyl ring can even be disubstituted by fluorine, with R13, R14A and R14B being hydrogen when R12 is not hydrogen, where R12 is hydrogen when one of the substituents R13, R14A and R14B is not hydrogen, or is a group of the Formula in which

[0127] #4 marks the bond to the carbonyl carbon atom,

[0128] Y is NR15, CR16AR16B, oxygen or sulfur, where

[0129] R15 is hydrogen or methyl,

[0130] R16A is hydrogen or methyl,

[0131] R 16B is hydrogen or methyl,

[0132] R3 is hydrogen or methyl,

[0133] R4 is hydrogen, fluorine, methyl, ethyl, methoxy, ethoxy, trifluoromethoxy, hydroxyl, mono-(C1-C4)-alkylamino or di-(C1-C4)-alkylamino, and methyl and ethyl can even be trisubstituted by fluorine,

[0134] R5 is hydrogen, fluorine or methyl, and methyl can even be trisubstituted by fluorine, or

[0135] R4 and R5 together with the carbon atom to which they are attached form a cyclopropyl ring, and the salts, solvates and solvates of the salts of the compounds of Formula (I).

[0136] Particular preference is given in the context of the present invention to compounds of General Formula (I) in which

[0137] A is -CH2-, -CH(CH3)-, -CH2CH2-, #5-CH2CH(CH3)-***, #5-CH2C(CH3)2-***, #5-CH2CHF- *** or #5-CH2CF2-***, where #5 marks the bond to the nitrogen atom of the 5-oxo-4,5-dihydro-1H- 1,2,4-triazol-1- ring ila, where *** marks the connection to the R1 group,

[0138] ,5-dihydro-1H-1,2,4-triazol-1-yl, where

[0139] R6 is hydrogen, fluorine, methyl, trifluoromethyl or hydroxyl,

[0140] R7 is hydrogen, fluorine or methyl, or

[0141] R6 and R7 together with the carbon atom to which they are attached form a cyclopropyl ring,

[0142] R1 is phenyl or heteroaryl with 5 to 6 members, with phenyl being substituted by 1 to 3 substituents independently selected from the group consisting of fluorine, chlorine, cyano, methyl, ethyl, trifluoromethyl, methoxy, difluoromethoxy, trifluoromethoxy, hydroxycarbonyl , methoxycarbonyl, ethoxycarbonyl, tert-butoxycarbonyl, methylaminocarbonyl, dimethylaminocarbonyl, methylsulfanyl, methylsulfonyl, methylsulfonimidoyl, aminosulfonyl or methylsulfinyl, or wherein phenyl can be fused to cyclopentyl, cyclohexyl, 5- to 6-membered heterocyclyl or 5- to 6-membered heteroaryl members, where cyclopentyl, cyclohexyl, (C5-C6)-heterocyclyl and 5- to 6-membered heteroaryl can be replaced by 1 or 2 methyl or ethyl substituents, or where the 5- to 6-membered heteroaryl can be replaced by 1 to 3 substituents independently selected from the group consisting of fluorine, chlorine, cyano, methyl, ethyl, trifluoromethyl, methoxy, ethoxy, difluoromethoxy, trifluoromethoxy, 2,2,2-trifluoroethoxy, methylaminocarbonyl, tert-butylaminocarbonyl, dimethylaminocarbonyl, the heteroaryl being with 5 to 6 members can be fused to cyclopentyl, cyclohexyl, 5 to 6 membered heterocyclyl, phenyl or 5 to 6 membered heteroaryl, and the 5 to 6 membered heteroaryl can be replaced by methyl, ethyl, chlorine, fluorine or methoxy , whereby cyclopentyl, cyclohexyl, 5- to 6-membered heterocyclyl, phenyl and 5 to 6-membered heteroaryl can be substituted by 1 or 2 (C1-C4)-alkyl substituents,

[0143] R2 is a group of the Formula in which

[0144] #3 marks the bond to the carbonyl carbon atom,

[0145] r is 0 or 1,

[0146] Z is S or CR14AR14B when r is 0,

[0147] Z is S, SO, SO2 or CR14AR14B when r is 1, in each of which

[0148] R14A is hydrogen, fluorine, methyl, trifluoromethyl, difluoromethyl, fluoromethyl, hydroxyl, methoxy, difluoromethoxy or trifluoromethoxy,

[0149] R14B is hydrogen or fluorine, or

[0150] R14A and R14B together with the carbon atom to which they are attached form a carbonyl group,

[0151] R12 is hydrogen, cyano, methyl, acetyl or formyl, with acetyl being substituted by hydroxyl or even trisubstituted by fluorine,

[0152] R13 is hydrogen, fluorine or methyl, or

[0153] R12 and R13 together with the carbon atoms to which they are attached form a cyclopropyl ring, or

[0154] R13 and R14A together with the carbon atom to which they are attached form a cyclopropyl ring, and the cyclopropyl ring can even be disubstituted by fluorine, or

[0155] R14A and R14B together with the carbon atom to which they are linked form a cyclopropyl ring, and the cyclopropyl ring can even be disubstituted by fluorine, with R13, R14A and R14B being hydrogen when R12 is not hydrogen, with R12 is hydrogen when one of the substituents R13, R14A and R14B is not hydrogen,

[0156] R3 is hydrogen,

[0157] R4 is hydrogen, fluorine or methyl,

[0158] R5 is hydrogen, and the salts, solvates and solvates of the salts of the compounds of Formula (I).

[0159] Particular preference is given in the context of the present invention to compounds of General Formula (I) in which

[0160] A is -CH2-, -CH(CH3)-, -CH2CH2-, #5-CH2CH(CH3)-***, #5-CH2C(CH3)2-***, #5-CH2CHF- *** or #5-CH2CF2-***, where #5 marks the bond to the nitrogen atom of the 5-oxo-4,5-dihydro-1H- 1,2,4-triazol-1- ring ila, where *** marks the connection to the R1 group,

[0161] ,5-dihydro-1H-1,2,4-triazol-1-yl, where

[0162] R6 is hydrogen, fluorine, methyl, trifluoromethyl or hydroxyl,

[0163] R7 is hydrogen, fluorine or methyl, or

[0164] R6 and R7 together with the carbon atom to which they are attached form a cyclopropyl ring,

[0165] R8 is hydrogen, fluorine, methyl or trifluoromethyl,

[0166] R9 is hydrogen, fluorine or methyl,

[0167] R1 is phenyl or heteroaryl with 5 to 6 members, with phenyl being substituted by 1 to 3 substituents independently selected from the group consisting of fluorine, chlorine, cyano, methyl, ethyl, trifluoromethyl, methoxy, difluoromethoxy, trifluoromethoxy, hydroxycarbonyl , methoxycarbonyl, ethoxycarbonyl, tert-butoxycarbonyl, methylaminocarbonyl, dimethylaminocarbonyl, methylsulfanyl, methylsulfonyl, methylsulfonimidoyl, aminosulfonyl or methylsulfinyl, or wherein phenyl can be fused to cyclopentyl, cyclohexyl, 5- to 6-membered heterocyclyl or 5- to 6-membered heteroaryl members, whereby cyclopentyl, cyclohexyl, 5- to 6-membered heterocyclyl and 5- to 6-membered heteroaryl may be substituted by 1 or 2 methyl or ethyl substituents, or wherein the 5- to 6-membered heteroaryl may be substituted by 1 to 3 substituents independently selected from the group consisting of fluorine, chlorine, cyano, methyl, ethyl, trifluoromethyl, methoxy, ethoxy, difluoromethoxy, trifluoromethoxy, 2,2,2-trifluoroethoxy, methylaminocarbonyl, tert-butylaminocarbonyl, dimethylaminocarbonyl, the heteroaryl being with 5 to 6 members can be fused to cyclopentyl, cyclohexyl, 5 to 6 membered heterocyclyl, phenyl or 5 to 6 membered heteroaryl, and the 5 to 6 membered heteroaryl can be replaced by methyl, ethyl, chlorine, fluorine or methoxy , whereby cyclopentyl, cyclohexyl, 5- to 6-membered heterocyclyl, phenyl and 5 to 6-membered heteroaryl can be substituted by 1 or 2 (C1-C4)-alkyl substituents,

[0168] R2 is a group of the Formula in which

[0169] #3 marks the bond to the carbonyl carbon atom,

[0170] r is 0 or 1,

[0171] Z is S or CR14AR14B when r is 0,

[0172] Z is S, SO, SO2 or CR14AR14B when r is 1, in each of which

[0173] R14A is hydrogen, fluorine, methyl, trifluoromethyl, difluoromethyl, fluoromethyl, hydroxyl, methoxy, difluoromethoxy or trifluoromethoxy,

[0174] R14B is hydrogen or fluorine, or

[0175] R14A and R14B together with the carbon atom to which they are attached form a carbonyl group,

[0176] R12 is hydrogen, cyano, methyl, acetyl or formyl, with acetyl being substituted by hydroxyl or even trisubstituted by fluorine,

[0177] R13 is hydrogen, fluorine or methyl, or

[0178] R12 and R13 together with the carbon atoms to which they are attached form a cyclopropyl ring, or

[0179] R13 and R14A together with the carbon atom to which they are linked form a cyclopropyl ring, and the cyclopropyl ring can even be disubstituted by fluorine, or

[0180] R14A and R14B together with the carbon atom to which they are linked form a cyclopropyl ring, and the cyclopropyl ring can even be disubstituted by fluorine, with R13, R14A and R14B being hydrogen when R12 is not hydrogen, with R12 is hydrogen when one of the substituents R13, R14A and R14B is not hydrogen,

[0181] R3 is hydrogen,

[0182] R4 is hydrogen, fluorine or methyl,

[0183] R5 is hydrogen, and the salts, solvates and solvates of the salts of the compounds of Formula (I).

[0184] Particular preference is given in the context of the present invention to compounds of General Formula (I) in which

[0185] A is -CH2-, -CH(CH3)-, -CH2CH2-, #5-CH2CH(CH3)-***, #5-CH2C(CH3)2-***, #5-CH2CHF- *** or #5-CH2CF2-***, where #5 marks the bond to the nitrogen atom of the 5-oxo-4,5-dihydro-1H- 1,2,4-triazol-1- ring ila, where *** marks the connection to the R1 group,

[0186] ,5-dihydro-1H-1,2,4-triazol-1-yl, where

[0187] R6 is hydrogen, fluorine, methyl, trifluoromethyl or hydroxyl,

[0188] R7 is hydrogen, fluorine or methyl, or

[0189] R6 and R7 together with the carbon atom to which they are attached form a cyclopropyl ring,

[0190] R8 is hydrogen, fluorine, methyl or trifluoromethyl,

[0191] R9 is hydrogen, fluorine or methyl,

[0192] R1 is phenyl, pyrazolyl, imidazolyl, thiazolyl, thiophenyl, oxazolyl, oxadiazolyl or pyridyl, with phenyl being substituted by 1 to 3 substituents independently selected from the group consisting of fluorine, chlorine, cyano, methyl, ethyl, trifluoromethyl, methoxy, difluoromethoxy, trifluoromethoxy, hydroxycarbonyl, methoxycarbonyl, ethoxycarbonyl, tert-butoxycarbonyl, methylaminocarbonyl, dimethylaminocarbonyl, methylsulfanyl, methylsulfonyl, methylsulfonimidoyl, aminosulfonyl or methylsulfinyl, or where phenyl can be fused to cyclopentyl, cyclohexyl, pyrazolyl or pyridyl, where cyclopentyl, cyclohexyl, pyrazolyl or pyridyl may be substituted by 1 or 2 methyl or ethyl substituents, or pyrazolyl, imidazolyl, thiazolyl, thiophenyl, oxazolyl, oxadiazolyl or pyridyl may be substituted by 1 to 3 substituents independently selected from the group consisting of fluorine, chlorine, cyano, methyl, ethyl, trifluoromethyl, methoxy, ethoxy, difluoromethoxy, trifluoromethoxy, 2,2,2-trifluoroethoxy, methylaminocarbonyl, tert-butylaminocarbonyl, dimethylaminocarbonyl, where pyrazolyl, imidazolyl, thiazolyl, thiophenyl, oxazolyl, oxadiazolyl or pyridyl may be fused to cyclopentyl, cyclohexyl, phenyl or pyridyl, and pyridyl can be replaced by methyl, ethyl, chlorine, fluorine or methoxy, and cyclopentyl, cyclohexyl, phenyl and pyridyl can be replaced by 1 or 2 substituents of (C1- C4)-alkyl,

[0193] R2 is a group of the Formula in which

[0194] #3 marks the bond to the carbonyl carbon atom,

[0195] r is 0 or 1,

[0196] Z is S or CR14AR14B when r is 0,

[0197] Z is S, SO, SO2 or CR14AR14B when r is 1, in each of which

[0198] R14A is hydrogen, fluorine, methyl, trifluoromethyl, difluoromethyl, fluoromethyl, hydroxyl, methoxy, difluoromethoxy or trifluoromethoxy,

[0199] R14B is hydrogen or fluorine, or

[0200] R14A and R14B together with the carbon atom to which they are attached form a carbonyl group,

[0201] R12 is hydrogen, cyano, methyl, acetyl or formyl, with acetyl being substituted by hydroxyl or even trisubstituted by fluorine,

[0202] R13 is hydrogen, fluorine or methyl, or

[0203] R12 and R13 together with the carbon atoms to which they are attached form a cyclopropyl ring, or

[0204] R13 and R14A together with the carbon atom to which they are attached form a cyclopropyl ring, and the cyclopropyl ring can even be disubstituted by fluorine, or

[0205] R14A and R14B together with the carbon atom to which they are linked form a cyclopropyl ring, and the cyclopropyl ring can even be disubstituted by fluorine, with R13, R14A and R14B being hydrogen when R12 is not hydrogen, with R12 is hydrogen when one of the substituents R13, R14A and R14B is not hydrogen,

[0206] R3 is hydrogen,

[0207] R4 is hydrogen, fluorine or methyl,

[0208] R5 is hydrogen, and the salts, solvates and solvates of the salts of the compounds of Formula (I).

[0209] In the context of the present invention, preference is also given to compounds of Formula (I) in which

[0210] A is -CH2-, -CH(CH3)-, -CH2CH2-, #5-CH2CH(CH3)-***, #5-CH2C(CH3)2-***, #5-CH2CHF- *** or #5-CH2CF2-***, where #5 marks the bond to the nitrogen atom of the 5-oxo-4,5-dihydro-1H- 1,2,4-triazol-1- ring ila, where *** marks the connection to the R1 group, and solvates, salts and solvates of salts.

[0211] Preference is also given in the context of the present invention to compounds of Formula (I) in which

[0212] A is -CH2-, -CH(CH3)- or -CH2CH2-, and solvates, salts and solvates of salts.

[0213] Preference is also given in the context of the present invention to compounds of Formula (I) in which

[0214] A is -CH2-, and solvates, salts and solvates of salts.

[0215] In the context of the present invention, preference is also given to compounds of Formula (I) in which

[0216] ,5-dihydro-1H-1,2,4-triazol-1-yl, where

[0217] R6 is hydrogen, fluorine, methyl, trifluoromethyl or hydroxyl,

[0218] R7 is hydrogen, fluorine or methyl, or

[0219] R6 and R7 together with the carbon atom to which they are attached form a cyclopropyl ring, and solvates, salts and solvates of salts.

[0220] In the context of the present invention, preference is also given to compounds of Formula (I) in which

[0221] ,5-dihydro-1H-1,2,4-triazol-1-yl, where

[0222] R6 is hydrogen, fluorine, methyl, trifluoromethyl or hydroxyl,

[0223] R7 is hydrogen, fluorine or methyl, or

[0224] R6 and R7 together with the carbon atom to which they are attached form a cyclopropyl ring,

[0225] R8 is hydrogen, fluorine, methyl or trifluoromethyl,

[0226] R9 is hydrogen, fluorine or methyl, and solvates, salts and solvates of salts.

[0227] Preference is also given in the context of the present invention to compounds of Formula (I) in which

[0228] ,5-dihydro-1H-1,2,4-triazol-1-yl, where

[0229] R6 is hydrogen, fluorine, methyl or trifluoromethyl,

[0230] R7 is hydrogen, and solvates, salts and solvates of salts.

[0231] Preference is also given in the context of the present invention to compounds of Formula (I) in which

[0232] ,5-dihydro-1H-1,2,4-triazol-1-yl, where

[0233] R6 is trifluoromethyl,

[0234] R7 is hydrogen,

[0235] R8 is hydrogen,

[0236] R9 is hydrogen, and solvates, salts and solvates of salts.

[0237] preference to compounds of Formula (I) in which

[0238] ,5-dihydro-1H-1,2,4-triazol-1-yl, where

[0239] R6 is hydrogen,

[0240] R7 is hydrogen,

[0241] R8 is hydrogen, fluorine, methyl or trifluoromethyl,

[0242] R9 is hydrogen, fluorine or methyl, and solvates, salts and solvates of salts.

[0243] Preference is also given in the context of the present invention to compounds of Formula (I) in which

[0244] ,5-dihydro-1H-1,2,4-triazol-1-yl, where

[0245] R6 is hydrogen,

[0246] R7 is hydrogen,

[0247] R8 is fluorine,

[0248] R9 is fluorine, and solvates, salts and solvates of salts.

[0249] Preference is also given in the context of the present invention to compounds of Formula (I) in which

[0250] ,5-dihydro-1H-1,2,4-triazol-1-yl, where

[0251] R6 is hydrogen,

[0252] R7 is hydrogen,

[0253] R8 is hydrogen,

[0254] R9 is hydrogen, and solvates, salts and solvates of salts.

[0255] In the context of the present invention, preference is also given to compounds of Formula (I) in which

[0256] R1 is 5- to 6-membered phenyl or heteroaryl, with phenyl being substituted by 1 to 3 substituents independently selected from the group consisting of fluorine, chlorine, cyano, methyl, ethyl, trifluoromethyl, methoxy, difluoromethoxy, trifluoromethoxy, hydroxycarbonyl , methoxycarbonyl, ethoxycarbonyl, tert-butoxycarbonyl, methylaminocarbonyl, dimethylaminocarbonyl, methylsulfanyl, methylsulfonyl, methylsulfonimidoyl, aminosulfonyl or methylsulfinyl, or wherein phenyl can be fused to cyclopentyl, cyclohexyl, 5- to 6-membered heterocyclyl or 5- to 6-membered heteroaryl members, where cyclopentyl, cyclohexyl, (C5-C6)-heterocyclyl and 5- to 6-membered heteroaryl can be replaced by 1 or 2 methyl or ethyl substituents, or where the 5- to 6-membered heteroaryl can be replaced by 1 to 3 substituents independently selected from the group consisting of fluorine, chlorine, cyano, methyl, ethyl, trifluoromethyl, methoxy, ethoxy, difluoromethoxy, trifluoromethoxy, 2,2,2-trifluoroethoxy, methylaminocarbonyl, tert-butylaminocarbonyl, dimethylaminocarbonyl, the heteroaryl being with 5 to 6 members can be fused to cyclopentyl, cyclohexyl, 5 to 6 membered heterocyclyl, phenyl or 5 to 6 membered heteroaryl, and the 5 to 6 membered heteroaryl can be replaced by methyl, ethyl, chlorine, fluorine or methoxy , with cyclopentyl, cyclohexyl, heterocyclyl with 5 to 6 members, phenyl and heteroaryl with 5 to 6 members can be substituted by 1 or 2 substituents of (C1-C4)-alkyl, and solvates, salts and solvates of salts.

[0257] In the context of the present invention, preference is also given to compounds of Formula (I) in which

[0258] R1 is a 5- to 6-membered heteroaryl, with the 5 to 6-membered heteroaryl being substituted by 1 to 3 substituents independently selected from the group consisting of fluorine, chlorine, cyano, methyl, ethyl, trifluoromethyl, methoxy, ethoxy , difluoromethoxy, trifluoromethoxy, 2,2,2-trifluoroethoxy, methylaminocarbonyl, tert-butylaminocarbonyl, dimethylaminocarbonyl, and the heteroaryl with 5 to 6 members can be fused to cyclopentyl, cyclohexyl, heterocyclyl with 5 to 6 members, phenyl or heteroaryl with 5 to 6 members, and the heteroaryl with 5 to 6 members can be replaced by methyl, ethyl, chlorine, fluorine or methoxy, and cyclopentyl, cyclohexyl, heterocyclyl with 5 to 6 members, phenyl and heteroaryl with 5 to 6 members can be substituted by 1 or 2 (C1-C4)-alkyl substituents, and solvates, salts and solvates of salts.

[0259] In the context of the present invention, preference is also given to compounds of Formula (I) in which

[0260] R1 is phenyl, pyrazolyl, imidazolyl, thiazolyl, thiophenyl, oxazolyl, oxadiazolyl or pyridyl, with phenyl being substituted by 1 to 3 substituents independently selected from the group consisting of fluorine, chlorine, cyano, methyl, ethyl, trifluoromethyl, methoxy, difluoromethoxy, trifluoromethoxy, hydroxycarbonyl, methoxycarbonyl, ethoxycarbonyl, tert-butoxycarbonyl, methylaminocarbonyl, dimethylaminocarbonyl, methylsulfanyl, methylsulfonyl, methylsulfonimidoyl, aminosulfonyl or methylsulfinyl, or where phenyl can be fused to cyclopentyl, cyclohexyl, pyrazolyl or pyridyl, where cyclopentyl, cyclohexyl, pyrazolyl or pyridyl may be substituted by 1 or 2 methyl or ethyl substituents, or pyrazolyl, imidazolyl, thiazolyl, thiophenyl, oxazolyl, oxadiazolyl or pyridyl may be substituted by 1 to 3 substituents independently selected from the group consisting of fluorine, chlorine, cyano, methyl, ethyl, trifluoromethyl, methoxy, ethoxy, difluoromethoxy, trifluoromethoxy, 2,2,2-trifluoroethoxy, methylaminocarbonyl, tert-butylaminocarbonyl, dimethylaminocarbonyl, where pyrazolyl, imidazolyl, thiazolyl, thiophenyl, oxazolyl, oxadiazolyl or pyridyl may be fused to cyclopentyl, cyclohexyl, phenyl or pyridyl, and pyridyl can be replaced by methyl, ethyl, chlorine, fluorine or methoxy, and cyclopentyl, cyclohexyl, phenyl and pyridyl can be replaced by 1 or 2 substituents of (C1- C4)-alkyl, and solvates, salts and solvates of salts.

[0261] In the context of the present invention, preference is also given to compounds of Formula (I) in which

[0262] R1 is phenyl, wherein phenyl is substituted by 1 to 3 substituents independently selected from the group consisting of fluorine, chlorine, cyano, methyl, ethyl, trifluoromethyl, methoxy, difluoromethoxy, trifluoromethoxy, hydroxycarbonyl, methoxycarbonyl, ethoxycarbonyl, tert- butoxycarbonyl, methylaminocarbonyl, dimethylaminocarbonyl, methylsulfanyl, methylsulfonyl, methylsulfonimidoyl, aminosulfonyl or methylsulfinyl, or where phenyl can be fused to cyclopentyl, cyclohexyl, pyrazolyl or pyridyl, whereby cyclopentyl, cyclohexyl, pyrazolyl or pyridyl can be replaced by 1 or 2 substituents of methyl or ethyl, and solvates, salts and solvates of salts.

[0263] Preference is also given in the context of the present invention to compounds of Formula (I) in which

[0264] R1 is pyrazolyl, imidazolyl, thiazolyl, thiophenyl, oxazolyl or oxadiazolyl, where phenyl can be fused to cyclopentyl, cyclohexyl, pyrazolyl or pyridyl, and cyclopentyl, cyclohexyl, pyrazolyl or pyridyl can be replaced by 1 or 2 substituents of methyl or ethyl, wherein pyrazolyl, imidazolyl, thiazolyl, thiophenyl, oxazolyl or oxadiazolyl may be substituted by 1 to 3 substituents independently selected from the group consisting of fluorine, chlorine, cyano, methyl, ethyl, trifluoromethyl, methoxy, ethoxy, difluoromethoxy, trifluoromethoxy , 2,2,2-trifluoroethoxy, methylaminocarbonyl, tert-butylaminocarbonyl, dimethylaminocarbonyl, where pyrazolyl, imidazolyl, thiazolyl, thiophenyl, oxazolyl, oxadiazolyl or pyridyl can be fused to cyclopentyl, cyclohexyl, phenyl or pyridyl, and pyridyl can be substituted by methyl, ethyl, chlorine, fluorine or methoxy, and cyclopentyl, cyclohexyl, phenyl and pyridyl can be replaced by 1 or 2 (C1-C4)-alkyl substituents, and solvates, salts and solvates of salts.

[0265] Preference is also given in the context of the present invention to compounds of Formula (I) in which

[0266] R1 is pyridyl, and the pyridyl can be replaced by 1 or 2 substituents independently of each other selected from the group consisting of fluorine, chlorine, trifluoromethyl and methoxy, and solvates, salts and solvates of salts.

[0267] In the context of the present invention, preference is also given to compounds of Formula (I) in which

[0268] R2 is a group of the Formula in which

[0269] #3 marks the bond to the carbonyl carbon atom,

[0270] r is 0 or 1,

[0271] Z is S or CR14AR14B when r is 0,

[0272] Z is S, SO, SO2 or CR14AR14B when r is 1, in each of which

[0273] R14A is hydrogen, fluorine, methyl, trifluoromethyl, difluoromethyl, fluoromethyl, hydroxyl, methoxy, difluoromethoxy or trifluoromethoxy,

[0274] R14B is hydrogen or fluorine, or

[0275] R14A and R14B together with the carbon atom to which they are attached form a carbonyl group,

[0276] R12 is hydrogen, cyano, methyl, acetyl or formyl, with acetyl being substituted by hydroxyl or even trisubstituted by fluorine,

[0277] R13 is hydrogen, fluorine or methyl, or

[0278] R12 and R13 together with the carbon atoms to which they are attached form a cyclopropyl ring, or

[0279] R13 and R14A together with the carbon atoms to which they are attached form a cyclopropyl ring, and the cyclopropyl ring can even be disubstituted by fluorine, or

[0280] R14A and R14B together with the carbon atom to which they are linked form a cyclopropyl ring, and the cyclopropyl ring can even be disubstituted by fluorine, with R13, R14A and R14B being hydrogen when R12 is not hydrogen, with R12 is hydrogen when one of the substituents R13, R14A and R14B is not hydrogen, and solvates, salts and solvates of salts.

[0281] In the context of the present invention, preference is also given to compounds of Formula (I) in which

[0282] R3 is hydrogen, and solvates, salts and solvates of salts.

[0283] In the context of the present invention, preference is also given to compounds of Formula (I) in which

[0284] R4 is hydrogen, fluorine or methyl, and solvates, salts and solvates of salts.

[0285] In the context of the present invention, preference is also given to compounds of Formula (I) in which

[0286] R5 is hydrogen, and solvates, salts and solvates of salts.

[0287] The invention further provides a process for preparing the inventive compounds of Formula (I), characterized by [A] a compound of Formula (II) in which

[0288] A1, R1, R3, R4, R5 and X each have the definitions indicated above, and

[0289] T1 is (C1-C4)-alkyl or benzyl, reacts in an inert solvent in the presence of a suitable base with a compound of Formula (III) in which

[0290] A1 is -CH2-, -CH(CH3)-, -CH2CH2-, #5-CH2CH(CH3)-***, #5-CH2C(CH3)2-***, #5-CH2CHF- *** or #5-CH2CF2-***, where #5 marks the bond to the nitrogen atom of the 5-oxo-4,5-dihydro-1H- 1,2,4-triazol-1- ring ila, where *** marks the connection to the R1 group,

[0291] R1 has the definitions given above, and

[0292] {[(4-nitrophenyl)sulfonyl]oxy} or {[(4-methylphenyl)sulfonyl]oxy} tosylate, to produce a compound of Formula (IV) in which

[0293] A1, R1, R3, R4, R5, X and T1 each have the definitions presented above, then the latter are converted by removing the "T1" group in an inert solvent in the presence of a suitable base or acid a compound of Formula (V) in which

[0294] A1, R1, R3, R4, R5 and -B) in which

[0295] Y, Z, R12 and R13 have the definitions given above, and then any protecting groups present are highlighted by methods known to those skilled in the art, and the resulting compounds of Formula (I) are optionally converted with the appropriate solvents ( i) and/or (ii) acids or bases for solvates, salts and/or solvates of their salts, or [B] a compound of Formula (II) in which

[0296] A1, R1, R3, R4, R5 and X each have the definitions indicated above, and

[0297] T1 is (C1-C4)-alkyl or benzyl, reacts in an inert solvent in the presence of a suitable base with an amine of Formula (VI-A) or (VI-B) in which

[0298] Y, Z, R12 and R13 have the definitions given above, to produce a compound of Formula (XXIII-A) or (XXIII-B) in which

[0299] R3, R4, R5, R12, R13, X, Y and Z each have the definitions presented above, the latter reacts in an inert solvent in the presence of a suitable base with a compound of Formula (III) in which

[0300] A1 is -CH2-, -CH(CH3)-, -CH2CH2-, #5-CH2CH(CH3)-***, #5-CH2C(CH3)2-***, #5-CH2CHF- *** or #5-CH2CF2-***, where #5 marks the bond to the nitrogen atom of the 5-oxo-4,5-dihydro-1H- 1,2,4-triazol-1- ring ila, where *** marks the connection to the R1 group,

[0301] R1 has the definitions given above, and

[0302] (4-nitrophenyl)sulfonyl]oxy} or {[(4-methylphenyl)sulfonyl]oxy} tosylate, and then any protecting groups present are highlighted by methods known to those skilled in the art, and the resulting compounds of Formula (I) are optionally converted with the appropriate solvents (i) and/or (ii) acids or bases to the solvates, salts and/or solvates of their salts, or [C] a compound of Formula (VII) in which

[0303] R3, R4, R5 and X each have the settings indicated above and

[0304] T1 is (C1-C4)-alkyl or benzyl,

[0305] T2 is 4-methoxybenzyl, benzyl, allyl, β- (trimethylsilyl) ethoxymethyl (SEM), methoxymethyl (MOM) or benzyloxymethyl, is converted by hydrolysis of the ester group in an inert solvent in the presence of a base or acid suitable for a compound of Formula (VIII) in which

[0306] R3, R4, R5, T2 and X each have the definitions indicated above, then the latter reacts in an inert solvent under conditions of amide coupling with the amine of Formula (VI-A) in which

[0307] Z, R12 and R13 have the definitions given above, to produce a compound of Formula (IX-A) or (IX-B) in which

[0308] R3, R4, R5, R12, R 13, T2, optionally in the presence of a suitable palladium catalyst and the resulting compound of Formula (XA) or (XB) in which

[0309] R3, R4, R5, R12, R13, X, Y and Z each have the definitions presented previously, reacts in an inert solvent in the presence of a suitable base with a compound of Formula (III) in which

[0310] A1 is -CH2-, -CH(CH3)-, -CH2CH2-, #5-CH2CH(CH3)-***, #5-CH2C(CH3)2-***, #5-CH2CHF- *** or #5-CH2CF2-***, where #5 marks the bond to the nitrogen atom of the 5-oxo-4,5-dihydro-1H- 1,2,4-triazol-1- ring ila, where *** marks the connection to the R1 group,

[0311] R1 has the definitions given above, and

[0312] (4-nitrophenyl)sulfonyl]oxy} or {[(4-methylphenyl)sulfonyl]oxy} tosylate, and then any protecting groups present are highlighted by methods known to those skilled in the art, and the resulting compounds of Formula (I) are optionally converted with the appropriate solvents (i) and/or (ii) acids or bases to the solvates, salts and/or solvates of their salts.

[0313] The compounds of Formulas (III), (VI-A) and (VI-B) are commercially available or known in the literature or can be prepared in analogy to processes known in the literature.

[0314] Inert solvents for process step (II) + (III) ^ (IV) or (X) + (III) ^ (I) are, for example, halohydrocarbons, such as dichloromethane, tetrachloromethane, trichlorethylene or chlorobenzene , ethers such as diethyl ether, dioxane, tetrahydrofuran, diethyl ether glycol or diethylene glycol dimethyl ether, hydrocarbons such as benzene, toluene, xylene, hexane, cyclohexane or mineral oil fractions, alcohols such as methanol, ethanol, n-propanol , isopropanol, n-butanol, 2,2,2-trifluoroethanol, or other solvents such as acetone, methyl ethyl ketone, ethyl acetate, acetonitrile, N,N-dimethylformamide, N,N-dimethylacetamide, dimethyl sulfoxide, N,N '-dimethylpropyleneurea (DMPU), N-methylpyrrolidone (NMP) or pyridine. It is also possible to use mixtures of the aforementioned solvents equally. Preference is given to the use of dimethylformamide or acetonitrile.

[0315] Suitable bases for process step (II) + (III) ^ (IV) or (X) + (III) ^ (I) are the usual inorganic or organic bases. They preferably include lithium, sodium, potassium, alkali metal hydroxides, for example lithium hydroxide, sodium hydroxide or potassium hydroxide, alkoxides, such as potassium tert-butoxide, methoxide, ethoxide, alkali metal or alkali metal carbonates. earth, such as lithium carbonate, sodium carbonate, potassium carbonate, calcium carbonate or cesium carbonate, optionally with the addition of an alkali metal iodide, for example sodium iodide or potassium iodide, or organic amines, such as triethylamine, N-methylmorpholine, N-methylpiperidine, N,N-diisopropylethylamine, 1,5-diazabicyclo [4.3.0] non-5-ene (DBN), 1,8-diazabicyclo [5.4.0] undec-7-ene (DBU ) or 1,4-diazabicyclo [2.2.2] octane (DABCO®). Preference is given to the use of cesium carbonate.

[0316] The reaction is generally conducted within a temperature range 0°C to +120°C, preferably at +20°C to +80°C, more preferably at room temperature, optionally in microwaves. The reaction can be carried out at standard, elevated or reduced pressure (e.g. from 0.5 to 5 bar).

[0317] The hydrolysis of esters in compounds (IV) for compounds of Formula (V) or in compounds (VII) for compounds of Formula (VIII) is carried out by usual methods, treating the esters in inert solvents with acids or bases, being In the latter case, the salts initially formed are converted into free carboxylic acids by acid treatment. In the case of tert-butyl esters, the hydrolysis of the ester is preferably carried out with acids.

[0318] Suitable inert solvents for these reactions are water or the usual organic solvents for ester cleavage. These preferably include alcohols, such as methanol, ethanol, n-propanol, isopropanol, n-butanol or tert-butanol, or ethers, such as diethyl ether, tetrahydrofuran, dioxane or glycol dimethyl ether or other solvents, such as acetone, dichloromethane, dimethylformamide or dimethyl sulfoxide. It is also possible to use mixtures of the aforementioned solvents equally. In the case of a basic ester hydrolysis, preference is given to the use of mixtures of water with dioxane, tetrahydrofuran, methanol and/or ethanol and/or n-propanol. In the case of the reaction with trifluoroacetic acid, preference is given to the use of dichloromethane and, in the case of the reaction with hydrogen chloride, preference is given to the use of tetrahydrofuran, diethyl ether, dioxane or water.

[0319] Suitable bases are the usual inorganic bases. These preferably include alkali metal or alkaline earth metal hydroxides, for example sodium hydroxide, lithium hydroxide, potassium hydroxide or barium hydroxide, or alkali or alkaline earth metal carbonates, such as sodium carbonate, potassium carbonate or calcium carbonate. Particular preference is given to sodium hydroxide or lithium hydroxide.

[0320] Suitable acids for ester hydrolysis are generally sulfuric acid, hydrogen chloride/hydrochloric acid, hydrogen bromide/hydrobromic acid, phosphoric acid, acetic acid, trifluoroacetic acid, toluenesulfonic acid, methanesulfonic acid or trifluoromethanesulfonic acid or mixtures thereof, optionally with addition of water. Preference is given to hydrogen chloride or trifluoroacetic acid, in the case of tert-butyl esters, and hydrochloric acid, in the case of methyl esters.

[0321] Ester hydrolysis is generally carried out within a temperature range between 0°C to +100°C, preferably at +0°C to +50°C, more preferably at room temperature.

[0322] These conversions can be carried out at atmospheric pressure, elevated or reduced (for example, from 0.5 to 5 bar). In general, standard pressure is used in each case.

[0323] Inert solvents for amide coupling (V) + (VI-A) ^ (I) or (V) + (VI-B) ^ (I) or (VIII) + (VI-A) ^ (IX -A) or (VIII) + (VI-B) ^ (IX-B) are, for example, ethers such as diethyl ether, dioxane, tetrahydrofuran, glycol dimethyl ether or diethylene glycol dimethyl ether, hydrocarbons such as benzene, toluene, xylene, hexane, cyclohexane or mineral oil fractions, halohydrocarbons such as dichloromethane, trichloromethane, tetrachloromethane, 1,2-dichloroethane, trichloroethylene or chlorobenzene, or other solvents such as acetone, ethyl acetate, acetonitrile, pyridine, dimethyl sulfoxide, N,N-dimethylformamide, N,N-dimethylacetamide, N,N'-dimethylpropyleneurea (DMPU) or N-methylpyrrolidone (NMP). It is also possible to use mixtures of the aforementioned solvents. Preference is given to dichloromethane, tetrahydrofuran, dimethylformamide or mixtures of these solvents.

[0324] Suitable quenching agents for the formation of amide v or (VIII) + (VI-A) ^ (IX-A) or (VIII) + (VI-B) ^ (IX-B) are, for example, carbodiimides, such as N,N'-diethyl-, N,N'-dipropyl-, N,N'-diisopropyl-, N,N'-dicyclohexylcarbodiimide (DCC) or N-(3-dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride (EDC), phosgene derivatives such as N,N'-carbonyldiimidazole (CDI), 1,2-oxazolium compounds such as 2-ethyl-5-phenyl-1,2-oxazolium 3-sulfate or 2-tert-butyl -5- methylisoxazolium, acylamino compounds such as 2-ethoxy-1-ethoxycarbonyl- 1,2-dihydroquinoline or isobutyl chloroformate, propanephosphonic anhydride (T3P), 1-chloro-N,N,2-trimethylprop-1- ene-1-amine, diethyl cyanophosphonate, bis(2-oxo-3-oxazolidinyl)phosphoryl chloride, benzotriazol-1-yloxy-tris(dimethylamino)phosphonium hexafluorophosphate, benzotriazol-1-yloxytris (pyrrolidine) hexafluorophosphate phosphonium (PyBOP), O-(benzotriazol-1-yl tetrafluoroborate)-N,N,N',N'-tetramethyluronium (TBTU), O-(benzotriazol-1-yl)-N,N,N' hexafluorophosphate ,N'-tetramethyluronium (HBTU), 2-(2-oxo-1-(2H)-pyridyl)-1,1,3,3-tetramethyluronium tetrafluoroborate (TPTU), O-(7-azabenzotriazole) hexafluorophosphate 1-yl)-N,N,N',N'-tetramethyluronium (HATU) or O-(1H-6-chlorobenzotriazol- 1-yl)-1,1,3,3-tetramethyluronium tetrafluoroborate (TCTU), optionally in combination with other auxiliaries, such as 1-hydroxybenzotriazole (HOBt) or N-hydroxysuccinimide (HOSu), and also, as alkali metal carbonate bases, e.g. sodium carbonate or potassium carbonate or sodium hydrogencarbonate or potassium hydrogencarbonate , or organic bases such as trialkylamines, for example triethylamine, N-methylmorpholine, N-methylpiperidine or N,N-diisopropylethylamine. Preference is given to the use of HATU.

[0325] The question (V) + (VI-A) ^ (I) or (V) + (VI-B) ^ (I) or (VIII) + (VI-A) ^ (IX-A) or (VIII) + (VI-B) ^ (IX-B) is generally carried out within a temperature range of -20°C to + 100°C, preferably at 0°C to + 60°C. The conversion can be carried out under normal, elevated or reduced pressure (e.g. from 0.5 to 5 bar). Standard pressure is generally employed.

[0326] Alternatively, the carboxylic acid of Formula (V) or (VIII) may also first be converted to the corresponding hot carbonyl chloride and the latter may then react directly or in a separate reaction with an amine of Formula (VI) to the compounds of the invention. The formation of carbonyl chlorides from carboxylic acids is carried out by methods known to those skilled in the art, for example, by treatment with thionyl chloride or oxalyl chloride, in the presence of a suitable base, for example, in the presence of pyridine and optionally with addition of dimethylformamide, optionally in a suitable inert solvent.

[0327] The separation of the protecting group in the reaction step (IX) ^ (X) is carried out here by conventional methods known from protecting group chemistry, preferably by reaction with acid, for example, trifluoroacetic acid in dichloromethane, by base, by e.g., ammonia in methanol, hydrogenolysis in the presence of a palladium catalyst, e.g., palladium on activated carbon, in an inert solvent, e.g., ethanol or ethyl acetate, 2,3-dichloro-5,6-dicyano-1 ,4-benzoquinone (DDQ) or cerium(IV) ammonium nitrate (CAN) [see also, e.g., T.W. Greene and P.G.M. Wuts, Protective Groups in Organic Synthesis, Wiley, New York, 1999].

[0328] Inert solvents for the reaction (II) + (VI-A) ^ (XXIII-A) or (II) + (VI-B) ^ (XXIII-B) are, for example, pyrrolidine, toluene, acetonitrile, tetrahydrofuran or dichloromethane. Preference is given to the use of pyrrolidine.

[0329] The reaction (II) + (VI-A) ^ (XXIII-A) or (II) + (VI-B) ^ (XXIII-B) is generally conducted within a temperature range of 20°C to + 200°C, preferably from 80°C to + 200°C. The conversion can be carried out at normal or elevated pressure (for example, from 1 to 5 bar). Standard pressure is generally employed.

[0330] The compounds of Formula (II) where X is #2-CR6R7- CR8R9-** and R3, R7 and R9 are hydrogen can be prepared by reacting a compound of Formula (XI) in which

[0331] T1 is (C1-C4)-alkyl or benzyl,

[0332] in which

[0333] T3 is benzyl or tert-butyl, to produce a compound of Formula (XIII) in which

[0334] R4, R6, R8, T1 and T3 each have the definitions given above, the protecting group T3 is separated in a suitable inert solvent by hydrogenolysis in the presence of a palladium catalyst and the resulting compound of Formula (XIV) in which

[0335] R4, R6, R8 and T1 each have the definitions given above, are cyclized in a suitable solvent with a phosgene derivative of Formula (XV) in which

[0336] R4, R6, R8 and T1 each have the definitions given above, and are then hydrogenated in a suitable solvent in the presence of a palladium catalyst in a hydrogen atmosphere, and the resulting compounds of Formulas (II) are optionally converted with the appropriate solvents (i) and/or acids (ii) in their solvates, salts and/or solvates of the salts.

[0337] Compounds of Formula (II) or (IV) where X is #2-CR6R7-CR8R9-** can be prepared by promoting the reaction of a compound of Formula (XVI) in which

[0338] T1 is (C1-C4)-alkyl or benzyl, and R3, R4, R5, R6, R7, R8 and R9 each have the definitions given above, in a suitable solvent in the presence of trimethyloxonium tetrafluoroborate with a compound of Formula (XVII-A) or (XVII-B) in which

[0339] T2 is 4-methoxybenzyl,

[0340] T4 is methyl or ethyl, and A1 and R1 each have the definitions presented above, to produce a compound of Formula (XVIII-A) or (XVIII-B) in which

[0341] A1, R1, R3, R4, R5, R6, R7, R8, R9, T1, T2 and T4 each have the definitions given above, the latter are cyclized in a suitable solvent to produce a compound of Formula (XIX -A) or (XIX-B) in which

[0342] A1, R1, R3, R4, R5, R6, R7, R8, R9, T1 and T2 each have the definitions given above, and, for the compounds of Formula (XIX-A), the protecting group T2 is then removed in an inert solvent in the presence of a suitable acid, and the resulting compounds of Formulas (II) are optionally converted with the appropriate solvents (i) and/or acids (ii) into their solvates, salts and/or solvates of the salts .

[0343] The compounds of Formula (XIX-B) correspond to the compounds of Formula (IV) when, in Formula (IV), X is #2-CR6R7-CR8R9-**.

[0344] The compounds of Formula (VII) correspond to the compounds of Formula (XIX) when, in Formula (VII), X is #2-CR6R7-CR8R9-**.

[0345] The compounds of Formula (II) where X is -CR6R7- can be prepared by reacting a compound of Formula (XX) in which

[0346] T1 is (C1-C4)-alkyl or benzyl, and R3, R4, R5, R6 and R7 each have the definitions presented above, in a suitable solvent, first in the presence of trimethyloxonium tetrafluoroborate and then with a compound of Formula (XXI) in which

[0347] T4 is methyl, ethyl, tert-butyl or benzyl, to produce a compound of Formula (XXII) in which

[0348] R3, R4, R5, R6, R7 and T1 each have the definitions presented above.

[0349] The compounds of Formulas (XI), (XII), (XVII-A), (XVII-B), (XX) and (XXI) are commercially available or known from the literature, or can be prepared in analogy to the literature processes.

[0350] The processes described are illustrated by way of example by the diagrams below (Schemes 1-3): Scheme 1: (a) tert-butanol, pyridine, p-toluenesulfonyl chloride, RT; b) benzyl carbazate, cesium carbonate, 1,1'-bis(diphenylphosphine)ferrocene, bis(dibenzylideneacetone)palladium(0) in toluene 80°C; c) Pd/C 5%, 1 bar H2 in toluene/methanol, RT; d) carbonyldiimidazole, THF, RT; (e) Pd/C 5%, 34.5 bar H2 in toluene/methanol, RT; f) cesium carbonate, 1-(bromomethyl)-3,5-dichlorobenzene in acetonitrile, RT; g) HCl in 1,4-dioxane, RT; h) HATU, triethylamine, pyrrolidine in THF, RT. Scheme 2: (b) 1. methyl (5RS)-6-oxopiperidine-2-carboxylate, trimethyloxonium tetrafluoroborate, dichloromethane, RT; 2. methyl 1-(4-methoxybenzyl)hydrazinecarboxylate, dichloromethane, RT; (b) DMF, 150°C; (c) lithium hydroxide, THF/water, RT; (d) HATU, triethylamine, pyrrolidine in DMF, RT; (e) trifluoroacetic acid, 150°C. Scheme 3: (c) 1. trimethyloxonium tetrafluoroborate and methyl 5-oxo-L-prolinate in dichloromethane, RT; 2. methyl hydrazinoformate, RT; 3. DMF, 170°C; (b) cesium carbonate, 1-(bromomethyl)-4-methylbenzene in acetonitrile, RT; (c) lithium hydroxide in water/THF, RT; (d) HATU, diisopropylethylamine, pyrrolidine in DMF/dichloromethane, RT.

[0351] The process step (XI) + (XII) ^ (XIII) is carried out in a solvent that is inert under the reaction conditions. Suitable solvents are, for example, ethers such as 1,4-dioxane, tetrahydrofuran, 2-methyltetrahydrofuran, diethyl ether, di-n-butyl ether, glycol dimethyl ether or diethylene glycol dimethyl ether, alcohols such as tert- butanol or amyl alcohols or other solvents such as dimethylformamide (DMF), dimethyl sulfoxide (DMSO), dimethylacetamide (DMA), toluene or acetonitrile. It is also possible to use mixtures of the aforementioned solvents equally. Preference is given to tert-butanol, 1,4-dioxane and toluene.

[0352] The process step (XI) + (XII) ^ (XIII) is carried out in the presence of a suitable palladium catalyst. An example of a suitable palladium catalyst is palladium on activated carbon, palladium(II) acetate, bis(dibenzylideneacetone)palladium(0), tetrakis(triphenylphosphine)palladium(0), bis(triphenylphosphine)palladium(II) chloride ), bis(acetonitrile)palladium(II) chloride, [1,1'-bis(diphenylphosphine)ferrocene]dichloropaladium(II) and the corresponding hot dichloromethane complex, optionally in conjunction with additional phosphine ligands, e.g. ,2'-bis(diphenylphosphine)-1,1'-binaphthyl (BINAP), (2-biphenyl)di-tert-butylphosphine, dicyclohexyl [2',4',6'-tris(1-methylethyl)biphenyl-2 -yl]phosphine (XPhos), bis(2-phenylphosphinophenyl) ether (DPEfos) or 4,5-bis(diphenylphosphine)-9,9-dimethylxanthene (Xantphos) [cf., e.g., Hassan J. et al., Chem. Rev. 2002, 102, 1359-1469], 2- (diddohexylphosphino^^-dimethoxy^^^-triisopropyMT-biphenyl (Brett-Phos), 2-dicyclohexylphosphino-2',6'-dimethoxybiphenyl (SPhos), 2- diddohexylphosphino ^^-diisopropoxybiphenyl (RuPhos), 2-(di-t-butylphosphine)-3-methoxy-6-methyl-2',4',6'-tri-i-propyl-1,1'-biphenyl (RockPhos) and 2-di-tert-butylphosphine-2',4',6'-triisopropylbiphenyl (tert-ButylXPhos), it is possible to use hot corresponding precatalysts, such as chloro-[2-(dicyclohexylphosphine)-3,6. -dimethoxy-2',4',6'-triisopropyl-1, 1'-biphenyl][2-(2-aminoethyl)-phenyl]palladium(II) (BrettPhos precatalyst) [cf., e.g., S. L. Buchwald et al., Chem. Sci. 2013, 4, 916], optionally together with additional phosphine ligands, such as 2-(dicyclohexylphosphine)-3,6-dimethoxy-2',4',6'-triisopropyl-1,1 '-biphenyl (Brett-Phos). )-3,6-dimethoxy-2',4',6'-triisopropyl-1,1'-biphenyl][2-(2-aminoethyl)phenyl]palladium(II) (BrettPhos precatalyst).

[0353] The conversion (XI) + (XII) ^ (XIII) is carried out in the presence of a suitable base. Suitable bases for this conversion are the usual inorganic or organic bases. They preferably include alkali metal or alkaline earth metal carbonates, such as lithium carbonate, sodium carbonate, potassium carbonate, calcium carbonate or cesium carbonate, alkali metal or alkaline earth metal hydroxides, such as sodium hydroxide, potassium or barium hydroxide, alkali or alkaline earth metal phosphates such as potassium phosphate, alkali metal alkoxides such as sodium tert-butoxide or potassium tert-butoxide and sodium methoxide, alkali metal phenoxides such as phenoxide sodium, amides such as sodium amide, lithium bis(trimethylsilyl)amide, sodium bis(trimethylsilyl)amide or potassium bis(trimethylsilyl)amide or lithium diisopropylamide or organic amines such as 1,5-diazabicyclo [4.3.0 ]non-5-ene (DBN), 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU). Preference is given to the use of cesium carbonate, potassium carbonate, sodium tert-butoxide or potassium tert-butoxide or lithium bis(trimethylsilyl)amide.

[0354] The process step (XI) + (XII) ^ (XIII) is generally conducted in a temperature range of 0°C to + 200°C, preferably + 10°C to + 150°C. Conversions can also be carried out in closed containers (microwave tubes) in the microwave. The conversion can be carried out at standard, elevated or reduced pressure (e.g. from 0.5 to 5 bar). Operations generally take place at standard pressure or in closed containers (microwave tubes) below or above the boiling point of the solvent used. Preference is given to reactions in closed containers (microwave tubes), at temperatures above the boiling point of the solvent and under high pressure, with or without the use of a microwave.

[0355] The separation of the protecting group in the reaction step (XIII) ^ (XIV) is carried out here by the usual methods known from protecting group chemistry, preferably by reaction with acid, for example, trifluoroacetic acid, hydrogenolysis in the presence of a palladium catalyst, e.g., palladium on activated carbon, in an inert solvent, e.g., ethanol or ethyl acetate [see also, e.g., T.W. Greene and P.G.M. Wuts, Protective Groups in Organic Synthesis, Wiley, New York, 1999].

[0356] Inert solvents for process step (XIV) ^ (XV) are, for example, ethers, such as diethyl ether, dioxane, tetrahydrofuran, glycol dimethyl ether or diethylene glycol dimethyl ether, hydrocarbons, such as benzene, toluene, xylene, hexane, cyclohexane or mineral oil fractions, halohydrocarbons such as dichloromethane, trichloromethane, tetrachloromethane, 1,2-dichloroethane, trichlorethylene or chlorobenzene, or other solvents such as acetone, ethyl acetate, acetonitrile, pyridine, dimethyl sulfoxide, N,N-dimethylformamide, N,N-dimethylacetamide, N,N'-dimethylpropyleneurea (DMPU) or N-methylpyrrolidone (NMP). It is also possible to use mixtures of the aforementioned solvents. Preference is given to dichloromethane, tetrahydrofuran, dimethylformamide or mixtures of these solvents.

[0357] Examples of suitable phosgene derivatives used for process step (XIV) ^ (XV) are, for example, N,N'-carbonyldiimidazole (CDI), trichloromethyl chlorocarbonate (diphosgene), bis(trichloromethyl) carbonate ( triphosgene) or aryl chloroformate. Preference is given to the use of N,N'-carbonyldiimidazole (CDI).

[0358] Process step (XIV) ^ (XV) is generally conducted in a temperature range of -20°C to + 100°C, preferably 0°C to + 60°C. The conversion can be carried out at normal, elevated or reduced pressure (e.g. from 0.5 to 5 bar). Standard pressure is generally employed.

[0359] Inert solvents for process step (XV) ^ (II) are, for example, ethers, such as diethyl ether, dioxane, tetrahydrofuran, glycol dimethyl ether or diethylene glycol dimethyl ether, hydrocarbons, such as benzene, toluene, xylene, hexane, cyclohexane or mineral oil fractions, or other solvents such as acetone, ethyl acetate, acetonitrile, N,N-dimethylformamide, N,N-dimethylacetamide, N,N'-dimethylpropyleneurea (DMPU) or N-methylpyrrolidone ( NMP). It is also possible to use mixtures of the aforementioned solvents. Preference is given to dichloromethane, tetrahydrofuran, dimethylformamide or mixtures of these solvents.

[0360] Process step (XV) ^ (II) is generally conducted in a temperature range of -20°C to + 100°C, preferably 0°C to + 60°C. The conversion can be carried out at normal or elevated hydrogen pressure (e.g. from 1.0 to 100 bar). In general, high hydrogen pressure is used.

[0361] Inert solvents for process step (XVI) + (XVII-A) ^ (XVIII-A) or (XVI) + (XVII-B) ^ (XVIII-B) or (XXI) + (XXI) ^ (XXII) are, for example, ethers such as diethyl ether, dioxane, tetrahydrofuran, glycol dimethyl ether or diethylene glycol dimethyl ether, hydrocarbons such as benzene, toluene, xylene, hexane, cyclohexane or mineral oil fractions, halohydrocarbons such as dichloromethane, trichloromethane, tetrachloromethane, 1,2-dichloroethane, trichloroethylene or chlorobenzene or other solvents such as N,N-dimethylformamide, N,N-dimethylacetamide, N,N'-dimethylpropyleneurea (DMPU) or N-methylpyrrolidone (NMP). It is also possible to use mixtures of the aforementioned solvents. Preference is given to dichloromethane.

[0362] The process step (XVI) + (XVII-A) ^ (XVIII-A) or (XVI) + (XVII-B) ^ (XVIII-B) or (XXI) + (XXI) ^ (XXII) is generally conducted at a range of temperatures from -20°C to +100°C, preferably 0°C to +60°C. The conversion can be carried out at normal, elevated or reduced pressure (for example from 0.5 to 5 bar). Standard pressure is generally employed.

[0363] Inert solvents for process step (XVI) + (XVII-A) ^ (XVIII-A) or (XVI) + (XVII-B) ^ (XVIII-B) or (XXI) + (XXI) ^ (XXII) are, for example, ethers such as dioxane, tetrahydrofuran, glycol dimethyl ether or diethylene glycol dimethyl ether, hydrocarbons such as benzene, toluene, xylene, hexane, cyclohexane or mineral oil fractions, halohydrocarbons such as trichloromethane , tetrachloromethane, 1,2-dichloroethane, trichloroethylene or chlorobenzene or other solvents such as acetone, ethyl acetate, acetonitrile, pyridine, dimethyl sulfoxide, N,N-dimethylformamide, N,N-dimethylacetamide, N,N'-dimethylpropyleneurea (DMPU ) or N-methylpyrrolidone (NMP). It is also possible to use mixtures of the aforementioned solvents. Preference is given to N,N-dimethylformamide.

[0364] The process step (XVI) + (XVII-A) ^ (XVIII-A) or (XVI) + (XVII-B) ^ (XVIII-B) is generally conducted at a temperature range of 20°C to + 100°C, preferably from 0°C to + 60°C, 20°C to + 250°C, preferably 100°C to + 200°C. The conversion can be carried out at normal, elevated or reduced pressure (e.g. from 0.5 to 5 bar). Standard pressure is generally employed.

[0365] Inert solvents for process step (XVIII-A) ^ (XIX-A) or (XVIII-B) ^ (XIX-B) are, for example, ethers, such as diethyl ether, dioxane, tetrahydrofuran, glycol dimethyl ether or diethylene glycol dimethyl ether, hydrocarbons such as benzene, toluene, xylene, hexane, cyclohexane or mineral oil fractions, halohydrocarbons such as dichloromethane, trichloromethane, tetrachloromethane, 1,2-dichloroethane, trichlorethylene or chlorobenzene, or others solvents such as acetone, ethyl acetate, acetonitrile, pyridine, dimethyl sulfoxide, N,N-dimethylformamide, N,N-dimethylacetamide, N,N'-dimethylpropyleneurea (DMPU) or N-methylpyrrolidone (NMP). It is also possible to use mixtures of the aforementioned solvents. Preference is given to dichloromethane and acetonitrile.

[0366] The process step (XVIII-A) ^ (XIX-A) or (XVIII-B) ^ (XIX-B) is generally conducted in a temperature range of 20°C to + +250°C, preferably 100°C to + +200°C. The conversion can be carried out at normal, elevated or reduced pressure (e.g. from 0.5 to 5 bar). Standard pressure is generally employed.

[0367] Any hydroxyl, amino and/or amide groups present in the starting compounds of Formulas (II) and (VII) can, if appropriate or necessary, also be used in temporarily protected form and then released again at the end of the reaction sequence particular [with regard to the suitability, introduction and removal of these protective groups, see, for example, T.W. Greene and P.G.M. Wuts, Protective Groups in Organic Synthesis, Wiley, New York, 1999].

[0368] Other compounds of the invention can optionally also be prepared by conversions of functional groups of individual substituents, especially those listed for R3, R4, R5, R6, R7, R8, R9, from the compounds of Formula (I) obtained by previous processes. Such conversions are conducted by the usual methods known to those skilled in the art and include, for example, reactions such as nucleophilic and electrophilic substitutions, oxidations, reductions, hydrogenations, transition metal catalyzed coupling reactions, eliminations, alkylation, amination, esterification, hydrolysis of ester, etherification, ether hydrolysis, formation of carbonamides, dehydrations and introduction and removal of temporary protecting groups.

[0369] Detailed procedures can also be found in the experiment, in the section on the preparation of starting and intermediate compounds. Explanations for the figures:

[0370] Figure 1: Example 237 in a complex with pork PREP.

[0371] Figure 2: Example 358 in a complex with pork PREP.

[0372] Figure 3: Example 454 in a complex with pork PREP.

[0373] Figure 4: Example 108 in a complex with pork PREP.

[0374] Figure 5: Example 113 in a complex with pork PREP.

[0375] Figure 6: Example 157 in a complex with pork PREP.

[0376] Figure 7: Example 026 in a complex with pork PREP.

[0377] The compounds of the invention have valuable pharmacological properties and can be used to prevent and treat diseases in humans and animals.

[0378] The compounds of the invention are potent and chemically stable inhibitors of human prolyl endopeptidase (PREP, PE, prolyl oligopeptidase, POP) and are, therefore, suitable for the treatment and/or prevention of disorders and pathological processes, especially those where PREP or the PREP product PGP (proline-glycine-proline) is involved in the course of an infectious or non-infectious inflammation event and/or tissue or vessel reconstruction.

[0379] In the context of the present invention, these diseases especially include airway and lung disorders, such as chronic obstructive pulmonary disease (COPD), cystic fibrosis (mucoviscidosis, CF), asthma and the group interstitial lung diseases (ILDs), and disorders of the cardiovascular system, such as arteriosclerosis and myocarditis.

[0380] Forms of COPD include especially cigarette smoke-induced pulmonary emphysema, chronic bronchitis (CB), pulmonary hypertension in COPD (PH-COPD), bronchiectasis (BE) and combinations thereof, especially in acute stages of disease exacerbation (AE-COPD) .

[0381] Forms of asthma include asthmatic disorders of different severity, with intermittent or persistent character, such as refractory asthma, bronchial asthma, allergic asthma, intrinsic asthma, extrinsic asthma and asthma induced by medication or dust.

[0382] The group interstitial lung diseases (ILDs) includes idiopathic pulmonary fibrosis (IPF), pulmonary sarcoidosis and acute interstitial pneumonia, non-specific interstitial pneumonia, lymphoid interstitial pneumonia, respiratory bronchiolitis with interstitial lung disorder, cryptogenic organizing pneumonia, desquamative interstitial pneumonia and classifiable idiopathic interstitial pneumonia, and also granulomatous interstitial lung disorders, interstitial lung disorders of known cause, and other interstitial lung disorders of unknown cause.

[0383] The compounds of the invention can also be used for the treatment and/or prevention of other airway and lung disorders, for example, pulmonary arterial hypertension (PAH) and other forms of pulmonary hypertension (PH), bronchiolitis obliterans, acute respiratory distress syndrome (ARDS), acute lung damage (ALI), alpha-1 antitrypsin deficiency (AATD) and cystic fibrosis (CF), various forms of bronchitis (chronic bronchitis, infectious bronchitis, eosinophilic bronchitis), bronchiectasis , pneumonia, farmer's lung and related diseases, cough and cold-type illnesses with infectious and non-infectious causes (chronic inflammatory cough, iatrogenic cough), inflammation of the mucous membrane (including rhinitis drug, vasomotor rhinitis and seasonally allergic rhinitis, e.g. hay fever) and polyps.

[0384] The compounds of the invention can also be used for the treatment and/or prevention of cardiovascular disorders, for example, high blood pressure (hypertension), heart failure, coronary artery diseases, stable and unstable angina pectoris, renal hypertension, peripheral disorders and cardiovascular disorders, arrhythmias, rhythm disorders of the atria and ventricles and conduction disorders, for example, atrioventricular blocks of degrees I-III, supraventricular tachycardia, atrial fibrillation, atrial flutter, ventricular fibrillation, ventricular flutter, ventricular tachycardia, Torsade de pointes tachycardia, atrial and ventricular extrasystoles, AV junctional extrasystoles, sick sinus syndrome, syncope, AV nodal reentry tachycardia, Wolff-Parkinson-White syndrome, acute coronary syndrome (ACS), autoimmune heart diseases (pericarditis, endocarditis, valvolitis, aortitis, cardiomyopathies), boxer cardiomyopathy, aneurysms, shock, such as cardiogenic shock, septic shock and anaphylactic shock and also for treatment and/or prevention of thromboembolic disorders and ischemia such as myocardial ischemia, myocardial infarction, stroke, cardiac hypertrophy, attacks transient and ischemic disorders, pre-eclampsia, cardiovascular inflammatory disorders, spasms of the coronary arteries and peripheral arteries, edema formation, such as pulmonary edema, cerebral edema, renal edema or edema caused by heart failure, peripheral circulatory disorders, reperfusion damage, arterial and venous thromboses, microalbuminuria, myocardial failure, endothelial dysfunction, micro- and macrovascular damage (vasculitis) and also to prevent restenosis, for example, after thrombolysis therapies, percutaneous transluminal angioplasties (PTA), percutaneous transluminal coronary angioplasties ( PTCA), heart transplants and bypass operations.

[0385] In the context of the present invention, the term “heart failure” encompasses acute and chronic forms of heart failure and also types of specific or related diseases, such as acute decompensated heart failure, right heart failure, left heart failure, global failure, cardiomyopathy ischemic, dilated cardiomyopathy, hypertrophic cardiomyopathy, idiopathic cardiomyopathy, congenital heart disease, valvular defects, heart failure associated with valvular defects, mitral valve stenosis, mitral valve insufficiency, aortic valve stenosis, aortic valve insufficiency, tricuspid valve stenosis, tricuspid valve insufficiency, pulmonary valve stenosis, pulmonary valve insufficiency, combined heart valve defects, myocardial inflammation (myocarditis), chronic myocarditis, acute myocarditis, viral myocarditis, diabetic heart failure, alcoholic cardiomyopathy, cardiac storage disorders, and diastolic and systolic heart failure.

[0386] The compounds of the invention are also suitable for the treatment and/or prevention of renal disorders, in particular renal failure. In the context of the present invention, the terms "renal failure" encompass its acute and critical manifestations and also underlying or related renal disorders, such as renal hypoperfusion, intradialytic hypotension, obstructive uropathy, glomerulopathies, glomerulonephritis, acute glomerulonephritis, glomerulosclerosis, tubulointerstitial diseases, nephropathic disorders such as primary and congenital kidney disease, nephritis, immunological renal disorders such as renal transplant rejection and immune complex induced renal disorders, toxic substance induced nephropathy, contrast agent induced nephropathy, diabetic and non-diabetic nephropathy, pyelonephritis, cysts kidney disease, nephrosclerosis, hypertensive nephrosclerosis and nephrotic syndrome which can be characterized by diagnosis, for example, by abnormal reduction in creatinine and/or water excretion, abnormally high blood concentrations of urea, nitrogen, potassium and/or creatinine, activity of renal enzymes , for example, glutamyl synthetase, altered urine osmolarity or urine volume, elevated microalbuminuria, macroalbuminuria, lesions in glomerulae and arterioles, tubular dilation, hyperphosphatemia and/or need for dialysis. The present invention also encompasses the use of the compounds of the invention for treating and/or preventing sequelae of renal failure, for example, hypertension, pulmonary edema, heart failure, uremia, anemia, electrolyte disturbances (e.g., hyperkalemia, hyponatremia) and diseases in bone and carbohydrate metabolism.

[0387] Furthermore, the compounds of the invention are suitable for the treatment and/or prevention of disorders of the urogenital system, for example, benign prostatic syndrome (BPS), benign prostatic hyperplasia (BPH), benign prostate enlargement (BPE ), bladder outlet obstruction (BOO), lower urinary tract syndromes (LUTS), neurogenic overactive bladder (OAB), incontinence, e.g. mixed urinary incontinence, urgency urinary incontinence, stress urinary incontinence or excessive urinary incontinence ( IUM, IUU, SUI, SUI), pelvic pain, and also erectile dysfunction and female sexual dysfunction.

[0388] The compounds of the invention can also be used to treat disorders of the female reproductive system, such as uterine fibroids, endometriosis, dysmenorrhea and premature contractions. Furthermore, they are suitable for prophylaxis or treatment of hirsutism or hypertrichosis.

[0389] Furthermore, the compounds of the invention have anti-inflammatory action and can, therefore, be used as anti-inflammatory agents for the treatment and/or prevention of sepsis (SIRS), multiple organ failure (MODS, MOF), disorders kidney inflammation, chronic intestinal inflammation (IBD, Crohn's disease, ulcerative colitis), pancreatitis, peritonitis, cystitis, urethritis, prostatitis, epidymitis, oophoritis, salpingitis, vulvovaginitis, rheumatoid disorders, osteoarthritis, inflammatory disorders of the central nervous system, multiple sclerosis , inflammatory skin disorders and inflammatory eye disorders.

[0390] The compounds of the invention are also suitable for treating and/or preventing fibrotic diseases of internal organs, for example, lung, heart, kidney, bone marrow and, in particular, the liver, in addition to dermatological fibrosis and fibrotic diseases of the eye. In the context of the present invention, the term "fibrotic disorders" includes in particular disorders such as liver fibrosis, cirrhosis of the liver, pulmonary fibrosis, endomyocardial fibrosis, nephropathy, glomerulonephritis, interstitial renal fibrosis, fibrotic damage resulting from diabetes, bone marrow fibrosis, peritoneal and similar fibrotic disorders, scleroderma, morphea, keloids, hypertrophic scarring, nevus, diabetic retinopathy, proliferative vitreoretinotopathy, and connective tissue disorders (e.g., sarcoidosis). The compounds of the invention can also be used to promote wound healing, to control post-operative scarring, for example after glaucoma operations and cosmetically against aging or keratinized skin.

[0391] The compounds of the invention can also be used for the treatment and/or prevention of anemias, such as hemolytic anemias, in particular hemoglobinopathies, such as sickle cell anemia and thalassemias, megaloblastic anemias, iron deficiency anemias, anemias due to acute blood loss , displacement anemias and aplastic anemias.

[0392] Furthermore, the compounds of the invention are suitable for the treatment of cancers, for example, skin cancer, brain tumors, breast cancer, bone marrow tumors, leukemias, liposarcomas, carcinomas of the gastrointestinal tract, liver, pancreas, lung, kidney, ureter, prostate and genital tract and also from malignant tumors of the lymphoproliferative system, for example, Hodgkin's and non-Hodgkin's lymphoma.

[0393] Furthermore, the compounds of the invention can be used for the treatment and/or prevention of arteriosclerosis, impaired lipid metabolism and dyslipidemias (hypopoproteinemia, hypertriglyceridemia, hyperlipidemia, combined hyperlipidemias, hypercholesterolemia, abetalipoproteinemia, sitosterolemia), xanthomatosis, Tangier disease, adiposity, obesity, metabolic disorders (metabolic syndrome, hyperglycemia, insulin-dependent diabetes, non-insulin-dependent diabetes, gestational diabetes, hyperinsulinemia, insulin resistance, glucose intolerance and diabetic sequelae such as retinopathy, nephropathy and neuropathy) , disorders of the gastrointestinal tract and abdomen (glossitis, gingivitis, periodontitis, esophagitis, eosinophilic gastroenteritis, mastocytosis, Crohn's disease, colitis, proctitis, anal itching, diarrhea, celiac disease, hepatitis, liver fibrosis, liver cirrhosis, pancreatitis and cholecystitis) , central nervous system disorders and neurodegenerative disorders (stroke, Alzheimer's disease, Parkinson's disease, dementia, epilepsy, depression, multiple sclerosis), immune disorders, thyroid disorders (hyperthyroreosis), skin disorders (psoriasis, acne, eczema, neurodermatitis, various forms of dermatitis, e.g. abacribus dermatitis, actinic dermatitis, allergic dermatitis, ammoniacal dermatitis, factitious dermatitis, autogenic dermatitis, atopic dermatitis, caloric dermatitis, combustionis dermatitis, freezer dermatitis, cosmetic dermatitis, escharotic dermatitis, exfoliative dermatitis , gangrenous dermatitis, stasis dermatitis, herpetiform dermatitis, lichenoid dermatitis, linear dermatitis, malignant dermatitis, medicinal eruption dermatitis, palmar and plantar dermatitis, parasitic dermatitis, photoallergic contact dermatitis, phototoxic dermatitis, pustular dermatitis, seborrheic dermatitis, sunburn, dermatitis toxic, Meleney's ulcer, dermatitis veneata, infectious dermatitis, pyrogenic dermatitis and perioral dermatitis and also keratitis, bolosis, vasculitis, cellulitis, panniculitis, lupus erythematosus, erythema, lymphomas, skin cancer, Sweet's syndrome, Weber-Christian syndrome, scar formation, wart formation, coldness), blepharitis, conjunctivitis, iritis, uveitis, chorioiditis, ophthalmitis), viral diseases (caused by influenza, adeno and corona viruses, e.g. HPV, HCMV, HIV, SARS), disorders of skeletal bone and joints and also skeletal muscle (various forms of arthritis, e.g., alkaptonuric arthritis, ankylosing arthritis, dysenteric arthritis, exudative arthritis, fungal arthritis, gonorrheal arthritis, arthritis mutilans, psoriatic arthritis, purulent arthritis, rheumatic arthritis, serous, syphilitic arthritis, tuberculous arthritis, uric arthritis, pigmented villonodular arthritis, atypical arthritis, hemophilic arthritis, juvenile chronic arthritis, rheumatoid arthritis and metastatic arthritis, and also Still's syndrome, Felty's syndrome, Sjorgen's syndrome, Clutton's syndrome, Poncet's syndrome, Pott's syndrome and Reiter's syndrome, various forms of arthropathy, e.g. deforming arthropathy, neuropathic arthropathy, ovarian arthropathy, psoriatic arthropathy and tabetic arthropathy, systemic sclerosis, various forms of inflammatory myopathies, e.g. epidemic myopathy, myopathy fibrosa, myoglobinuric myopathy, myopathy ossificans, neurotic myopathy ossificans, progressive multiple progressive myopathy, purulent myopathy, rheumatic myopathy, trichinous myopathy, tropic myopathy and typhoid myopathy and also Günther's syndrome and Münchmeyer's syndrome), inflammatory changes in the arteries ( various forms of arteritis, e.g. endarteritis, mesarteritis, periarteritis, panarteritis, rheumatic arteritis, arteritis deformans, temporal arteritis, cranial arteritis, gigantocellular arteritis and granulosa arteritis and also Horton syndrome, Churg-Strauss syndrome and Takayasu arteritis), Muckle-Well syndrome, Kikuchi disease, polychondritis, dermatosclerosis and also other disorders with an inflammatory or immunological component, such as cataracts, cachexia, osteoporosis, gout, incontinence, leprosy, Sezary syndrome and paraneoplastic syndrome, in the case of rejection reactions following organ transplants and for wound healing and angiogenesis, particularly in the case of chronic wounds.

[0394] Due to their profile of biochemical and pharmacological properties, the compounds of the invention are especially suitable for the treatment and/or prevention of inflammatory lung disorders, particularly chronic obstructive pulmonary disease (COPD), pulmonary emphysema, chronic bronchitis, bronchiectasis, pulmonary hypertension in COPD (PH-COPD), acute exacerbation in COPD, cystic fibrosis (mucoviscidosis, CF), asthma and idiopathic pulmonary fibrosis (IPF), bronchiolitis obliterans syndrome (BOS) , arteriosclerosis, myocarditis and inflammatory disorders of the skin and eyes or inflammatory disorders of internal organs.

[0395] Due to their profile of biochemical and pharmacological properties, the compounds of the invention are very particularly suitable for the treatment and/or prevention of inflammatory lung disorders, particularly chronic obstructive pulmonary disease (COPD), pulmonary emphysema, chronic bronchitis, bronchiectasis, pulmonary hypertension in COPD (PH-COPD), acute exacerbation in COPD, cystic fibrosis (mucoviscidosis, CF), asthma and idiopathic pulmonary fibrosis (IPF) and bronchiolitis obliterans syndrome (BDS).

[0396] The well-characterized diseases mentioned above in humans can also occur with comparable etiology in other mammals and can likewise be treated with the compounds of the present invention.

[0397] In the context of the present invention, the term "treatment" or "treat" includes inhibiting, delaying, checking, alleviating, mitigating, restricting, reducing, suppressing, repelling or curing a disease, a condition, a disorder, an injury or a health problem or the development, course or progression of such conditions and/or symptoms of such conditions. The term "therapy" is understood as synonymous with the term "treatment".

[0398] The terms "prevention", "prophylaxis" and "prevention" are used synonymously in the context of the present invention and refer to the avoidance or reduction of the risk of contracting, feeling, suffering from or having a disease, a condition, a disorder, an injury or a health problem or a development or advancement of these states and/or the symptoms of these states.

[0399] The treatment or prevention of a disease, a condition, a disorder, an injury or a health problem can be partial or complete.

[0400] The present invention further provides the use of the compounds of the invention for the treatment and/or prevention of disorders, especially the aforementioned disorders.

[0401] The present invention also offers the use of the compounds of the invention for the production of a medicine for the treatment and/or prevention of diseases, especially the diseases mentioned above.

[0402] The present invention further provides a medicament comprising at least one of the compounds of the invention for the treatment and/or prevention of disorders, especially the aforementioned disorders.

[0403] The present invention further provides the use of the compounds of the invention in a method for treating and/or preventing disorders, especially the aforementioned disorders.

[0404] The present invention further provides a method of treating and/or preventing disorders, especially the aforementioned disorders, using an effective amount of at least one of the compounds of the invention.

[0405] The compounds of the invention can be used alone, if necessary, in conjunction with one or more pharmacologically active substances, as long as this combination does not cause undesirable and unacceptable side effects. Therefore, the present invention also provides medicaments comprising at least one of the compounds of the invention and one or more additional medicaments, especially for the treatment and/or prevention of the aforementioned disorders. Preferred examples of combination active ingredients suitable for this purpose include: • organic nitrates and NO donors, for example, sodium nitroprusside, nitroglycerin, isosorbide mononitrate, isosorbide dinitrate, molsidomine or SIN-1 and inhalant NO; • compounds that inhibit the degradation of cyclic guanosine monophosphate (cGMP) and/or cyclic adenosine monophosphate (cAMP), for example, phosphodiesterase (PDE) 1, 2, 3, 4 and/or 5 inhibitors, especially PDE 5 inhibitors , such as sildenafil, vardenafil, tadalafil, udenafil, desantafil, avanafil, midrodenafil, or lodenafil; • NO-independent and hemoindependent soluble guanylate cyclase (sGC) activators such as, in particular, the compounds described in WO 01/19355, WO 01/19776, WO 01/19778, WO 01/19780, WO 02/070462 and WO 02/070510; • NO-independent but hemoindependent soluble guanylate cyclase (sGC) stimulators, such as, in particular, riociguat and the compounds described in WO 00/06568, WO 00/06569, WO 02/42301, WO 03/095451, WO 2011/147809, WO 2012/004258, WO 2012/028647 and WO 2012/059549; • prostacyclin analogues and IP receptor agonists, by way of example and preferably iloprost, beraprost, treprostinil, epoprostenol or selexipag; • edothelin receptor antagonists, for example and preferably bosentan, darusentan, ambrisentan or sitax-sonan; • compounds that inhibit human neutrophil elastase (HNE), for example and preferably sivelestat or DX-890 (reltran); • compounds that inhibit the signal transduction cascade, by way of example and preferably from the group of kinase inhibitors, in particular from the group of tyrosine kinase and/or serine/threonine kinase inhibitors, by way of example and with preference nintedanib, dasatinib, nilotinib, bosutinib, regorafenib, sorafenib, sunitinib, cediranib, axitinib, telatinib, imatinib, brivib, Pazopanib, vatalanib, gefitinib, erlotinib, lapatinib, canertinib, lestaurinib, pelitinib, semaxanib or tandutinib; • compounds that inhibit the degradation and alteration of the extracellular matrix, for example and with preferential inhibitors of matrix metalloproteases (MMPs), especially inhibitors of stromelysin, collagenases, gelatinases and aggrecanases (in this context particularly of MMP-1, MMP- 3, MMP-8, MMP-9, MMP-10, MMP-11 and MMP-13) and metalloelastase (MMP-12); • compounds that block the binding of serotonin to its receptor, for example and with preferred 5-HT2B receptor antagonists, such as PRX-08066; • antagonists of growth factors, cytokines and chemokines, by way of example and preferably antagonists of TGF-β, CTGF, IL-1, IL-4, IL-5, IL-6, IL-8, IL-13 and integrins; • Rho kinase inhibitor compounds, by way of example and preferably fasudil, Y-27632, SLx-2119, BF-66851, BF-66852, BF-66853, KI-23095 or BA-1049; • compounds that inhibit soluble epoxide hydrolase (sEH), e.g. N,N'-dicyclohexylurea, 12-(3-adamantan-1-ylureido)dodecanoic acid or 1-adamantan-1-yl-3-{5 -[2-(2-ethoxy ethoxy)ethoxy]pentyl}urea; • compounds that influence the energy metabolism of the heart, such as, for example, and preferably, etomoxir, dichloroacetate, ranolazine and trimetazidine; • anti-obstructive agents, as used, for example, for the treatment of chronic obstructive pulmonary disease (COPD) or bronchial asthma, by way of example and with preference from the group of agonists administered via inhalation or systemically of the β-adrenergic receptor (|. 3-mimetics) and antimuscarinergic substances administered via inhalation; • anti-inflammatory, immunomodulatory, immunosuppressive and/or cytotoxic agents, by way of example and preferably from the group of corticosteroids administered systemically or by inhalation and also acetylcysteine, montelukast, azathioprine, cyclophosphamide, hydroxycarbamide, azithromycin, pirfenidone or etanercept; • antifibrotic agents, by way of example and preferably, adenosine A2b receptor antagonists, sphingosine-1-phosphate receptor 3 (S1P3) antagonists, autotaxin inhibitors, lysophosphatidic acid receptor 1 (LPA-1) antagonists and lysophosphatidic acid receptor 2 (LPA-2), lysyl oxidase (LOX) inhibitors, lysyl oxidase 2-type inhibitors, CTGF inhibitors, IL-13 antagonists, αvβ6-integrin antagonists, TGF-β antagonists, pathway inhibitors Wnt signaling or CCR2 antagonists; • antithrombotic agents, for example and preferably from the group of platelet aggregation inhibitors, anticoagulants and profibrinolytic substances; • hypotensive active ingredients, by way of example and preferably from the group of calcium antagonists, angiotensin AII antagonists, ACE inhibitors, vasopeptidase inhibitors, endothelin antagonists, renin inhibitors, α receptor blockers, receptor blockers β, mineralocorticoid receptor antagonists and also diuretics; • modifiers of lipid metabolism, by way of example and preferably from the group of thyroid receptor agonists, cholesterol synthesis inhibitors, by way of example and preferably inhibitors of the synthesis of HMG-CoA reductase or squalene, ACAT inhibitors, CETP inhibitors, MTP inhibitors, PPAR-α, PPAR-γ and/or PPAR-δ agonists, cholesterol absorption inhibitors, lipase inhibitors, polymeric bile acid adsorbents, bile acid reabsorption inhibitors and lipoprotein antagonists ( The); and/or • chemotherapies such as those used, for example, for the therapy of neoplasms in the lung or other organs.

[0406] In a preferred embodiment of the invention, the compounds of the invention are administered in combination with a β adrenergic receptor agonist, by way of example and preferably albuterol, isoproterenol, metaproterenol, terbutalin, fenoterol, formoterol, reproterol, salbutamol or salmeterol .

[0407] In a preferred representation of the invention, the compounds of the invention are administered in combination with an antimuscarinergic substance, by way of example and preferably ipratropium bromide, tiotropium bromide or oxitropium bromide.

[0408] In a preferred embodiment of the invention, the compounds of the invention are administered in combination with a corticosteroid, by way of example and preferably prednisone, prednisolone, methylprednisolone, triamcinolone, dexamethasone, beclomethasone, betamethasone, flunisolide, budesonide or fluticasone .

[0409] Antithrombotic agents are preferably understood to mean compounds from the group of platelet aggregation inhibitors, anticoagulants and profibrinolytic substances.

[0410] In a preferred representation of the invention, the compounds of the invention are administered in combination with a platelet aggregation inhibitor, by way of example and preferably aspirin, clopidogrel, ticlopidine or dipyridamole.

[0411] In a preferred embodiment of the invention, the compounds of the invention are administered in combination with a thrombin inhibitor, by way of example and preferably ximelagatran, melagatran, dabigatran, bivalirudin or clexane.

[0412] In a preferred representation of the invention, the compounds of the invention are administered in combination with a GPIIb/IIIa antagonist, by way of example and preferably girofiban or abciximab.

[0413] In a preferred embodiment of the invention, the compounds of the invention are administered in combination with a factor PMD-3112, YM-150, KFA-1982, EMD-503982, MCM-17, MLN-1021, DX 9065a, DPC 906, JTV 803, SSR-126512 or SSR-128428.

[0414] In a preferred embodiment of the invention, the compounds of the invention are administered in combination with heparin or a low molecular weight heparin derivative (LMW).

[0415] In a preferred representation of the invention, the compounds of the invention are administered in combination with a vitamin K antagonist, by way of example and preferably coumarin.

[0416] Hypotensive agents are preferably understood to mean compounds from the group of calcium antagonists, angiotensin AII antagonists, ACE inhibitors, endothelin antagonists, renin inhibitors, α-receptor blockers, β-receptor blockers, mineralocorticoids and diuretics.

[0417] In a preferred representation of the invention, the compounds of the invention are administered in combination with a calcium antagonist, by way of example and preferably nifedipine, amlodipine, verapamil or diltiazem.

[0418] In a preferred representation of the invention, the compounds of the invention are administered in combination with an α1 receptor blocker, by way of example, and preferably Prazosin.

[0419] In a preferred embodiment of the invention, the compounds of the invention are administered in combination with a β-receptor blocker, by way of example and preferably propranolol, atenolol, timolol, pindolol, alprenolol, oxprenolol, penbutolol, bupranolol, metipranolol, nadolol, mepindolol, carazalol, sotalol, metoprolol, betaxolol, celiprolol, bisoprolol, carteolol, esmolol, labetalol, carvedilol, adaprolol, landiolol, nebivolol, epanolol or bucindolol.

[0420] In a preferred embodiment of the invention, the compounds of the invention are administered in combination with an angiotensin AII antagonist, by way of example and preferably losartan, candesartan, valsartan, telmisartan, embursaran, irbesartan, olmesartan, eprosartan or azilsartan or a dual angiotensin AII antagonist/NEP inhibitor, for example and preferably LCZ696 (valsartan/sacubitrile).

[0421] In a preferred embodiment of the invention, the compounds of the invention are administered in combination with an ACE inhibitor, by way of example and preferably enalapril, captopril, lisinopril, ramipril, delapril, fosinopril, quinopril, perindopril or trandopril.

[0422] In a preferred representation of the invention, the compounds of the invention are administered in combination with an endothelin antagonist, by way of example and preferably bosentan, darusentan, ambrisentan or sitaxsentan.

[0423] In a preferred representation of the invention, the compounds of the invention are administered in combination with a renin inhibitor, by way of example and preferably aliskiren, SPP-600 or SPP-800.

[0424] In a preferred embodiment of the invention, the compounds of the invention are administered in combination with a mineralocorticoid receptor antagonist, by way of example and preferably spironolactone, eplerenone or finerenone.

[0425] In a preferred embodiment of the invention, the compounds of the invention are administered in combination with a diuretic, by way of example and preferably furosemide, bumetanide, torsemide, bendroflumethiazide, chlorothiazide, hydrochlorothiazide, hydroflumethiazide, methiclothiazide, polythiazide, trichlormethiazide , chlorthalidone, indapamide, metolazone, quinetazone, acetazolamide, dichlorphenamide, methazolamide, glycerol, isosorbide, mannitol, amiloride or triamterene.

[0426] Lipid metabolism modifiers are preferably understood to mean compounds from the group of CETP inhibitors, thyroid receptor agonists, cholesterol synthesis inhibitors, such as HMG-CoA reductase inhibitors or squalene synthesis inhibitors, cholesterol inhibitors. ACAT, MTP inhibitors, PPAR-α, PPAR-γ and/or PPAR-δ agonists, cholesterol absorption inhibitors, polymeric bile acid adsorbents, bile acid reabsorption inhibitors, lipase inhibitors and lipoprotein (a) antagonists .

[0427] In a preferred representation of the invention, the compounds of the invention are administered in combination with a CETP inhibitor, by way of example and preferably torcetrapib (CP-529 414), JJT-705 vaccine or CETP (Avant).

[0428] In a preferred representation of the invention, the compounds of the invention are administered in combination with a thyroid receptor agonist, by way of example and preferably D-thyroxine, 3,5,3'-triiodothyronine (T3) , CGS 23425 or axithyromous (CGS 26214).

[0429] In a preferred embodiment of the invention, the compounds of the invention are administered in combination with an HMG-CoA reductase inhibitor of the statin class, by way of example and preferably lovastatin, simvastatin, pravastatin, fluvastatin, atorvastatin, rosuvastatin or pitavastatin.

[0430] In a preferred representation of the invention, the compounds of the invention are administered in combination with a squalene synthesis inhibitor, by way of example and preferably BMS-188494 or TAK-475.

[0431] In a preferred representation of the invention, the compounds of the invention are administered in combination with an ACAT inhibitor, by way of example and preferably avasimib, melinamide, pactimibe, eflucimib or SMP-797.

[0432] In a preferred representation of the invention, the compounds of the invention are administered in combination with an MTP inhibitor, by way of example and preferably implitapide, BMS-201038, R-103757 or JTT-130.

[0433] In a preferred representation of the invention, the compounds of the invention are administered in combination with a PPAR-γ agonist, by way of example and preferably pioglitazone or rosiglitazone.

[0434] In a preferred representation of the invention, the compounds of the invention are administered in combination with a PPAR-δ agonist, by way of example and preferably GW 501516 or BAY 68-5042.

[0435] In a preferred embodiment of the invention, the compounds of the invention are administered in combination with a cholesterol absorption inhibitor, by way of example and preferably ezetimibe, tichiside or pamaqueside.

[0436] In a preferred representation of the invention, the compounds of the invention are administered in combination with a lipase inhibitor, by way of example and preferably orlistat.

[0437] In a preferred representation of the invention, the compounds of the invention are administered in combination with a polymeric bile acid adsorber, by way of example and preferably cholestyramine, colestipol, colesolvam, CholestaGel or colestimide.

[0438] In a preferred representation of the invention, the compounds of the invention are administered in combination with a bile acid reabsorption inhibitor, by way of example and preferably ASBT inhibitors (= IBAT), for example AZD-7806, S- 8921, AK-105, BARI-1741, SC-435 or SC-635.

[0439] In a preferred representation of the invention, the compounds of the invention are administered in combination with a lipoprotein (a) antagonist, by way of example and preferably gemcabene-calcium (CI-1027) or nicotinic acid.

[0440] Particular preference is given to combinations of the compounds of the invention with one or more active ingredients selected from the group consisting of PDE 5 inhibitors, sGC activators, sGC stimulators, prostacyclin analogues, IP receptor agonists, antagonists endothelin, compounds that inhibit the signal transduction cascade and pirfenidone.

[0441] The present invention also provides medicaments comprising at least one compound of the invention, generally together with one or more inert, non-toxic, pharmaceutically suitable excipients for use in the purposes mentioned above.

[0442] The compounds of the invention can act systemically and/or locally. For this purpose, they may be administered in a suitable manner, for example, orally, parenterally, pulmonaryly, nasally, sublingually, lingually, buccally, rectally, cutaneously, transcutaneously, conjunctively or optically or as an implant or stent.

[0443] The compounds of the invention can be administered in administration forms suitable for these administration routes.

[0444] Suitable forms of administration for oral administration are those that function in accordance with the prior art and release the compounds of the invention rapidly and/or in a modified manner and that contain the compounds of the invention in crystalline and/or amorphous form and/or or dissolved, for example, tablets (uncoated or coated tablets, for example, with gastric juice-resistant or delayed-dissolving or insoluble coatings that control the release of the compound of the invention), tablets or films/oblates that disintegrate rapidly in the cavity oral, films/lyophilisates, capsules (e.g. hard or soft gelatin capsules), sugar-coated tablets, granules, pellets, powders, emulsions, suspensions, aerosols or solutions.

[0445] Parenteral administration can avoid an absorption step (e.g., occurs intravenously, intra-arterial, intracardiac, intraspinal or intralumbar) or include absorption (e.g., occurs intramuscularly, subcutaneously, intracutaneous, percutaneous or intraperitoneal). Administration forms suitable for parenteral administration include injection and infusion preparations in the form of solutions, suspensions, emulsions, lyophilisates or sterilized powders.

[0446] For other routes of administration, suitable examples are inhalation medications (including powder inhalers, nebulizers, dosing aerosols), nasal drops, solutions or sprays; tablets for lingual, sublingual or buccal administration, films/oblates or capsules, suppositories, ear or eye preparations, vaginal capsules, aqueous suspensions (lotions, shaking mixtures), lipophilic suspensions, ointments, creams, transdermal therapeutic systems (e.g. , adhesives), milk, pastes, foams, powders, implants or stents.

[0447] Oral and parenteral administrations are preferred, especially oral, intravenous and intrapulmonary (inhalant) administration.

[0448] The compounds of the invention can be converted into the aforementioned forms of administration. This can be done in a known way by mixing with inert, non-toxic and pharmaceutically suitable excipients. Such excipients include carriers (e.g., microcrystalline cellulose, lactose, mannitol), solvents (e.g., liquid polyethylene glycols, emulsifiers and dispersants or wetting agents (e.g., sodium dodecyl sulfate, polyoxysorbitan oleate), binders (e.g., polyvinylpyrrolidone ), synthetic and natural polymers (e.g. albumin), stabilizers (e.g. antioxidants, e.g. ascorbic acid), colorants (e.g. inorganic pigments, e.g. iron oxides) and flavor correctors and/or or odors.

[0449] In general, it has proven advantageous, in the case of parenteral administration, to administer amounts of approximately 0.001 to 1 mg/kg, preferably approximately 0.01 to 0.5 mg/kg, of body weight to achieve efficient results. In the case of oral administration, the dosage is approximately 0.01 to 100 mg/kg, preferably approximately 0.01 to 20 mg/kg and more preferably 0.1 to 10 mg/kg of body weight. In the case of intrapulmonary administration, the amount is generally about 0.1 to 50 mg per inhalation.

[0450] However, it may be necessary, in some cases, to deviate from the determined amounts, specifically depending on body weight, route of administration, individual response to the active ingredient, nature of the preparation and time or interval at which administration occurs. Therefore, in some cases it may be sufficient to administer less than the minimum quantity mentioned above, while in other cases the maximum limit mentioned must be exceeded. If larger quantities are administered, it may be recommended to divide them into several individual doses throughout the day.

[0451] The following functional examples illustrate the invention. The invention is not restricted to the examples.

[0452] The present invention also provides pharmaceutical compositions of medicines comprising at least one compound of the invention, generally together with one or more inert, non-toxic, pharmaceutically suitable excipients for use in the purposes mentioned above.

[0453] The compounds of the invention can act systemically and/or locally. For this purpose, they may be administered in a suitable manner, for example, orally, parenterally, pulmonaryly, nasally, sublingually, lingually, buccally, rectally, vaginally, cutaneously, transcutaneously, conjunctively or optically or as an implant or stent.

[0454] The compounds of the invention can be administered in administration forms suitable for these administration routes.

[0455] Suitable forms of administration for oral administration are those that function in accordance with the prior art and deliver the compounds of the invention rapidly and/or in a modified form and that contain the compounds of the invention in crystalline and/or amorphic form and/or or dissolved, for example, tablets (uncoated or coated tablets, e.g. with enteric coatings or insoluble or delayed-dissolving coatings, which control the release of the compound according to the invention), tablets that disintegrate rapidly in the mouth or films/wafers, films/lyophilisates, capsules (e.g., hard or soft gelatin capsules), sugar-coated tablets, granules, pellets, powders, emulsions, suspensions, aerosols or solutions.

[0456] Parenteral administration can be carried out avoiding a resorption step (for example, intravenously, intraarterial, intracardiac, intraspinal or intralumbar) or with the inclusion of a resorption (for example, intramuscularly, subcutaneously, intracutaneously , percutaneous, intravitreal or intraperitoneal). Administration forms suitable for parenteral administration include injection and infusion preparations in the form of solutions, suspensions, emulsions, lyophilisates or sterilized powders.

[0457] Suitable forms of administration for other routes of administration are, for example, pharmaceutical inhalation forms (including powder inhalers, nebulizers), nasal drops, solutions or sprays; tablets for lingual, sublingual or buccal administration, films/wafers or capsules, suppositories, eye drops, eye ointments, eye wash preparations, eye inserts, ear preparations, sprays, powders, washing liquid or tampons, vaginal capsules, aqueous suspensions (lotions, shaking mixtures), lipophilic suspensions, emulsions, microemulsions, ointments, creams, transdermal therapeutic systems (e.g. patches), milk, pastes, foams, powders, implants or stents.

[0458] The compounds of the invention can be converted into the aforementioned forms of administration. This can be accomplished in a known manner by mixing with pharmaceutically suitable excipients. These excipients include • fillers and carriers (e.g. cellulose, microcrystalline cellulose, e.g. Avicel®, lactose, mannitol, starch, calcium phosphate, e.g. Di-Cafos®), • ointment bases (e.g. petroleum jelly, paraffins, triglycerides, waxes, wool wax, wool wax alcohols, lanolin, hydrophilic ointment, polyalkylene glycols), • suppository base (e.g. polyalkylene glycols, cocoa butter, hard fat), • solvents (e.g. water , ethanol, isopropanol, glycerol, propylene glycol, fatty oils, medium chain triglycerides, liquid polyethylene glycols, paraffins), • surfactants, emulsifiers, dispersants or wetting agents (e.g. sodium dodecyl sulfate, lecithin, phospholipids, alcohols fatty acids, e.g. Lanette®, sorbitan fatty acid esters, e.g. Span®, polyoxyethylene sorbitan fatty acid esters, e.g. Tween®, polyoxyethylene fatty acid glycerides, e.g. Cremophor®, ethers of polyoxyethylene fatty alcohols, glycerol fatty acid esters, poloxamers, e.g. Pluronic®), • buffering substances and also acids and bases (e.g. phosphates, carbonates, citric acid, acetic acid, hydrochloric acid, sodium hydroxide , ammonium carbonate, trometamol, triethanolamine), • isotonic agents (e.g. glucose, sodium chloride), • adsorbents (e.g. finely divided silicas), • viscosity increasing agents, gel formers, thickeners or binders (e.g. polyvinylpyrrolidone, methyl cellulose, hydroxypropyl methyl cellulose, hydroxypropyl cellulose, sodium carboxymethyl cellulose, starch, carbomers, polyacrylic acids, e.g. Carbopol®, alginates, gelatins), • disintegrants (e.g. modified starch, sodium carboxymethyl cellulose, sodium starch glycolate, e.g. Explotab®, cross-linked polyvinylpyrrolidone, croscarmellose sodium, e.g. AcDiSol®), • flow regulators, lubricants, glidants and rust releasing agents (e.g. magnesium stearate, acid stearic acid, talc, finely divided silicas, e.g. Aerosil®), • coating agents (e.g. sugar, shellac) and film formers for rapidly dissolving or modified diffusion films or membranes (e.g. by polyvinylpyrrolidones , e.g. Kollidon®, polyvinyl alcohol, hydroxypropyl methyl cellulose, hydroxypropyl cellulose, ethyl cellulose, hydroxypropyl methyl cellulose, phthalate, cellulose acetate, cellulose acetate phthalate, polyacrylates, polymethacrylates, e.g. Eudragit®), • materials of capsules (e.g. gelatins, hydroxypropyl methyl cellulose), • synthetic polymers (e.g. polyactides, polyacrylates, polymethacrylates, e.g. Eudragit®, polyvinyl pyrrolidones, e.g. Kollidon®, polyvinyl alcohols, polyvinyl acetates, polyethylene, polyalkylene glycols and their copolymers and block copolymers), • plasticizers (e.g. polyethylene glycols, propylene glycol, glycerol, triacetin, triacetyl citrate, dibutyl phthalate), • penetration enhancers, • stabilizers (e.g. antioxidants, e.g. example, ascorbic acid ascorbyl palmitate, sodium ascorbate, butylhydroxyanisole, butylhydroxytoluene, propyl gallate), • preservatives (e.g. parabens, sorbic acid, thiomersal, benzalkonium chloride, chlorhexidine acetate, sodium benzoate), • Dyes (e.g. inorganic pigments, e.g. iron oxides, titanium dioxide), • aromas, sweeteners, flavor and/or odor correctors.

[0459] Preference is given to oral or parenteral administration, especially oral administration.

[0460] The compounds of the invention can be converted into the aforementioned forms of administration. This can be done in a known way by mixing with inert, non-toxic and pharmaceutically suitable excipients. Such excipients include carriers (e.g., microcrystalline cellulose, lactose, mannitol), solvents (e.g., liquid polyethylene glycols, emulsifiers and dispersants or wetting agents (e.g., sodium dodecyl sulfate, polyoxysorbitan oleate), binders (e.g., polyvinylpyrrolidone ), synthetic and natural polymers (e.g. albumin), stabilizers (e.g. antioxidants, e.g. ascorbic acid), colorants (e.g. inorganic pigments, e.g. iron oxides) and flavor correctors and/or or odors.

[0461] In the case of parenteral administration, it has generally been found to be advantageous to administer amounts of about 0.1 to 6 mg/kg to obtain effective results. In the case of oral administration, the dose is about 0.1 to 10 mg/kg of body weight.

[0462] However, it may be necessary, in some cases, to deviate from the determined amounts, specifically depending on body weight, route of administration, individual response to the active ingredient, nature of the preparation and time or interval at which administration occurs. Therefore, in some cases it may be sufficient to administer less than the minimum quantity mentioned above, while in other cases the maximum limit mentioned must be exceeded. If larger quantities are administered, it may be recommended to divide them into several individual doses throughout the day.

[0463] The following functional examples illustrate the invention. The invention is not restricted to the examples.

[0464] Unless otherwise defined, percentages in the following tests and examples are percentages by weight; parts by weight. The solvent ratios, dilution ratios, and concentration data for the liquid/liquid solutions in each case are based on volume. A. Examples Abbreviations and acronyms: HP LC, GC-MS and LC-MS Methods Method 1:

[0465] Instrument: Agilent MS Quad 6150; HPLC: Agilent 1290; column: Waters Acquity UPLC HSS T3 1.8 μ 50 x 2.1 mm; eluent A: 1 l water + 0.25 mL, 99% formic acid, eluent B: 1 l acetonitrile + 0.25 mL, 99% formic acid; gradient: 0.0 min 90% A ^ 0.3 min 90% A ^ 1.7 min 5% A ^ 3.0 min 5% Oven: 50°C; flow rate: 1.20 ml/min; UV detection: 205305 nm. Method 2:

[0466] Instrument: Thermo DFS, Trace GC Ultra; column: Restek RTX-35, 15 m x 200 μm x 0.33 μm; constant helium flow rate: 1.20 ml/min; oven: 60°C; inlet: 220°C; gradient: 60°C, 30°C/min. ^ 300°C (hold for 3.33 min.). Method 3:

[0467] MS instrument type: Thermo Scientific FT-MS; UHPLC+ instrument type: Thermo Scientific UltiMate 3000; column: Waters, HSST3, 2.1 x 75 mm, C18 1.8 μm; eluent A: 1 l of water + 0.01% formic acid; eluent B: 1 l of acetonitrile + 0.01% formic acid; gradient: 0.0 min 10% B^2.5 min 95% B^3.5 min 95% B; oven: 50°C; flow rate: 0.90 ml/min; UV detection: 210 nm/optimal integration path 210-300 nm Method 4:

[0468] Instrument: Waters ACQUITY SQD UPLC System; column: Waters Acquity UPLC HSS T3 1.8 μ 50 x 1 mm; eluent A: 1 l water + 0.25 mL, 99% formic acid, eluent B: 1 l acetonitrile + 0.25 mL, 99% formic acid; gradient: 0.0 min 90% A^1.2 min 5% A^2.0 min 5% A; oven: 50°C; flow rate: 0.40 ml/min; UV detection: 208-400 nm. Method 5:

[0469] Instrument: HP 1100 Series with LC/MSD SL; column: CS MultoKrom 100-3 C18 60x4.6 mm; eluent A: 1 l water + 10 mL, 99% formic acid, eluent B: 1 l + 10 mL, 99% formic acid; gradient: 0.0 min. 80% A -> 8.0 min 10% A -> 10.0 min. 10% A; flow rate: 1.00 ml/min.; DAD detection: 120 - 800 nm. Method 6:

[0470] MS Instrument: Waters (Micromass) Quattro Micro; Waters UPLC Acquity Instrument; column: Waters BEH C18 1.7 μ 50 x 2.1 mm; eluent A: 1 l of water + 0.01 mol ammonium formate, eluent B: 1 acetonitrile; gradient: 0.0 min 95% A ^ 0.1 min 95% A ^ 2.0 min 15% A ^ 2.5 min 15% A > 2.51 min 10% A ^ 3.0 min 10% A; oven: 40°C; flow rate: 0.5 ml/min; UV detection: 210 nm Method 7:

[0471] Instrument: Waters Acquity, Waters Acquity Autosampler; column: XBridge BEH C18 2.5 μm 2.1 x 50 mm (UPLC LG 500 nm); eluent A: 10 mM ammonium hydrogen carbonate pH 10, eluent B: acetonitrile; gradient: 2-98% B in 0.80 min, maintain at 98% B for 1.30 min. Method 8:

[0472] Instrument: Waters ACQUITY SQD UPLC System; column: Waters Acquity UPLC HSS T3 1.8 μ 50 x 1 mm; eluent A: 1 l water + 0.25 mL, 99% formic acid, eluent B: 1 l acetonitrile + 0.25 mL, 99% formic acid; gradient: 0.0 min 95% A^6.0 min 5% A^7.5 min 5% A; oven: 50°C; flow rate: 0.35 ml/min; UV detection: 210-400 nm. Method 9:

[0473] MS instrument type: ThermoFisher Scientific LTQ- Orbitrap-XL; HPLC instrument type: Agilente 1200SL; column: Agilent, POROSHELL 120, 3 x 150 mm, SB - C18 2.7 μm; eluent A: 1 l of water + 0.1% trifluoroacetic acid; eluent B: 1 l of acetonitrile + 0.1% trifluoroacetic acid; gradient: 0.0 min 2% B ^ 0.3 min 2% B ^ 5.0 min 95% B ^ 10.0 min 95% B; oven: 40°C; flow rate: 0.75 ml/min; UV detection: 210 nm Method 10:

[0474] Instrument: Waters Prep LC/MS System, column: XBridge C18 5μm 100x30 mm; eluent A: water, eluent B: acetonitrile, flow rate: 65 ml/min plus 5 mL of 2% formic acid in water, room temperature, wavelength 200-400 nm, column injection (full injection); gradient profile: between 0 and 2 min 10% eluent B, between 2 and 2.2 min at 20% eluent B, between 2.2 and 7 min at 60% eluent B, between 7 and 7.5 min at 92% eluent B, between 7.5 and 9 min at 92% B. Method 11:

[0475] Instrument: Waters Prep LC/MS System, column: XBridge C18 5μm 100x30 mm; eluent A: water, eluent B: acetonitrile, flow rate: 65 ml/min plus 5 mL of 2% formic acid in water, room temperature, wavelength 200-400 nm, column injection (full injection); gradient profile: between 0 and 2 min 7.5% eluent B, between 2 and 7 min at 35% eluent B, between 7 and 7.5 min at 92% eluent B, between 7.5 and 9 min at 92% B. Method 12:

[0476] Instrument: Waters Prep LC/MS System, column: XBridge C18 5μm 100x30 mm; eluent A: water, eluent B: acetonitrile, flow rate: 65 ml/min plus 5 mL of 2% ammonia in water, room temperature, wavelength 200-400 nm, column injection (full injection); gradient profile: between 0 and 2 min 7.5% eluent B, between 2 and 7 min at 35% eluent B, between 7 and 7.5 min at 92% eluent B, between 7.5 and 9 min at 92% B. Method 13:

[0477] MS Instrument: Waters SQD2; HPLC instrument: Waters UPLC; column: Zorbax SB-Aq (Agilent), 50 mm x 2.1 mm, 1.8 μm; eluent A: water + 0.025% formic acid, eluent B: acetonitrile (ULC) + 0.025% formic acid; gradient: 0.0 min 98%A - 0.9 min 25%A - 1.0 min 5%A - 1.4 min 5%A - 1.41 min 98%A - 1.5 min 98%A; oven: 40°C; flow rate: 0.600 ml/min; UV detection: DAD; 210nm. Method 14:

[0478] Instrument: Waters Prep LC/MS System, column: Phenomenex Kinetex C18 5μm 100x30 mm; eluent A: water, eluent B: acetonitrile, flow rate: 65 ml/min plus 5 mL of 2% formic acid in water, room temperature, wavelength 200-400 nm, column injection (full injection); gradient profile: between 0 and 2 min 10% eluent B, between 2 and 2.2 min at 20% eluent B, between 2.2 and 7 min at 60% eluent B, between 7 and 7.5 min at 92% eluent B, between 7.5 and 9 min at 92% B. Method 15:

[0479] Instrument: Waters Single Quad MS System; Instrument: Waters UPLC Acquity; column: Waters BEH C18 1.7 μm 50 x 2.1 mm; eluent A: 1 l water + 1.0 mL (25% ammonia)/L, eluent B: 1 l acetonitrile; gradient: 0.0 min 92% A ^ 0.1 min 92% A ^ 1.8 min 5% A ^ 3.5 min 5% Oven: 50°C; flow rate: 0.45 ml/min; UV detection: 210 nm (208-400 nm). Additional Details:

[0480] In the case of purifications of the compounds of the invention by chromatography, particularly by column chromatography, pre-packaged silica gel cartridges are used, for example, SNAP Biotage, KP-Sil® or KP-NH® cartridges, in combination with a Biotage system (SP4® or Isolera Four®). The eluents used are hexane/ethyl acetate or dichloromethane/methanol gradients.

[0481] In the case of purifications of compounds of the invention by preparatory HPLC by the methods described above in which the eluents contain additives, for example, trifluoroacetic acid, formic acid or ammonia, the compounds of the invention can be obtained in salt form, e.g. such as trifluoroacetate salt, formate or ammonium salt, if the compounds of the invention contain a sufficiently basic or acidic functionality. This salt can be converted to the corresponding free base or acid while hot by various methods known to those skilled in the art.

[0482] Furthermore, amidines may be present as free compounds or partially (depending on the preparation if acetic acid is involved) as acetate salts or acetate solvates.

[0483] In the case of synthetic intermediates and functional examples of the invention described below, any compound specified in the form of a corresponding hot base or acid salt is generally a salt of unknown exact stoichiometric composition, as obtained by the respective process preparation and/or purification. Unless specified in more detail, additions to names and structural Formulas such as "hydrochloride", "trifluoroacetate", "sodium salt” or "x hydrochloric acid, “x CF3COOH”, “x Na+” should therefore not be be understood in a stoichiometric manner in the case of these salts, but are only descriptive in relation to the salt-forming components included here.

[0484] This will apply correspondingly if the synthetic intermediates or functional examples or their salts are obtained in the form of solvates, e.g. hydrates, of unknown stoichiometric composition (if they are of a defined type) by the preparation processes and /or purification described.

[0485] Furthermore, the secondary amides according to the invention may be present as rotating isomers/mixtures of isomers, in particular in NMR studies. Purity values are generally based on hot corresponding peak integrations in the LC/MS chromatogram, but may also have been determined with the help of the 1H NMR spectrum. If purity is not indicated, purity is generally 100% according to automated integration of the peak into the LC/MS chromatogram, or purity has not been explicitly determined.

[0486] Yields stated in % of theory are generally corrected for purity if purity <100% is indicated. In batches containing solvents or contaminated, the formal yield may be ">100%"; In these cases, the yield is not corrected for solvent or purity.

[0487] In all 1H NMR spectra data, chemical shifts δ[ppm] = are indicated in ppm.

[0488] The multiplicities of proton signals in the 1H NMR spectra reported in the following paragraphs represent the signal shape observed in each case and do not take into account any higher order signal phenomena. In general, the chemical change indicated refers to the center of the signal being concerned. In the case of wide multiplets, a range is given. Signals obscured by solvent or water were temporarily assigned or not listed. Significantly broadened signals - caused, for example, by rapid rotation of molecular parts or by proton exchange - have also been assigned temporally (often referred to as a broad multiplet or broad singlet) or are not listed.

[0489] Melting points and melting point ranges, if indicated, are not corrected.

[0490] 1H NMR data from synthetic intermediates and selected functional examples are presented in the form of 1H NMR peak lists. For each signal peak, first δ[ppm]= value in ppm, and then the signal intensity in parentheses. The intensity number pairs of δ[ppm]= value/signal for different signal peaks are listed separated by semicolons. The peak list for an example therefore takes the following form: δ[ppm] = 1 (intensity1), δ[ppm] = 2 (intensity2), ... , δ[ppm] = i (intensityi), . .. , δ[ppm] = n (intensityn).

[0491] The intensity of the sharp signals is related to the height of the signals in a printed example of an NMR spectrum in cm and shows the actual relationships of the signal intensities compared to other signals. In the case of broad signals, several peaks or the center of the signal and their relative intensity can be shown in comparison to the most intense signal in the spectrum. 1H NMR peak lists are similar to conventional 1H NMR printouts and, as such, generally contain all of the peaks listed in a conventional NMR interpretation. Furthermore, like conventional 1H NMR prints, they can show solvent signals, stereoisomer signals of the target compounds, which are also provided by the invention, and/or impurity peaks. Stereoisomer peaks of target compounds and/or impurity peaks generally have a lower intensity on average than peaks of target compounds (e.g., with a purity > 90%). These stereoisomers and/or impurities may be common to the particular preparation process. Its peaks can thus help in identifying the reproduction of our preparation process with reference to "by-product fingerprints". An expert, who calculates the peaks of the target compounds by known methods (MestreC, ACD simulation or use of empirically evaluated expected values), can, if necessary, isolate the peaks of the target compounds, using additional intensity filters as an option. This isolation would be similar to peak selection being an issue in conventional 1H NMR interpretation. A detailed description of NMR data in the form of peak lists can be found in the publication "Citation of NMR Peaklist Data within Patent Applications" (cf. Research Dissemination Database No. 605005, 2014, August 1, 2014 or http://www.researchdisclosure.com/searching-disclosures). In the peak picking routine described in Research Dissemination Database #605005, the "MinimumHeight" parameter can be set between 1% and 4%. Depending on the type of chemical structure and/or depending on the concentration of the compound to be analyzed, it may be recommended to set the "MinimumHeight" parameter to values < 1%.

[0492] All reagents or reagents whose preparation is not explicitly described below were purchased commercially from generally accessible sources. For all other reagents or reagents whose preparation is also not described below and which were not commercially obtained or were obtained from sources that are not generally accessible, reference is made to published literature and their preparation is described.

[0493] In the intermediates and working examples described below, an identifier "5RS" in the IUPAC name of the example being in question, in conjunction with the term "racemate", means that this is a racemic mixture of the 5R enantiomer (^ 1st letter after the position number in "5RS") with the corresponding hot 5S enantiomers (^2nd letter after the position number). The identifier "5RS" in conjunction with the explanations of "enantiomer 1" and "enantiomer 2" means that these are the two enantiomers in separate, isolated form, without having assumed an assignment of the absolute configuration (5R or 5S) to these enantiomers. Similar identifiers, such as "5SR", that arise from changed priority and/or sequence of named constituents due to IUPAC naming rules should be interpreted analogously in accordance with these instructions.

[0494] In the intermediates and processing examples described below, an identifier "5RS, 7RS" in the IUPAC name of the example being in question, together with the term "racemate", means that this is a racemic mixture of the 5R, 7R enantiomer ( ^ 1st letter in each case after the position number in "5RS, 7RS") with the corresponding hot enantiomer 5S, 7S (^ 2nd letter in each case after the position number). The identifier "5RS",7RS” in conjunction with the explanations of "enantiomer 1" and "enantiomer 2" means that these are the two enantiomers in separate, isolated form, without having assumed an assignment of the absolute configuration (5R,7R or 5S ,7S) to these enantiomers. Similar identifiers, such as "5SR,7SR", that arise from changed priority and/or sequence of named constituents due to IUPAC naming rules should be interpreted analogously in accordance with these instructions.

[0495] The (5S) configuration was assigned based on the elucidation of the crystal structure to Examples 26, 108, 113, 157, 237, 358 and 454. In analogy, the (5S) configuration was assigned to examples 183-188 , 190-219, 275-279, 342-402, 404-415, 418-563. Starting compounds and intermediates: Intermediate 1 Methyl 3-fluoro-2-(trifluoromethyl)isonicotinate

[0496] 3-Fluoro-2-(trifluoromethyl)isocotinic acid (1.00 g, 4.78 mmol) was dissolved in methanol (10 mL) and sulfuric acid (310 μl, 5.7 mmol) was added. The reaction mixture was heated to 60°C for 30 minutes and then stirred at room temperature overnight. The reaction mixture was concentrated under reduced pressure and the residue was dissolved in ethyl acetate and washed with saturated sodium hydrogen carbonate solution. The organic phase was dried over sodium sulfate and filtered, and the filtrate was concentrated. 890 mg (70% purity, 58% possibility) of the title compound was obtained. LC-MS (Method 1): Rt = 1.15 min; MS (ESIpos): m /z = 224 [M+H]+ Intermediate 2 [3-Fluoro-2-(trifluoromethyl)pyridin-4-yl]methanol

[0497] Methyl 3-fluoro-2-(trifluoromethyl)isonicotinate (890 mg, 70% purity, 3.99 mmol) was dissolved in methanol (5.0 mL) and sodium borohydride (166 mg, 4.39 mmol) in portions at 0°C. After stirring overnight, the reaction mixture was mixed at room temperature with saturated aqueous ammonium chloride solution, and methanol was removed under reduced pressure. The residue was mixed with ethyl acetate and water. The aqueous phase was extracted three times with ethyl acetate. The combined organic phases were dried over sodium sulfate and filtered, and the filtrate was concentrated. 420 mg (54% chance) of the title compound was obtained. The compound was converted more directly. Intermediate 3 4-(Chloromethyl)-3-fluoro-2-(trifluoromethyl)pyridine hydrochloride

[0498] [3-Fluoro-2-(trifluoromethyl) pyridin-4-yl]methanol (420 mg, 2.15 mmol) was dissolved in dichloromethane (10 mL) and thionyl dichloride (310 μl, 4.3 mmol) at room temperature. After the reaction mixture was stirred at room temperature overnight, thionyl dichloride (310 µl, 4.3 mmol) and a drop of dimethylformamide were added again. The reaction mixture was stirred at room temperature for one hour and then thionyl dichloride (620 μl, 8.6 mmol) and a drop of dimethylformamide were added again. After stirring again at room temperature for 2 hours, the solvent was removed under reduced pressure. 379 mg (70% chance) of the title compound was obtained. GC-MS (Method 2): Rt = 2.74 min; MS (ESIpos): m /z = 213 [M+H]+ Intermediate 4 5-Chloro-4-(trifluoromethyl)pyridin-2-yl]methanol

[0499] Methyl 5-chloro-4-(trifluoromethyl)pyridine-2-carboxylate (412 mg, 1.72 mmol) was dissolved in methanol (20 mL) and sodium borohydride (78.1 mg, 2.06 mmol) was added in portions at 0°C. After stirring at room temperature overnight, the reaction mixture was again mixed with sodium borohydride (35 mg, 0.9 mmol). After stirring for 2 days at room temperature, the reaction mixture was mixed with saturated aqueous ammonium chloride solution and methanol was removed under reduced pressure. The residue was mixed with ethyl acetate and water. The aqueous phase was extracted three times with ethyl acetate. The combined organic phases were dried over sodium sulfate and filtered, and the filtrate was concentrated. 295 mg (77% chance) of the title compound was obtained. LC-MS (Method 3): Rt = 1.32 min; MS (ESIpos): m /z = 212 [M+H]+ Intermediate 5 5-Chloro-2-(chloromethyl)-4-(trifluoromethyl)pyridine hydrochloride

[0500] [5-Chloro-4-(trifluoromethyl) pyridin-2-yl] methanol (295 mg, 1.39 mmol) was dissolved in dichloromethane (20 mL) and thionyl dichloride (200, 2.8 mmol) was added ) at room temperature. After the reaction mixture was stirred at room temperature for 72 hours, the solvent was removed under reduced pressure. 274 mg (85% purity, 63% possibility) of the title compound were obtained. 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: 0.008 (0.42), 3.937 (2.06), 4.644 (1.11), 4.903 (16.00), 7.839 (0.47), 8.078 (5.73), 8.296 (0.43) , 8,857 (0.51), 8,957 (5.04), 9,102 (0.45). Intermediate 6 4-(Chloromethyl)-2-(trifluoromethyl)quinoline hydrochloride

[0501] [2-(Trifluoromethyl)quinolin-4-yl]methanol (350 mg, 1.54 mmol) was dissolved in dichloromethane (10 mL) and thionyl dichloride (220, 3.1 mmol) was added at 0° W. After the reaction mixture was stirred at room temperature overnight, the solvent was removed under reduced pressure. The residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/gradient water). The fractions containing the product were concentrated under reduced pressure and 336 mg (74% purity, 57% chance) of the title compound were obtained. LC-MS (Method 4): Rt = 1.06 min; MS (ESIpos): m /z = 246 [M+H]+ Intermediate 7 4-(Chloromethyl)-2-(trifluoromethyl)pyrimidine hydrochloride

[0502] [2-(Trifluoromethyl)pyrimidin-4-yl]methanol (313 mg, 1.76 mmol) was dissolved in dichloromethane (10 mL), and thionyl dichloride (260 μl, 3.5 mmol) was added to the room temperature. After the reaction mixture was stirred at room temperature for 4 hours, the solvent was removed under reduced pressure. 134 mg (61% purity, 20% chance) of the title compound was obtained. 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: 3.678 (0.60), 4.946 (16.00), 5.366 (0.57), 7.993 (2.80), 8.006 (2.88), 9.129 (3.11), 9.142 (3.06) . Intermediate 8 Methyl 6-[1-(tert-butoxycarbonyl)hydrazino]pyridine-2-carboxylate

[0503] Methyl 6-chloropyridine-2-carboxylate (32.5 g, 189 mmol), tert-butyl hydrazinecarboxylate (25.0 g, 189 mmol) and cesium carbonate (61.6 g, 189 mmol) in toluene (325 mL) were degassed with argon, before [1,1'-bis(diphenylphosphine)ferrocene]dichloropalladium (II) (6.9 g, 10 mmol) was added. The reaction mixture was stirred at 100°C overnight. The reaction mixture was diluted with dichloromethane and filtered through kieselguhr. The filtrate was concentrated under reduced pressure, and the residue was purified via column chromatography (silica gel, eluent: methanol/dichloromethane 4/96). The product-containing fractions were concentrated under reduced pressure and stirred with methyl tert-butyl ether. 28.8 g (57% possibility) of the title compound were obtained. LC-MS (Method 5): Rt = 3.45 min; MS (ESIpos): m /z = 268 [M+H]+ Intermediate 9 2-(Diazan-2-io-1-yl)-6-(methoxycarbonyl)pyridinium dichloride

[0504] Methyl 6-{1-[(benzyloxy)carbonyl]hydrazino}pyridine-2-carboxylate (29.8 g, 112 mmol) was dissolved in dioxane (150 mL) and hydrochloric acid (112 mL, 446 mmol, 4 m in dioxane) was added. The reaction mixture was stirred at room temperature for 4 hours and diluted with methyl tert-butyl ether (500 mL). After stirring for 1 h, the solids were filtered, washed with methyl tert-butyl ether and dried. 28.8 g (> 100%) of the title compound were obtained. LC-MS (Method 5): Rt = 0.88 min; MS (ESIpos): m /z = 168 [M+H]+ Intermediate 10 Methyl 3-oxo-2,3-dihydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylate

[0505] 2-(Diazan-2-ium-1-yl)-6-(methoxycarbonyl)pyridinium dichloride (28.8 g, 112 mmol) was dissolved in THF (500 mL), and triethylamine (46 mL, 335 mmol ) was added. The reaction mixture was stirred at room temperature for 15 min. Subsequently, 1,1-carbonyldiimidazole (19.9 g, 123 mmol) was added. The reaction mixture was stirred at 70°C for 2 hours. The reaction mixture was filtered, and the filtrate was concentrated under reduced pressure. The residue was taken up in dilute aqueous hydrochloric acid and extracted with 9/1 dichloromethane/methanol. The combined organic phases were dried over sodium sulfate and filtered, and the filtrate was concentrated. The residue was suspended in ethyl acetate and stirred overnight. After filtering and drying, 11.4 g (53% possibility) of the title compound were obtained. LC-MS (Method 5): Rt = 1.40 min; MS (ESIpos): m /z = 194 [M+H]+ Intermediate 11 Methyl (5RS)-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazole [4,3-a]pyridine-5-carboxylate (racemate)

[0506] Methyl 3-oxo-2,3-dihydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylate (17.6 g, 91.1 mmol) and palladium on charcoal (1.0 g, 10%) were suspended in methanol (500 mL), and the mixture was stirred at room temperature in a hydrogen atmosphere (10 bar) overnight. The reaction mixture was filtered through kieselguhr. The filtrate was concentrated, and 17.8 g (99% possibility) of the compound was obtained. LC-MS (Method 5): Rt = 1.35 min; MS (ESIpos): m /z = 198 [M+H]+ 1H-NMR (500 MHz, MeOD) δ [ppm]= 1.64 - 1.74 (br, 1H), 1.89 - 1.97 (br, 1H), 2.15 - 2.29 (br, 2H), 2.60 - 2.69 (m, 1H), 2.77 (dt, 1H), 3.79 (s, 3H), 4.63 (dd, 1H). Intermediate 12 Methyl (5RS)-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylate (enantiomer 1)

[0507] Methyl (5RS)-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylate (racemate) was separated by chiral preparatory SFC [sample preparation: 33.20 g dissolved in 200 mL of methanol; injection volume: 4.0 mL; column: Daicel Chiralpak® IC 20 μm, 360 x 50 mm; eluent: CO2/i-propanol 80/20; flow rate: 400 g/min; temperature 35°C; UV detection: 210 nm]. After separation, 15.7 g of enantiomer 1, which eluted first, and 15.8 g of enantiomer 2, which eluted later, were isolated. Enantiomer 1

[0508] Analytical chiral SFC: Rt = 2.76 min, de = 100% [column: Daicel Chiralpak® IC 50 x 4.6 mm; eluent: CO2/i-propanol 80:20; flow rate: 3 ml/min; UV detection: 210 nm]. LC-MS (Method 3): Rt = 0.54 min; MS (ESIpos): m /z = 198 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]= 1.45 - 1.60 (m, 1H), 1.75 - 1.84 (m, 1H), 1.98 - 2.17 (m, 2H), 2.48 - 2.58 (m, 1H), 2.59 - 2.68 (m, 1H), 3.69 (s, 3H), 4.51 (dd, 1H), 11.42 (s, 1H). Intermediate 13 Methyl (5RS)-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylate (enantiomer 2)

[0509] Methyl (5RS)-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylate (racemate) was separated by chiral preparatory SFC [sample preparation: 33.20 g dissolved in 200 mL of methanol; injection volume: 4.0 mL; column: Daicel Chiralpak® IC 20 μm, 360 x 50 mm; eluent: CO2/i-propanol 80/20; flow rate: 400 g/min; temperature 35°C; UV detection: 210 nm]. After separation, 15.7 g of enantiomer 1, which eluted first, and 15.8 g of enantiomer 2, which eluted later, were isolated. Enantiomer 2

[0510] Analytical chiral SFC: Rt = 3.90 min, o.d. = 100% [column: Daicel Chiralpak® IC 50 x 4.6 mm; eluent: CO2/i-propanol 80:20; flow rate: 3 ml/min; UV detection: 210 nm]. LC-MS (Method 3): Rt = 0.54 min; MS (ESIpos): m /z = 198 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]= 1.42 - 1.59 (m, 1H), 1.72 - 1.86 (m, 1H), 1.96 - 2.17 (m, 2H), 2.44 - 2.59 (m, 1H), 2.59 - 2.69 (m, 1H), 3.69 (s, 3H), 4.51 (dd, 1H), 11.42 (s, 1H).

[0511] The (5S) configuration was assigned based on the elucidation of the crystal structure for Examples 26, 108, 113, 157, 237, 358 and 454. Methyl (5S)-3-oxo-2,3,5,6 ,7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylate Intermediate 14 Methyl 1-(4-methoxybenzyl)hydrazinecarboxylate

[0512] (4-Methoxybenzyl)hydrazine dihydrochloride (1.50 g, 80% purity, 5.33 mmol) was dissolved in dichloromethane (50 mL), triethylamine (2.6 mL, 19 mmol) was added, and the mixture was stirred at room temperature for 30 minutes. This mixture was subsequently cooled to 0°C, and methyl carbonchloridate (450 μl, 5.9 mmol), dissolved in dichloromethane (10 mL), was added. After stirring overnight, the reaction mixture was mixed with water. The organic phase was removed, washed with saturated aqueous sodium chloride solution, dried over sodium sulfate and filtered, and the filtrate was concentrated. The residue was purified via column chromatography (silica gel, eluent: cyclohexane/ethyl acetate gradient). The fractions containing the product were concentrated under reduced pressure and 1.04 g (92% purity, 85% possibility) of the title compound were obtained. LC-MS (Method 3): Rt = 1.08 min; MS (ESIpos): m /z = 211 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: 1.988 (0.46), 3.314 (7.32), 3.541 (0.79), 3.622 (16.00 ), 4,397 (7.56), 4,553 (4.94), 6,861 (0.47), 6,868 (3.43), 6,873 (1.30), 6,885 (1.38), 6,890 (3.96), 6,897 (0.47), 7,161 (3.22), 7,182 (2.79 ). Intermediate 15 Methyl (2S)-6-oxopiperidine-2-carboxylate (enantiomer)

[0513] To an initial charge of methanol (15 mL) at 0°C was added thionyl dichloride (560 μl, 7.7 mmol) and then, in portions, (2S)-6-oxopiperidine-2-carboxylic acid (1 .00 g, 6.99 mmol). After stirring at room temperature overnight, the solvent was removed under reduced pressure, and the residue was mixed with toluene and triethylamine (1.9 mL, 14 mmol). The mixture was stirred at room temperature for 30 minutes, then filtered, and the filtrate was concentrated. 805 mg (70% chance) of the title compound was obtained. LC-MS (Method 4): Rt = 0.26 min; MS (ESIpos): m /z = 158 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.008 (1.70), 0.008 (1.69), 1.541 (0.78), 1.550 ( 1.05), 1.560 (1.24), 1.566 (1.90), 1.575 (2.78), 1.584 (3.48), 1.591 (3.19), 1.594 (3.57), 1.600 (4.36), 1.610 (3.31), 1.619 (4.16), 1.628 ( 3.71), 1.636 (3.43), 1.644 (5.02), 1.652 (4.23), 1.660 (4.33), 1.668 (4.60), 1.676 (2.96), 1.684 (2.78), 1.693 (1.99), 1.702 (1.75), 1.708 ( 1.01), 1.717 (0.85), 1.745 (1.91), 1.754 (2.09), 1.759 (2.49), 1.768 (2.39), 1.778 (3.46), 1.787 (3.35), 1.793 (3.60), 1.802 (3.22), 1.810 ( 2.52), 1819 (1.83), 1901 (2.92), 1910 (3.42), 1916 (3.20), 1925 (4.72), 1935 (4.50), 1941 (3.46), 1949 (4.49), 1959 (3.35), 1968 ( 1.78) ( 0.61), 2.192 (0.69), 2.208 (0.70), 2.289 (0.72), 2.306 (1.34), 2.324 (0.85), 2.523 (0.72), 3.168 (4.31), 3.311 (4.19), 3.409 (0.45), 3.480 ( 0.73), 3.581 (8.47), 3.635 (7.91), 3.849 (0.72), 4.049 (4.37), 4.055 (4.73), 4.063 (8.78), 4.069 (8.78), 4.077 (4.66), 4.083 (4.33), 7.542 ( 6.15). Intermediate 16 Methyl (5S)-2-(4-methoxybenzyl)-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine -5-carboxylate (enantiomer)

[0514] Methyl (2S)-6-oxopiperidine-2-carboxylate (enantiomer) (300 mg, 1.91 mmol) was initially loaded into dichloromethane (6.0 mL, 93 mmol) at room temperature and under argon. Subsequently, trimethyloxonium tetrafluoroborate (311 mg, 2.10 mmol) was added, and the mixture was stirred at room temperature for 2 days. The solvent was removed under reduced pressure, and the residue was mixed with DMF (5 ml). Subsequently, methyl 1-(4-methoxybenzyl)hydrazinecarboxylate (401 mg, 1.91 mmol) was added, and the reaction mixture was stirred at 170 ° C for 4 hours. The reaction mixture was mixed with water and ethyl acetate. The organic phase was removed and the aqueous phase was extracted three times with ethyl acetate. The combined organic phases were washed with saturated aqueous sodium chloride solution, dried over sodium sulfate and filtered, and the filtrate was concentrated. The residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/gradient water). The fractions containing the product were concentrated under reduced pressure and 156 mg (26% possibility) of the title compound were obtained. LC-MS (Method 3): Rt = 1.20 min; MS (ESIpos): m /z = 318 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.008 (1.02), 1.784 (0.43), 1.795 (0.46), 2.045 ( 0.41), 2.055 (0.68), 2.068 (0.64), 2.076 (0.62), 2.084 (0.47), 2.092 (0.40), 2.100 (0.48), 2.112 (0.44), 2.120 (0.47), 2.128 (0.45), 2.564 ( 0.76), 2,578 (0.61), 2,603 (0.56), 2,615 (1.06), 2,627 (0.59), 2,657 (0.47), 2,669 (0.42), 2,829 (0.43), 3,700 (14.01), 3,730 (16.00), 3.743 ( 0.70), 4.581 (0.93), 4.591 (1.04), 4.597 (1.20), 4.607 (0.91), 4.749 (6.71), 6.882 (3.25), 6.903 (3.86), 7.161 (3.37), 7.183 (2.94). Intermediate 17 Methyl (5S)-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylate (enantiomer)

[0515] Methyl (5S)-2-(4-methoxybenzyl)-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a] pyridine-5-carboxylate (155 mg, 488 μmol) (enantiomer) was dissolved in trifluoroacetic acid (4.5 mL), and the mixture was stirred at 150 ° C in a microwave apparatus for one hour. saturated aqueous sodium chloride solution was added to the reaction mixture, and the solution was adjusted to pH 7 with saturated aqueous sodium hydrogen carbonate solution. Dichloromethane was added, and the aqueous phase was extracted three times with dichloromethane. The combined organic phases were dried over sodium sulfate and filtered, and the filtrate was concentrated. The residue was purified via column chromatography (silica gel, eluent: dichloromethane/methanol gradient). The fractions containing the product were concentrated under reduced pressure, mixed with ethyl acetate and filtered. The filtrate was concentrated to one milliliter, and the product was crystallized with 10 mL of petroleum ether. The solids were filtered and dried under reduced pressure. 53.1 mg (53% chance) of the title compound was obtained with an ee of 88%. Enantiomeric excess is determined via chiral HPLC: Comparative values for racemate:

[0516] Analytical chiral HPLC: 1 enantiomer Rt = 3.40, 2 enantiomer Rt = 4.09 min, ratio 1:1 [column: Daicel Chiraltek® AY-3 3μm 50 x 4.6 mm; eluent: i-hexane/ethanol 1:1, flow rate: 1 ml/min; UV detection: 220 nm]. Enantiomer:

[0517] Analytical chiral HPLC: enantiomer 1 Rt = 3.35, enantiomer 2 Rt = 4.01 min, ratio 6:94 [column: Daicel Chiraltek® AY-3 3μm 50 x 4.6 mm; eluent: i-hexane/ethanol 1:1, flow rate: 1 ml/min; UV detection: 220 nm]. 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: 1.506 (0.41), 1.540 (0.44), 1.774 (0.50), 1.787 (0.56), 1.800 (0.48), 1.808 (0.40), 2.026 (0.49) , 2037 (0.75), 2050 (0.70), 2061 (0.71), 2069 (0.52), 2077 (0.48), 2085 (0.55), 2096 (0.54), 2105 (0.55), 2113 (0.53), 2560 (0.95) , 2,574 (0.73), 2,601 (0.65), 2,613 (1.22), 2,626 (0.67), 2,655 (0.55), 2,669 (0.46), 3.586 (0.54), 3.687 (16.00), 4,496 (1.07), 4.506 (1.20) , 4,511 (1.37), 4,521 (1.06), 11,424 (1.40).

[0518] The (5S) configuration was assigned based on the elucidation of the crystal structure for Examples 26, 108, 113, 157, 237, 358 and 454. Intermediate 18 Methyl (5RS)-2-(4-methoxybenzyl)-5 -Methyl-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylate (racemate)

[0519] Methyl (5RS)-2-methyl-6-oxopiperidine-2-carboxylate (racemate) (500 mg, 93% purity, 2.72 mmol, CAS 89115-90-2) was initially loaded into dichloromethane (10 mL ) at room temperature and under argon. Subsequently, trimethyloxonium tetrafluoroborate (442 mg, 2.99 mmol) was added, and the mixture was stirred at room temperature for 2 days. The solvent was removed under reduced pressure, and the residue was mixed with DMF (5 ml). Subsequently, methyl 1-(4-methoxybenzyl)hydrazinecarboxylate (571 mg, 571 mg, 2.72 mmol, 92% purity) was added, and the reaction mixture was stirred at 170 ° C for 8 hours. The reaction mixture was mixed with water and ethyl acetate. The organic phase was removed and the aqueous phase was extracted three times with ethyl acetate. The combined organic phases were washed with saturated aqueous sodium chloride solution, dried over sodium sulfate and filtered, and the filtrate was concentrated. The residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/gradient water). The product-containing fractions were concentrated under reduced pressure and 186 mg (91% purity, 19% possibility) of the title compound were obtained. LC-MS (Method 3): Rt = 1.42 min; MS (ESIpos): m /z = 332 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: 1.589 (0.43), 1.597 (0.42), 1.606 (0.51), 1.623 (0.42 ), 1.697 (11.51), 1.769 (0.47), 1.782 (0.56), 1.802 (0.43), 1.907 (0.40), 1.935 (0.74), 1.942 (0.63), 1.960 (0.63), 2.023 (0.59), 2.030 (0.65 ), 2.042 (0.59), 2.050 (0.53), 2.058 (0.40), 2.570 (2.79), 2.586 (1.50), 2.829 (3.14), 3.531 (0.70), 3.645 (0.69), 3.665 (13.44), 3.730 (16.00 ), 3.742 (4.13), 4.677 (0.71), 4.716 (2.98), 4.736 (2.97), 4.774 (0.71), 5.753 (5.67), 6.885 (3.42), 6.906 (4.16), 6.922 (0.90), 7.148 (3.49 ), 7,169 (3.14), 7,232 (0.92), 7,253 (0.84), 7,632 (0.93). Intermediate 19 Methyl (5RS)-Methyl-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3- a]pyridine-5-carboxylate (racemate )

[0520] Methyl 2-(4-methoxybenzyl)-5-methyl-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a] pyridine-5-carboxylate (racemate) (186 mg, 560 μmol) was dissolved in trifluoroacetic acid (5.0 mL), and the mixture was stirred at 150 ° C (microwave apparatus) for one hour. saturated aqueous sodium chloride solution was added to the reaction mixture, and the solution was adjusted to pH 7 with saturated aqueous sodium hydrogen carbonate solution. Dichloromethane was added, and the aqueous phase was extracted three times with dichloromethane. The combined organic phases were dried over sodium sulfate and filtered, and the filtrate was concentrated. The residue was purified via column chromatography (silica gel, eluent: dichloromethane/methanol gradient). The fractions containing the product were concentrated under reduced pressure and 40.5 mg (34% possibility) of the title compound were obtained. LC-MS (Method 3): Rt = 0.70 min; MS (ESIpos): m /z = 212 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.008 (0.64), 0.008 (0.61), 1.622 (0.54), 1.631 ( 0.51), 1.640 (0.78), 1.654 (15.63), 1.757 (0.51), 1.771 (0.63), 1.777 (0.57), 1.785 (0.46), 1.792 (0.52), 1.880 (0.46), 1.887 (0.52), 1.903 ( 0.40), 1.915 (0.92), 1.922 (0.83), 1.938 (0.81), 1.946 (0.65), 1.990 (0.78), 1.998 (0.84), 2.010 (0.73), 2.018 (0.68), 2.025 (0.49), 2.033 ( 0.43), 2.045 (0.43), 2.568 (3.91), 2.584 (1.91), 3.309 (16.00), 11.369 (1.45). Intermediate 20 tert-Butyl 6-chloropyridine-2-carboxylate

[0521] 6-chloropicolinic acid (80.0 g, 0.51 mol) was dissolved in pyridine (300 mL) and tert-butanol (1.60 l), then p-toluenesulfonyl chloride (194 g, 1.02 mol ) was added in portions. The reaction mixture was stirred at room temperature overnight. After addition of saturated aqueous sodium hydrogen carbonate solution, the mixture was stirred at room temperature for 1 h. The reaction mixture was concentrated to a volume of 1.50 l and diluted with heptane (500 mL), ethyl acetate (500 mL) and water (500 mL). The organic phase was removed, washed with saturated aqueous sodium chloride solution, dried over magnesium sulfate and filtered, and the filtrate was concentrated. 104 g (96% chance) of the title compound were obtained. 1H-NMR (400 MHz, CDCI3) δ [ppm]= 1.61 (s, 9H), 7.45 - 7.48 (dd, 1H), 7.74 - 7.77 (t, 1H), 7.93 - 7.95 (dd, 1H). Intermediate 21 tert-Butyl 6-{1-[(benzyloxy)carbonyl]hydrazino}pyridine-2-carboxylate

[0522] tert-Butyl 6-chloropyridine-2-carboxylate (91.1 g, 0.43 mol), benzyl hydrazinecarboxylate (70.9 g, 0.43 mol), cesium carbonate (174 g, 0.53 mol ) and 1,1'-bis(diphenylphosphine)ferrocene (17.1 g, 32.0 mmol) were suspended in toluene (1.00 l) under argon. Bis(dibenzylideneacetone)palladium(0) (9.76 g, 10.7 mmol) was added, and the reaction mixture was stirred at 80 ° C for 3 h. The reaction mixture was mixed with water and ethyl acetate, filtered through kieselguhr and washed through ethyl acetate. The organic phase was removed, washed with water and aqueous sodium chloride solution, dried over magnesium sulfate and filtered. The filtrate was mixed with silica gel, stirred for 10 min. and then it was filtered and washed with ethyl acetate. The filtrate was concentrated and the residue was purified via column chromatography (silica gel, eluent: heptane/ethyl acetate 4/1, 2/1, 1/1). The fractions containing the product were concentrated under reduced pressure and 112 g (77% possibility) of the title compound were obtained. LC-MS (Method 7): Rt = 0.81 min; MS (ESIpos): m /z = 344 [M+H]+ 1H-NMR (400 MHz, CDCI3) δ [ppm]= 1.59 (s, 9H), 5.30 (s, 2H), 7.31 - 7.39 (m, 3H), 7.42 - 7.45 (m, 2H), 7.76 - 7.78 (m, 2H), 7.98 - 8.12 (dd, 1H). Intermediate 22 tert-Butyl 6-hydrazinopyridine-2-carboxylate

[0523] tert-Butyl 6-{1-[(benzyloxy)carbonyl]hydrazino}pyridine-2-carboxylate (112 g, 0.33 mol) and palladium on charcoal (11.2 g, 5%) were suspended in toluene (100 ml) and methanol (1.12 l), and the mixture was stirred at room temperature in a hydrogen atmosphere (1 bar) overnight. The reaction mixture was filtered through kieselguhr and washed with methanol. The solvent was removed under reduced pressure, and 79.9 g (> 100%) of the title compound were obtained. 1H-NMR (400 MHz, CDCl3) δ [ppm]= 1.61 (s, 9H), 6.92 - 6.95 (d, 1H), 7.38 - 7.41 (d, 1H), 7.53 - 7.58 (dd, 1H). Intermediate 23 tert-Butyl 3-oxo-2,3-dihydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylate

[0524] tert-Butyl 6-hydrazinopyridine-2-carboxylate (79.9 g, 0.33 mol) was dissolved in THF (1.40 l), and 1,1-carbonyldiimidazole (74.3 g, 0.46 mol) was added at room temperature while stirring. The reaction mixture was stirred at room temperature overnight. After adding water (1.0 l), the mixture was stirred for 15 min. and volatile solvents were removed under reduced pressure. The aqueous residue was saturated with sodium chloride and extracted with ethyl acetate. The combined organic phases were washed with saturated aqueous sodium chloride solution, dried over sodium sulfate and filtered, and the filtrate was concentrated. The organic phase was removed, dried over magnesium sulfate and silica gel, and filtered. The filtrate was concentrated and the residue was purified via column chromatography (SiO2; eluent: heptane/ethyl acetate 4/1, 2/1, 1/1, 1/2). The fractions containing the product were concentrated under reduced pressure and 62.4 g (80% possibility in two stages) of the title compound were obtained. LC-MS (Method 7): Rt = 0.50 min; MS (ESIpos): m /z = 180 [M+H]+ 1H-NMR (400 MHz, CDCI3) δ [ppm]= 1.62 (s, 9H), 6.62 - 6.64 (dd, 1H), 7.00 - 7.06 ( dd, 1H), 7.15 - 7.19 (dd, 1H), 10.86 (br s, 1H). Intermediate 24 tert-Butyl (5RS)-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3- a]pyridine-5-carboxylate (racemate )

[0525] tert-Butyl 3-oxo-2,3-dihydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylate (34.5 g, 0.15 mol) and palladium in charcoal (6.90 g, 5%) were suspended in toluene (60 mL) and methanol (500 mL), and the mixture was stirred at room temperature in a hydrogen atmosphere (34.5 bar) for 24 h. The reaction mixture was filtered through kieselguhr and washed with 9/1 dichloromethane/methanol. The filtrate was concentrated and the residue was stirred with ethyl acetate for 30 minutes, then filtered and concentrated. 36.8 g (89% possibility) of the title compound was obtained. LC-MS (Method 7): Rt = 1.28 min; MS (ESIpos): m /z = 240 [M+H]+ 1H-NMR (400 MHz, CDCI3) δ [ppm]= 0.53 (s, 9H), 0.74 - 0.91 (m, 1H), 1.01 - 1.13 ( m, 1H), 1.21 - 1.32 (m, 1H), 1.47 - 1.56 (m, 1H), 1.88 - 2.00 (m, 1H), 2.17 - 2.26 (dt, 1H), 4.29 - 4.34 (dd, 1H), 11.9 (br s, 1H). Intermediate 25 tert-Butyl (5RS)-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3- a]pyridine-5-carboxylate (enantiomer two)

[0526] tert-Butyl (5RS)-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylate ( racemate) was separated by chiral preparatory SFC [sample preparation: 6.00 g dissolved in 88 mL of methanol; injection volume: 4.5 mL; column: Daicel Chiralpak® IC 20 μm, 370 x 50 mm; eluent: CO2/i-propanol: 0.0 min 35% i-propanol, flow rate: 200 g/min; 14.0 min 35% isopropanol, flow rate: 200 g/min; 15.0 min 60% i-propanol, flow rate: 115 g/min; 37.0 min 60% i-propanol, flow rate: 115 g/min; 38.0 min 35% i-propanol, flow rate: 200 g/min; 42.0 min 35% i-propanol, flow rate: 200 g/min; temperature 38°C; UV detection: 210 nm]. After separation, 2.78 g of enantiomer 1, which eluted first, and 2.79 g of enantiomer 2, which eluted later, were isolated. Analytical chiral SFC enantiomer 2: Rt = 4.20 min, d.e. = 100% [column: Daicel Chiralpak® IC 50 x 4.6 mm; eluent: CO2/i-propanol 70:30; flow rate: 3 ml/min; UV detection: 210 nm] LC-MS (Method 4): Rt = 0.60 min; MS (ESIpos): m /z = 239 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]= 1.41 (s, 9H), 1.49 (dq, 1H), 1.72 - 1.84 ( m, 1H), 1.95 - 2.10 (m, 2H), 2.46 - 2.56 (m, 1H), 2.59 - 2.68 (m, 1H), 4.35 (t, 1H), 11.36 (s, 1H).

[0527] The (5S) configuration was assigned based on the elucidation of the crystal structure for Examples 26, 108, 113, 157, 237, 358 and 454. tert-Butyl (5S)-3-oxo-2,3,5 ,6,7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylate Intermediate 26 tert-Butyl (5RS)3-oxo-2,3,5,6, 7,8-hexahydro[1,2,4]triazolo[4,3- a]pyridine-5-carboxylate (enantiomer 1)

[0528] tert-Butyl (5RS)-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylate (racemate ) was separated by chiral preparatory SFC [sample preparation: 6.00 g dissolved in 88 mL of methanol; injection volume: 4.5 mL; column: Daicel Chiralpak® IC 20 μm, 370 x 50 mm; eluent: CO2/i-propanol: 0.0 min 35% i-propanol, flow rate: 200 g/min; 14.0 min 35% isopropanol, flow rate: 200 g/min; 15.0 min 60% i-propanol, flow rate: 115 g/min; 37.0 min 60% i-propanol, flow rate: 115 g/min; 38.0 min 35% i-propanol, flow rate: 200 g/min; 42.0 min 35% i-propanol, flow rate: 200 g/min; temperature 38°C; UV detection: 210 nm]. After separation, 2.78 g of enantiomer 1, which eluted first, and 2.79 g of enantiomer 2, which eluted later, were isolated. Enantiomer 1

[0529] Analytical chiral SFC: Rt = 1.67 min, de = 100% [column: Daicel Chiralpak® IC 50 x 4.6 mm; eluent: CO2/i-propanol 70:30; flow rate: 3 ml/min; UV detection: 210 nm]. LC-MS (Method 4): Rt = 0.60 min; MS (ESIpos): m /z = 239 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]= 1.41 (s, 9H), 1.49 (dq, 1H), 1.81 (dt, 1H), 2.00 - 2.10 (m, 2H), 2.45 - 2.56 (m, 1H), 2.58 - 2.67 (m, 1H), 4.35 (t, 1H), 11.36 (s, 1H). Intermediate 27 tert-Butyl 6-chloro-4-methylpyridine-2-carboxylate

[0530] 6-Chloro-4-methylpyridine-2-carboxylic acid (2.50 g, 14.6 mmol) was dissolved in pyridine (10 mL) and tert-butanol (50 mL, 520 mmol), and 4-methylbenzenesulfonyl chloride (5.56 g, 29.1 mmol) was added. The reaction mixture was stirred at room temperature overnight and diluted with 90/10 saturated aqueous sodium hydrogen carbonate and cyclohexane/ethyl acetate solution. The organic phase was separated, and the aqueous phase was extracted with 90/10 cyclohexane/ethyl acetate. The combined organic phases were washed with saturated aqueous sodium chloride solution, dried over sodium sulfate and filtered, and the filtrate was concentrated. 2.89 g (87% purity, 75% possibility) of the title compound were obtained. 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: 1.325 (0.86), 1.340 (0.86), 1.553 (16.00), 7.614 (0.68), 7.830 (0.80). Intermediate 28 tert-Butyl 6-{1-[(benzyloxy)carbonyl]hydrazino}-4-methylpyridine-2-carboxylate

[0531] Under argon, tert-butyl 6-chloro-4-methylpyridine-2-carboxylate (2.89 g, 12.7 mmol) and benzyl hydrazinecarboxylate (2.32 g, 14.0 mmol) were dissolved in toluene ( 32 mL) and 1,1'-bis(diphenylphosphine)ferrocene (657 mg, 635 μmol), tris(dibenzylideneacetone)dipalladium-chloroform complex (704 mg, 1.27 mmol) and cesium carbonate (4, 96 g, 15.2 mmol). The reaction mixture was stirred at 80°C for 4 hours, and then water and ethyl acetate were added. The organic phase was removed and the aqueous phase was extracted three times with ethyl acetate. The combined organic phases were washed with saturated aqueous sodium chloride solution, dried over magnesium sulfate and filtered, and the filtrate was concentrated. The residue was purified via column chromatography (silica gel; eluent: isocratic: methanol/dichloromethane 4/96). The fractions containing the product were concentrated under reduced pressure and 4.25 g (86% purity, 81% possibility) of the title compound were obtained. LC-MS (Method 3): Rt = 1.96 min; MS (ESIpos): m /z = 358 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: 1.317 (0.87), 1.329 (0.87), 1.549 (16.00), 2.387 (5.39 ), 5.192 (4.02), 5.277 (3.65), 7.314 (0.79), 7.331 (1.05), 7.344 (1.30), 7.360 (1.75), 7.380 (0.82), 7.421 (2.12), 7.440 (1.40), 7.618 (1.55 ), 7,649 (1.81). Intermediate 29 tert-Butyl 7-methyl-3-oxo-2,3-dihydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylate

[0532] To an initial charge of palladium on charcoal (299 mg, 10%) under argon was added tert-butyl 6-{1-[(benzyloxy)carbonyl]hydrazino}-4-methylpyridine-2-carboxylate (1.80 g, 5.04 mmol) in methanol (20 mL). The reaction mixture was stirred in a hydrogen atmosphere (1 bar) at room temperature overnight. The suspension was diluted with methanol, filtered through kieselguhr and washed with methanol. The reaction mixture was concentrated and converted directly.

[0533] The residue was dissolved in THF (40 mL), and di-1H-imidazol-1-ylmethanone (980 mg, 6.04 mmol) was added. The reaction mixture was stirred at room temperature for 30 minutes. The solvent was removed under reduced pressure, and the residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/water gradient). HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/gradient water). The fractions containing the product were concentrated under reduced pressure and 1.05 g (90% purity, 75% possibility) of the title compound were obtained. LC-MS (Method 1): Rt = 0.98 min; MS (ESIneg): m /z = 248 [MH]- 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: 1.536 (16.00), 1.553 (0.97), 2.218 (3.39), 3.318 (0.65), 6,597 (1.20), 7,051 (0.96), 12,345 (0.65). Intermediate 30 tert-Butyl (5RS,7RS)-7-methyl-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine -5-carboxylate (mixture of diastereomer; 4 isomers)

[0534] To an initial charge of palladium on charcoal (740 mg, 10%) under argon was added tert-butyl 7-methyl-3-oxo-2,3-dihydro[1,2,4]triazolo[4 ,3-a]pyridine-5-carboxylate (3.1 g, 12.44 mmol) in methanol (124 mL). The reaction mixture was stirred in a hydrogen atmosphere (1 bar) at room temperature overnight. The suspension was diluted with methanol and filtered through kieselguhr and washed with methanol. The solvent was removed under reduced pressure. The residue was taken up in methanol (124 mL) and mixed with palladium on charcoal (740 mg, 10%). The reaction mixture was stirred in a hydrogen atmosphere (2 bar) at room temperature for 48 hours. The suspension was diluted with methanol and filtered through kieselguhr and washed with methanol. The solvent was removed under reduced pressure and 2.71 g (86% possibility) of the title compound were obtained. LC-MS (Method 3): Rt = 1.24 min; MS (ESIpos): m /z = 507 [2M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: 1.015 (2.13), 1.032 (2.20), 1.400 (0.73), 1.405 (1.16 ), 1,416 (16.00), 1,432 (0.48), 2,181 (0.46), 2,209 (0.56), 4,184 (0.45), 4,195 (0.43), 11,342 (0.73). Intermediate 31 Ethyl 6-{1-[(benzyloxy)carbonyl]hydrazino}-3-methylpyridine-2-carboxylate

[0535] Under argon, ethyl 6-chloro-3-methylpyridine-2-carboxylate (970 mg, 4.86 mmol) and benzyl hydrazinecarboxylate (969 mg, 5.83 mmol) were dissolved in toluene (9.7 mL), and tris(dibenzylidene-acetone)dipalladium-chloroform complex (251 mg, 243 μmol), 1,1'-bis(diphenylphosphine)ferrocene (269 mg, 486 μmol) and cesium carbonate (1.90 g, 5.83 mmol ) were added. The reaction mixture was stirred at 80°C for 4 hours, and then water and ethyl acetate were added. The organic phase was removed and the aqueous phase was extracted three times with ethyl acetate. The combined organic phases were washed with saturated aqueous sodium chloride solution, dried over magnesium sulfate and filtered, and the filtrate was concentrated. The residue was purified via column chromatography (SiO2; eluent: isocratic, methanol/dichloromethane 8/92). The product-containing fractions were concentrated under reduced pressure and 1.89 g (47% purity, 55% possibility) of the title compound were obtained. LC-MS (Method 4): Rt = 0.89 min; MS (ESIpos): m /z = 330 [M+H]+ Intermediate 32 Ethyl 6-hydrazino-3-methylpyridine-2-carboxylate dihydrochloride

[0536] To an initial charge of palladium on charcoal (232 mg, 10%) under argon was added ethyl 6-{1-[(benzyloxy)carbonyl]hydrazino}-3-methylpyridine-2-carboxylate (1.89 g, 5.74 mmol) in methanol (60 mL). The reaction mixture was stirred in a hydrogen atmosphere (1 bar) at room temperature overnight. The suspension was diluted with methanol and filtered through kieselguhr and washed with methanol. The solvent was removed under reduced pressure, and the residue was taken up in dioxane and mixed with dioxane/hydrochloric acid (4M). The precipitated solids were filtered and washed with methyl tert-butyl ether and converted directly. Intermediate 33 Ethyl 6-methyl-3-oxo-2,3-dihydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylate

[0537] Ethyl 6-hydrazino-3-methylpyridine-2-carboxylate dihydrochloride (419 mg, 1.56 mmol) was mixed in THF (12 mL), and di-1H-imidazol-1-ylmethanone (261 mg, 1.61 mmol) was added. The reaction mixture was stirred at room temperature for 2 hours. The reaction mixture was mixed with water and dichloromethane and basified with saturated aqueous sodium hydrogen carbonate solution. The organic phase was removed and the aqueous phase was extracted three times with ethyl acetate. The combined organic phases were washed with saturated aqueous sodium chloride solution, dried over magnesium sulfate and filtered, and the filtrate was concentrated. 347 mg (89% purity, 104% chance) of the title compound were obtained. LC-MS (Method 1): Rt = 0.77 min; MS (ESIneg): m /z = 220 [MH]- 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: 1.282 (5.00), 1.299 (10.60), 1.317 (5.79), 1.335 (0.84), 1,356 (2.69), 2,078 (16.00), 2,118 (0.45), 2,280 (0.45), 2,395 (0.71), 2,428 (0.75), 4,331 (1.67), 4,349 (4.92), 4,367 (4.80), 4,385 (1.58), 7,060 (2.57), 7,084 (3.35), 7,239 (3.24), 7,263 (2.51), 7,632 (0.45), 12,533 (1.43). Intermediate 34 Ethyl (5RS,6RS)-6-methyl-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine-5 -carboxylate (mixture of diastereomer; 4 isomers)

[0538] To an initial charge of palladium on charcoal (63 mg, 10%) under argon was added ethyl 6-methyl-3-oxo-2,3-dihydro[1,2,4]triazolo[4,3 -a]pyridine-5-carboxylate (297 mg, 1.34 mmol) in methanol (10 mL), and the reaction mixture was stirred in a hydrogen atmosphere (1 bar) at room temperature overnight. The suspension was diluted with methanol and filtered through kieselguhr and washed with methanol. The solvent was removed under reduced pressure, and the residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/water gradient). HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/gradient water). The fractions containing the product were concentrated under reduced pressure.

[0539] The residue was dissolved in methanol (5.0 mL) and, after addition of palladium on charcoal (25 mg, 10%), the reaction mixture was stirred in a hydrogen atmosphere (1 bar) at room temperature during the night. The suspension was diluted with methanol and filtered through kieselguhr and washed with methanol. The solvent was removed under reduced pressure and 117 mg (39% possibility) of the title compound were obtained. LC-MS (Method 3): Rt = 0.93 min; MS (ESIpos): m /z = 226 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: 1.015 (11.82), 1.033 (12.24), 1.175 (7.82), 1.193 (16.00 ), 1.211 (8.16), 1.236 (0.40), 1.428 (0.40), 1.441 (0.50), 1.459 (1.16), 1.473 (1.29), 1.492 (1.47), 1.505 (1.43), 1.522 (0.71), 1.536 (0.62 ), 1.691 (1.35), 1.698 (1.45), 1.706 (1.50), 1.717 (0.89), 1.724 (1.18), 1.732 (1.11), 1.739 (1.07), 2.246 (0.67), 2.252 (0.78), 2.263 (1.08 ), 2,269 (1.18), 2,278 (1.20), 2,284 (1.18), 2,292 (1.12), 2,299 (1.03), 2,309 (0.72), 2,316 (0.63), 2,557 (1.30), 2,569 (1.98), 2,584 (1.68 ), 2,600 (1.66), 2,615 (1.39), 2,656 (1.71), 2,661 (2.10), 2,669 (2.15), 2,675 (1.92), 2,698 (0.96), 2,703 (1.08), 2,711 (1.03), 2,717 (0.80 ), 4.098 (0.91), 4.107 (1.22), 4.116 (1.20), 4.125 (4.30), 4.134 (1.05), 4.142 (6.35), 4.151 (1.07), 4.160 (4.32), 4.169 (1.26), 4.178 (1.27 ), 4,187 (0.95), 4,419 (4.25), 4,435 (4.22), 11,412 (1.99). Intermediate 35 Ethyl 6-hydrazino-4-(trifluoromethyl)pyridine-2-carboxylate

[0540] Under argon, ethyl 6-chloro-4-(trifluoromethyl)pyridine-2-carboxylate (1000 mg, 3.94 mmol) and benzyl hydrazinecarboxylate (721 mg, 4.34 mmol) were dissolved in toluene (10 mL) , and tris(dibenzylideneacetone)dipalladium-chloroform complex (204 mg, 197 μmol), 1,1'-bis(diphenylphosphine)ferrocene (219 mg, 394 μmol) and cesium carbonate (1.54 g, 4.73 mmol) were added. The reaction mixture was stirred at 80°C for 4 hours and water and ethyl acetate were added. The organic phase was removed and the aqueous phase was extracted three times with ethyl acetate. The combined organic phases were washed with saturated aqueous sodium chloride solution, dried over magnesium sulfate and filtered, and the filtrate was concentrated. The residue was purified via column chromatography (SiO2; eluent: isocratic, methanol/dichloromethane 8/92). The fractions containing the product were concentrated under reduced pressure and the residue obtained was converted directly. The residue was dissolved in methanol (50 mL) under argon, and palladium on charcoal (223 mg, 10%) was added. The reaction mixture was stirred in a hydrogen atmosphere (1 bar) at room temperature overnight. Additional palladium on charcoal (223 mg, 10%) was added and the mixture was stirred in a hydrogen atmosphere (1 bar) at room temperature overnight. The suspension was diluted with methanol, filtered through kieselguhr and washed with methanol. The solvent was removed under reduced pressure, and the residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/water gradient). HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/gradient water). The product-containing fractions were concentrated under reduced pressure and 385 mg (93% purity, 38% chance) of the title compound were obtained. LC-MS (Method 1): Rt = 0.91 min; MS (ESIpos): m /z = 250 [M+H]+ Intermediate 36 Ethyl 3-oxo-7-(trifluoromethyl)-2,3-dihydro[1,2,4]triazolo[4,3-a ]pyridine-5-carboxylate

[0541] Ethyl 6-hydrazino-4-(trifluoromethyl)pyridine-2-carboxylate (384 mg, 1.54 mmol) was initially loaded into THF (19 mL), di-1H-imidazol-1-ylmethanone (300 mg, 1.85 mmol) was added, and the mixture was stirred at room temperature overnight. The reaction mixture was mixed with water and dichloromethane. The organic phase was removed and the aqueous phase was extracted three times with dichloromethane. The combined organic phases were washed with water and saturated aqueous sodium chloride solution, dried over magnesium sulfate and filtered, and the filtrate was concentrated. 391 mg (94% purity, 87% chance) of the title compound was obtained. LC-MS (Method 4): Rt = 0.71 min; MS (ESIpos): m /z = 276 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: 1.299 (7.46), 1.316 (16.00), 1.334 (7.58), 1.345 (0.42 ), 1.357 (1.20), 1.363 (0.66), 2.525 (0.47), 4.336 (2.37), 4.354 (7.32), 4.371 (7.27), 4.389 (2.27), 7.044 (4.79), 7.048 (4.79), 7.954 (2.71 ), 7,957 (3.98), 7,960 (2.90). Intermediate 37 Ethyl (5RS,7RS)-3-oxo-7-(trifluoromethyl)-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine -5-carboxylate (mixture of diastereomer; 4 isomers)

[0542] To an initial charge of palladium on charcoal (30 mg, 10%) under argon was added ethyl 3-oxo-7-(trifluoromethyl)-2,3-dihydro[1,2,4]triazolo[4 ,3-a]pyridine-5-carboxylate (100 mg, 363 μmol) in methanol (5.0 mL). The reaction mixture was stirred in a hydrogen atmosphere (1 bar) at room temperature for 40 hours. The suspension was diluted with methanol and filtered through kieselguhr and washed with methanol. The solvent was removed under reduced pressure and 97.8 mg (87% purity, 84% chance) of the title compound were obtained. LC-MS (Method 4): Rt = 0.64 min; MS (ESIpos): m /z = 280 [M+H]+ 1H-NMR (500 MHz, DMSO-d6) δ [ppm]: 1.042 (1.06), 1.056 (2.04), 1.070 (1.10), 1.199 (8.42 ), 1.214 (16.00), 1.228 (8.00), 1.305 (0.45), 1.356 (1.36), 1.738 (1.02), 1.763 (2.47), 1.787 (2.58), 1.812 (1.20), 2.696 (1.56), 2.721 (2.08 ), 2,728 (2.47), 2,752 (2.57), 2,869 (2.23), 2,896 (1.50), 2,901 (1.51), 3,057 (1.19), 3,064 (1.13), 3,072 (1.13), 3,165 (1.54), 3,174 (1.56 ), 3.429 (0.48), 3.439 (0.55), 3.452 (0.48), 4.141 (0.78), 4.149 (1.47), 4.156 (2.22), 4.163 (4.00), 4.170 (4.33), 4.177 (4.39), 4.184 (3.95 ), 4.191 (2.27), 4.198 (1.47), 4.205 (0.83), 4.319 (0.42), 4.331 (0.60), 4.432 (2.24), 4.444 (2.52), 4.455 (2.47), 4.466 (2.20), 7.628 (0.41 ), 11,601 (3.48). Intermediate 38 Methyl (2RS)-6-[(4-methoxybenzyl)(methoxycarbonyl)hydrazono]piperidine-2-carboxylate (racemate)

[0543] To methyl (2RS)-6-oxopiperidine-2-carboxylate (racemate) (685 mg, 4.36 mmol) in dichloromethane (15 mL) under argon was added trimethyloxonium tetrafluoroborate (678 mg, 95% purity, 4 .36 mmol), and the reaction mixture was stirred at room temperature overnight. Then, methyl 1-(4-methoxybenzyl)hydrazinecarboxylate (1.29 g, 71% purity, 4.36 mmol) was added, and the mixture was stirred at room temperature with occasional checking of the conversion for several days. For elaboration, volatile components were removed under reduced pressure. The remaining crude product (1.52 g, 100% possibility) was further converted without further purification. LC-MS (Method 4): Rt = 0.51 min; MS (ESIpos): m /z = 350 [M+H]+ Intermediate 39 Methyl (5RS)-2-(4-methoxybenzyl)-3-oxo-2,3,5,6,7,8-hexahydro [1,2,4]triazolo[4,3-a]pyridine-5-carboxylate (racemate)

[0544] Methyl (2RS)-6-[(4-methoxybenzyl)(methoxycarbonyl)hydrazono]piperidine-2-carboxylate (racemate) (1.52 g, 4.35 mmol) in DMF (5 mL) was stirred at 150 °C at night. For preparation, the cooled mixture was added to approximately 50 mL of water, and the mixture was alkalized to a pH of approximately 9 with aqueous sodium hydroxide solution and extracted three times with 50 mL of dichloromethane. The combined organic phases were washed with saturated aqueous sodium chloride solution, dried over magnesium sulfate, filtered and concentrated under reduced pressure. The crude product thus obtained was purified by silica gel chromatography (PuriFlash cartridge of 50g silica gel, 100% dichloromethane => dichloromethane: MeOH 80:1). In this way, two fractions of the title compound were obtained: 327 mg at 60% purity (14% possibility) and 858 mg at 72% purity (45% possibility). Analysis results for the second fraction: LC-MS (Method 6): Rt = 1.33 min; MS (ESIpos): m /z = 318 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: 2.615 (0.90), 2.731 (9.35), 2.890 (12.58), 3.700 (13.65 ), 3,730 (16.00), 3,736 (6.83), 3,742 (2.33), 4,492 (1.54), 4,582 (0.85), 4,591 (0.94), 4,597 (1.08), 4,607 (0.82), 4,750 (5.88), 6,882 (3.29 ), 6.887 (2.11), 6.899 (1.66), 6.904 (4.11), 6.908 (1.73), 7.162 (3.09), 7.167 (1.04), 7.178 (1.35), 7.183 (3.40), 7.203 (1.01), 7.923 (0.79 ), 7,952 (1.25). Intermediate 40 (5RS)-2-(4-Methoxybenzyl)-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine- 5-carboxylic acid (racemate)

[0545] Methyl (5RS)-2-(4-methoxybenzyl)-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a] pyridine-5-carboxylate (racemate) (320 mg, 60% purity, 605 μmol) was dissolved in water/THF (5 ml/5 mL), lithium hydroxide (72.4 mg, 3.03 mmol) was added , and the reaction mixture was stirred at room temperature over a weekend. For elaboration, water was added, the pH was adjusted to 3 with 1 N aqueous hydrochloric acid, and the mixture was saturated with sodium chloride and extracted three times with 30 mL each time of ethyl acetate. The combined organic phases were dried with magnesium sulfate, filtered, concentrated under reduced pressure and dried. 250 mg (71% purity, 97% possibility) of the title compound was obtained. Thus, the product obtained was used without further purification.

[0546] In a second batch conducted in a similar manner, 850 mg of methyl (5RS)-2-(4-methoxybenzyl)-3-oxo-2,3,5,6,7,8-hexahydro[1, 2,4]triazolo[4,3-a]pyridine-5-carboxylate (72% purity, 1.93 mmol) were used to obtain 625 mg of the title compound (89% purity, 95% chance). LC-MS (Method 3): Rt = 1.00 min; MS (ESIpos): m /z = 304 [M+H]+ Intermediate 41 (5RS)-5-(Pyrrolidin-1-ylcarbonyl)-5,6,7,8-tetrahydro[1,2,4] triazolo[4,3- a]pyridin-3(2H)-one (racemate) Variant a)

[0547] (5RS)-2-(4-Methoxybenzyl)-5-(pyrrolidin-1-ylcarbonyl)-5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a ]pyridin-3(2H)-one (racemate) (670 mg, 1.88 mmol) was dissolved in trifluoroacetic acid (15 mL) and stirred at 150 ° C in a microwave apparatus for 1 h. For elaboration, the cooled mixture was concentrated, and the residue was purified in 2 injections via preparatory HPLC (column: Chromatorex C18, 250x40mm 10μm. Flow rate: 50 ml/min. Gradient (A = water + 0.1% formic acid , B = acetonitrile): 0 min 10% B, 6 min 10% B, 27 min 95% B, 38 min 95% B, 40 min 10% B. Run time per separation 40 min Detection: 210 nm) . The product fractions were concentrated and lyophilized. In this way, 0.36 g (80% possibility) of the title compound were obtained. Variant b)

[0548] Methyl (5RS)-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylate (racemate) (500 mg, 2.54 mmol) in a mixture with pyrrolidine (5.0 mL, 60 mmol) was stirred at 50°C first for 2 h, then for a further 18 h, then at 60°C for approximately another 24 h (HPLC/LC-MS conversion monitoring). For elaboration, the mixture was mixed with water, diluted with ethyl acetate and extracted. The aqueous phase was extracted twice more with ethyl acetate. The organic phases were discarded after an LC-MS check. The aqueous phase containing the product was concentrated and dried under reduced pressure. By grinding the residue with ethyl acetate/methanol, concentrating the main solution and grinding again with the solvent mixture, two fractions of the title compound were obtained: 45.7 mg (8%) and 112 mg (19%). Analysis data for the second fraction: LC-MS (Method 6): Rt = 0.80 min; MS (ESIpos): m /z = 237 [M+H]+ 1H-NMR (500 MHz, DMSO-d6) δ [ppm]: 1.147 (0.62), 1.662 (1.69), 1.673 (2.39), 1.682 (4.36 ), 1,690 (6.79), 1,700 (8.57), 1,710 (6.71), 1,720 (3.20), 1,757 (2.60), 1,771 (9.56), 1,784 (16.00), 1,798 (11.83), 1,812 (3.41), 1,894 (3.39 ), 1,907 (11.19), 1,921 (15.40), 1,935 (10.59), 1,948 (4,95), 1,956 (5.06), 1,965 (4,50), 1,972 (2.37), 1,978 (2.52), 1,990 (3.30), 1,999 (3.57 ), 2,007 (3.10), 2,019 (2.87), 2,036 (1.28), 2,049 (0.83), 2,472 (2.42), 2,518 (5.78), 2,524 (4.83), 2,571 (3.49), 2,580 (6.69), 2,590 (3.51 ), 2.604 (1.94), 2.613 (3.22), 2.623 (1.57), 2.636 (0.62), 3.013 (0.68), 3.027 (1.51), 3.041 (0.64), 3.225 (2.19), 3.238 (4.42), 3.248 (4.27 ), 3.262 (7.12), 3.276 (3.96), 3.288 (5.24), 3.324 (12.41), 3.333 (4.62), 3.338 (5.10), 3.347 (4.83), 3.362 (2.48), 3.375 (0.68), 3.437 (2.33 ), 3,451 (4.93), 3,457 (3.84), 3,465 (3.28), 3,471 (6.13), 3,485 (2.81), 3,579 (2.85), 3,593 (5.88), 3,599 (3.34), 3,606 (3.61), 3,612 (4.77 ), 3,626 (2.17), 4,637 (5.45), 4,644 (6.46), 4,650 (7.06), 4,657 (5.49), 11,270 (6.83). Intermediate 42 Ethyl 2-isopropylidene-1-(4-methylbenzyl)hydrazinecarboxylate

[0549] To ethyl 2-isopropylidenehydrazinecarboxylate (CAS 663760-1; 3.23 g, 22.4 mmol) in 55 mL of toluene were added, under argon, potassium hydroxide powder (4.11 g, 29.7 mmol ) and tetra-n-butylammonium hydrogen sulfate (734 mg, 2.16 mmol). For better stirring capacity, 10 mL of toluene was added. After heating to 50°C, a solution of 1-(bromomethyl)-4-methylbenzene (5.00 g, 27.0 mmol) in 15 mL of toluene was added dropwise, and the mixture was heated to 80°C and stirred for another 2.5 h. For elaboration, the mixture was mixed with water, and the organic phase was removed after extraction. The organic phase was extracted twice more with water, then the combined organic phases were re-extracted once with toluene. The organic phases were washed with saturated aqueous sodium chloride solution, dried over concentrated sodium sulfate and dried under reduced pressure. The crude product obtained was purified by chromatography using silica gel (instrument: Isolera column: 340g SNAP eluent: cyclohexane and EtOAc gradient: 0 min cyclohexane, 10 min cyclohexane, 35 min 30% EtOAc, 40 min 30% EtOAc) . The fractions containing the product were combined, concentrated and dried. In this way, 3.76 g (56% possibility) of the title compound were obtained. LC-MS (Method 4): Rt = 0.96 min; MS (ESIpos): m /z = 249 [M+H]+ Intermediate 43 Ethyl 1-(4-methylbenzyl)hydrazinecarboxylate

[0550] Ethyl 2-isopropylidene-1-(4-methylbenzyl)hydrazinecarboxylate (3.77 g, 15.2 mmol, according to LC-MS already partially hydrolyzed to the title compound) was dissolved in ethanol/water (100 ml /66 mL), heated to reflux and stirred for 3 h. For preparation, the mixture was very considerably concentrated, and the residue was mixed in dichloromethane/water and extracted. After separation of the phases, the aqueous phase was extracted twice more with dichloromethane, and the combined organic phases were washed with saturated sodium chloride solution, dried over sodium sulfate, concentrated and dried under reduced pressure. In this way, 3.25 g (87% purity, 89% possibility) of the compound were obtained, which was converted without further purification. LC-MS (Method 6): Rt = 1.53 min; MS (ESIpos): m /z = 209 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: 1.159 (0.80), 1.168 (1.91), 1.185 (3.86), 1.203 (1.95 ), 1,667 (1.33), 1,927 (1.25), 2,267 (1.24), 2,275 (9.41), 4,035 (1.18), 4,053 (3.64), 4,071 (3.59), 4,088 (1.13), 4,425 (5.48), 4,548 (3.26 ), 7,126 (16.00). Intermediate 44 Methyl (2RS)-6-[(ethoxycarbonyl)(4-methylbenzyl)hydrazono]piperidine-2-carboxylate (racemate)

[0551] To methyl (2RS)-6-oxopiperidine-2-carboxylate (racemate) (1.58 g, 10.1 mmol) in 20 mL of dichloromethane under argon, trimethyloxonium tetrafluoroborate (1.57 g, 95%) was added purity, 10.1 mmol), and the reaction mixture was stirred at room temperature for 18 h. Then, ethyl 1-(4-methylbenzyl)hydrazine carboxylate (2.41 g, 87% purity, 10.1 mmol), dissolved in 10 mL of dichloromethane, was added dropwise, and the mixture was stirred at room temperature. for 26 h. For elaboration, the volatile components were removed under reduced pressure, and the residue was separated using silica gel. (Instrument: Isolera; column: 100g SNAP Cartridge, eluent: cyclohexane and EtOAc // Gradient EtOAc and MeOH: 0min 30% EtOAc, 3min 30% EtOAc, 13min 100% EtOAc, 18min 100% EtOAc, 18.01min 10% MeOH , 33min 10% MeOH). The product-containing fractions were combined, concentrated and dried under reduced pressure. This yielded 1.46 g (88% purity, 37% possibility) of the title compound, which was converted as such. LC-MS (Method 3): Rt = 0.98 min; MS (ESIpos): m /z = 348 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: 1.055 (0.58), 1.149 (1.00), 1.157 (1.01), 1.167 (1.78 ), 1.175 (1.73), 1.184 (0.92), 1.192 (0.87), 1.644 (0.91), 1.908 (0.76), 1.988 (2.45), 2.128 (2.05), 2.141 (2.19), 2.144 (2.23), 2.148 (1.42 ), 2.156 (0.95), 2.164 (0.99), 2.274 (3.39), 2.279 (4.35), 3.162 (0.90), 3.175 (0.90), 3.538 (3.77), 3.578 (0.99), 3.585 (1.56), 3.638 (3.98 ), 3.667 (16.00), 3.675 (1.67), 3.684 (2.39), 3.701 (3.26), 4.021 (0.67), 4.038 (0.81), 4.049 (1.01), 4.056 (1.07), 4.063 (1.50), 4.069 (1.44 ), 4,775 (1.21), 7,127 (1.68), 7,134 (2.17), 7,174 (1.17). Intermediate 45 Methyl (5RS)-2-(4-methylbenzyl)-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine -5-carboxylate (racemate)

[0552] Methyl (2RS)-6-[(ethoxycarbonyl)(4-methylbenzyl)hydrazono]piperidine-2-carboxylate (racemate) (730 mg, 88% purity, 1.85 mmol) in DMF (15 mL ) was stirred at 150°C overnight. For preparation, the mixture was added to water, alkalinized with 3 N sodium hydroxide solution and extracted with dichloromethane. The aqueous phase was saturated with sodium chloride and extracted twice more with dichloromethane. The combined organic phases were washed with saturated aqueous sodium chloride solution, dried over sodium sulfate, filtered and concentrated under reduced pressure. This yielded 288 mg (52% chance) of the title compound. LC-MS (Method 3): Rt = 1.42 min; MS (ESIpos): m /z = 302 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: 2.274 (12.04), 2.580 (0.80), 2.616 (1.19), 2.731 (10.86 ), 2,890 (12.92), 3,285 (1.12), 3,700 (16.00), 4,588 (1.05), 4,598 (1.19), 4,604 (1.34), 4,614 (1.04), 4,775 (6.63), 7,105 (0.94), 7,119 (1.09 ), 7,127 (7.35), 7,134 (6.83), 7,155 (1.02), 7,952 (1.56). Alternative synthesis:

[0553] Methyl(5RS)-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylate (500 mg , 2.54 mmol) was initially loaded into acetonitrile (10 mL). Cesium carbonate (909 mg, 2.79 mmol) and 1-(bromomethyl)-4-methylbenzene (493 mg, 2.66 mmol) were subsequently added. After stirring overnight, the reaction mixture was mixed with water and ethyl acetate at room temperature. The organic phase was removed and the aqueous phase was extracted three times with ethyl acetate. The combined organic phases were washed with saturated aqueous sodium chloride solution, dried over sodium sulfate and filtered, and the filtrate was concentrated. The residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/gradient water). The fractions containing the product were concentrated under reduced pressure and 560 mg (73% possibility) of the title compound were obtained. LC-MS (Method 1): Rt = 1.05 min; MS (ESIpos): m /z = 302 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.008 (0.61), 0.008 (0.56), 1.787 (0.45), 1.798 ( 0.49), 1.812 (0.42), 2.050 (0.42), 2.060 (0.71), 2.072 (0.83), 2.080 (0.64), 2.088 (0.52), 2.096 (0.44), 2.104 (0.52), 2.108 (0.45), 2.116 ( 0.53), 2.124 (0.51), 2.132 (0.48), 2.274 (11.08), 2.523 (0.63), 2.566 (0.81), 2.580 (0.64), 2.605 (0.58), 2.616 (1.09), 2.629 (0.60), 2.659 ( 0.49), 3.701 (16.00), 4.588 (0.99), 4.598 (1.12), 4.604 (1.28), 4.614 (0.97), 4.775 (6.33), 7.106 (0.87), 7.127 (6.84), 7.134 (6.17), 7.154 ( 0.82). Intermediate 46 Methyl (5RS)-2-(4-methylbenzyl)-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a ]pyridine-5-carboxylate (enantiomer 1)

[0554] Methyl(5RS)-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylate (enantiomer 2 )(700 mg, 3.55 mmol) was initially loaded into acetonitrile (31 mL). Cesium carbonate (1.27 g, 3.90 mmol) and 1-(bromomethyl)-4-methylbenzene (690 mg, 3.73 mmol) were subsequently added. After stirring overnight, the reaction mixture was mixed with water and ethyl acetate at room temperature. The organic phase was removed and the aqueous phase was extracted twice with ethyl acetate. The combined organic phases were washed with saturated aqueous sodium chloride solution, dried over magnesium sulfate and filtered, and the filtrate was concentrated. 1.05 g (91% purity, 89% possibility) of the title compound was obtained. LC-MS (Method 3): Rt = 1.46 min; MS (ESIpos): m /z = 302 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: 1.497 (0.40), 1.519 (0.42), 1.524 (0.43), 1.532 (0.43 ), 1.788 (0.50), 1.797 (0.54), 1.811 (0.47), 1.821 (0.43), 1.988 (0.48), 2.049 (0.50), 2.060 (0.81), 2.073 (0.80), 2.080 (0.72), 2.087 (0.59 ), 2.095 (0.51), 2.104 (0.58), 2.115 (0.59), 2.124 (0.56), 2.131 (0.52), 2.273 (12.47), 2.292 (0.91), 2.523 (0.62), 2.566 (0.84), 2.580 (0.68 ), 2.604 (0.64), 2.616 (1.20), 2.628 (0.66), 2.658 (0.55), 3.310 (16.00), 3.683 (0.71), 4.588 (1.13), 4.598 (1.28), 4.604 (1.44), 4.614 (1.10 ), 4,674 (0.43), 4,775 (6.90), 7,106 (1.01), 7,127 (8.08), 7,133 (7.29), 7,154 (1.06).

[0555] The (5S) configuration was assigned based on the elucidation of the crystal structure for Examples 26, 108, 113, 157, 237, 358 and 454. Methyl (5S)-2-(4-methylbenzyl)-3-oxo -2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylate Intermediate 47 Methyl (5S)-3-oxo-2 ,5,6,7-tetrahydro-3H-pyrrole[2,1-c][1,2,4]triazol-5-carboxylate (enantiomer)

[0556] Methyl 5-oxo-L-prolinate (24.0 g, 168 mmol, CAS 4931-66-2) was initially loaded into dichloromethane (210 mL) at room temperature. Subsequently, trimethyloxonium tetrafluoroborate (24.8 g, 168 mmol) was added, and the mixture was stirred at room temperature overnight. The solvent was removed under reduced pressure, and the residue was mixed with DMF (240 mL). Subsequently, methyl hydrazinecarboxylate (15.1 g, 168 mmol) was added, and the reaction mixture was stirred at 170 ° C overnight. The reaction mixture was concentrated under reduced pressure, and the residue was purified via column chromatography (silica gel, eluent: dichloromethane/methanol gradient). The fractions containing the product were concentrated under reduced pressure and 7.57 g (25% possibility) of the title compound were obtained. The latter was directly converted. GC-MS (WUP-GC/MS): Rt = 6.48 min; MS (ESIpos): m /z = 183 [M+H]+ Intermediate 48 Methyl (5S)-2-(4-methylbenzyl)-3-oxo-2,5,6,7-tetrahydro-3H-pyrrole [2,1- c][1,2,4]triazol-5-carboxylate (enantiomer)

[0557] Methyl (5S)-3-oxo-2,5,6,7-tetrahydro-3H-pyrrolo[2,1- c][1,2,4]triazol-5-carboxylate (enantiomer) ( 250 mg, 1.36 mmol) was initially loaded into acetonitrile (3.0 mL). Cesium carbonate (489 mg, 1.50 mmol) and 1-(bromomethyl)-4-methylbenzene (265 mg, 1.43 mmol, CAS 104-81-4) were subsequently added. After stirring overnight, the reaction mixture was mixed with water and ethyl acetate at room temperature. The organic phase was removed and the aqueous phase was extracted three times with dichloromethane. The combined organic phases were washed with saturated aqueous sodium chloride solution, dried over sodium sulfate and filtered, and the filtrate was concentrated. 412 mg (91% purity, 96% possibility) of the title compound were obtained. LC-MS (Method 3): Rt = 1.32 min; MS (ESIpos): m /z = 288 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: 2.072 (1.11), 2.275 (9.70), 2.303 (0.99), 2.458 (0.51 ), 2.465 (0.54), 2.720 (1.21), 2.743 (1.93), 2.758 (1.66), 2.837 (0.42), 2.857 (0.41), 2.869 (0.51), 2.892 (0.49), 3.708 (1.25), 3.722 (12.20 ), 4,758 (2.95), 4,763 (3.01), 4,776 (1.05), 4,791 (1.07), 4,799 (0.95), 4,937 (0.40), 5,753 (0.46), 7,141 (16.00). Intermediate 49 Methyl (5S)-2-[(6-chloropyridin-3-yl)methyl]-3-oxo-2,5,6,7-tetrahydro-3H-pyrrole[2,1-c][1 ,2,4]triazol-5-carboxylate (enantiomer)

[0558] Methyl (5S)-3-oxo-2,5,6,7-tetrahydro-3H-pyrrolo[2,1- c][1,2,4]triazol-5-carboxylate (enantiomer) ( 300 mg, 1.64 mmol) was initially loaded into acetonitrile (10 mL). After stirring for 5 min, cesium carbonate (587 mg, 1.80 mmol) and 5-(bromomethyl)-2-chloropyridine (355 mg, 1.72 mmol, CAS 182924-36-3) were added. After stirring overnight, the reaction mixture was mixed with water and ethyl acetate at room temperature. The organic phase was removed and the aqueous phase was extracted three times with ethyl acetate. The combined organic phases were washed with saturated aqueous sodium chloride solution, dried over sodium sulfate and filtered, and the filtrate was concentrated. The residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/gradient water). The fractions containing the product were concentrated under reduced pressure and 430 mg (85% possibility) of the title compound were obtained. LC-MS (Method 1): Rt = 0.80 min; MS (ESIpos): m /z = 309 [M+H]+ Intermediate 50 Methyl (5S)-3-oxo-2-{[6-(trifluoromethyl)pyridin-3-yl]methyl}-2,5,6 ,7-tetrahydro-3H-pyrrole[2,1-c][1,2,4]triazol-5-carboxylate (enantiomer)

[0559] Methyl (5S)-3-oxo-2,5,6,7-tetrahydro-3H-pyrrolo[2,1- c][1,2,4]triazol-5-carboxylate (enantiomer) ( 300 mg, 1.64 mmol) was initially loaded into acetonitrile (10 mL). Cesium carbonate (587 mg, 1.80 mmol) and 5-(bromomethyl)-2-(trifluoromethyl)pyridine (413 mg, 1.72 mmol, CAS 108274-33-5) were subsequently added. After stirring overnight, the reaction mixture was mixed with water and ethyl acetate at room temperature. The organic phase was removed and the aqueous phase was extracted three times with ethyl acetate. The combined organic phases were washed with saturated aqueous sodium chloride solution, dried over sodium sulfate and filtered, and the filtrate was concentrated. The residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/gradient water). The fractions containing the product were concentrated under reduced pressure and 441 mg (79% possibility) of the title compound were obtained. LC-MS (Method 1): Rt = 0.92 min; MS (ESIpos): m /z = 343 [M+H]+ Intermediate 51 Methyl (5S)-2-(3-chloro-4-fluorobenzyl)-3-oxo-2,5,6,7-tetrahydro -3H- pyrrole[2,1-c][1,2,4]triazole-5-carboxylate (enantiomer)

[0560] Methyl (5S)-3-oxo-2,5,6,7-tetrahydro-3H-pyrrolo[2,1- c][1,2,4]triazol-5-carboxylate (enantiomer) ( 300 mg, 1.64 mmol) was initially loaded into acetonitrile (530 μl). After stirring for 5 min, cesium carbonate (587 mg, 1.80 mmol) and 4-(bromomethyl)-2-chloro-1-fluorobenzene (384 mg, 1.72 mmol, CAS 192702-01-5) were added. . After stirring overnight, the reaction mixture was mixed with water and ethyl acetate at room temperature. The organic phase was removed and the aqueous phase was extracted three times with ethyl acetate. The combined organic phases were washed with saturated aqueous sodium chloride solution, dried over sodium sulfate and filtered, and the filtrate was concentrated. The residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/gradient water). The fractions containing the product were concentrated under reduced pressure and 460 mg (86% possibility) of the title compound were obtained. LC-MS (Method 3): Rt = 1.42 min; MS (ESIpos): m /z = 326 [M+H]+ Intermediate 52 Methyl (5S)-3-oxo-2-[3-(trifluoromethyl)benzyl]-2,5,6,7-tetrahydro- 3H- pyrrole[2,1-c][1,2,4]triazol-5-carboxylate (enantiomer)

[0561] Methyl (5S)-3-oxo-2,5,6,7-tetrahydro-3H-pyrrolo[2,1- c][1,2,4]triazol-5-carboxylate (enantiomer) ( 150 mg, 819 μmol) was initially loaded into acetonitrile (8.0 mL). After stirring for 5 min, cesium carbonate (294 mg, 901 μmol) and 1-(bromomethyl)-3-(trifluoromethyl)benzene (206 mg, 860 μmol, CAS 402-23-3) were added. After stirring overnight, the reaction mixture was mixed with water and ethyl acetate at room temperature. The organic phase was removed and the aqueous phase was extracted three times with ethyl acetate. The combined organic phases were washed with saturated aqueous sodium chloride solution, dried over sodium sulfate and filtered, and the filtrate was concentrated. The residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/gradient water). The fractions containing the product were concentrated under reduced pressure and 150 mg (53% possibility) of the title compound were obtained. LC-MS (Method 1): Rt = 1.09 min; MS (ESIpos): m /z = 342 [M+H]+ Intermediate 53 Methyl (5S)-2-[(2-chloropyridin-4-yl)methyl]-3-oxo-2,5,6,7- tetrahydro-3H-pyrrole[2,1-c][1,2,4]triazol-5-carboxylate (enantiomer)

[0562] Methyl (5S)-3-oxo-2,5,6,7-tetrahydro-3H-pyrrolo[2,1- c][1,2,4]triazol-5-carboxylate (enantiomer) ( 150 mg, 819 μmol) was initially loaded into acetonitrile (7.0 mL). After stirring for 5 min, cesium carbonate (294 mg, 901 μmol) and 4-(bromomethyl)-2-chloropyridine (178 mg, 860 μmol, CAS 83004-15-3) were added. After stirring overnight, the reaction mixture was mixed with water and ethyl acetate at room temperature. The organic phase was removed and the aqueous phase was extracted three times with ethyl acetate. The combined organic phases were washed with saturated aqueous sodium chloride solution, dried over sodium sulfate and filtered, and the filtrate was concentrated. The residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/gradient water). The fractions containing the product were concentrated under reduced pressure and 250 mg (99% possibility) of the title compound were obtained. LC-MS (Method 1): Rt = 0.78 min; MS (ESIpos): m /z = 309 [M+H]+ Intermediate 54 Methyl (5RS)-2-(4-chlorobenzyl)-3-oxo-2,3,5,6,7,8-hexahydro [1,2,4]triazolo[4,3-a]pyridine-5-carboxylate (racemate)

[0563] Methyl (2RS)-6-[(tert-butoxycarbonyl)hydrazono]piperidine-2-carboxylate (racemate) (2.20 g, 7.21 mmol) in DMF (15 mL) was stirred at 150 ° C for at night. The reaction mixture (theoretical yield: 1.42 g) was divided into aliquots and used directly. To the solution of an aliquot of the crude product, methyl (5RS)-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine- 5-carboxylate (racemate) (calculated as 473 mg, 2.40 mmol) into 5 mL of DMF were added cesium carbonate (1.17 g, 3.60 mmol) and 1-(bromomethyl)-4-chlorobenzene (518 mg, 2.52 mmol). The reaction mixture was stirred at room temperature overnight. Then, more 1-(bromomethyl)-4-chlorobenzene was added (493 mg, 2.40 mmol), and the mixture was stirred at 50°C overnight. For elaboration, water was added, the mixture was extracted twice with 15 ml each time of ethyl acetate, and the combined organic phases were washed once with saturated aqueous sodium chloride solution, dried with magnesium sulfate, filtered and concentrated under reduced pressure. The residue was separated into 2 portions via preparatory HPLC (column: Chromatorex, 125x40mm 10μm. Flow rate: 50 ml/min. Gradient (A = water + 0.1% formic acid, B = acetonitrile): 0min 10% B, 5min 10%B, 27min 98%B, 35min 98%B, 35.01min 10%B, 38min 10%B. Run time per separation 38 min. Concentration of the product fractions yielded 80 mg (96% purity, 9.6% possibility) of the title compound. LC-MS (Method 3): Rt = 1.78 min; MS (ESIpos): m /z = 388 [M+H]+ Intermediate 55 (5RS)-2-(4-methylbenzyl)-3-oxo-2,3,5,6,7,8-hexahydro[ 1,2,4]triazolo[4,3-a]pyridine-5-carboxylate (enantiomer 1)

[0564] tert-Butyl(5RS)-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylate ( Enantiomer 2) (1.77 g, 7.38 mmol) was initially loaded into acetonitrile (71 mL). Cesium carbonate (2.40 g, 7.38 mmol) and 1-(bromomethyl)-4-methylbenzene (1.37 g, 7.38 mmol) were subsequently added. After stirring overnight, the reaction mixture was mixed with water and ethyl acetate at room temperature. The organic phase was removed and the aqueous phase was extracted with ethyl acetate. The combined organic phases were washed with saturated aqueous sodium chloride solution, dried over magnesium sulfate and filtered, and the filtrate was concentrated. 2.65 g (>100% chance) of the title compound were obtained. LC-MS (Method 4): Rt = 0.97 min; MS (ESIpos): m /z = 343 [M+H]+ Intermediate 56 tert-Butyl (5RS)-2-[(5-chloropyridin-2-yl)methyl]-3-oxo-2,3,5, 6,7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylate (racemate)

[0565] tert-Butyl(5RS)-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylate ( racemate) (300 mg, 1.25 mmol) was initially loaded into acetonitrile (6.0 mL). Cesium carbonate (613 mg, 1.88 mmol) and 2-(bromoethyl)-5-chloropyridine (272 mg, 1.32 mmol, CAS 60568101-4) were subsequently added. After stirring overnight, the reaction mixture was mixed with water and ethyl acetate at room temperature. The organic phase was removed and the aqueous phase was extracted three times with ethyl acetate. The combined organic phases were washed with saturated aqueous sodium chloride solution, dried over sodium sulfate and filtered, and the filtrate was concentrated. The residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/gradient water). The fractions containing the product were concentrated under reduced pressure and 306 mg (65% possibility) of the title compound were obtained. LC-MS (Method 3): Rt = 1.61 min; MS (ESIpos): m /z = 365 [M+H]+ 1H-NMR (600 MHz, DMSO-d6) δ [ppm]: 1.410 (16.00), 2.078 (0.62), 2.085 (0.56), 2.637 (0.42 ), 4.453 (0.46), 4.459 (0.48), 4.463 (0.58), 4.469 (0.43), 4.932 (1.44), 4.947 (1.43), 7.232 (0.89), 7.246 (0.91), 7.928 (0.56), 7.932 (0.56 ), 7,942 (0.53), 7,946 (0.52), 8,578 (0.90), 8,582 (0.88). Intermediate 57 tert-Butyl (5RS)-3-oxo-2-{[6-(trifluoromethyl)pyridin-3-yl]methyl}-2,3,5,6,7,8-hexahydro-[1, 2,4]triazolo[4,3-a]pyridine-5-carboxylate (racemate)

[0566] tert-Butyl(5RS)-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylate ( racemate) (300 mg, 1.25 mmol) was initially loaded into acetonitrile (6.0 mL). Cesium carbonate (613 mg, 1.88 mmol) and 5-(bromomethyl)-2-(trifluoromethyl)pyridine (316 mg, 1.32 mmol, CAS 108274-33-5) were subsequently added. After stirring at room temperature for 48 h, the reaction mixture was mixed with water and ethyl acetate. The organic phase was removed and the aqueous phase was extracted three times with ethyl acetate. The combined organic phases were washed with saturated aqueous sodium chloride solution, dried over sodium sulfate and filtered, and the filtrate was concentrated. The residue was suspended in diethyl ether, and the solids were filtered off and dried under reduced pressure. 345 mg (66% chance) of the title compound was obtained. LC-MS (Method 4): Rt = 0.92 min; MS (ESIpos): m /z = 399 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: 1.383 (16.00), 1.404 (0.51), 2.069 (0.60), 2.081 (0.48 ), 4,457 (0.62), 5,036 (2.03), 7,923 (1.20), 7,933 (0.73), 7,937 (0.70), 8,665 (0.72). Intermediate 58 tert-Butyl (5RS)-2-(3,5-dichlorobenzyl)-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3 -a]pyridine-5-carboxylate (racemate)

[0567] tert-Butyl(5RS)-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylate ( racemate) (300 mg, 1.25 mmol) was initially loaded into acetonitrile (6.0 mL). Cesium carbonate (613 mg, 1.88 mmol) and 1-(bromomethyl)-3,5-dichlorobenzene (316 mg, 1.32 mmol, CAS 7778-01-0) were subsequently added. After stirring overnight, the reaction mixture was mixed with water and ethyl acetate at room temperature. The organic phase was removed and the aqueous phase was extracted three times with ethyl acetate. The combined organic phases were washed with saturated aqueous sodium chloride solution, dried over sodium sulfate and filtered, and the filtrate was concentrated. 445 mg (82% purity, 89% possibility) of the title compound were obtained. LC-MS (Method 3): Rt = 2.12 min; MS (ESIpos): m /z = 342 [M+H]+ Intermediate 59 tert-Butyl (5RS)-3-oxo-2-(pyridin-3-ylmethyl)-2,3,5,6,7,8 -hexa-hydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylate (racemate)

[0568] tert-Butyl(5RS)-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylate ( racemate) (300 mg, 1.25 mmol) was initially loaded into acetonitrile (6.0 mL). Cesium carbonate (1.02 g, 3.13 mmol) and 3-(bromomethyl)pyridine hydrobromide (333 mg, 1.32 mmol, CAS 4916-55-6) were subsequently added. After stirring overnight, the reaction mixture was mixed with water and ethyl acetate at room temperature. The organic phase was removed and the aqueous phase was extracted three times with ethyl acetate. The combined organic phases were washed with saturated aqueous sodium chloride solution, dried over sodium sulfate and filtered, and the filtrate was concentrated. 366 mg (88% chance) of the title compound was obtained. LC-MS (Method 4): Rt = 0.58 min; MS (ESIpos): m /z = 331 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: 1.390 (16.00), 1.405 (12.47), 2.037 (0.58), 2.050 (0.73 ), 2.060 (0.77), 2.070 (0.65), 2.523 (0.58), 2.617 (0.41), 2.627 (0.42), 4.348 (0.50), 4.444 (0.59), 4.526 (0.81), 4.896 (1.69), 7.359 (0.43 ), 7.371 (0.43), 7.378 (0.45), 7.391 (0.45), 7.642 (0.49), 7.661 (0.42), 8.483 (0.82), 8.500 (0.55), 8.504 (0.55), 8.513 (0.52). Intermediate 60 Methyl (5RS)-2-[(5-methyl-1,2-oxazol-3-yl)methyl]-3-oxo-2,3,5,6,7,8-hexahydro[1, 2,4]triazolo[4,3-a]pyridine-5-carboxylate (racemate)

[0569] Methyl(5RS)-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylate (racemate) (50.0 mg, 254 μmol) was initially loaded into acetonitrile (3.6 mL). Cesium carbonate (124 mg, 380 μmol) and 3-(bromomethyl)-5-methyl-1,2-oxazole (46.9 mg, 266 μmol, CAS 130628-75-0) were subsequently added. After stirring at room temperature for 24 h, the reaction mixture was mixed with water and ethyl acetate. The organic phase was removed and the aqueous phase was extracted three times with ethyl acetate. The combined organic phases were washed with saturated aqueous sodium chloride solution, dried over sodium sulfate and filtered, and the filtrate was concentrated. 58.0 mg (93% purity, 73% chance) of the title compound was obtained. LC-MS (Method 1): Rt = 0.78 min; MS (ESIpos): m /z = 293 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.008 (0.58), 0.008 (0.51), 1.527 (0.40), 1.532 ( 0.40), 1.540 (0.42), 1.798 (0.45), 1.806 (0.50), 1.820 (0.43), 2.055 (0.46), 2.072 (3.66), 2.084 (0.69), 2.092 (0.58), 2.100 (0.46), 2.108 ( 0.53), 2.113 (0.51), 2.120 (0.49), 2.129 (0.51), 2.136 (0.47), 2.206 (1.02), 2.376 (10.50), 2.518 (0.88), 2.560 (0.90), 2.575 (0.76), 2.587 ( 0.75), 2.601 (0.66), 2.624 (0.60), 2.636 (1.04), 2.648 (0.59), 2.678 (0.48), 3.687 (1.59), 3.703 (16.00), 4.591 (0.92), 4.600 (1.03), 4.607 ( 1.24), 4.616 (0.92), 4.854 (7.94), 4.981 (0.43), 6.065 (2.10). Intermediate 61 tert-Butyl (5RS)-2-(3,4-difluorobenzyl)-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3 -a]pyridine-5-carboxylate (racemate)

[0570] tert-Butyl(5RS)-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylate ( racemate) (300 mg, 1.25 mmol) was initially loaded into acetonitrile (10 mL). Cesium carbonate (429 mg, 1.32 mmol) and 4-(bromomethyl)-1,2-dichlorobenzene (273 mg, 1.32 mmol, CAS 85118-01-0) were subsequently added. The reaction mixture was stirred at room temperature overnight and at 90°C for one hour. Water and ethyl acetate were then added to the reaction mixture. The organic phase was removed and the aqueous phase was extracted three times with ethyl acetate. The combined organic phases were washed with saturated aqueous sodium chloride solution, dried over sodium sulfate and filtered, and the filtrate was concentrated. 455 mg (99% chance) of the title compound was obtained. 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.008 (0.57), 0.008 (0.51), 1.393 (16.00), 1.404 (3.82), 1.908 (1.06), 1.988 (0.61), 2.064 (0.60 ), 2.074 (0.56), 2.523 (0.73), 4.433 (0.44), 4.443 (0.41), 4.448 (0.56), 4.699 (0.90), 4.847 (1.99), 7.400 (0.49), 7.428 (0.45). Intermediate 62 tert-Butyl (5RS)-2-(3-chloro-4-fluorobenzyl)-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4 ,3-a]pyridine-5-carboxylate (racemate)

[0571] tert-Butyl(5RS)-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylate ( racemate) (311 mg, 1.30 mmol) was initially loaded into acetonitrile (10 mL). Cesium carbonate (445 mg, 1.36 mmol) and 4-(bromomethyl)-2-chloro-1-fluorobenzene (305 mg, 1.36 mmol, CAS 192702-01-5) were subsequently added. The reaction mixture was stirred at room temperature overnight and at 90°C for one hour. Water and ethyl acetate were then added to the reaction mixture. The organic phase was removed and the aqueous phase was extracted three times with ethyl acetate. The combined organic phases were washed with saturated aqueous sodium chloride solution, dried over sodium sulfate and filtered, and the filtrate was concentrated. 491 mg (90% purity, 89% chance) of the title compound was obtained. LC-MS (Method 1): Rt = 1.32 min; MS (ESIpos): m /z = 326 [M-tBu+H]+ Intermediate 63 Methyl (5RS)-2-(3-chlorobenzyl)-3-oxo-2,3,5,6,7,8-hexa - hydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylate (racemate)

[0572] Methyl(5RS)-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylate (racemate) (50.0 mg, 254 μmol) was initially loaded into acetonitrile (3.6 mL). Cesium carbonate (124 mg, 380 μmol) and 1-(bromomethyl)-3-chlorobenzene (54.7 mg, 266 μmol, CAS 76680-3) were subsequently added. After stirring at room temperature for 24 h, the reaction mixture was mixed with water, 1 N aqueous hydrochloric acid, and ethyl acetate. The organic phase was removed and the aqueous phase was extracted three times with ethyl acetate. The combined organic phases were washed with saturated aqueous sodium chloride solution, dried over sodium sulfate and filtered, and the filtrate was concentrated. The residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/gradient water). The fractions containing the product were concentrated under reduced pressure and 66.0 mg (81% possibility) of the title compound were obtained. LC-MS (Method 4): Rt = 0.82 min; MS (ESIpos): m /z = 322 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.008 (1.42), 0.008 (1.25), 1.526 (0.41), 1.532 ( 0.41), 1.802 (0.49), 1.811 (0.51), 1.825 (0.45), 1.836 (0.42), 2.065 (0.46), 2.075 (0.77), 2.088 (0.74), 2.095 (0.70), 2.102 (0.56), 2.110 ( 0.46), 2.118 (0.54), 2.130 (0.51), 2.139 (0.53), 2.146 (0.50), 2.523 (1.49), 2.564 (1.03), 2.579 (0.83), 2.591 (0.83), 2.605 (0.68), 2.631 ( 0.63), 2.642 (1.16), 2.654 (0.67), 2.673 (0.53), 2.684 (0.51), 3.708 (16.00), 4.615 (1.04), 4.625 (1.16), 4.631 (1.33), 4.640 (1.01), 4.863 ( 5.05), 7.190 (1.12), 7.208 (1.43), 7.282 (1.86), 7.343 (0.46), 7.359 (1.33), 7.364 (2.10), 7.369 (2.85), 7.387 (1.85), 7.407 (0.62). Intermediate 64 tert-Butyl (5RS)-2-[(2-methoxypyridin-4-yl)methyl]-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4] triazolo[4,3-a]pyridine-5-carboxylate (racemate)

[0573] tert-Butyl(5RS)-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylate ( racemate) (357 mg, 1.49 mmol) was initially loaded into acetonitrile (10 mL). Cesium carbonate (510 mg, 1.57 mmol) and 4-(bromomethyl)-2-dichlorobenzene (381 mg, 83% purity, 1.57 mmol, CAS 120277-15-8) were subsequently added. After stirring overnight, the reaction mixture was mixed at room temperature with water, 1 N aqueous hydrochloric acid, and ethyl acetate. The organic phase was removed and the aqueous phase was extracted three times with ethyl acetate. The combined organic phases were washed with saturated aqueous sodium chloride solution, dried over sodium sulfate and filtered, and the filtrate was concentrated. The residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/gradient water). The fractions containing the product were concentrated under reduced pressure and 144 mg (27% possibility) of the title compound were obtained. LC-MS (Method 3): Rt = 1.52 min; MS (ESIpos): m /z = 361 [M+H]+ Intermediate 65 tert-Butyl (5RS)-2-(3-fluorobenzyl)-3-oxo-2,3,5,6,7,8-hexa - hydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylate (racemate)

[0574] tert-Butyl(5RS)-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylate ( racemate) (300 mg, 1.25 mmol) was initially loaded into acetonitrile (10 mL). Cesium carbonate (429 mg, 1.32 mmol) and 1-(bromomethyl)-3-fluorobenzene (249 mg, 1.32 mmol, CAS 45641-7) were subsequently added. After stirring overnight, the reaction mixture was mixed at room temperature with water, 1 N aqueous hydrochloric acid, and ethyl acetate. The organic phase was removed and the aqueous phase was extracted three times with ethyl acetate. The combined organic phases were washed with saturated aqueous sodium chloride solution, dried over sodium sulfate and filtered, and the filtrate was concentrated. The residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/gradient water). The fractions containing the product were concentrated under reduced pressure and 297 mg (68% possibility) of the title compound were obtained. LC-MS (Method 1): Rt = 1.23 min; MS (ESIpos): m /z = 291 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.008 (1.11), 0.008 (0.97), 1.397 (16.00), 2.067 ( 0.49), 2.077 (0.52), 2.518 (1.08), 2.523 (0.83), 4.451 (0.57), 4.865 (1.75), 4.872 (1.37), 7.078 (0.48), 7.097 (0.65), 7.380 (0.40), 7.396 ( 0.42). Intermediate 66 tert-Butyl (5RS)-2-(3-chloro-4-methoxybenzyl)-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4 ,3-a]pyridine-5-carboxylate (racemate)

[0575] tert-Butyl(5RS)-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylate ( racemate) (300 mg, 1.25 mmol) was initially loaded into acetonitrile (6.0 mL). Cesium carbonate (613 mg, 1.88 mmol) and 4-(bromomethyl)-2-chloro-1-methoxybenzene (314 mg, 99% purity, 1.32 mmol, CAS 320407-92-9) were subsequently added . After stirring overnight, the reaction mixture was mixed with water and ethyl acetate at room temperature. The organic phase was removed and the aqueous phase was extracted three times with ethyl acetate. The combined organic phases were washed with saturated aqueous sodium chloride solution, dried over sodium sulfate and filtered, and the filtrate was concentrated. The residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/gradient water). The fractions containing the product were concentrated under reduced pressure and 365 mg (74% possibility) of the title compound were obtained. LC-MS (Method 4): Rt = 0.96 min; MS (ESIpos): m /z = 393 [M]+ Intermediate 67 tert-Butyl (5RS)-3-oxo-2-[3-(trifluoromethyl)benzyl]-2,3,5,6,7,8- hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylate (racemate)

[0576] tert-Butyl(5RS)-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylate ( racemate) (300 mg, 1.25 mmol) was initially loaded into acetonitrile (6.0 mL). Cesium carbonate (613 mg, 1.88 mmol) and 1-(bromomethyl)-3-(trifluoromethyl)benzene (315 mg, 1.32 mmol, CAS 402-23-3) were subsequently added. After stirring overnight, the reaction mixture was mixed with water and ethyl acetate at room temperature. The organic phase was removed and the aqueous phase was extracted three times with ethyl acetate. The combined organic phases were washed with saturated aqueous sodium chloride solution, dried over sodium sulfate and filtered, and the filtrate was concentrated. The residue was suspended in diethyl ether, and the solids were filtered off and dried under reduced pressure. 388 mg (75% chance) of the title compound was obtained. LC-MS (Method 1): Rt = 1.35 min; MS (ESIpos): m /z = 342 [M+H]+ Intermediate 68 tert-Butyl (5RS)-2-(3-methoxybenzyl)-3-oxo-2,3,5,6,7,8-hexa - hydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylate (racemate)

[0577] tert-Butyl(5RS)-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylate ( racemate) (300 mg, 1.25 mmol) was initially loaded into acetonitrile (6.0 mL). Cesium carbonate (613 mg, 1.88 mmol) and 1-(bromomethyl)-3-methoxybenzene (265 mg, 1.32 mmol, CAS 87498-6) were subsequently added. After stirring overnight, the reaction mixture was mixed with water and ethyl acetate at room temperature. The organic phase was removed and the aqueous phase was extracted three times with ethyl acetate. The combined organic phases were washed with saturated aqueous sodium chloride solution, dried over sodium sulfate and filtered, and the filtrate was concentrated. The residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/gradient water). The product-containing fractions were concentrated under reduced pressure and 340 mg (94% purity, 71% possibility) of the title compound were obtained. LC-MS (Method 4): Rt = 0.91 min; MS (ESIpos): m /z = 360 [M+H]+ Intermediate 69 tert-Butyl (5RS)-2-[(1-methyl-1H-pyrazol-3-yl)methyl]-3-oxo-2, 3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylate (racemate)

[0578] tert-Butyl(5RS)-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylate ( racemate) (145 mg, 606 μmol) was initially loaded into acetonitrile (6.0 mL). Cesium carbonate (207 mg, 636 μmol) and 3-(bromomethyl)-1-methyl-1H-pyrazole (106 mg, 606 μmol, CAS 102846-13-9) were subsequently added. The reaction mixture was stirred at room temperature overnight and then at 70°C for 3 h. The reaction mixture was cooled to room temperature, and water and ethyl acetate were added. The organic phase was removed and the aqueous phase was extracted three times with ethyl acetate. The combined organic phases were washed with saturated aqueous sodium chloride solution, dried over sodium sulfate and filtered, and the filtrate was concentrated. The residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/gradient water). The fractions containing the product were concentrated under reduced pressure and 150 mg (74% possibility) of the title compound were obtained. LC-MS (Method 1): Rt = 0.97 min; MS (ESIpos): m /z = 278 [M-tBu+H]+ Intermediate 70 tert-Butyl (5RS)-3-oxo-2-(5,6,7,8-tetrahydronaphthalen-2-ylmethyl) - 2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylate (racemate)

[0579] tert-Butyl(5RS)-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylate ( racemate) (400 mg, 1.67 mmol) was initially loaded into acetonitrile (10 mL). Cesium carbonate (572 mg, 1.76 mmol) and 6-(chloromethyl)-1,2,3,4-tetrahydronaphthalene (317 mg, 1.76 mmol, CAS 17450-63-4) were subsequently added. After stirring overnight, the reaction mixture was mixed with water and ethyl acetate at room temperature. The organic phase was removed and the aqueous phase was extracted three times with ethyl acetate. The combined organic phases were washed with saturated aqueous sodium chloride solution, dried over sodium sulfate and filtered, and the filtrate was concentrated. The residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/gradient water). The fractions containing the product were concentrated under reduced pressure and 280 mg (43% possibility) of the title compound were obtained. LC-MS (Method 1): Rt = 1.44 min; MS (ESIpos): m /z = 328 [M-tBu+H]+ Intermediate 71 tert-Butyl (5RS)-3-oxo-2-(2,4,5-trifluorobenzyl)-2,3,5,6 ,7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylate (racemate)

[0580] tert-Butyl(5RS)-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylate ( racemate) (400 mg, 1.67 mmol) was initially loaded into acetonitrile (10 mL). Cesium carbonate (572 mg, 1.76 mmol) and 1-(chloromethyl)-2,4,5-trifluorobenzene (317 mg, 1.76 mmol, CAS 243139-71-1) were subsequently added. After stirring overnight, the reaction mixture was mixed with water and ethyl acetate at room temperature. The organic phase was removed and the aqueous phase was extracted three times with ethyl acetate. The combined organic phases were washed with saturated aqueous sodium chloride solution, dried over sodium sulfate and filtered, and the filtrate was concentrated. The residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/gradient water). The fractions containing the product were concentrated under reduced pressure and 390 mg (61% possibility) of the title compound were obtained. LC-MS (Method 1): Rt = 1.29 min; MS (ESIpos): m /z = 328 [M-tBu+H]+ Intermediate 72 tert-Butyl (5RS)-2-[(2-chloropyridin-4-yl)methyl]-3-oxo-2,3, 5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylate (racemate)

[0581] tert-Butyl(5RS)-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylate ( racemate) (370 mg, 1.54 mmol) was initially loaded into acetonitrile (10 mL). Cesium carbonate (528 mg, 1.62 mmol) and 4-(bromomethyl)-2-chloropyridine (360 mg, 93% purity, 1.62 mmol, CAS 83004-15-3) were subsequently added. After stirring overnight, the reaction mixture was mixed with water and ethyl acetate at room temperature. The organic phase was removed and the aqueous phase was extracted three times with ethyl acetate. The combined organic phases were washed with saturated aqueous sodium chloride solution, dried over sodium sulfate and filtered, and the filtrate was concentrated. 490 mg (83% chance) of the title compound was obtained. LC-MS (Method 3): Rt = 1.54 min; MS (ESIpos): m /z = 365 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.008 (1.57), 0.008 (1.54), 1.405 (16.00), 2.084 ( 0.54), 2.094 (0.44), 2.523 (0.99), 2.568 (0.41), 2.669 (0.51), 4.476 (0.54), 4.944 (1.40), 4.949 (1.35), 7.240 (0.51), 7.250 (0.53), 7.328 ( 0.82), 8.377 (0.75), 8.389 (0.75). Intermediate 73 tert-Butyl (5RS)-2-[(5-chloro-2-thienyl)methyl]-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4] triazolo[4,3-a]pyridine-5-carboxylate (racemate)

[0582] tert-Butyl(5RS)-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylate ( racemate) (300 mg, 1.25 mmol) was initially loaded into acetonitrile (10 mL). Cesium carbonate (429 mg, 1.32 mmol) and 2-chloro-5-(chloromethyl)thiophene (220 mg, 1.32 mmol, CAS 2378496-5) were subsequently added. After stirring overnight, the reaction mixture was mixed with water and ethyl acetate at room temperature. The organic phase was removed and the aqueous phase was extracted three times with ethyl acetate. The combined organic phases were washed with saturated aqueous sodium chloride solution, dried over sodium sulfate and filtered, and the filtrate was concentrated. 414 mg (83% purity, 74% possibility) of the title compound were obtained. LC-MS (Method 3): Rt = 1.88 min; MS (ESIpos): m /z = 313 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: 1.175 (0.45), 1.335 (0.71), 1.384 (16, 00), 1.397 (0.99), 1.988 (0.79), 2.045 (0.50), 2.057 (0.51), 4.420 (0.56), 4.950 (2.59), 4.986 (2.46 ), 6.922 (0.61), 6.931 (0.84), 6.976 (1.11), 6.986 (0.79), 7.011 (0.48), 7.020 (0.65), 7.079 (0.51) . Intermediate 74 Methyl (5RS)-2-[(4-methyl-1,2,5-oxadiazol-3-yl)methyl]-3-oxo-2,3,5,6,7,8-hexahydro[ 1,2,4]triazolo[4,3-a]pyridine-5-carboxylate (racemate)

[0583] Methyl(5RS)-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylate (racemate) (300 mg, 1.52 mmol) was initially loaded into acetonitrile (10 mL). Cesium carbonate (545 mg, 1.67 mmol) and 3-(bromomethyl)-4-methyl-1,2,5-oxadiazole (283 mg, 1.60 mmol, CAS 90507-32-7) were subsequently added. After stirring overnight, the reaction mixture was mixed with water and ethyl acetate at room temperature. The organic phase was removed and the aqueous phase was extracted three times with ethyl acetate. The combined organic phases were washed with saturated aqueous sodium chloride solution, dried over sodium sulfate and filtered, and the filtrate was concentrated. The residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/gradient water). The fractions containing the product were concentrated under reduced pressure and 281 mg (63% possibility) of the title compound were obtained. LC-MS (Method 3): Rt = 1.06 min; MS (ESIpos): m /z = 294 [M+H]+ Intermediate 75 Methyl (5RS)-2-[(6-methylpyridin-3-yl)methyl]-3-oxo-2,3,5,6, 7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylate (racemate)

[0584] Methyl(5RS)-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylate (racemate) (300 mg, 1.52 mmol) was initially loaded into acetonitrile (10 mL). Cesium carbonate (1.24 g, 3.80 mmol) and 5-(chloromethyl)-2-methylpyridine hydrochloride (298 mg, 1.67 mmol, CAS 106651-81-4) were subsequently added. After stirring overnight, the reaction mixture was mixed at room temperature with water, 1 N aqueous hydrochloric acid, and ethyl acetate. The organic phase was removed and the aqueous phase was extracted three times with ethyl acetate. The combined organic phases were washed with saturated aqueous sodium chloride solution, dried over sodium sulfate and filtered, and the filtrate was concentrated. The residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/gradient water). The fractions containing the product were concentrated under reduced pressure and 236 mg (51% possibility) of the title compound were obtained. LC-MS (Method 4): Rt = 0.26 min; MS (ESIpos): m /z = 303 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.008 (0.57), 0.008 (0.57), 1.511 (0.41), 1.517 ( 0.41), 1.525 (0.42), 1.787 (0.49), 1.798 (0.53), 1.812 (0.45), 1.822 (0.42), 2.051 (0.47), 2.061 (0.80), 2.073 (3.59), 2.086 (0.68), 2.095 ( 0.50), 2.103 (0.56), 2.107 (0.49), 2.115 (0.52), 2.123 (0.54), 2.131 (0.51), 2.439 (12.07), 2.523 (0.56), 2.557 (0.88), 2.569 (0.86), 2.583 ( 0.68), 2.609 (0.63), 2.621 (1.16), 2.633 (0.65), 2.663 (0.57), 3.700 (16.00), 4.594 (1.02), 4.603 (1.12), 4.610 (1.31), 4.619 (1.00), 4.835 ( 5.24), 7.216 (1.67), 7.236 (1.95), 7.506 (1.19), 7.512 (1.20), 7.526 (1.07), 7.532 (1.07), 8.337 (1.47), 8.342 (1.45). Intermediate 76 Methyl (5RS)-2-[(6-methoxypyridin-3-yl)methyl]-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[ 4,3-a]pyridine-5-carboxylate (racemate)

[0585] Methyl(5RS)-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylate (racemate) (300 mg, 1.52 mmol) was initially loaded into acetonitrile (10 mL). Cesium carbonate (1.24 g, 3.80 mmol) and 5-(chloromethyl)-2-methoxypyridine hydrochloride (325 mg, 1.67 mmol, CAS 120276-36-0) were subsequently added. After stirring overnight, the reaction mixture was mixed at room temperature with water, 1 N aqueous hydrochloric acid, and ethyl acetate. The organic phase was removed and the aqueous phase was extracted three times with ethyl acetate. The combined organic phases were washed with saturated aqueous sodium chloride solution, dried over sodium sulfate and filtered, and the filtrate was concentrated. The residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/gradient water). The fractions containing the product were concentrated under reduced pressure and 206 mg (42% possibility) of the title compound were obtained. LC-MS (Method 4): Rt = 0.61 min; MS (ESIpos): m /z = 319 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.008 (1.39), 0.008 (1.28), 1.795 (0.43), 2.073 ( 5.67), 2.091 (0.40), 2.099 (0.45), 2.111 (0.42), 2.120 (0.44), 2.127 (0.41), 2.523 (0.87), 2.568 (0.68), 2.582 (0.55), 2.608 (0.50), 2.620 ( 0.92), 2,631 (0.52), 2,662 (0.50), 3,698 (13.67), 3,828 (16.00), 3,851 (0.46), 4,585 (0.90), 4,594 (0.95), 4,600 (1.13), 4,610 (0.82), 4,794 ( 5.64), 6.793 (1.69), 6.815 (1.80), 7.560 (1.13), 7.566 (1.15), 7.582 (1.09), 7.588 (1.11), 8.066 (1.53), 8.071 (1.49). Intermediate 77 Methyl (5RS)-2-[2,5-bis(trifluoromethyl)benzyl]-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4 ,3-a]pyridine-5-carboxylate (racemate)

[0586] Methyl(5RS)-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylate (racemate) (300 mg, 1.52 mmol) was initially loaded into acetonitrile (10 mL). Cesium carbonate (1.24 g, 3.80 mmol) and 2-(bromomethyl)-1,4-bis-(trifluoromethyl)benzene (514 mg, 1.67 mmol, CAS 302911-98-4) were subsequently added . After stirring overnight, the reaction mixture was mixed at room temperature with water, 1 N aqueous hydrochloric acid, and ethyl acetate. The organic phase was removed and the aqueous phase was extracted three times with ethyl acetate. The combined organic phases were washed with saturated aqueous sodium chloride solution, dried over sodium sulfate and filtered, and the filtrate was concentrated. 649 mg (95% chance) of the title compound was obtained. LC-MS (Method 4): Rt = 1.00 min; MS (ESIpos): m /z = 424 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.008 (0.90), 0.008 (0.79), 1.157 (0.56), 1.175 ( 1.14), 1.193 (0.59), 1.539 (0.40), 1.815 (0.51), 1.825 (0.49), 1.839 (0.42), 1.850 (0.43), 1.988 (2.13), 2.073 (0.47), 2.091 (0.47), 2.103 ( 0.89), 2.111 (1.07), 2.134 (0.56), 2.147 (0.48), 2.155 (0.51), 2.163 (0.47), 2.576 (0.89), 2.591 (0.71), 2.603 (0.74), 2.617 (0.61), 2.649 ( 0.57), 2.660 (1.10), 2.671 (0.76), 2.702 (0.47), 3.702 (16.00), 4.021 (0.51), 4.038 (0.50), 4.660 (1.05), 4.669 (1.11), 4.675 (1.37), 4.684 ( 1.00), 5.056 (0.60), 5.097 (1.96), 5.130 (2.04), 5.171 (0.61), 7.632 (2.12), 7.934 (0.89), 7.953 (1.38), 8.025 (1.90), 8.045 (1.28). Intermediate 78 Methyl (5RS)-3-oxo-2-({5-[3-(trifluoromethyl)phenyl]-1,2,4-oxadiazol-3-yl}methyl)-2,3,5,6,7 ,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylate (racemate)

[0587] Methyl(5RS)-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylate (racemate) (300 mg, 1.52 mmol) was initially loaded into acetonitrile (10 mL). Cesium carbonate (1.24 g, 3.80 mmol) and 3-(chloromethyl)-5-[3-(trifluoromethyl)phenyl]-1,2,4-oxadiazole (439 mg, 1.67 mmol) were added subsequently. After stirring overnight, the reaction mixture was mixed at room temperature with water, 1 N aqueous hydrochloric acid, and ethyl acetate. The organic phase was removed and the aqueous phase was extracted three times with ethyl acetate. The combined organic phases were washed with saturated aqueous sodium chloride solution, dried over sodium sulfate and filtered, and the filtrate was concentrated. 642 mg (90% purity, 90% possibility) of the title compound were obtained. LC-MS (Method 3): Rt = 1.68 min; MS (ESIpos): m /z = 424 [M+H]+ 8.334 (2.40), 8.391 (1.51), 8.410 (1.42). Intermediate 79 Methyl (5RS)-2-(2-methylbenzyl)-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine -5-carboxylate (racemate)

[0588] Methyl(5RS)-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylate (racemate) (200 mg, 1.01 mmol) was initially loaded into acetonitrile (10 mL). Cesium carbonate (364 mg, 1.12 mmol) and 1-(bromomethyl)-2-methylbenzene (197 mg, 1.06 mmol, CAS 89-92-9) were subsequently added. After stirring overnight, the reaction mixture was mixed with water and ethyl acetate at room temperature. The organic phase was removed and the aqueous phase was extracted three times with ethyl acetate. The combined organic phases were washed with saturated aqueous sodium chloride solution, dried over sodium sulfate and filtered, and the filtrate was concentrated. The residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/gradient water). The product-containing fractions were concentrated under reduced pressure and 196 mg (93% purity, 60% possibility) of the title compound were obtained. LC-MS (Method 1): Rt = 1.04 min; MS (ESIpos): m /z = 302 [M+H]+ Intermediate 80 Methyl (5RS)-2-[4-fluoro-3-(trifluoromethyl)benzyl]-3-oxo-2,3,5,6, 7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylate (racemate)

[0589] Methyl(5RS)-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylate (racemate) (300 mg, 1.52 mmol) was initially loaded into acetonitrile (10 mL). Cesium carbonate (1.24 g, 3.80 mmol) and 4-(bromomethyl)-1-fluoro-2-(trifluoromethyl)benzene (430 mg, 1.67 mmol, CAS 184970-26-1) were subsequently added . After stirring overnight, the reaction mixture was mixed at room temperature with water, 1 N aqueous hydrochloric acid, and ethyl acetate. The organic phase was removed and the aqueous phase was extracted three times with ethyl acetate. The combined organic phases were washed with saturated aqueous sodium chloride solution, dried over sodium sulfate and filtered, and the filtrate was concentrated. 569 mg (90% purity, 90% chance) of the title compound was obtained. LC-MS (Method 4): Rt = 0.90 min; MS (ESIpos): m /z = 374 [M+H]+ Intermediate 81 Methyl (5RS)-2-[4-methoxy-3-(trifluoromethyl)benzyl]-3-oxo-2,3,5,6, 7,8- hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylate (racemate)

[0590] Methyl(5RS)-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylate (racemate) (200 mg, 1.01 mmol) was initially loaded into acetonitrile (10 mL). Cesium carbonate (347 mg, 1.06 mmol) and 4-(bromomethyl)-1-methoxy-2-(trifluoromethyl)benzene (300 mg, 1.11 mmol, CAS 261951-89-7) were subsequently added. After stirring overnight, the reaction mixture was mixed with water and ethyl acetate at room temperature. The organic phase was removed and the aqueous phase was extracted three times with ethyl acetate. The combined organic phases were washed with saturated aqueous sodium chloride solution, dried over sodium sulfate and filtered, and the filtrate was concentrated. The residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/gradient water). The fractions containing the product were concentrated under reduced pressure and 316 mg (80% possibility) of the title compound were obtained. LC-MS (Method 3): Rt = 1.60 min; MS (ESIpos): m /z = 386 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.008 (0.97), 0.008 (0.99), 1.492 (0.42), 1.513 ( 0.43), 1.519 (0.45), 1.526 (0.45), 1.789 (0.53), 1.798 (0.55), 1.813 (0.47), 1.823 (0.45), 2.052 (0.49), 2.062 (0.82), 2.073 (0.90), 2.096 ( 0.50), 2.104 (0.57), 2.116 (0.52), 2.125 (0.55), 2.132 (0.51), 2.560 (0.84), 2.572 (0.84), 2.587 (0.67), 2.613 (0.64), 2.625 (1.19), 2.637 ( 0.68), 2,668 (0.66), 3,696 (15.68), 3,873 (16.00), 4,600 (1.06), 4,609 (1.20), 4,615 (1.38), 4,625 (1.04), 4,844 (4,92), 7,239 (1.72), 7,260 ( 2.01), 7,489 (1.35), 7,510 (1.41), 7,520 (2.68). Intermediate 82 Methyl (5RS)-2-[(1-methyl-1H-indazol-5-yl)methyl]-3-oxo-2,3,5,6,7,8-hexahydro[1,2, 4]triazolo[4,3-a]pyridine-5-carboxylate (racemate)

[0591] Methyl(5RS)-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylate (racemate) (200 mg, 1.01 mmol) was initially loaded into acetonitrile (10 mL). Cesium carbonate (347 mg, 1.06 mmol) and 5-(bromomethyl)-1-methyl-1H-indazole (251 mg, 1.11 mmol, CAS 1092961-01-7) were subsequently added. After stirring at room temperature for 72 h, the reaction mixture was mixed with water and ethyl acetate. The organic phase was removed and the aqueous phase was extracted three times with ethyl acetate. The combined organic phases were washed with saturated aqueous sodium chloride solution, dried over sodium sulfate and filtered, and the filtrate was concentrated. The residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/gradient water). The fractions containing the product were concentrated under reduced pressure and 87.0 mg (25% possibility) of the title compound were obtained. LC-MS (Method 3): Rt = 1.10 min; MS (ESIpos): m /z = 342 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.008 (1.77), 0.008 (1.59), 1.447 (0.66), 1.456 ( 0.44), 1.783 (0.44), 1.794 (0.48), 1.808 (0.41), 2.049 (0.42), 2.060 (0.69), 2.073 (0.71), 2.080 (0.63), 2.087 (0.51), 2.095 (0.41), 2.103 ( 0.49), 2.115 (0.45), 2.123 (0.48), 2.131 (0.44), 2.563 (0.85), 2.578 (0.63), 2.602 (0.59), 2.613 (1.08), 2.626 (0.61), 2.656 (0.49), 2.669 ( 0.50), 3.706 (14.99), 4,024 (16.00), 4,597 (0.97), 4,607 (1.09), 4,613 (1.27), 4,623 (0.94), 4,922 (6,84), 7,285 (1.33), 7,307 (1.37), 7,310 ( 1.55), 7,593 (1.89), 7,614 (3.97), 8,019 (3.08). Intermediate 83 Methyl (5RS)-2-[(1-ethyl-1H-imidazol-2-yl)methyl]-3-oxo-2,3,5,6,7,8-hexahydro[1,2, 4]triazolo[4,3-a]pyridine-5-carboxylate (racemate)

[0592] Methyl(5RS)-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylate (racemate) (200 mg, 1.01 mmol) was initially loaded into acetonitrile (6.0 mL). Cesium carbonate (364 mg, 1.12 mmol) and 2-(chloromethyl)-1-ethyl-1H-imidazole (154 mg, 1.06 mmol, CAS 780722-30-7) were subsequently added. After stirring overnight, the reaction mixture was mixed with water and ethyl acetate at room temperature. The organic phase was removed and the aqueous phase was extracted three times with ethyl acetate. The combined organic phases were washed with saturated aqueous sodium chloride solution, dried over sodium sulfate and filtered, and the filtrate was concentrated. The residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/gradient water). The fractions containing the product were concentrated under reduced pressure and 54.0 mg (17% possibility) of the title compound were obtained. LC-MS (Method 1): Rt = 0.29 min; MS (ESIpos): m /z = 306 [M+H]+ Intermediate 84 Methyl (5RS)-2-[(1-methyl-1H-benzimidazol-2-yl)methyl]-3-oxo-2,3, 5,6,7,8- hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylate (racemate)

[0593] Methyl(5RS)-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylate (racemate) (200 mg, 1.01 mmol) was initially loaded into acetonitrile (6.0 mL). Cesium carbonate (364 mg, 1.12 mmol) and 2-(bromomethyl)-1-methyl-1H-benzimidazole (240 mg, 1.06 mmol, CAS 136099-52-0) were subsequently added. After stirring overnight, the reaction mixture was mixed with water and ethyl acetate at room temperature. The organic phase was removed and the aqueous phase was extracted three times with ethyl acetate. The combined organic phases were washed with saturated aqueous sodium chloride solution, dried over sodium sulfate and filtered, and the filtrate was concentrated. The residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/gradient water). The fractions containing the product were concentrated under reduced pressure and 137 mg (40% possibility) of the title compound were obtained. LC-MS (Method 1): Rt = 0.73 min; MS (ESIpos): m /z = 342 [M+H]+ Intermediate 85 Methyl (5RS)-2-[3-chloro-4-(trifluoromethoxy)benzyl]-3-oxo-2,3,5,6, 7,8- hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylate (racemate)

[0594] Methyl(5RS)-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylate (racemate) (200 mg, 1.01 mmol) was initially loaded into acetonitrile (10 mL). Cesium carbonate (347 mg, 1.06 mmol) and 4-(bromomethyl)-2-chlorophenyl trifluoromethyl ether (323 mg, 1.11 mmol, CAS 261763-18-2) were subsequently added. After stirring overnight, the reaction mixture was mixed with water and ethyl acetate at room temperature. The organic phase was removed and the aqueous phase was extracted three times with ethyl acetate. The combined organic phases were washed with saturated aqueous sodium chloride solution, dried over sodium sulfate and filtered, and the filtrate was concentrated. The residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/gradient water). The fractions containing the product were concentrated under reduced pressure and 302 mg (73% possibility) of the title compound were obtained. LC-MS (Method 3): Rt = 1.81 min; MS (ESIpos): m /z = 406 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.008 (0.94), 0.008 (0.87), 1.805 (0.43), 1.815 ( 0.45), 2.070 (0.41), 2.079 (0.69), 2.094 (0.77), 2.104 (0.63), 2.112 (0.43), 2.120 (0.49), 2.124 (0.42), 2.132 (0.44), 2.140 (0.47), 2.148 ( 0.44), 2.524 (0.61), 2.569 (0.83), 2.583 (0.70), 2.595 (0.73), 2.609 (0.58), 2.636 (0.54), 2.647 (1.01), 2.660 (0.61), 2.690 (0.45), 3.708 ( 16.00), 4.619 (0.97), 4.629 (1.06), 4.635 (1.29), 4.644 (0.95), 4.911 (5.85), 7.317 (1.07), 7.322 (1.12), 7.338 (1.27), 7.344 (1.31), 7.533 ( 2.04), 7,539 (1.93), 7,564 (1.23), 7,567 (1.21), 7,585 (1.04), 7,588 (1.02). Intermediate 86 Methyl (5RS)-2-{[3-chloro-5-(trifluoromethyl)pyridin-2-yl]methyl}-3-oxo-2,3,5,6,7,8-hexahydro[1 ,2,4]triazolo[4,3-a]pyridine-5-carboxylate (racemate)

[0595] Methyl(5RS)-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylate (racemate) (200 mg, 1.01 mmol) was initially loaded into acetonitrile (5.0 mL). Cesium carbonate (364 mg, 1.12 mmol) and 3-chloro-2-(chloromethyl)-5-(trifluoromethyl)pyridine (245 mg, 1.06 mmol, CAS 175277-52-8) were subsequently added. After stirring overnight, the reaction mixture was mixed with water and ethyl acetate at room temperature. The organic phase was removed and the aqueous phase was extracted three times with ethyl acetate. The combined organic phases were washed with saturated aqueous sodium chloride solution, dried over sodium sulfate and filtered, and the filtrate was concentrated. The residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/gradient water). The fractions containing the product were concentrated under reduced pressure and 293 mg (74% possibility) of the title compound were obtained. LC-MS (Method 1): Rt = 1.08 min; MS (ESIpos): m /z = 391 [M+H]+ Intermediate 87 Methyl (5RS)-2-[3-fluoro-4-(trifluoromethoxy)benzyl]-3-oxo-2,3,5,6, 7,8- hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylate (racemate)

[0596] Methyl(5RS)-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylate (racemate) (200 mg, 1.01 mmol) was initially loaded into acetonitrile (6.0 mL). Cesium carbonate (364 mg, 1.12 mmol) and 4-(bromomethyl)-2-fluorophenyl trifluoromethyl ether (291 mg, 1.06 mmol, CAS 886499-04-3) were subsequently added. After stirring overnight, the reaction mixture was mixed with water and ethyl acetate at room temperature. The organic phase was removed and the aqueous phase was extracted three times with ethyl acetate. The combined organic phases were washed with saturated aqueous sodium chloride solution, dried over sodium sulfate and filtered, and the filtrate was concentrated. The residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/gradient water). The fractions containing the product were concentrated under reduced pressure and 263 mg (66% possibility) of the title compound were obtained. LC-MS (Method 1): Rt = 1.22 min; MS (ESIpos): m /z = 390 [M+H]+ Intermediate 88 Methyl (5RS)-2-{[2-methyl-4-(trifluoromethyl)-1,3-thiazol-5-yl]methyl}- 3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylate (racemate)

[0597] Methyl(5RS)-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylate (racemate) (200 mg, 1.01 mmol) was initially loaded into acetonitrile (10 mL). Cesium carbonate (347 mg, 1.06 mmol) and 5-(bromomethyl)-2-methyl-4-(trifluoromethyl)-1,3-thiazole (290 mg, 1.11 mmol, CAS 1000339-73-0) were added subsequently. After stirring at room temperature for 72 h, the reaction mixture was mixed with water and ethyl acetate. The organic phase was removed and the aqueous phase was extracted three times with ethyl acetate. The combined organic phases were washed with saturated aqueous sodium chloride solution, dried over sodium sulfate and filtered, and the filtrate was concentrated. 384 mg (99% chance) of the title compound was obtained. LC-MS (Method 3): Rt = 1.33 min; MS (ESIpos): m /z = 377 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.008 (1.01), 0.008 (1.10), 1.157 (1.51), 1.175 ( 3.06), 1.193 (1.55), 1.793 (0.43), 1.804 (0.48), 1.818 (0.41), 1.988 (5.82), 2.051 (0.42), 2.062 (0.77), 2.073 (0.86), 2.086 (0.67), 2.094 ( 0.45), 2.102 (0.51), 2.114 (0.46), 2.122 (0.50), 2.130 (0.46), 2.524 (0.72), 2.568 (0.84), 2.583 (0.72), 2.594 (0.74), 2.608 (0.61), 2.639 ( 1.12), 2,651 (15.16), 2,668 (1.55), 2,679 (0.51), 2,687 (0.68), 3,697 (16.00), 4003 (0.46), 4,021 (1.39), 4,038 (1.38), 4,056 (0.46), 4,594 ( 1.02), 4.603 (1.12), 4.609 (1.32), 4.619 (0.98), 5.171 (4.60). Intermediate 89 Methyl (5RS)-2-[(3-methyl-1,2-oxazol-5-yl)methyl]-3-oxo-2,3,5,6,7,8-hexahydro[1, 2,4]triazolo[4,3-a]pyridine-5-carboxylate (racemate)

[0598] Methyl(5RS)-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylate (racemate) (200 mg, 1.01 mmol) was initially loaded into acetonitrile (10 mL). Cesium carbonate (347 mg, 1.06 mmol) and 5-(bromomethyl)-3-methyl-1,2-oxazole (196 mg, 1.11 mmol, CAS 36958-61-9) were subsequently added. After stirring overnight, the reaction mixture was mixed with water and ethyl acetate at room temperature. The organic phase was removed and the aqueous phase was extracted three times with ethyl acetate. The combined organic phases were washed with saturated aqueous sodium chloride solution, dried over sodium sulfate and filtered, and the filtrate was concentrated. 259 mg (86% purity, 75% possibility) of the title compound were obtained. LC-MS (Method 3): Rt = 0.94 min; MS (ESIpos): m /z = 293 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ 1.510 (0.40), 1.531 (0.43), 1.536 1.809 (0.54), 1.824 (0.47), 1.988 2.065 (0.75), 2.071 (0.80), 2.078 2.104 (0.53), 2.112 (0.61), 2.117 2.141 (0.55), 2.205 (15.12), 2.218 2.567 (0.86), 2.581 (0.78), 2.593 .641 (1.15), 2.653 (0.66), 2.683 3.703 (16.00), 4.596 (1.03), 4.606 4.773 (1.74), 4.981 (6.40), 6.237 (3. Intermediate 90 Methyl (5RS)-2-[(1-methyl-1H-1.2 ,4-triazol-3-yl)methyl]-3-oxo-2,3,5,6,7,8- hexahydro[1,2,4]triazolo[4,3-a]pyridine-5- carboxylate (racemate)

[0599] Methyl(5RS)-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylate (racemate) (200 mg, 1.01 mmol) was initially loaded into acetonitrile (11 mL). Cesium carbonate (793 mg, 2.43 mmol) and 3-(chloromethyl)-1-methyl-1H-1,2,4-triazole hydrochloride (187 mg, 1.11 mmol, CAS 135206-76-7) were added subsequently. After stirring overnight, the reaction mixture was mixed with water and ethyl acetate at room temperature. The organic phase was removed and the aqueous phase was extracted three times with ethyl acetate. The combined organic phases were washed with saturated aqueous sodium chloride solution, dried over sodium sulfate and filtered, and the filtrate was concentrated. The residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/gradient water). The fractions containing the product were concentrated under reduced pressure and 178 mg (74% purity, 44% chance) of the title compound were obtained. LC-MS (Method 3): Rt = 0.61 min; MS (ESIpos): m /z = 293 [M+H]+ Intermediate 91 Methyl (5RS)-2-[2-fluoro-3-(trifluoromethyl)benzyl]-3-oxo-2,3,5,6, 7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylate (racemate)

[0600] Methyl(5RS)-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylate (racemate) (200 mg, 1.01 mmol) was initially loaded into acetonitrile (5.0 mL). Cesium carbonate (364 mg, 1.12 mmol) and 1-(bromomethyl)-2-fluoro-3-(trifluoromethyl)benzene (274 mg, 1.06 mmol, CAS 184970-25-0) were added after stirring for 5 minutes. After stirring overnight, the reaction mixture was mixed with water and ethyl acetate at room temperature. The organic phase was removed and the aqueous phase was extracted three times with ethyl acetate. The combined organic phases were washed with saturated aqueous sodium chloride solution, dried over sodium sulfate and filtered, and the filtrate was concentrated. The residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/gradient water). The fractions containing the product were concentrated under reduced pressure and 184 mg (49% possibility) of the title compound were obtained. LC-MS (Method 1): Rt = 1.16 min; MS (ESIpos): m /z = 374 [M+H]+ Intermediate 92 Methyl (5RS)-2-[3-fluoro-5-(trifluoromethyl)benzyl]-3-oxo-2,3,5,6, 7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylate (racemate)

[0601] Methyl(5RS)-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylate (racemate) (200 mg, 1.01 mmol) was initially loaded into acetonitrile (5.0 mL). Cesium carbonate (364 mg, 1.12 mmol) and 1-(bromomethyl)-3-fluoro-5-(trifluoromethyl)benzene (274 mg, 1.06 mmol, CAS 239087-09-3) were added after stirring for 5 minutes. After stirring overnight, the reaction mixture was mixed with water and ethyl acetate at room temperature. The organic phase was removed and the aqueous phase was extracted three times with ethyl acetate. The combined organic phases were washed with saturated aqueous sodium chloride solution, dried over sodium sulfate and filtered, and the filtrate was concentrated. The residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/gradient water). The fractions containing the product were concentrated under reduced pressure and 154 mg (41% possibility) of the title compound were obtained. LC-MS (Method 1): Rt = 1.19 min; MS (ESIpos): m /z = 374 [M+H]+ Intermediate 93 Methyl (5RS)-3-oxo-2-{[2-(trifluoromethyl)pyridin-4-yl]methyl}-2,3,5 ,6,7,8- hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylate (enantiomer 1)

[0602] Methyl(5RS)-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylate (enantiomer 2 )(200 mg, 1.01 mmol) was initially loaded into acetonitrile (5.0 mL). Cesium carbonate (364 mg, 1.12 mmol) and 4-(chloromethyl)-2-(trifluoromethyl)pyridine hydrochloride (247 mg, 1.06 mmol) were added after stirring for 5 minutes. After stirring overnight, the reaction mixture was mixed with water and ethyl acetate at room temperature. The organic phase was removed and the aqueous phase was extracted three times with ethyl acetate. The combined organic phases were washed with saturated aqueous sodium chloride solution, dried over sodium sulfate and filtered, and the filtrate was concentrated. The residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/gradient water). The fractions containing the product were concentrated under reduced pressure and 279 mg (77% possibility) of the title compound were obtained. LC-MS (Method 4): Rt = 0.71 min; MS (ESIpos): m /z = 357 [M+H]+

[0603] The (5S) configuration was assigned based on the elucidation of the crystal structure for Examples 26, 108, 113, 157, 237, 358 and 454. Methyl (5S)-3-oxo-2-{[2-( trifluoromethyl)pyridin-4-yl]methyl}-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylate Intermediate 94 Methyl ( 5RS)-2-{[3-fluoro-2-(trifluoromethyl)pyridin-4-yl]methyl}-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4 ]triazolo[4,3-a]pyridine-5-carboxylate (enantiomer 1)

[0604] Methyl(5RS)-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylate (enantiomer 2 )(200 mg, 1.01 mmol) was initially loaded into acetonitrile (5.0 mL). Cesium carbonate (364 mg, 1.12 mmol) and 4-(chloromethyl)-3-fluoro-2-(trifluoromethyl)pyridine hydrochloride (266 mg, 1.06 mmol) were subsequently added. After stirring overnight, the reaction mixture was mixed again with cesium carbonate (199 mg, 0.61 mmol) and stirred at 60 ° C for 2 hours. Subsequently, the reaction mixture was cooled to room temperature, and water and ethyl acetate were added. The organic phase was removed and the aqueous phase was extracted three times with ethyl acetate. The combined organic phases were washed with saturated aqueous sodium chloride solution, dried over sodium sulfate and filtered, and the filtrate was concentrated. The residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/gradient water). The fractions containing the product were concentrated under reduced pressure and 181 mg (48% possibility) of the title compound were obtained. LC-MS (Method 3): Rt = 1.42 min; MS (ESIpos): m /z = 375 [M+H]+

[0605] The (5S) configuration was assigned based on the elucidation of the crystal structure for Examples 26, 108, 113, 157, 237, 358 and 454. Methyl (5S)-2-{[3-fluoro-2-( trifluoromethyl)pyridin-4-yl]methyl}-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylate Intermediate 95 Methyl (5RS)-2-{[5-chloro-4-(trifluoromethyl)pyridin-2-yl]methyl}-3-oxo-2,3,5,6,7,8-hexahydro[1 ,2,4]triazolo[4,3-a]pyridine-5-carboxylate (enantiomer 1)

[0606] Methyl(5RS)-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylate (enantiomer 2 )(164 mg, 829 μmol) was initially loaded into acetonitrile (4.0 mL). Cesium carbonate (594 mg, 1.82 mmol) and 5-chloro-2-(chloromethyl)-4-(trifluoromethyl)pyridine hydrochloride (274 mg, 85% purity, 871 μmol) were subsequently added. The reaction mixture was stirred at room temperature overnight at 85°C for 5 hours and again at room temperature overnight. The reaction mixture was mixed with water and ethyl acetate. The organic phase was removed and the aqueous phase was extracted three times with ethyl acetate. The combined organic phases were washed with saturated aqueous sodium chloride solution, dried over sodium sulfate and filtered, and the filtrate was concentrated. 269 mg (93% purity, 77% chance) of the title compound were obtained. LC-MS (Method 3): Rt = 1.55 min; MS (ESIpos): m /z = 391 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.008 (0.42), 0.008 (0.46), 1.157 (1.75), 1.175 ( 3.60), 1.193 (1.82), 1.352 (0.61), 1.534 (0.40), 1.540 (0.41), 1.807 (0.47), 1.816 (0.49), 1.830 (0.41), 1.989 (6.73), 2.074 (0.58), 2.086 ( 0.74), 2.098 (0.77), 2.119 (0.46), 2.126 (0.53), 2.131 (0.46), 2.139 (0.47), 2.148 (0.52), 2.155 (0.46), 2.520 (0.80), 2.563 (0.87), 2.578 ( 0.72), 2.590 (0.72), 2.604 (0.62), 2.630 (0.57), 2.642 (1.01), 2.654 (0.60), 2.671 (0.40), 2.684 (0.45), 3.688 (1.91), 3.704 (16.00), 3.936 ( 0.71), 4.003 (0.54), 4.021 (1.59), 4.039 (1.58), 4.057 (0.52), 4.628 (1.01), 4.637 (1.55), 4.643 (1.37), 4.652 (1.42), 5.074 (7.18), 7.727 ( 3.53), 7.832 (0.45), 8.858 (0.45), 8.910 (3.33).

[0607] The (5S) configuration was assigned based on the elucidation of the crystal structure for Examples 26, 108, 113, 157, 237, 358 and 454. Methyl (5S)-2-{[5-chloro-4-( trifluoromethyl)pyridin-2-yl]methyl}-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylate Intermediate 96 Methyl (5RS)-3-oxo-2-{[2-(trifluoromethyl)quinolin-4-yl]methyl}-2,3,5,6,7,8-hexahydro[1,2,4 ]triazolo[4,3-a]pyridine-5-carboxylate (enantiomer 1)

[0608] Methyl(5RS)-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylate (enantiomer 2 )(166 mg, 839 μmol) was initially loaded in acetonitrile (4.1 mL). Cesium carbonate (301 mg, 923 μmol) and 4-(chloromethyl)-2-(trifluoromethyl)quinoline hydrochloride (336 mg, 74% purity, 881 μmol) were added after stirring for 5 minutes. After stirring overnight, the reaction mixture was mixed with water and ethyl acetate at room temperature. The organic phase was removed and the aqueous phase was extracted three times with ethyl acetate. The combined organic phases were washed with saturated aqueous sodium chloride solution, dried over sodium sulfate and filtered, and the filtrate was concentrated. The residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/gradient water). The fractions containing the product were concentrated under reduced pressure and 111 mg (33% possibility) of the title compound were obtained. LC-MS (Method 1): Rt = 1.19 min; MS (ESIpos): m /z = 407 [M+H]+

[0609] The (5S) configuration was assigned based on the elucidation of the crystal structure for Examples 26, 108, 113, 157, 237, 358 and 454. Methyl (5S)-3-oxo-2-{[2-( trifluoromethyl)quinolin-4-yl]methyl}-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylate Intermediate 97 Methyl ( 5RS)-2-{[3-chloro-5-(trifluoromethyl)pyridin-2-yl]methyl}-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4 ]triazolo[4,3-a]pyridine-5-carboxylate (enantiomer 1)

[0610] Methyl(5RS)-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylate (enantiomer 2 )(200 mg, 1.01 mmol) was initially loaded into acetonitrile (5.0 mL). Cesium carbonate (364 mg, 1.12 mmol) and 3-chloro-2-(chloromethyl)-5-(trifluoromethyl)pyridine (245 mg, 1.06 mmol, CAS 175277-52-8) were added after stirring for 5 minutes. After stirring overnight, the reaction mixture was mixed with water and ethyl acetate at room temperature. The organic phase was removed and the aqueous phase was extracted three times with ethyl acetate. The combined organic phases were washed with saturated aqueous sodium chloride solution, dried over sodium sulfate and filtered, and the filtrate was concentrated. The residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/gradient water). The fractions containing the product were concentrated under reduced pressure and 216 mg (55% possibility) of the title compound were obtained. LC-MS (Method 3): Rt = 1.49 min; MS (ESIpos): m /z = 391 [M+H]+

[0611] The (5S) configuration was assigned based on the elucidation of the crystal structure for Examples 26, 108, 113, 157, 237, 358 and 454. Methyl (5S)-2-{[3-chloro-5-( trifluoromethyl)pyridin-2-yl]methyl}-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylate Intermediate 98 Methyl (5RS)-3-oxo-2-[(3,5,6-trimethylpyrazin-2-yl)methyl]-2,3,5,6,7,8-hexahydro[1,2, 4]triazolo[4,3-a]pyridine-5-carboxylate (enantiomer 1)

[0612] Methyl(5RS)-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylate (enantiomer 2 )(250 mg, 1.27 mmol) was initially loaded into acetonitrile (5.0 mL). Cesium carbonate (454 mg, 1.39 mmol) and 2-(bromomethyl)-3,5,6-trimethylpyrazine (286 mg, 1.33 mmol, CAS 79074-45-6) were added after stirring for 5 minutes. After stirring overnight, the reaction mixture was mixed with water and ethyl acetate at room temperature. The organic phase was removed and the aqueous phase was extracted three times with ethyl acetate. The combined organic phases were washed with saturated aqueous sodium chloride solution, dried over sodium sulfate and filtered, and the filtrate was concentrated. The residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/gradient water). The fractions containing the product were concentrated under reduced pressure and 261 mg (62% possibility) of the title compound were obtained. LC-MS (Method 3): Rt = 1.02 min; MS (ESIpos): m /z = 332 [M+H]+ Intermediate 99 Methyl (5RS)-3-oxo-2-{[4-(trifluoromethyl)pyridin-2-yl]methyl}-2,3,5 ,6,7,8- hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylate (enantiomer 1)

[0613] Methyl(5RS)-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylate (enantiomer 2 )(300 mg, 1.52 mmol) was initially loaded into acetonitrile (6.0 mL). Cesium carbonate (744 mg, 2.28 mmol) and 2-(chloromethyl)-4-(trifluoromethyl)pyridine hydrochloride (371 mg, 1.60 mmol, CAS 215867-87-1) were subsequently added. After stirring at room temperature for 4 hours, the reaction mixture was mixed with water and ethyl acetate. The organic phase was removed and the aqueous phase was extracted three times with ethyl acetate. The combined organic phases were washed with saturated aqueous sodium chloride solution, dried over sodium sulfate and filtered, and the filtrate was concentrated. The residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/gradient water). The fractions containing the product were concentrated under reduced pressure and 282 mg (52% possibility) of the title compound were obtained. LC-MS (Method 3): Rt = 1.35 min; MS (ESIpos): m /z = 357 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.008 (0.50), 1.811 (0.48), 1.821 (0.49), 1.835 ( 0.42), 2.073 (0.44), 2.079 (0.46), 2.090 (0.74), 2.103 (0.69), 2.110 (0.66), 2.118 (0.53), 2.126 (0.46), 2.133 (0.53), 2.138 (0.46), 2.146 ( 0.48), 2.154 (0.50), 2.162 (0.46), 2.519 (0.45), 2.570 (0.85), 2.585 (0.73), 2.597 (0.75), 2.611 (0.61), 2.636 (0.59), 2.647 (1.03), 2.660 ( 0.59), 2.690 (0.44), 3.706 (16.00), 4.636 (1.03), 4.646 (1.11), 4.652 (1.26), 4.661 (0.93), 5.075 (7.03), 7.551 (2.03), 7.713 (1.09), 7.724 ( 1.09), 8.822 (1.50), 8.834 (1.43).

[0614] The (5S) configuration was assigned based on the elucidation of the crystal structure for Examples 26, 108, 113, 157, 237, 358 and 454. Methyl (5S)-3-oxo-2-{[4-( trifluoromethyl)pyridin-2-yl]methyl}-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylate Intermediate 100 Methyl ( 5RS)-3-oxo-2-{[2-(trifluoromethyl)pyrimidin-4-yl]methyl}-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4 ,3-a]pyridine-5-carboxylate (enantiomer 1)

[0615] Methyl(5RS)-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylate (enantiomer 2 )(108 mg, 548 μmol) was initially loaded into acetonitrile (2.0 mL). Cesium carbonate (268 mg, 822 μmol) and 4-(chloromethyl)-2-(trifluoromethyl)pyrimidine hydrochloride (134 mg, 575 μmol) were subsequently added. After stirring at room temperature overnight and refluxing overnight, they were washed with saturated aqueous sodium chloride solution, dried over sodium sulfate and filtered, and the filtrate was concentrated. The residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/gradient water). The fractions containing the product were concentrated under reduced pressure and 49.3 mg (25% possibility) of the title compound were obtained. LC-MS (Method 4): Rt = 0.69 min; MS (ESIpos): m /z = 358 [M+H]+

[0616] The (5S) configuration was assigned based on the elucidation of the crystal structure for Examples 26, 108, 113, 157, 237, 358 and 454. Methyl (5S)-3-oxo-2-{[2-( trifluoromethyl)pyrimidin-4-yl]methyl}-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylate Intermediate 101 Methyl ( 5RS)-3-oxo-2-(2,4,5-trimethylbenzyl)-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine -5-carboxylate (enantiomer 1)

[0617] Methyl(5RS)-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylate (enantiomer 2 )(200 mg, 1.01 mmol) was initially loaded into acetonitrile (5.0 mL). Cesium carbonate (364 mg, 1.12 mmol) and 1-(bromomethyl)-2,4,5-trimethylbenzene (227 mg, 1.06 mmol, CAS 35509-98-9) were subsequently added. After stirring overnight, the reaction mixture was mixed with water and ethyl acetate at room temperature. The organic phase was removed and the aqueous phase was extracted three times with ethyl acetate. The combined organic phases were washed with saturated aqueous sodium chloride solution, dried over sodium sulfate and filtered, and the filtrate was concentrated. The residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/gradient water). The fractions containing the product were concentrated under reduced pressure and 198 mg (59% possibility) of the title compound were obtained. LC-MS (Method 4): Rt = 0.91 min; MS (ESIpos): m /z = 330 [M+H]+

[0618] The (5S) configuration was assigned based on the elucidation of the crystal structure for Examples 26, 108, 113, 157, 237, 358 and 454. Methyl (5S)-3-oxo-2-(2,4, 5-trimethylbenzyl)-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylate Intermediate 102 Methyl (5RS)-2-[ 4-(tert-butoxycarbonyl)benzyl]-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylate ( racemate)

[0619] Aa methyl (5RS)-3-oxo-2,3,5,6,7,8-hexa hydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylate (racemate) (300 mg, 1.52 mmol) and cesium carbonate (744 mg, 2.28 mmol) in 15 mL of acetonitrile was added tert-butyl 4-(bromomethyl)benzoate (433 mg, 1.60 mmol), then , the reaction mixture was stirred at room temperature overnight. For elaboration, the present precipitate was filtered, and the filtrate was mixed and extracted with ethyl acetate/water. The aqueous phase was extracted twice more with ethyl acetate. The combined organic phases were washed with saturated sodium chloride solution, dried with sodium sulfate and concentrated and dried under reduced pressure. 676 mg (88% purity, 101% possibility) of the title compound, which was converted as such. LC-MS (Method 3): Rt = 1.78 min; MS (ESIpos): m /z = 388 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.008 (1.08), 0.008 (1.04), 1.175 (0.71), 1.537 ( 16.00), 1,988 (1.29), 3,286 (1.03), 3,709 (5.39), 4,915 (1.64), 7,323 (0.99), 7,344 (1.09), 7,857 (1.29), 7,878 (1.18). Intermediate 103 tert-Butyl (5RS)-2-(4-methylbenzyl)-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a ]pyridine-5-carboxylate (racemate)

[0620] To tert-butyl (5RS)-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylate (racemate) (5.00 g, 20.9 mmol) and cesium carbonate (10.2 g, 31.3 mmol) in 180 mL of acetonitrile was added 1-(bromomethyl)-4-methylbenzene (4.06 g , 21.9 mmol), then the reaction mixture was stirred at room temperature overnight. For elaboration, the present precipitate was filtered, the filtrate was considerably concentrated in a rotary evaporator, and the residue was mixed and extracted with ethyl acetate/water. For better phase separation, saturated aqueous sodium chloride solution and a little methanol were added here. The aqueous phase was extracted twice more with ethyl acetate. The combined organic phases were washed with saturated aqueous sodium chloride solution, dried with sodium sulfate and concentrated and dried under reduced pressure. 7.14 g (94% purity, 94% possibility) of the title compound were obtained, which were used as such. LC-MS (Method 6): Rt = 1.80 min; MS (ESIpos): m /z = 344 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: 1.396 (16.00), 1.402 (2.28), 2.270 (4.79), 4.771 (2.95 ), 7,129 (7.75). Intermediate 104 tert-Butyl (5RS)-2-[(1RS)-1-(4-chlorophenyl)ethyl]-3-oxo-2,3,5,6,7,8-hexahydro[1,2, 4]triazolo[4,3-a]pyridine-5-carboxylate (mixture of diastereomer; 4 isomers)

[0621] To tert-butyl (5RS)-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylate (racemate) (500 mg, 2.09 mmol) and cesium carbonate (1.02 g, 3.13 mmol) in 30 mL of acetonitrile was added 1-[(1RS)-1-bromoethyl]-4-chlorobenzene ( racemate) (550 mg, 2.51 mmol), then the reaction mixture was stirred at room temperature overnight. For elaboration, the present precipitate was filtered, the filtrate was considerably concentrated in a rotary evaporator, and the residue was mixed and extracted with ethyl acetate/water. For better phase separation, saturated aqueous sodium chloride solution and a little methanol were added here. The aqueous phase was extracted twice more with ethyl acetate. The combined organic phases were washed with saturated sodium chloride solution, dried with sodium sulfate and concentrated and dried under reduced pressure. 755 mg (87% purity, 83% possibility) of the title compound was obtained as a diastereomer mixture, which was later converted as such. LC-MS (Method 8): Rt = 3.28 min; MS (ESIpos): m /z = 378 [M+H]+; Rt = 3.33 min; MS (ESIpos): m /z = 378 [ M +H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.008 (1.98), 0.008 (1.51), 1.157 (0.78), 1.175 ( 1.54), 1,192 (0.85), 1,329 (15.89), 1,342 (1.34), 1,405 (16.00), 1,416 (1.42), 1,438 (1.47), 1,597 (2.79), 1.603 (2.55), 1,614 (2.71), 1.620 ( 2.46), 1.988 (2.92), 2.063 (1.04), 2.661 (0.78), 3.287 (1.01), 4.020 (0.72), 4.038 (0.70), 4.403 (0.81), 4.418 (0.94), 7.323 (1.58), 7.344 ( 3.21), 7,378 (2.24), 7,385 (2.41), 7,399 (1.19), 7,406 (1.69). Intermediate 105 tert-Butyl (5R S,)-3-oxo-2-(4-sulfamoylbenzyl)-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3 -a]pyridine-5-carboxylate (racemate)

[0622] To tert-butyl (5RS)-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylate (racemate) (500 mg, 2.09 mmol) in 10 mL of acetonitrile were added cesium carbonate (1.02 g, 3.13 mmol) and 4-(bromomethyl)benzene sulfonamide (627 mg, 2.51 mmol) , then the reaction mixture was stirred twice at room temperature under argon overnight. For preparation, the mixture was mixed with water and extracted twice with dichloromethane. The combined organic phases were dried with magnesium sulfate, filtered and concentrated under reduced pressure. The remaining residue was purified via preparatory HPLC (column: RP, Chromatorex C18, 250x40mm 10μm. Flow rate: 50 ml/min. Gradient (A = water + 0.1% formic acid, B = acetonitrile): 0min 10% B , 5min 10%B, 27min 98%B, 35min 98%B, 35.01min 10%B, 38min 10%B. Run time per separation 38 min. 755 mg (87% purity, 83% possibility) were obtained. Concentrating the product fractions, 37 mg (4.3% possibility) of the title compound were obtained. LC-MS (Method 6): Rt = 1.35 min; MS (ESIneg): m /z = 407 [MH]- 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: 1.404 (16.00), 2.072 (1.17), 4.451 (0.63), 4.920 (2.40), 7,331 (2.07), 7,401 (1.29), 7,422 (1.42), 7,772 (1.69), 7,793 (1.46). Intermediate 106 tert-Butyl (5RS)-2-[4-(methylsulfanyl)benzyl]-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4, 3-a]pyridine-5-carboxylate (racemate)

[0623] To tert-butyl (5RS)-3-oxo-2,3,5,6,7,8-hexa - hydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylate (racemate) (500 mg, 2.09 mmol) and cesium carbonate (1.02 g, 3.13 mmol) in 18 mL of acetonitrile was added 1-(bromomethyl)-4-(methylsulfanyl)benzene (476 g, 2.19 mmol), then the reaction mixture was stirred at room temperature for 4 hours. For elaboration, the precipitate present was filtered, and the filtrate was mixed and extracted with ethyl acetate/water. The aqueous phase was extracted twice more with ethyl acetate. The combined organic phases were washed with saturated sodium chloride solution, dried with sodium sulfate and concentrated and dried under reduced pressure. 776 mg (92% purity, 91% chance) of the title compound, which was converted as such. LC-MS (Method 3): Rt = 1.88 min; MS (ESIpos): m /z = 376 [M+H]+ 1H-NMR (500 MHz, DMSO-d6) δ [ppm]: 1.395 (16.00), 1.403 (1.34), 1.988 (0.68), 2.452 (7.33 ), 4,783 (2.62), 7,181 (0.76), 7,198 (1.88), 7,221 (2.16), 7,238 (0.85). Intermediate 107 tert-Butyl (5RS)-2-[(6-chloropyridin-3-yl)methyl]-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4] triazolo[4,3-a]pyridine-5-carboxylate (racemate)

[0624] To tert-butyl (5RS)-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylate (racemate) (1.00 g, 4.18 mmol) and cesium carbonate (2.04 g, 6.27 mmol) in 25 mL of acetonitrile was added 2-chloro-5-(chloromethyl)pyridine (711 g, 4.39 mmol), then the reaction mixture was stirred at room temperature overnight. For elaboration, the mixture was added to water and extracted twice with ethyl acetate. The combined organic phases were washed with saturated sodium chloride solution, dried with magnesium sulfate and concentrated and dried under reduced pressure. 1.48 g (89% purity, 87% possibility) of the title compound was obtained, which was later used as such. LC-MS (Method 4): Rt = 0.84 min; MS (ESIpos): m /z = 365 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: 1.369 (0.99), 1.387 (16.00), 1.405 (3.22), 1.988 (0.89 ), 2.060 (0.76), 2.496 (4.74), 2.501 (6.51), 2.505 (5.26), 4.443 (0.68), 4.910 (2.74), 7.510 (0.80), 7.530 (0.98), 8.313 (0.82), 8.319 (0.82 ). Intermediate 108 tert-Butyl (5RS)-2-[(6-cyanopyridin-3-yl)methyl]-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4] triazolo[4,3-a]pyridine-5-carboxylate (racemate)

[0625] To tert-butyl (5RS)-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylate (racemate) (200 mg, 836 μmol) and cesium carbonate (409 mg, 1.25 mmol) in 8.0 mL of acetonitrile was added 5-(bromomethyl)pyridine-2-carbonitrile (173 mg, 878 μmol), then the reaction mixture was stirred first for 2 hours, then at room temperature overnight. Then, 5-(bromomethyl)pyridine-2-carbonitrile (32.9 mg, 167 μmol) was added once again (HPLC conversion monitoring). For elaboration, after stirring at room temperature for another 2 hours, the precipitate present was filtered, and the filtrate was mixed and extracted with ethyl acetate/water. The aqueous phase was extracted twice more with ethyl acetate. The combined organic phases were washed with saturated sodium chloride solution, dried with sodium sulfate and concentrated and dried under reduced pressure. 303 mg (>100% chance) of the title compound was obtained. LC-MS (Method 4): Rt = 0.79 min; MS (ESIpos): m /z = 356 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.008 (1.79), 0.008 (1.80), 1.175 (0.81), 1.394 ( 16.00), 1,406 (1.87), 1,988 (1.44), 3,287 (1.33), 4,459 (0.60), 5,033 (2.16), 8,034 (0.73), 8,037 (0.79). Intermediate 109 tert-Butyl (5RS)-2-[4-chloro-3-(trifluoromethyl)benzyl]-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4] triazolo[4,3-a]pyridine-5-carboxylate (racemate)

[0626] To tert-butyl (5RS)-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylate (racemate) (200 mg, 836 μmol) and cesium carbonate (409 mg, 1.25 mmol) in 8.0 mL of acetonitrile was added 4-(bromomethyl)-1-chloro-2-(trifluoromethyl)benzene (274 mg, 1.00 mmol), then the reaction mixture was stirred first for 4 hours, then at room temperature overnight (HPLC conversion monitoring). For elaboration, the present precipitate was filtered, and the filtrate was mixed and extracted with ethyl acetate/water. The aqueous phase was extracted twice more with ethyl acetate. The combined organic phases were washed with saturated sodium chloride solution, dried with sodium sulfate and concentrated and dried under reduced pressure. 323 mg (87% possibility) of the title compound was obtained, which was further used as such. LC-MS (Method 3): Rt = 2.12 min; MS (ESIpos): m /z = 376 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: 1.377 (16.00), 4.946 (1.13), 4.962 (1.09). Intermediate 110 tert-Butyl (5RS)-2-(3-chlorobenzyl)-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a ]pyridine-5-carboxylate (racemate)

[0627] To tert-butyl (5RS)-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylate (racemate) (200 mg, 836 μmol) and cesium carbonate (409 mg, 1.25 mmol) in 8.0 mL of acetonitrile was added 1-(bromomethyl)-3-chlorobenzene (130 μl, 1.0 mmol) Then, the reaction mixture was stirred first for 4 hours, then at room temperature overnight (HPLC conversion monitoring). For elaboration, the present precipitate was filtered, and the filtrate was mixed and extracted with ethyl acetate/water. The aqueous phase was extracted twice more with ethyl acetate. The combined organic phases were washed with saturated sodium chloride solution, dried with sodium sulfate and concentrated and dried under reduced pressure. 284 mg (84% purity, 78% chance) of the title compound, which was converted as such. LC-MS (Method 3): Rt = 1.91 min; MS (ESIpos): m /z = 308 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: 1.395 (16.00), 1.406 (0.97), 1.988 (0.71), 4.856 (1.40 ), 4,862 (1.37), 7,360 (1.24), 7,379 (0.68). Intermediate 111 tert-Butyl (5RS)-2-(3,4-dichlorobenzyl)-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3 -a]pyridine-5-carboxylate (racemate)

[0628] To tert-butyl (5RS)-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylate (racemate) (200 mg, 836 μmol) and cesium carbonate (409 mg, 1.25 mmol) in 8.0 mL of acetonitrile was added 4-(bromomethyl)-1,2-dichlorobenzene (241 mg, 1.00 mmol), then the reaction mixture was stirred at room temperature over a weekend. For elaboration, the present precipitate was filtered, and the filtrate was mixed and extracted with ethyl acetate/water. The aqueous phase was extracted twice more with ethyl acetate. The combined organic phases were washed with saturated sodium chloride solution, dried with sodium sulfate and concentrated and dried under reduced pressure. 330 mg (78% purity, 77% chance) of the title compound, which was converted as such. LC-MS (Method 4): Rt = 1.08 min; MS (ESIpos): m /z = 398 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: 1.392 (16.00), 4.867 (1.86), 7.503 (0.82), 7.508 (0.81 ), 7,610 (1.04), 7,631 (0.95). Intermediate 112 Methyl (5RS)-Methyl-2-(4-methylbenzyl)-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a ]pyridine-5-carboxylate (racemate)

[0629] Methyl(5RS)-methyl-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine-5- carboxylate (racemate) (40.0 mg, 189 μmol) was initially loaded into acetonitrile (2.0 mL). Cesium carbonate (67.9 mg, 208 μmol) and 1-(bromomethyl)-4-methylbenzene (36.8 mg, 199 μmol) were subsequently added. After stirring overnight, the reaction mixture was mixed with water and ethyl acetate at room temperature. The organic phase was removed and the aqueous phase was extracted three times with ethyl acetate. The combined organic phases were washed with saturated aqueous sodium chloride solution, dried over sodium sulfate and filtered, and the filtrate was concentrated. The residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/gradient water). The fractions containing the product were concentrated under reduced pressure and 32.0 mg (54% possibility) of the title compound were obtained. LC-MS (Method 3): Rt = 1.59 min; MS (ESIpos): m /z = 316 [M+H]+ Intermediate 113 tert-Butyl (5RS,7RS)-7-methyl-3-oxo-2-{[6-(trifluoromethyl)pyridin-3-yl] methyl}-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylate (mixture of diastereomer; 4 isomers)

[0630] tert-Butyl (5RS,7RS)-7-methyl-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a] Pyridine-5-carboxylate (diastereomer mixture, 4 isomers) (238 mg, 940 μmol) was initially loaded into acetonitrile (10 mL). Cesium carbonate (612 mg, 1.88 mmol) and 5-(bromomethyl)-2-(trifluoromethyl)pyridine (237 mg, 987 μmol) were subsequently added. After stirring overnight, the reaction mixture was mixed with water and ethyl acetate at room temperature. The organic phase was removed and the aqueous phase was extracted three times with ethyl acetate. The combined organic phases were washed with saturated aqueous sodium chloride solution, dried over magnesium sulfate and filtered, and the filtrate was concentrated. 383 mg (92% purity, 91% possibility) of the title compound was obtained. LC-MS (Method 1): Rt = 1.30 min; MS (ESIpos): m /z = 357 [M-tBu+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.008 (1.52), 0.008 (1.72), 1.012 (2.06), 1,028 (2.14), 1,371 (0.43), 1,406 (16.00), 2,217 (0.48), 2,230 (0.62), 2,258 (0.49), 4,295 (0.45), 4,305 (0.44), 4,835 (0.45), 5,019 (2.25), 7,922 (1.31), 7,936 (0.83), 8,668 (0.83). Intermediate 114 Ethyl (5RS,6RS)-6-methyl-2-(4-methylbenzyl)-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4 ,3-a]pyridine-5-carboxylate (mixture of diastereomer; 4 isomers)

[0631] Ethyl (5RS,6RS)-6-methyl-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine- 5-carboxylate (mixture of diastereomer, 4 isomers) (80.0 mg, 355 μmol) was initially loaded into acetonitrile (3.0 mL). Cesium carbonate (174 mg, 533 μmol) and 1-(bromomethyl)-4-methylbenzene (69.0 mg, 373 μmol) were subsequently added. After stirring overnight, the reaction mixture was mixed with water and ethyl acetate at room temperature. The organic phase was removed and the aqueous phase was extracted three times with ethyl acetate. The combined organic phases were washed with saturated aqueous sodium chloride solution, dried over magnesium sulfate and filtered, and the filtrate was concentrated. The residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/gradient water). The product-containing fractions were concentrated under reduced pressure and 108 mg (71% purity, 65% possibility) of the title compound were obtained. LC-MS (Method 4): Rt = 0.94 min; MS (ESIpos): m /z = 330 [M+H]+ Intermediate 115 Ethyl (5RS,7RS)-2-(4-methylbenzyl)-3-oxo-7-(trifluoromethyl)-2,3,5,6 ,7,8- hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylate (mixture of diastereomer; 4 isomers)

[0632] Ethyl (5RS,7RS)-3-oxo-7-(trifluoromethyl)-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a] Pyridine-5-carboxylate (diastereomer mixture, 4 isomers) (80.0 mg, 287 μmol) was initially loaded into acetonitrile (3.5 mL). Cesium carbonate (140 mg, 430 μmol) and 1-(bromomethyl)-4-methylbenzene (55.7 mg, 301 μmol) were subsequently added. After stirring overnight, the reaction mixture was mixed with water and ethyl acetate at room temperature. The organic phase was removed and the aqueous phase was extracted three times with ethyl acetate. The combined organic phases were washed with saturated aqueous sodium chloride solution, dried over magnesium sulfate and filtered, and the filtrate was concentrated. 102 mg (81% purity, 75% chance) of the title compound was obtained. LC-MS (Method 1): Rt = 1.33 min; MS (ESIpos): m /z = 384 [M+H]+ Intermediate 116 Methyl ((5RS)-2-[2-(4-methylphenyl)ethyl]-3-oxo-2,3,5,6,7 ,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylate (racemate)

[0633] Methyl(5RS)-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylate (racemate) (180 mg, 913 μmol) was initially loaded into acetonitrile (8.0 mL). Cesium carbonate (312 mg, 959 μmol) and 1-(2-bromoethyl)-4-methylbenzene (200 mg, 1.00 mmol, CAS 6529-51-7) were subsequently added. After stirring overnight, the reaction mixture was mixed with water and ethyl acetate at room temperature. The organic phase was removed and the aqueous phase was extracted three times with ethyl acetate. The combined organic phases were washed with saturated aqueous sodium chloride solution, dried over sodium sulfate and filtered, and the filtrate was concentrated. The residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/gradient water). The fractions containing the product were concentrated under reduced pressure and 88.0 mg (30% possibility) of the title compound were obtained. LC-MS (Method 4): Rt = 0.85 min; MS (ESIpos): m /z = 316 [M+H]+ 1H-NMR (500 MHz, DMSO-d6) δ [ppm]: 1.356 (0.66), 2.257 (8.94), 2.567 (0.54), 2.579 (0.46 ), 2.588 (0.48), 2.649 (0.66), 2.870 (0.95), 2.885 (1.81), 2.900 (1.02), 3.680 (12.74), 3.783 (0.71), 3.788 (0.75), 3.798 (1.46), 3.804 (1.47 ), 3.813 (0.68), 3.819 (0.66), 4.525 (0.70), 4.533 (0.78), 4.538 (0.88), 4.546 (0.69), 7.085 (16.00). Intermediate 117 tert-Butyl (5RS)-3-oxo-2-{[4-(trifluoromethyl)cyclohexyl]methyl}-2,3,5,6,7,8-hexahydro[1,2,4]triazole [4,3-a]pyridine-5-carboxylate (mixture of diastereomer; 4 isomers)

[0634] To tert-butyl (5RS)-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylate (racemate) (250 mg, 1.04 mmol) and cesium carbonate (511 mg, 1.57 mmol) in 15 mL of acetonitrile was added 1-(bromomethyl)-4-(trifluoromethyl)cyclohexane (diastereomer mixture; 2 isomers) (307 mg, 1.25 mmol), then the reaction mixture was stirred at room temperature overnight, then for another 24 h. For further conversion, there were two more additions of 1-(bromomethyl)-4-(trifluoromethyl)cyclohexane (128 mg, 522 μmol each time) and cesium carbonate (272 mg, 836 μmol each time) and stirring for another 24 h each time (HPLC conversion monitoring). For elaboration, the mixture was concentrated, and the residue was mixed and extracted with ethyl acetate/water. The aqueous phase was extracted twice more with ethyl acetate. The combined organic phases were washed with saturated sodium chloride solution, dried with sodium sulfate and concentrated and dried under reduced pressure. 466 mg (81% purity, 90% chance) of the title compound, which was converted as such. LC-MS (Method 4): Rt = 1.08 min; MS (ESIpos): m /z = 404 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.008 (1.25), 1.395 (16.00), 1.406 (2.62), 1.420 ( 1.08), 1.499 (1.33), 1.508 (0.84), 1.522 (0.93), 1.546 (0.75), 1.595 (0.83), 1.606 (1.20), 1.625 (1.14), 1.643 (1.63), 3.287 (0.76), 3.563 ( 2.36), 3.581 (2.34). Intermediate 118 tert-Butyl (5RS)-2-[(4,4-difluorocyclohexyl)methyl]-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[ 4,3-a]pyridine-5-carboxylate (racemate)

[0635] To tert-butyl (5RS)-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylate (racemate) (67.4 mg, 282 μmol) and cesium carbonate (138 mg, 422 μmol) in 4.0 mL of acetonitrile was added 4-(bromomethyl)-1,1-difluorocyclohexane (72.0 mg, 338 μmol), then the reaction mixture was stirred at room temperature over a weekend. For elaboration, the present precipitate was filtered, the filtrate was concentrated, and the residue was mixed and extracted with ethyl acetate/water. The aqueous phase was extracted twice more with ethyl acetate. The combined organic phases were washed with saturated sodium chloride solution, dried with sodium sulfate and concentrated and dried under reduced pressure. The residue was separated by preparatory HPLC (column: Kromasila C18, 125x30mm, 10μm, eluent: acetonitrile (B)/water + 0.1% TFA (A), gradient: 0min 90% A, 6min 90% A, 18min 5%A, 20min 5%A, 21min 90%A, flow rate: 75ml/min, detector: 210nm). Combining the fractions containing the product, after removing the solvents under reduced pressure, 41.0 mg (39% possibility) of the title compound were obtained. LC-MS (Method 6): Rt = 1.76 min; MS (ESIpos): m /z = 372 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: 1.396 (16.00), 2.072 (2.01), 3.528 (1.35), 3.545 (1.33 ), 4,399 (0.62). Intermediate 119 (5S)-2-[(6-Chloropyridin-3-yl)methyl]-3-oxo-2,5,6,7-tetrahydro-3H-pyrrolo[2,1-c][1, 2,4]triazol-5-carboxylic acid (enantiomer)

[0636] Methyl (5S)-2-[(6-chloropyridin-3-yl)methyl]-3-oxo-2,5,6,7-tetrahydro-3H-pyrrolo[2,1-c][ 1,2,4]triazol-5-carboxylate (enantiomer) (430 mg, 1.39 mmol) was initially loaded into THF (10 mL) and lithium hydroxide (167 mg, 6.96 mmol) dissolved in water was added . After stirring at room temperature overnight, the reaction mixture was concentrated under reduced pressure at room temperature for and then mixed with water, 1N aqueous hydrochloric acid and saturated aqueous sodium chloride solution. The aqueous phase was extracted three times with ethyl acetate. The combined organic phases were dried over sodium sulfate and filtered, and the filtrate was concentrated. 185 mg (45% chance) of the title compound was obtained. LC-MS (Method 3): Rt = 0.71 min; MS (ESIpos): m /z = 295 [M+H]+ Intermediate 120 (5S)-3-Oxo-2-{[6-(trifluoromethyl)pyridin-3-yl]methyl}-2,5,6, 7-tetrahydro-3H- pyrrolo[2,1-c][1,2,4]triazol-5-carboxylic acid (enantiomer)

[0637] Methyl (5S)-3-oxo-2-{[6-(trifluoromethyl)pyridin-3-yl]methyl}-2,5,6,7-tetrahydro-3H-pyrrolo[2,1- c][1,2,4]triazole-5-carboxylate (enantiomer) (441 mg, 1.29 mmol) was initially loaded into THF (10 mL) and lithium hydroxide (154 mg, 6.44 mmol) was added. dissolved in water. After stirring overnight, the reaction mixture was mixed at room temperature with water, 1 N aqueous hydrochloric acid, and saturated aqueous sodium chloride solution. The organic phase was removed and the aqueous phase was extracted three times with ethyl acetate. The combined organic phases were dried over sodium sulfate and filtered, and the filtrate was concentrated. 376 mg (89% chance) of the title compound was obtained. LC-MS (Method 3): Rt = 0.85 min; MS (ESIpos): m /z = 329 [M+H]+ Intermediate 121 (5S)-2-(4-Methylbenzyl)-3-oxo-2,5,6,7-tetrahydro-3H-pyrrolo[ 2,1- c][1,2,4]triazol-5-carboxylic acid (enantiomer)

[0638] Methyl (5S)-2-(4-methylbenzyl)-3-oxo-2,5,6,7-tetrahydro-3H-pyrrolo[2,1-c][1,2,4]triazole -5-carboxylate (enantiomer) (280 mg, 975 μmol) was initially loaded into THF (4.0 mL) and lithium hydroxide (117 mg, 4.87 mmol) dissolved in water was added. After stirring at room temperature overnight, the reaction mixture was concentrated under reduced pressure at room temperature for and then mixed with water, 1N aqueous hydrochloric acid and saturated aqueous sodium chloride solution. The aqueous phase was extracted three times with ethyl acetate. The combined organic phases were dried over sodium sulfate and filtered, and the filtrate was concentrated. 251 mg (94% chance) of the title compound was obtained. LC-MS (Method 4): Rt = 0.59 min; MS (ESIpos): m /z = 274 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: 0.008 (0.73), 1.157 (0.99), 1.174 (2.01), 1.192 (1.01 ), 1.988 (3.62), 2.274 (10.45), 2.423 (0.43), 2.430 (0.52), 2.439 (0.46), 2.446 (0.46), 2.455 (0.52), 2.463 (0.55), 2.708 (1.26), 2.720 (0.84 ), 2.730 (2.22), 2.745 (1.81), 2.822 (0.50), 2.841 (0.44), 2.853 (0.62), 2.876 (0.50), 4.020 (0.87), 4.038 (0.87), 4.603 (1.09), 4.610 (1.19 ), 4,625 (1.25), 4,633 (1.04), 4,708 (0.51), 4,747 (2.97), 4,761 (2.99), 4,800 (0.51), 7,140 (16.00), 13,346 (0.50). Intermediate 122 (5S)-2-(3-Chloro-4-fluorobenzyl)-3-oxo-2,5,6,7-tetrahydro-3H-pyrrolo[2,1-c][1,2,4 ]triazol-5-carboxylic acid (enantiomer)

[0639] Methyl (5S)-2-(3-chloro-4-fluorobenzyl)-3-oxo-2,5,6,7-tetrahydro-3H-pyrrolo[2,1-c][1,2 ,4]triazole-5-carboxylate (enantiomer) (460 mg, 1.41 mmol) was initially loaded into THF (10 mL) and lithium hydroxide (169 mg, 7.06 mmol) dissolved in water was added. After stirring overnight, the reaction mixture was mixed at room temperature with water, 1 N aqueous hydrochloric acid, and saturated aqueous sodium chloride solution. The organic phase was removed and the aqueous phase was extracted three times with ethyl acetate. The combined organic phases were dried over sodium sulfate and filtered, and the filtrate was concentrated. 281 mg (64% chance) of the title compound was obtained. LC-MS (Method 3): Rt = 1.12 min; MS (ESIpos): m /z = 312 [M+H]+ Intermediate 123 (5S)-2-[(2-Chloropyridin-4-yl)methyl]-3-oxo-2,5,6,7-tetra -hydro-3H- pyrrolo[2,1-c][1,2,4]triazol-5-carboxylic acid (enantiomer)

[0640] Methyl (5S)-2-[(2-chloropyridin-4-yl)methyl]-3-oxo-2,5,6,7-tetrahydro-3H-pyrrolo[2,1-c][ 1,2,4]triazole-5-carboxylate (enantiomer) (250 mg, 810 μmol) was initially loaded into THF (7.5 mL) and dissolved lithium hydroxide (97.0 mg, 4.05 mmol) was added in water. After stirring overnight, the reaction mixture was mixed at room temperature with water, 1 N aqueous hydrochloric acid, and saturated aqueous sodium chloride solution. The organic phase was removed and the aqueous phase was extracted three times with ethyl acetate. The combined organic phases were dried over sodium sulfate and filtered, and the filtrate was concentrated. 230 mg (96% chance) of the title compound was obtained. LC-MS (Method 4): Rt = 0.43 min; MS (ESIpos): m /z = 295 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (0.93), 0.145 (0.82), 2.371 (1.71), 2.715 ( 1.98), 2.758 (4.35), 2.781 (8.27), 2.795 (7.03), 2.838 (1.67), 2.861 (2.25), 2.891 (2.91), 2.915 (1.98), 4.532 (0.78), 4.662 (3.88), 4.670 ( 4.35) ( 1.01). Intermediate 124 (5S)-3-Oxo-2-[3-(trifluoromethyl)benzyl]-2,5,6,7-tetrahydro-3H-pyrrolo[2,1-c][1,2,4] triazole-5-carboxylic acid (enantiomer)

[0641] Methyl (5S)-3-oxo-2-[3-(trifluoromethyl)benzyl]-2,5,6,7-tetrahydro-3H-pyrrolo[2,1-c][1,2, 4]triazole-5-carboxylate (enantiomer) (150 mg, 440 μmol) was initially loaded into THF (4.5 mL) and lithium hydroxide (52.6 mg, 2.20 mmol) in water was added. After stirring overnight, the reaction mixture was mixed at room temperature with water, 1 N aqueous hydrochloric acid, and saturated aqueous sodium chloride solution. The organic phase was removed and the aqueous phase was extracted three times with ethyl acetate. The combined organic phases were dried over sodium sulfate and filtered, and the filtrate was concentrated. 129 mg (90% chance) of the title compound was obtained. LC-MS (Method 4): Rt = 0.70 min; MS (ESIpos): m /z = 328 [M+H]+ Intermediate 125 (5RS)-2-(4-Methylbenzyl)-3-oxo-2,3,5,6,7,8-hexahydro[ 1,2,4]triazolo[4,3- a]pyridine-5-carboxylic acid (racemate) Variant a)

[0642] Methyl (5RS)-2-(4-methylbenzyl)-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a] pyridine-5-carboxylate (racemate) (854 mg, 95% purity, 2.69 mmol) was initially charged into 20 mL of THF/water (3:1), lithium hydroxide (322 mg, 13.5 mmol), and the reaction mixture was stirred at room temperature overnight. For elaboration, the mixture was diluted with water, acidified with 1 N hydrochloric acid, dichloromethane and a little saturated sodium chloride solution were added, and the mixture was extracted. The aqueous phase was extracted twice more with dichloromethane, and the combined organic phases were washed with saturated sodium chloride solution, dried over sodium sulfate, concentrated and dried under reduced pressure. This yielded 436 mg (56% chance) of the title compound. LC-MS (Method 3): Rt = 1.15 min; MS (ESIpos): m /z = 288 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: 2.075 (0.98), 2.084 (0.97), 2.092 (0.92), 2.272 (9.23 ), 4,458 (1.29), 4,770 (4.43), 7,128 (16.00). Variant b)

[0643] To a solution of tert-butyl (5RS)-2-(4-methylbenzyl)-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[ 4,3-a]pyridine-5-carboxylate (7.14 g, 20.8 mmol) in 100 mL of dichloromethane was added 10 mL (130 mmol) of trifluoroacetic acid, and the mixture was stirred at room temperature overnight . After adding another 5 mL (65 mmol) of trifluoroacetic acid and stirring at room temperature for another day, the mixture was mixed with 14 mL of 3 N NaOH while cooling with an ice bath and vigorous stirring, diluted with dichloromethane/ water and extracted. The aqueous phase was extracted twice more with dichloromethane, and the combined organic phases were washed with saturated sodium chloride solution, dried over sodium sulfate, concentrated and dried under reduced pressure. Therefore, the product obtained (6.63 g, > 100% possibility) was used without further purification. LC-MS (Method 3): Rt = 1.18 min; MS (ESIpos): m /z = 288 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.008 (1.24), 0.008 (1.06), 1.397 (0.62), 1.534 ( 0.77), 2,272 (8.87), 4,459 (1.36), 4,770 (4.02), 7,128 (16.00). Intermediate 126 (5RS)-2-[4-(tert-Butoxycarbonyl)benzyl]-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3 -a]pyridine-5-carboxylic acid (racemate)

[0644] Methyl (5RS)-2-[4-(tert-butoxycarbonyl) benzyl] -3-oxo- 2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4 ,3-a]pyridine-5-carboxylate (racemate) (676 mg, 87% purity, 1.52 mmol) was initially loaded into 15 mL of THF/water, lithium hydroxide (182 mg, 7.59 mmol) was added, and the reaction mixture was stirred at room temperature overnight. For elaboration, the mixture was adjusted to pH 6 with 1 N hydrochloric acid, mixed with dichloromethane and extracted. The aqueous phase was extracted twice more with dichloromethane, and the combined organic phases were washed with saturated sodium chloride solution, dried over sodium sulfate, concentrated and dried under reduced pressure. This yielded a product fraction of 99 mg (71% purity, 12% possibility).

[0645] The same aqueous phase containing the product was adjusted to pH 3 with 1 N hydrochloric acid, mixed with ethyl acetate and extracted a total of three times. The combined ethyl acetate phases were washed with saturated sodium chloride solution, dried over sodium sulfate, and concentrated and dried under reduced pressure. This yielded 147 mg (26% chance) of the title compound. LC-MS (Method 3): Rt = 1.53 min; MS (ESIneg): m /z = 372 [MH]- 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: 1.536 (16.00), 4.911 (2.17), 7.328 (1.14), 7.349 (1.23), 7,846 (1.40), 7,867 (1.28). Intermediate 127 (5RS)-2-[(1RS)-1-(4-Chlorophenyl)ethyl]-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazole [4,3-a]pyridine-5-carboxylic acid (mixture of diastereomer; 4 isomers)

[0646] To a solution of tert-butyl (5RS)-2-[(1RS)-1-(4-chlorophenyl)ethyl]-3-oxo-2,3,5,6,7,8-hexahydro [1,2,4]triazolo[4,3-a]pyridine-5-carboxylate (mixture of diastereomer; 4 isomers) (755 mg, 2.00 mmol) in 10 mL of dichloromethane was added 1.2 mL (16 mmol) of trifluoroacetic acid, and the mixture was stirred at room temperature overnight. After adding an additional 600 μl (7.8 mmol) of trifluoroacetic acid and stirring at room temperature for an additional 5 h, the mixture was adjusted to pH 3 with 3 N NaOH while cooling with an ice bath and vigorous stirring, diluted with dichloromethane/water and extracted. The aqueous phase was extracted twice more with dichloromethane, and the combined organic phases were washed with saturated sodium chloride solution, dried over sodium sulfate, concentrated and dried under reduced pressure. In this way, 392 mg (79% purity, 48% possibility) of the title compound were obtained as a diastereomer mixture. LC-MS (Method 3): Rt = 1.33 min; MS (ESIpos): m /z = 322 [M+H]+; Rt = 1.36 min; MS (ESIpos): m /z = 322 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (1.83), -0.008 (16.00), 0.008 (13.62), 0.146 (1.78) 76 (5.07) (4.94), 7325 (4.75), 7331 (10.88), 7340 (10.10), 7346 (4.25), 7353 (4.30), 7355 (14.45), 7375 (11.93), 7379 (15.41), 7385 (4.75), 96 (6.86), 7,401 (7.54), 7,484 (4.66). Intermediate 128 (5RS)-3-Oxo-2-(4-sulfamoylbenzyl)-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine- 5-carboxylic acid (racemate)

[0647] To a solution of tert-butyl (5RS)-3-oxo-2-(4-sulfamoylbenzyl)-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[ 4,3-a]pyridine-5-carboxylate (racemate) (35.0 mg, 85.7 μmol) in 5.0 mL of dichloromethane was added 500 μL (6.5 mmol) of trifluoroacetic acid, and the mixture was stirred at room temperature over the weekend. For elaboration, the mixture was concentrated and dried under reduced pressure. In this way, 30 mg (99% possibility) of the title compound was obtained, which was used without further purification. LC-MS (Method 6): Rt = 0.66 min; MS (ESIpos): m /z = 353 [M+H]+ Intermediate 129 (5RS)-2-[4-(Methylsulfanyl)benzyl]-3-oxo-2,3,5,6,7,8-hexa - hydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylic acid (racemate)

[0648] To a solution of tert-butyl (5RS)-2-[4-(methylsulfanyl)benzyl]-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4 ]triazolo[4,3- a]pyridine-5-carboxylate (racemate) (160 mg, 89% purity, 379 μmol) in 5.0 mL of dichloromethane were added 500 μL (6.5 mmol) of trifluoroacetic acid, and the mixture was stirred at room temperature over a weekend. For further conversion, an additional 100 μl (1.3 mmol) of trifluoroacetic acid was added, and the mixture was stirred at room temperature for another day (conversion monitoring by HPLC). For elaboration, the mixture was adjusted to pH 3 with 3 N NaOH while cooling with an ice bath and vigorous stirring, diluted with dichloromethane/water and extracted. The aqueous phase was extracted twice more with dichloromethane, and the combined organic phases were washed with saturated sodium chloride solution, dried over sodium sulfate, concentrated and dried under reduced pressure. 137 mg (109% possibility) of the title compound were obtained, which was further converted as such. LC-MS (Method 3): Rt = 1.20 min; MS (ESIpos): m /z = 320 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.008 (2.62), 0.008 (2.24), 1.396 (0.96), 2.452 ( 16.00), 4,461 (1.33), 4,782 (4.61), 5,754 (0.68), 7,174 (1.26), 7,196 (3.98), 7,215 (4.58), 7,221 (1.06), 7,237 (1.41). Intermediate 130 (5RS)-2-[(6-Chloropyridin-3-yl)methyl]-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4 ,3-a]pyridine-5-carboxylic acid (racemate)

[0649] To a solution of tert-butyl (5RS)-2-[(6-chloropyridin-3-yl)methyl]-3-oxo-2,3,5,6,7,8-hexahydro[1 ,2,4]triazolo[4,3-a]pyridine-5-carboxylate (racemate) (1.84 g, 5.04 mmol) in 25 mL of dichloromethane was added 5.0 mL (65 mmol) of trifluoroacetic acid , and the mixture was stirred at room temperature overnight. For elaboration, the mixture was adjusted to pH 3 with 3 N NaOH while cooling with an ice bath and vigorous stirring, diluted with water and extracted twice with dichloromethane. The combined organic phases were washed with saturated sodium chloride solution, dried over magnesium sulfate, concentrated and dried under reduced pressure. 1.59 g (92% purity, 94% possibility) of the title compound was obtained, which was further converted as such. LC-MS (Method 3): Rt = 0.83 min; MS (ESIpos): m /z = 309 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.008 (1.94), 0.008 (1.83), 1.157 (3.09), 1.175 ( 6.27), 1.193 (3.15), 1.387 (3.56), 1.406 (0.95), 1.506 (0.97), 1.519 (1.00), 1.534 (0.85), 1.795 (0.84), 1.809 (1.23), 1.820 (1.25), 1.830 ( 1.04), 1841 (1.01), 1909 (1.25), 1988 (11.31), 2069 (1.57), 2078 (2.11), 2084 (2.94), 2090 (3.28), 2101 (3.07), 2113 (1.63), 2568 ( 1.70), 2.582 (1.28), 2.614 (1.39), 2.627 (2.10), 2.636 (1.49), 2.656 (0.78), 2.666 (1.09), 4.003 (1.24), 4.021 (3.03), 4.038 (3.02), 4.056 ( 1.29), 4.218 (0.77), 4.462 (2.60), 4.474 (4.68), 4.487 (2.49), 4.828 (1.17), 4.910 (16.00), 5.093 (0.74), 7.500 (4.57), 7.521 (5.54), 7.703 ( 3.17), 7,709 (3.32), 7,724 (2.78), 7,730 (2.79), 8,310 (4.06), 8,316 (3.98). Intermediate 131 (5RS)-2-[(5-Chloropyridin-2-yl)methyl]-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4 ,3-a]pyridine-5-carboxylic acid (racemate)

[0650] To a solution of tert-butyl (5RS)-2-[(5-chloropyridin-2-yl)methyl]-3-oxo-2,3,5,6,7,8-hexahydro[1 ,2,4]triazolo[4,3-a]pyridine-5-carboxylate (racemate) (268 mg, 83% purity, 602 μmol) in 3.0 mL of dichloromethane was added 600 μL (7.8 mmol) of trifluoroacetic acid, and the mixture was stirred at room temperature overnight. For elaboration, the mixture was concentrated and dried under reduced pressure. In this way, 220 mg (80% purity, 95% possibility) of the compound were obtained, which was used without further purification. LC-MS (Method 3): Rt = 0.87 min; MS (ESIpos): m /z = 309 [M+H]+ Intermediate 132 (5RS)-2-[(6-Cyanopyridin-3-yl)methyl]-3-oxo-2,3,5,6,7 ,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylic acid (racemate)

[0651] To a solution of tert-butyl (5RS)-2-[(6-cyanopyridin-3-yl)methyl]-3-oxo-2,3,5,6,7,8-hexahydro[1 ,2,4]triazolo[4,3-a]pyridine-5-carboxylate (racemate) (303 mg, 853 μmol) in 8.0 mL of dichloromethane was added 1.0 mL (13 mmol) of trifluoroacetic acid, and the mixture was stirred at room temperature overnight. For further conversion, an additional 200 μl (2.6 mmol) and 100 μl (1.3 mmol) of trifluoroacetic acid were added, and the mixture was stirred for an additional 3.5 h and 2.5 h respectively. (Conversion monitoring by HPLC and LC-MS). For preparation, the mixture was diluted with dichloromethane/water and extracted. The aqueous phase was extracted twice more with dichloromethane, and the combined organic phases were washed with saturated sodium chloride solution, dried over sodium sulfate, concentrated and dried under reduced pressure. 191 mg (67% purity, 50% chance) of the title compound, which was converted as such. LC-MS (Method 3): Rt = 0.72 min; MS (ESIpos): m /z = 300 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (0.84), -0.008 (6.61), 0.008 (6.11), 0.146 (0.76), 1.394 (4.32), 1.400 (16.00), 2.094 (1.18), 2.366 (0.89), 2.665 (0.82), 2.710 (0.84) (1.79) (1.26). Intermediate 133 (5RS)-2-[4-Chloro-3-(trifluoromethyl)benzyl]-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4 ,3-a]pyridine-5-carboxylic acid (racemate)

[0652] To a solution of tert-butyl (5RS)-2-[4-chloro-3-(trifluoromethyl)benzyl]-3-oxo-2,3,5,6,7,8-hexahydro[1 ,2,4]triazolo[4,3- a]pyridine-5-carboxylate (racemate) (332 mg, 97% purity, 746 μmol) in 7.0 mL of dichloromethane was added 700 μL (9.1 mmol) of trifluoroacetic acid, and the mixture was stirred at room temperature for 4 h. For further conversion, an additional 200 μl (2.6 mmol) of trifluoroacetic acid was added, and the mixture was stirred overnight. For preparation, the mixture was diluted with dichloromethane/water and extracted. The aqueous phase was extracted twice more with dichloromethane, and the combined organic phases were washed with saturated sodium chloride solution, dried over sodium sulfate, concentrated and dried under reduced pressure. 273 mg (94% possibility) of the title compound was obtained, which was further used as such. LC-MS (Method 3): Rt = 1.50 min; MS (ESIpos): m /z = 376 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (0.97), -0.008 (8.63), 0.008 (7.66), 0.146 (0.97) (1.09) (2.04) (2.38) (4.21), 7,748 (5.47), 7,754 (5.23), 13,264 (0.73). Intermediate 134 (5RS)-2-(3-Chlorobenzyl)-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine- 5-carboxylic acid (racemate)

[0653] To a solution of tert-butyl (5RS)-2-(3-chlorobenzyl)-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[ 4,3-a]pyridine-5-carboxylate (racemate) (284 mg, 84% purity, 656 μmol) in 6.0 mL of dichloromethane was added 600 μL (7.8 mmol) of trifluoroacetic acid, and the mixture was stirred at room temperature for 4 hours. For further conversion, an additional 200 μl (2.6 mmol) of trifluoroacetic acid was added, and the mixture was stirred overnight. For preparation, the mixture was diluted with dichloromethane/water and extracted. The aqueous phase was extracted twice more with dichloromethane, and the combined organic phases were washed with saturated sodium chloride solution, dried over sodium sulfate, concentrated and dried under reduced pressure. 224 mg (83% purity, 92% chance) of the title compound, which was converted as such. LC-MS (Method 3): Rt = 1.20 min; MS (ESIpos): m /z = 308 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (1.79), -0.008 (16.00),

[0654] Methyl (5RS)-2-(3-chlorobenzyl)-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a] pyridine-5-carboxylate (racemate) (63.0 mg, 196 μmol) was initially loaded into THF (2.5 mL) and lithium hydroxide (23.4 mg, 979 μmol) dissolved in water (2.5 mL) was added. mL). The reaction mixture was stirred at room temperature for 65 h and then water and 1N aqueous hydrochloric acid were added. The organic phase was removed and the aqueous phase was repeatedly extracted with ethyl acetate. The combined organic phases were dried over sodium sulfate and filtered, and the filtrate was concentrated. 55.0 mg (91% chance) of the title compound was obtained. LC-MS (Method 4): Rt = 0.68 min; MS (ESIpos): m /z = 308 [M+H]+ Intermediate 135 (5RS)-2-(3,4-Dichlorobenzyl)-3-oxo-2,3,5,6,7,8-hexa- hydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylic acid (racemate)

[0655] To a solution of tert-butyl (5RS)-2-(3,4-dichlorobenzyl)-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4] triazolo[4,3-a]pyridine-5-carboxylate (racemate) (330 mg, 78% purity, 646 μmol) in 8.0 mL of dichloromethane was added 900 μL (12 mmol) of trifluoroacetic acid, and the mixture was stirred at room temperature overnight. For further conversion, an additional 100 μl (1.3 mmol) of trifluoroacetic acid was added, and the mixture was stirred for 5 h. For preparation, the mixture was diluted with dichloromethane/water and extracted. The aqueous phase was extracted twice more with dichloromethane, and the combined organic phases were washed with saturated sodium chloride solution, dried over sodium sulfate, concentrated and dried under reduced pressure. 282 mg (80% purity, >100%) of the title compound were obtained, which was further converted as such. LC-MS (Method 3): Rt = 1.39 min; MS (ESIpos): m /z = 342 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.008 (0.99), 0.008 (0.93), 1.365 (0.65), 1.392 ( 6.32), 1.510 (0.93), 1.523 (0.96), 1.535 (1.07), 1.538 (0.85), 1.801 (0.81), 1.811 (1.13), 1.815 (1.18), 1.825 (1.21), 1.836 (1.01), 1.847 ( 1.01), 2.077 (1.57), 2.086 (2.08), 2.092 (2.91), 2.099 (3.24), 2.108 (3.04), 2.121 (1.63), 2.521 (1.06), 2.563 (1.64), 2.576 (1.70), 2.591 ( 1.29), 2.621 (1.34), 2.631 (1.97), 2.635 (2.09), 2.644 (1.52), 2.664 (0.79), 2.674 (1.03), 4.475 (2.28), 4.487 (4.46), 4.499 (2.26), 4.706 ( 0.69), 4.868 (16.00), 5.423 (1.28), 7.221 (2.81), 7.226 (2.94), 7.242 (3.18), 7.247 (3.31), 7.486 (4.76), 7.491 (4.55), 7.603 (7.05), 7.623 ( 6.45), 7.631 (0.66). Intermediate 136 (5RS)-2-(3,5-Dichlorobenzyl)-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a] pyridine-5-carboxylic acid hydrochloride (racemate)

[0656] tert-Butyl (5RS)-2-(3,5-dichlorobenzyl)-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4, 3-a]pyridine-5-carboxylate (racemate) (445 mg, 1.12 mmol) was dissolved in 1,4-dioxane (2.0 mL) and hydrochloric acid dissolved in 1,4-dioxane (2.0 mL) was added. 8 mL, 4.0 M, 11 mmol). The reaction mixture was stirred at room temperature for 2 hours and then hydrochloric acid in 1,4-dioxane (2.8 mL, 4.0 M, 11 mmol) was added again. After stirring at room temperature overnight, the solvent was removed under reduced pressure and 493 mg (79% purity, 92% chance) of the title compound were obtained. LC-MS (Method 4): Rt = 0.80 min; MS (ESIpos): m /z = 342 [M+H]+ 4.514 (3.22), 4.768 (0.61), 4.845 (0.78), 4.886 (13.41), 4.931 (0.74), 7.279 (15.72), 7.284 (16.00) , 7,299 (0.60), 7,303 (0.53), 7,347 (2.08), 7,352 (2.18), 7,414 (0.50), 7,419 (0.52), 7,451 (1.08), 7,533 (3.64), 7,538 (6.48), 7,543 (3.88) , 11,356 (0.56), 13,281 (0.55). Intermediate 137 (5RS)-3-Oxo-2-{[6-(trifluoromethyl)pyridin-3-yl]methyl}-2,3,5,6,7,8-hexahydro[1,2,4] triazolo[4,3-a]pyridine-5-carboxylic acid:trifluoroacetic acid (racemate)

[0657] tert-Butyl (5RS)-3-oxo-2-{[6-(trifluoromethyl)pyridin-3-yl]methyl}-2,3,5,6,7,8-hexahydro[1, 2,4]triazolo[4,3-a]pyridine-5-carboxylate (racemate) (364 mg, 913 μmol) was dissolved in dichloromethane (10 mL), and trifluoroacetic acid (1.1 mL, 14 mmol) was added at room temperature. After the reaction mixture was stirred at room temperature overnight, the solvent was removed under reduced pressure. 465 mg (> 100%) of the title compound were obtained. LC-MS (Method 4): Rt = 0.58 min; MS (ESIpos): m /z = 343 [M+H]+ Intermediate 138 (5RS)-2-(3,4-Difluorobenzyl)-3-oxo-2,3,5,6,7,8-hexa- hydro[1,2,4]triazolo[4,3-a]pyridine-5-hydrochloride carboxylic acid (racemate)

[0658] tert-Butyl (5S, R)-2-(3,4-difluorobenzyl)-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[ 4,3-a]pyridine-5-carboxylate (racemate) (451 mg, 1.23 mmol) was dissolved in 1,4-dioxane (10 mL, 120 mmol) and hydrochloric acid dissolved in 1,4-dioxane was added (3.1 mL, 4.0 M, 12 mmol). The reaction mixture was stirred at room temperature for 65 hours and at 50°C overnight. Hydrochloric acid dissolved in 1,4-dioxane (3.1 mL, 4.0 M, 12 mmol) was added again, and the mixture was stirred at room temperature for 1 hour. The solvent was removed under reduced pressure and 420 mg (98% possibility) of the title compound were obtained. 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.008 (3.02), 0.008 (2.73), 1.393 (1.69), 1.810 (0.44), 2.098 (1.23), 2.107 (1.13), 2.327 (0.53 ), 2.562 (0.67), 2.575 (0.60), 2.589 (0.48), 2.621 (0.48), 2.631 (0.77), 2.642 (0.55), 2.670 (0.77), 3.568 (16.00), 4.472 (0.85), 4.484 (1.55 ), 4.496 (0.75), 4.849 (4.79), 7.101 (0.55), 7.236 (0.48), 7.265 (0.57), 7.285 (0.50), 7.370 (0.55), 7.392 (1.04), 7.398 (0.62), 7.413 (0.59 ), 7,419 (1.09), 7,440 (0.52). Intermediate 139 (5RS)-2-(3-Chloro-4-fluorobenzyl)-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3- a]pyridine-5-carboxylic acid hydrochloride (racemate)

[0659] tert-Butyl (5RS)-2-(3-chloro-4-fluorobenzyl)-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[ 4,3-a]pyridine-5-carboxylate (racemate) (391 mg, 1.02 mmol) was dissolved in 1,4-dioxane (10 mL, 120 mmol) and hydrochloric acid dissolved in 1,4-dioxane was added (2.6 mL, 4.0 M, 10 mmol). The reaction mixture was stirred at room temperature for 65 hours and at 50°C for 3 h. Hydrochloric acid dissolved in 1,4-dioxane (1.3 mL, 4.0 M, 5 mmol) was added again, and the mixture was stirred at 50°C under reduced pressure and the title compound was obtained. 1H-NMR (400 MHz, DMSO-d6) δ 1.391 (4.37), 1.476 (0.51), 1.492 1.538 (0.96), 1.551 (0.66), 1.799 1.833 (1.20), 1.844 (1.17), 1.909 2.106 (3.58 ), 2,118 (1.94), 2,519 2,589 (1.51), 2,620 (1.53), 2,633 2,672 (1.24), 2,685 (0.72), 3,390 3,502 (0.60), 3,593 (0.97), 3,671 3,709 (0.46), 3. 733 (0.41), 3.831 4,020 (0.56), 4,189 (0.69), 4,210 4,472 (2.61), 4,484 (4.91), 4,496 6,348 (0.77), 7,239 (1.31), 7,245 7,260 (2.09), 7,266 (2.12), 7,272 7. 377 (0.46), 7,391 (4.96), 7.413 7.448 (2.69), 7.454 (2.57), 8.133 (0 Intermediate 140 (5RS)-2-[(2-Methoxypyridin-4-yl)methyl]-3-oxo-2,3,5,6 ,7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylic acid hydrochloride (racemate)

[0660] tert-Butyl (5RS)-2-[(2-methoxypyridin-4-yl)methyl]-3-oxo- 2,3,5,6,7,8-hexahydro[1,2,4 ]triazolo[4,3-a]pyridine-5-carboxylate (racemate) (144 mg, 400 μmol) was dissolved in 1,4-dioxane (4.0 mL, 47 mmol) and hydrochloric acid dissolved in 1. 4-dioxane (1000 μl, 4.0 M, 4.0 mmol). The reaction mixture was stirred at room temperature for 65 hours and at 50°C overnight. The solvent was removed under reduced pressure, and 165 mg (>100%) of the title compound were obtained. 1H-NMR (400 MHz, DMSO-d6): d [ppm] = 1.46 - 1.60 (m, 2H), 1.79 - 1.89 (m, 2H), 2.05 - 2.15 (m, 2H), 3.83 (s, 3H) 4.49 (d, 1H), 4.85 (d, 2H), 6.59 (s, 1H), 6.82 (d, 1H), 8.10 (d, 1H). 1.53 (s, 2H), 1.83 (s, 2H), 2.11 (br s, 5H), 2.63-2.71 (m, 5H), 3.83 (s, 3H), 4.49 (d, 2H), 4.68 (s, 1H ), 4.66 - 4.70 (m, 1H), 4.85 (d, 2H), 6.04 (s, 1H), 6.59 (s, 1H), 6.82 (d, 1H), 7.32 (s, 1H), 8.10 (d, 1H). Intermediate 141 (5RS)-2-(3-Chloro-4-methoxybenzyl)-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3- a]pyridine-5-carboxylic acid:trifluoroacetic acid (racemate)

[0661] tert-Butyl (5RS)-2-3-chloro-4-methoxybenzyl)-3-oxo-- 2,3,5,6,7,8-hexahydro[1,2,4]triazolo[ 4,3-a]pyridine-5-carboxylate (racemate) (365 mg, 925 μmol) was dissolved in dichloromethane (20 mL), and trifluoroacetic acid (710 μL, 9.3 mmol) was added at room temperature. After the reaction mixture was stirred at room temperature for 48 h, the solvent was removed under reduced pressure. 454 mg (> 100%) of the title compound were obtained. LC-MS (Method 4): Rt = 0.66 min; MS (ESIpos): m /z = 338 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.008 (0.90), 0.008 (0.79), 1.111 (1.03), 1.157 ( 0.90), 1.175 (1.82), 1.193 (0.92), 1.228 (0.41), 1.391 (1.94), 1.474 (0.43), 1.488 (0.67), 1.508 (0.88), 1.522 (0.94), 1.535 (2.44), 1.550 ( 0.56), 1.790 (0.81), 1.802 (1.21), 1.813 (1.21), 1.824 (1.06), 1.835 (1.01), 1.848 (0.68), 1.988 (3.28), 2.067 (1.72), 2.080 (3.10), 2.087 ( 3.19), 2096 (2.97), 2108 (1.57), 2520 (1.36), 2563 (1.66), 2577 (1.26), 2609 (1.33), 2620 (2.11), 2631 (1.48), 2650 (0.75), 2661 ( 1.03), 2.673 (0.66), 2.690 (0.53), 2.731 (2.17), 2.890 (2.79), 4.021 (0.77), 4.039 (0.76), 4.458 (2.30), 4.470 (4.46), 4.482 (2.24), 4.771 ( 16.00), 5.753 (1.45), 7.094 (4.56), 7.115 (6.97), 7.185 (3.46), 7.190 (3.61), 7.206 (2.20), 7.211 (2.39), 7.298 (5.41), 7.303 (4.82). Intermediate 142 (5RS)-2-(3-Fluorobenzyl)-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine- 5-carboxylic acid hydrochloride (racemate)

[0662] tert-Butyl (5RS)-2-(3-fluorobenzyl)-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3- a]pyridine-5-carboxylate (racemate) (150 mg, 432 μmol) was dissolved in 1,4-dioxane (4.3 mL, 51 mmol) and hydrochloric acid dissolved in 1,4-dioxane (1.1 mL, 4.0 M, 4.3 mmol). The reaction mixture was stirred at room temperature for 65 hours. Hydrochloric acid dissolved in 1,4-dioxane (1.1 mL, 4.0 M, 4.3 mmol) was added again, and the mixture was stirred at 50 ° C overnight. The solvent was removed under reduced pressure, and 165 mg (89% purity, >100%) of the title compound were obtained. LC-MS (Method 4): Rt = 0.59 min; MS (ESIpos): m /z = 292 [M+H]+ Intermediate 143 (5RS)-2-(3-Methoxybenzyl)-3-oxo-2,3,5,6,7,8-hexahydro[ 1,2,4]triazolo[4,3-a]pyridine-5-trifluoroacetic acid (racemate)

[0663] tert-Butyl (5RS)-2-(3-methoxybenzyl)-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3- a]pyridine-5-carboxylate (racemate) (340 mg, 947 μmol) was dissolved in dichloromethane (20 mL), and trifluoroacetic acid (730 μl, 9.5 mmol) was added at room temperature. After the reaction mixture was stirred at room temperature overnight, the solvent was removed under reduced pressure. 435 mg (> 100%) of the title compound were obtained. LC-MS (Method 3): Rt = 1.04 min; MS (ESIpos): m /z = 304 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.008 (1.85), 0.008 (1.73), 1.111 (1.34), 1.399 ( 3.15), 1.482 (0.86), 1.515 (1.77), 1.534 (5.41), 1.544 (1.65), 1.557 (1.10), 1.576 (0.53), 1.797 (1.69), 1.810 (2.41), 1.820 (2.43), 1.831 ( 2.06), 1.843 (1.97), 1.855 (1.32), 1.988 (0.50), 2.047 (0.43), 2.075 (3.45), 2.088 (6.07), 2.095 (6.31), 2.105 (5.87), 2.117 (3.12), 2.328 ( 0.42), 2.524 (1.98), 2.569 (3.23), 2.583 (2.50), 2.613 (2.67), 2.626 (4.07), 2.636 (2.95), 2.655 (1.45), 2.666 (2.17), 2.678 (1.24), 3.696 ( 0.64), 3.705 (0.58), 3,750 (0.42), 3,765 (1.85), 4,466 (4.47), 4,477 (8,57), 4,490 (4,32), 4,759 (1.51), 4,799 (16,00), 4,805 (15,56), 4,845 ( 1.43), 5.398 (0.68), 5.753 (4.67), 6.789 (14.05), 6.809 (6.64), 6.824 (4.19), 6.830 (3.47), 6.845 (4.90), 6.851 (4.14), 7.220 (6.34), 7.240 ( 8.92), 7.259 (4.69). Intermediate 144 (5RS)-3-Oxo-2-[3-(trifluoromethyl)benzyl]-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a ]pyridine-5-carboxylic acid:trifluoroacetic acid (racemate)

[0664] tert-Butyl (5RS)-3-oxo-2-[3-trifluoromethyl)benzyl]-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4, 3-a]pyridine-5-carboxylate (racemate) (388 mg, 975 μmol) was dissolved in dichloromethane (20 mL), and trifluoroacetic acid (750 μl, 9.8 mmol) was added at room temperature. After the reaction mixture was stirred at room temperature overnight, trifluoroacetic acid (750 μl, 9.8 mmol) was added again. After stirring at 40°C for 2 hours, the solvent was removed under reduced pressure. 534 mg (> 100%) of the title compound were obtained. LC-MS (Method 3): Rt = 1.34 min; MS (ESIpos): m /z = 342 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: 1.110 (0.81), 1.385 (1.82), 1.535 (3.66), 1.815 (1.57 ), 2,100 (4.20), 2,328 (0.90), 2,562 (2.17), 2,575 (2.21), 2,590 (1.50), 2,634 (2.53), 2,674 (1.98), 4,482 (2.72), 4,493 (5.55), 4,506 (2.60 ), 4,958 (16.00), 7,525 (2.56), 7,544 (4.75), 7,569 (2.81), 7,588 (5.17), 7,615 (6.53), 7,649 (4.29), 7,668 (2.58). Intermediate 145 (5RS)-2-[(1-Methyl-1H-pyrazol-3-yl)methyl]-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4 ]triazolo[4,3-a]pyridine-5-carboxylic acid:trifluoroacetic acid (racemate)

[0665] tert-Butyl (5RS)-2-[(1-methyl-1H-pyrazol-3-yl)methyl-3-oxo-- 2,3,5,6,7,8-hexahydro[1 ,2,4]triazolo[4,3-a]pyridine-5-carboxylate (racemate) (150 mg, 450 μmol) was dissolved in dichloromethane (3.0 mL), and trifluoroacetic acid (350 μl, 4.5 mmol) was added at room temperature. The reaction mixture was stirred at room temperature overnight, and then trifluoroacetic acid (350 μl, 4.5 mmol) was added again. After the reaction mixture was stirred at room temperature overnight, the solvent was removed under reduced pressure. 170 mg (97% chance) of the title compound was obtained. LC-MS (Method 4): Rt = 0.36 min; MS (ESIpos): m /z = 278 [M+H]+ Intermediate 146 (5RS)-3-Oxo-2-(5,6,7,8-tetrahydronaphthalen-2-ylmethyl)-2,3, 5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylic acid:trifluoroacetic acid (racemate)

[0666] tert-Butyl (5RS)-3-oxo-2-(5,6, 7,8-tetrahydronaphthalen-2-ylmethyl)-2,3,5,6,7,8-hexahydro[ 1,2,4]triazolo[4,3-a]pyridine-5-carboxylate (racemate) (280 mg, 730 μmol) was dissolved in dichloromethane (5.0 mL), and trifluoroacetic acid (2.0 mL, 26 mmol) was added at room temperature. After the reaction mixture was stirred at room temperature overnight, the solvent was removed under reduced pressure. 320 mg (94% chance) of the title compound was obtained. LC-MS (Method 4): Rt = 0.81 min; MS (ESIpos): m /z = 328 [M+H]+ Intermediate 147 (5RS)-2-[(5-Methyl-1,2-oxazol-3-yl)methyl]-3-oxo-2,3 ,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylic acid (racemate)

[0667] Methyl (5RS)-2-[(5-methyl-1,2-oxazol-3-yl)methyl]-3-oxo-2,3,5,6,7,8-hexahydro[1 ,2,4]triazolo[4,3-a]pyridine-5-carboxylate (racemate) (412 mg, 1.41 mmol) was initially loaded into THF (14 mL) and lithium hydroxide (169 mg, 7 .05 mmol) dissolved in water (4.0 mL). After stirring at room temperature overnight, the reaction mixture was concentrated under reduced pressure and then mixed with water, 1N aqueous hydrochloric acid and saturated aqueous sodium chloride solution. The aqueous phase was extracted three times with ethyl acetate. The combined organic phases were dried over sodium sulfate and filtered, and the filtrate was concentrated. 136 mg (83% purity, 29% chance) of the title compound was obtained. LC-MS (Method 3): Rt = 0.67 min; MS (ESIpos): m /z = 279 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: 1.157 (1.10), 1.174 (2.26), 1.181 (0.48), 1.192 (1.13 ), 1.356 (2.56), 1.405 (0.76), 1.499 (0.43), 1.513 (0.60), 1.526 (0.61), 1.541 (0.53), 1.797 (0.52), 1.809 (0.79), 1.820 (0.78), 1.831 (0.66 ), 1,842 (0.64), 1,908 (2.86), 1,988 (4.00), 2,083 (1.98), 2,089 (2.11), 2,099 (2.04), 2,111 (1.09), 2,201 (1.26), 2,369 (16.00), 2,561 (1.03 ), 2.573 (1.03), 2.587 (0.81), 2.617 (0.84), 2.629 (1.39), 2.639 (0.93), 2.659 (0.50), 2.670 (0.78), 4.020 (0.97), 4.038 (0.95), 4.426 (0.98 ), 4.441 (1.01), 4.450 (1.39), 4.462 (2.65), 4.474 (1.38), 4.807 (0.40), 4.847 (6.28), 4.852 (6.39), 4.892 (0.41), 6.069 (3.43), 6.180 (0.58 ). Intermediate 148 (5RS)-3-Oxo-2-(pyridin-3-ylmethyl)-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a] pyridine-5-carboxylic acid:trifluoroacetic acid (racemate)

[0668] tert-Butyl (5RS)-3-oxo-2-(pyridin-3-ylmethyl)-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4, 3-a]pyridine-5-carboxylate (racemate) (366 mg, 1.11 mmol) was dissolved in dichloromethane (10 mL), and trifluoroacetic acid (1.7 mL, ambient. After mixing the ambient overnight, reduced. 442 mg (83% purity, 29% chance) of the title compound were obtained LC-MS (Method 9): Rt = 3.31 min; +H]+ Intermediate 149 (5RS)-3-Oxo-2-(2,4,5-trifluorobenzyl)-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[ 4,3-a]pyridine-5-carboxylic acid:trifluoroacetic acid (racemate)

[0669] tert-Butyl (5RS)-3-oxo-2-(2,4,5-trifluorobenzyl)-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[ 4,3-a]pyridine-5-carboxylate (racemate) (390 mg, 1.02 mmol) was dissolved in dichloromethane (8 mL), and trifluoroacetic acid (3.3 mL, 43 mmol) was added at room temperature . After the reaction mixture was stirred at room temperature overnight, the solvent was removed under reduced pressure. 445 mg (95% chance) of the title compound was obtained. LC-MS (Method 3): Rt = 1.17 min; MS (ESIpos): m /z = 328 [M+H]+ Intermediate 150 (5RS)-2-[(2-Chloropyridin-4-yl)methyl]-3-oxo-2,3,5,6,7 ,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylic acid:trifluoroacetic acid (racemate)

[0670] tert-Butyl (5RS)-2-[(2-chloropyridin-4-yl)methyl]-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4 ]triazolo[4,3-a]pyridine-5-carboxylate (racemate) (490 mg, 1.34 mmol) was dissolved in dichloromethane (12 mL, 190 mmol), and trifluoroacetic acid (1.9 mL, 25 mmol ) was added at room temperature. After the reaction mixture was stirred at room temperature overnight, the solvent was removed under reduced pressure. 581 mg (94% purity, 96% chance) of the title compound was obtained. LC-MS (Method 4): Rt = 0.50 min; MS (ESIpos): m /z = 309 [M+H]+ Intermediate 151 (5RS)-2-[(5-Chloro-2-thienyl)methyl]-3-oxo-2,3,5,6,7 ,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylic acid:trifluoroacetic acid (racemate)

[0671] tert-Butyl (5RS)-2-[(5-chloro-2-thienyl)methyl]-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4 ]triazolo[4,3-a]pyridine-5-carboxylate (racemate) (414 mg, 1.12 mmol) was dissolved in dichloromethane (10 mL, 160 mmol), and trifluoroacetic acid (1.7 mL, 22 mmol ) was added at room temperature. After the reaction mixture was stirred at room temperature for 5 hours, the solvent was removed under reduced pressure. 516 mg (> 100%) of the title compound were obtained. LC-MS (Method 3): Rt = 1.16 min; MS (ESIpos): m /z = 314 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: 1.110 (1.14), 1.384 (7.34), 1.535 (2.17), 1.568 (1.23 ), 1,802 (2.23), 1,814 (2.29), 1,824 (1.91), 2,058 (3.54), 2,071 (5.97), 2,081 (5.66), 2,328 (1.63), 2,366 (0.97), 2,565 (2.91), 2,578 (2.97 ), 2.592 (2.34), 2.623 (2.46), 2.635 (3.91), 2.646 (2.66), 2.675 (2.77), 2.710 (1.09), 4.438 (5.80), 4.451 (9.29), 4.463 (5.60), 4.555 (2.31 ) 3 ), 7,079 (0.63). Intermediate 152 (5RS)-2-[(4-Methyl-1,2,5-oxadiazol-3-yl)methyl]-3-oxo-2,3,5,6,7,8-hexahydro[1 ,2,4]triazolo[4,3-a]pyridine-5-carboxylic acid (racemate)

[0672] Methyl (5RS)-2-[(4-methyl-1,2,5-oxadiazol-3-yl)methyl]-3-oxo- 2,3,5,6,7,8-hexahydro [1,2,4]triazolo[4,3-a]pyridine-5-carboxylate (racemate) (281 mg, 958 μmol) was initially loaded into THF (5.0 mL) and lithium hydroxide (115 mg) was added. , 4.79 mmol) dissolved in water. After stirring at room temperature overnight, the reaction mixture was concentrated under reduced pressure and then mixed with water, 1N aqueous hydrochloric acid and saturated aqueous sodium chloride solution. The aqueous phase was extracted three times with ethyl acetate. The combined organic phases were dried over sodium sulfate and filtered, and the filtrate was concentrated. 91.0 mg (88% purity, 30% chance) of the title compound was obtained. LC-MS (Method 1): Rt = 0.61 min; MS (ESIpos): m /z = 280 [M+H]+ Intermediate 153 (5RS)-2-(2-Methylbenzyl)-3-oxo-2,3,5,6,7,8-hexahydro[ 1,2,4]triazolo[4,3- a]pyridine-5-carboxylic acid (racemate)

[0673] Methyl (5RS)-2-(2-methylbenzyl)-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a] Pyridine-5-carboxylate (racemate) (196 mg, 650 μmol) was initially loaded into THF (5.0 mL) and lithium hydroxide (77.9 mg, 3.25 mmol) dissolved in water was added. After stirring at room temperature overnight, the reaction mixture was concentrated under reduced pressure and then mixed with water, 1N aqueous hydrochloric acid and saturated aqueous sodium chloride solution. The aqueous phase was extracted three times with ethyl acetate. The combined organic phases were dried over sodium sulfate and filtered, and the filtrate was concentrated. 150 mg (80% chance) of the title compound was obtained. LC-MS (Method 1): Rt = 0.88 min; MS (ESIpos): m /z = 288 [M+H]+ Intermediate 154 (5RS)-2-[4-Fluoro-3-(trifluoromethyl)benzyl]-3-oxo-2,3,5,6,7 ,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylic acid (racemate)

[0674] Methyl (5RS)-2-[4-fluoro-3-(trifluoromethyl)benzyl]-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazole [4,3-a]pyridine-5-carboxylate (racemate) (569 mg, 1.52 mmol) was initially loaded into THF (8.0 mL) and lithium hydroxide (183 mg, 7.62 mmol) was added. dissolved in water. After stirring at room temperature overnight, the reaction mixture was concentrated under reduced pressure and then mixed with water, 1N aqueous hydrochloric acid and saturated aqueous sodium chloride solution. The aqueous phase was extracted three times with ethyl acetate. The combined organic phases were dried over sodium sulfate and filtered, and the filtrate was concentrated. 251 mg (94% purity, 43% chance) of the title compound were obtained. LC-MS (Method 4): Rt = 0.77 min; MS (ESIpos): m /z = 360 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.008 (2.89), 0.008 (2.76), 1.157 (2.61), 1.170 ( 1.52), 1.175 (5.50), 1.193 (2.73), 1.559 (1.10), 1.748 (1.40), 1.905 (1.45), 1.948 (1.17), 1.988 (10.96), 2.129 (1.67), 2.159 (1.21), 2.328 ( 0.45), 2.458 (0.96), 2.473 (1.31), 2.595 (2.13), 2.634 (1.08), 2.670 (0.46), 3.314 (0.58), 4.003 (0.74), 4.021 (2.44), 4.039 (2.45), 4.056 ( 0.80), 4.319 (2.46), 4.328 (2.44), 4.549 (0.88), 4.918 (16.00), 7.458 (2.32), 7.480 (3.39), 7.506 (3.05), 7.587 (1.95), 7.600 (2.29), 7.678 ( 3.14), 7,696 (3.13). Intermediate 155 (5RS)-2-[2,5-Bis(trifluoromethyl)benzyl]-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4, 3-a]pyridine-5-carboxylic acid (racemate)

[0675] Methyl (5RS)-2-[2,5-bis(trifluoromethyl)benzyl]-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[ 4,3-a]pyridine-5-carboxylate (racemate) (634 mg, 1.50 mmol) was initially loaded into THF (8.0 mL) and dissolved lithium hydroxide (179 mg, 7.48 mmol) was added in water. After stirring at room temperature overnight, the reaction mixture was concentrated under reduced pressure and then mixed with water, 1N aqueous hydrochloric acid and saturated aqueous sodium chloride solution. The aqueous phase was extracted three times with ethyl acetate. The combined organic phases were dried over sodium sulfate and filtered, and the filtrate was concentrated. 242 mg (91% purity, 36% chance) of the title compound were obtained. LC-MS (Method 4): Rt = 0.86 min; MS (ESIpos): m /z = 410 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (0.54), -0.008 (4.55), 0.008 ( 3.70), 0.146 (0.50), 1.170 (2.38), 1.234 (0.54), 1.573 (1.56), 1.755 (1.93), 1.949 (1.55), 1.988 (2 .59), 2.153 (2.28), 2.188 (1.65), 2.328 (1.13), 2.367 (0.71), 2.611 (2.68), 2.666 (1.51), 2.710 (0. 66), 3.313 (2.26), 3.405 (1.49), 4.038 (0.40), 4.324 (2.78), 4.746 (1.49), 4.911 (2.40), 5.082 (16.00 ), 7.649 (8.11), 7.912 (3.70), 7.932 (6.12), 8.013 (7.38), 8.033 (4.99), 8.065 (1.22), 8.098 (0.71) . Intermediate 156 (5RS)-2-[(6-Methylpyridin-3-yl)methyl]-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4 ,3-a]pyridine-5-carboxylic acid (racemate)

[0676] Methyl (5RS)-2-[(6-methylpyridin-3-yl)methyl]-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazole [4,3-a]pyridine-5-carboxylate (racemate) (231 mg, 764 μmol) was initially loaded into THF (5.0 mL) and lithium hydroxide (91.5 mg, 3.82 mmol) was added. dissolved in water. After stirring at room temperature overnight, the reaction mixture was concentrated under reduced pressure and then mixed with water, 1N aqueous hydrochloric acid and saturated aqueous sodium chloride solution. The aqueous phase was extracted three times with ethyl acetate. The aqueous phase was concentrated and suspended with tetrahydrofuran/ethanol (1/1). The solids were removed and the filtrate was concentrated to yield the product. 262 mg (> 100%) of the title compound were obtained. LC-MS (Method 4): Rt = 0.19 min; MS (ESIpos): m /z = 288 [M]+ [ppm]: -0.149 (0.62), -0.008 (5.32), (7.69), 1.055 (16.00), 1.072 (8.00), (2.83), 1.776 ( 0.99), 2.090 (0.88), (2.65), 2.620 (0.56), 2.670 (0.90), (8.60), 3.448 (8.67), 3.466 (3.40), (1.62), 4.465 (0.59), 4.475 (1.11), 4,936 (1.69), 8,492 (0.70). Intermediate 157 (5RS)-2-[(6-Methoxypyridin-3-yl)methyl]-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3 -a]pyridine-5-carboxylic acid (racemate)

[0677] Methyl (5RS)-2-[(6-methoxypyridin-3-yl)methyl]-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazole [4,3-a]pyridine-5-carboxylate (racemate) (202 mg, 636 μmol) was initially loaded into THF (5.0 mL) and lithium hydroxide (76.1 mg, 3.18 mmol) was added. dissolved in water. After stirring at room temperature overnight, the reaction mixture was concentrated under reduced pressure and then mixed with water, 1N aqueous hydrochloric acid and saturated aqueous sodium chloride solution. The aqueous phase was extracted three times with ethyl acetate. The combined organic phases were dried over sodium sulfate and filtered, and the filtrate was concentrated. 45 mg (23% chance) of the title compound was obtained. LC-MS (Method 3): Rt = 0.78 min; MS (ESIpos): m /z = 305 [M]+ Intermediate 158 (5RS)-2-[4-methoxy-3-(trifluoromethyl)benzyl]-3-oxo-2,3,5,6,7,8 -hexa-hydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylic acid (racemate)

[0678] Methyl (5RS)-2-[4-methoxy-3-(trifluoromethyl)benzyl]-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazole [4,3-a]pyridine-5-carboxylate (racemate) (305 mg, 791 μmol) was initially loaded into THF (8.0 mL) and lithium hydroxide (94.8 mg, 3.96 mmol) was added. dissolved in water. After stirring at room temperature overnight, the reaction mixture was concentrated under reduced pressure and then mixed with water, 1N aqueous hydrochloric acid and saturated aqueous sodium chloride solution. The aqueous phase was extracted three times with ethyl acetate. The combined organic phases were dried over sodium sulfate and filtered, and the filtrate was concentrated. 151 mg (51% chance) of the title compound was obtained. LC-MS (Method 3): Rt = 1.34 min; MS (ESIpos): m /z = 372 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.008 (1.34), 0.008 (1.63), 1.157 (2.20), 1.175 ( 4.44), 1.192 (2.26), 1.529 (0.44), 1.785 (0.53), 1.797 (0.50), 1.807 (0.43), 1.819 (0.43), 1.988 (8.02), 2.045 (0.43), 2.079 (1.23), 2.088 ( 1.19), 2.562 (0.66), 2.598 (0.58), 2.610 (0.95), 2.620 (0.64), 2.650 (0.43), 3.869 (16.00), 4.002 (0.65), 4.020 (1.93), 4.038 (1.92), 4.056 ( 0.63), 4.419 (0.71), 4.429 (0.98), 4.835 (7.06), 7.223 (1.56), 7.244 (1.81), 7.498 (1.32), 7.520 (4.16). Intermediate 159 (5RS)-2-[(1-Methyl-1H-benzimidazol-2-yl)methyl]-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4 ]triazolo[4,3-a]pyridine-5-carboxylic acid (racemate)

[0679] Methyl (5RS)-2-[(1-methyl-1H-benzimidazol-2-yl)methyl]-3-oxo-2,3,5,6,7,8-hexahydro[1,2 ,4]triazolo[4,3-a]pyridine-5-carboxylate (racemate) (137 mg, 401 μmol) was initially loaded into THF (3.0 mL) and lithium hydroxide (48.1 mg, 2 .01 mmol) dissolved in water. After stirring at room temperature overnight, the reaction mixture was concentrated under reduced pressure and then mixed with water, 1N aqueous hydrochloric acid and saturated aqueous sodium chloride solution. The aqueous phase was extracted three times with ethyl acetate. The combined organic phases were dried over sodium sulfate and filtered, and the filtrate was concentrated. 120 mg (91% chance) of the title compound was obtained. LC-MS (Method 3): Rt = 0.60 min; MS (ESIpos): m /z = 328 [M+H]+ Intermediate 160 (5RS)-2-[(1-Ethyl-1H-imidazol-2-yl)methyl]-3-oxo-2,3,5 ,6,7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylic acid (racemate)

[0680] Methyl (5RS)-2-[(1-ethyl-1H-imidazol-2-yl)methyl]-3-oxo-2,3,5,6,7,8-hexahydro[1,2 ,4]triazolo[4,3-a]pyridine-5-carboxylate (racemate) (54.0 mg, 177 μmol) was initially loaded into THF (2.0 mL) and lithium hydroxide (21.2 mg) was added. , 884 μmol) dissolved in water. After stirring at room temperature overnight, the reaction mixture was concentrated under reduced pressure and then mixed with water, 1N aqueous hydrochloric acid and saturated aqueous sodium chloride solution. The aqueous phase was extracted three times with ethyl acetate. The combined organic phases were dried over sodium sulfate and filtered, and the filtrate was concentrated. 80.0 mg (60% purity, 93% possibility) of the title compound was obtained. LC-MS (Method 9): Rt = 3.44 min; MS (ESIpos): m /z = 292 [M+H]+ Intermediate 161 (5RS)-2-[(1-Methyl-1H-indazol-5-yl)methyl]-3-oxo-2,3,5 ,6,7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylic acid (racemate)

[0681] Methyl (5RS)-2-[(1-methyl-1H-indazol-5-yl)methyl]-3-oxo-2,3,5,6,7,8-hexahydro[1,2 ,4]triazolo[4,3-a]pyridine-5-carboxylate (racemate) (87.0 mg, 98% purity, 250 μmol) was initially loaded into THF (2.5 mL) and lithium hydroxide was added. (29.9 mg, 1.25 mmol) dissolved in water. After stirring at room temperature overnight, the reaction mixture was concentrated under reduced pressure at room temperature for and then mixed with water, 1N aqueous hydrochloric acid and saturated aqueous sodium chloride solution. The aqueous phase was extracted three times with ethyl acetate. The combined organic phases were dried over sodium sulfate and filtered, and the filtrate was concentrated. 67.0 mg (80% chance) of the title compound was obtained. LC-MS (Method 3): Rt = 0.87 min; MS (ESIpos): m /z = 328 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.008 (0.92), 0.008 (0.91), 1.157 (1.12), 1.175 ( 2.28), 1.192 (1.13), 1.796 (0.45), 1.807 (0.50), 1.908 (0.74), 1.988 (4.27), 2.082 (1.22), 2.327 (0.41), 2.523 (2.15), 2.565 (0.61), 2.596 ( 0.54), 2.608 (0.89), 2.619 (0.60), 2.648 (0.42), 2.669 (0.50), 4.002 (0.41), 4.021 (16.00), 4.038 (1.11), 4.457 (0.87), 4.468 (1.72), 4.481 ( 0.89), 4.916 (3.28), 4.921 (3.27), 7.294 (1.26), 7.298 (1.26), 7.316 (1.45), 7.320 (1.49), 7.580 (1.84), 7.608 (2.57), 8.004 (3.39), 13.222 ( 0.63). Intermediate 162 (5RS)-3-Oxo-2-({5-[3-(trifluoromethyl)phenyl]-1,2,4-oxadiazol-3-yl}methyl)- 2,3,5,6,7, 8-hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylic acid (racemate)

[0682] Methyl (5RS)-3-oxo-2-({5-[3-(trifluoromethyl)phenyl]-1,2,4-oxadiazol-3-yl}methyl)-2,3,5,6, 7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylate (racemate) (640 mg, 1.51 mmol) was initially loaded into THF (15 mL) and was added lithium hydroxide (181 mg, 7.56 mmol) dissolved in water. After stirring at room temperature overnight, the reaction mixture was concentrated under reduced pressure at room temperature for and then mixed with water, 1N aqueous hydrochloric acid and saturated aqueous sodium chloride solution. The aqueous phase was extracted three times with ethyl acetate. The combined organic phases were dried over sodium sulfate and filtered, and the filtrate was concentrated. 588 mg (88% purity, 84% chance) of the title compound was obtained. LC-MS (Method 3): Rt = 1.42 min; MS (ESIpos): m /z = 410 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.008 (1.41), 0.008 (1.36), 1.094 (1.28), 1.157 ( 4.33), 1.175 (8.82), 1.193 (4.46), 1.519 (0.93), 1.533 (1.05), 1.546 (1.17), 1.556 (1.03), 1.570 (0.87), 1.582 (0.66), 1.803 (0.93), 1.814 ( 1.46), 1.825 (1.48), 1.836 (1.29), 1.847 (1.23), 1.861 (0.85), 1.909 (2.18), 1.989 (16.00), 2.084 (2.29), 2.096 (4.23), 2.107 (4.15), 2.120 ( 2.23), 2.520 (2.12), 2.562 (2.37), 2.577 (1.87), 2.589 (1.95), 2.604 (1.50), 2.631 (1.58), 2.642 (2.66), 2.654 (1.73), 2.673 (1.07), 2.684 ( 1.24), 2.697 (0.66), 3.396 (0.92), 4.003 (1.25), 4.021 (3.77), 4.039 (3.73), 4.056 (1.23), 4.485 (2.76), 4.498 (5.49), 4.509 (2.71), 4.654 ( 0.81), 4,936 (1.26), 5.001 (1.44), 5,059 (3.19), 5,099 (10.70), 5,126 (10.72), 5,166 (3.27), 7,875 (2.15), 7,894 (4,91), 7,914 (3.01), 8,100 (8,01) 3.54), 8,120 (3.11), 8,327 (5.27), 8,391 (3.58), 8,411 (3.46), 13,270 (1.29). Intermediate 163 (5RS)-2-{[3-Chloro-5-(trifluoromethyl)pyridin-2-yl]methyl}-3-oxo-2,3,5,6,7,8-hexahydro[1, 2,4]triazolo[4,3-a]pyridine-5-carboxylic acid (racemate)

[0683] Methyl (5RS)-2-{[3-chloro-5-(trifluoromethyl)pyridin-2-yl]methyl}-3-oxo-2,3,5,6,7,8-hexahydro[ 1,2,4]triazolo[4,3-a]pyridine-5-carboxylate (racemate) (293 mg, 750 μmol) was initially loaded into THF (6.0 mL) and lithium hydroxide (89.8 mL) was added. mg, 3.75 mmol) dissolved in water. After stirring at room temperature overnight, the reaction mixture was concentrated under reduced pressure and then mixed with water, 1N aqueous hydrochloric acid and saturated aqueous sodium chloride solution. The aqueous phase was extracted three times with ethyl acetate. The combined organic phases were dried over sodium sulfate and filtered, and the filtrate was concentrated. 243 mg (86% chance) of the title compound was obtained. LC-MS (Method 3): Rt = 1.16 min; MS (ESIpos): m /z = 377 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: 1.175 (0.73), 1.988 (1.31), 2.079 (0.50), 2.091 (0.90 ), 2.101 (0.88), 2.107 (0.79), 2.558 (0.47), 2.610 (0.60), 2.621 (0.40), 4.466 (0.65), 4.479 (1.30), 4.491 (0.64), 5.151 (2.36), 5.155 (2.31 ), 5,753 (16.00), 8,487 (1.31), 8,491 (1.32), 8,903 (1.28), 8,905 (1.29). Intermediate 164 (5RS)-2-[3-Fluoro-4-(trifluoromethoxy)benzyl]-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4 ,3-a]pyridine-5-carboxylic acid (racemate)

[0684] Methyl (5RS)-2-[3-fluoro-4-(trifluoromethoxy)benzyl]-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazole [4,3-a]pyridine-5-carboxylate (racemate) (263 mg, 676 μmol) was initially loaded into THF (5.0 mL) and lithium hydroxide (80.9 mg, 3.38 mmol) was added. dissolved in water. After stirring at room temperature for 72 hours, the reaction mixture was concentrated under reduced pressure at room temperature for and then mixed with water, 1N aqueous hydrochloric acid and saturated aqueous sodium chloride solution. The aqueous phase was extracted three times with ethyl acetate. The combined organic phases were dried over sodium sulfate and filtered, and the filtrate was concentrated. 180 mg (71% chance) of the title compound was obtained. LC-MS (Method 3): Rt = 1.43 min; MS (ESIpos): m /z = 376 [M+H]+ Intermediate 165 (5RS)-2-[3-Chloro-4-(trifluoromethoxy)benzyl]-3-oxo-2,3,5,6,7 ,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylic acid (racemate)

[0685] Methyl (5RS)-2-[3-chloro-4-trifluoromethoxy)benzyl]-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[ 4,3-a]pyridine-5-carboxylate (racemate) (293 mg, 99% purity, 715 μmol) was initially loaded into THF (7.2 mL) and lithium hydroxide (85.6 mg, 3.0 mL) was added. 57 mmol) dissolved in water. After stirring at room temperature for 2 hours, the reaction mixture was concentrated under reduced pressure and then mixed with water, 1N aqueous hydrochloric acid and saturated aqueous sodium chloride solution. The aqueous phase was extracted three times with ethyl acetate. The combined organic phases were dried over sodium sulfate and filtered, and the filtrate was concentrated. 85.0 mg (29% chance) of the title compound was obtained. LC-MS (Method 3): Rt = 1.55 min; MS (ESIpos): m /z = 391 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (0.78), -0.008 (7.90), 0.008 (6.70), 0.146 (0.88) (0.48) (3.14) (2.16) (1.36) (3.62), 7,353 (3.38), 7,531 (5.82), 7,536 (5.94), 7,545 (3.42), 7,549 (3.28), 7,566 (2.76), 7,570 (2.58). Intermediate 166 (5RS)-2-{[2-Methyl-4-(trifluoromethyl)-1,3-thiazol-5-yl]methyl}-3-oxo-2,3,5,6,7,8-hexa -hydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylic acid (racemate)

[0686] Methyl (5RS)-2-{[2-methyl-4-(trifluoromethyl)-1,3-thiazol-5-yl]methyl}-3-oxo-2,3,5,6,7,8 -hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylate (racemate) (380 mg, 1.01 mmol) was initially loaded into THF (10 mL) and hydrogen hydroxide was added. lithium (121 mg, 5.05 mmol) dissolved in water. After stirring at room temperature for 3 hours, the reaction mixture was concentrated under reduced pressure and then mixed with water, 1N aqueous hydrochloric acid and saturated aqueous sodium chloride solution. The aqueous phase was extracted three times with ethyl acetate. The combined organic phases were dried over sodium sulfate and filtered, and the filtrate was concentrated. 156 mg (41% chance) of the title compound was obtained. LC-MS (Method 4): Rt = 0.61 min; MS (ESIpos): m /z = 363 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.008 (1.08), 0.008 (0.89), 1.157 (2.79), 1.175 ( 5.61), 1.193 (2.81), 1.356 (0.90), 1.797 (0.50), 1.810 (0.50), 1.820 (0.40), 1.832 (0.41), 1.908 (0.41), 1.988 (10.16), 2.050 (0.44), 2.064 ( 0.79), 2.075 (1.54), 2.086 (1.45), 2.097 (0.74), 2.343 (0.59), 2.519 (1.18), 2.563 (0.72), 2.576 (0.73), 2.590 (0.59), 2.627 (0.71), 2.643 ( 16.00), 2.670 (0.82), 2.679 (0.57), 4.003 (0.80), 4.021 (2.41), 4.038 (2.39), 4.056 (0.77), 4.431 (0.85), 4.441 (1.46), 4.455 (0.85), 5.162 ( 3.10). Intermediate 167 (5RS)-2-[(3-Methyl-1,2-oxazol-5-yl)methyl]-3-oxo-2,3,5,6,7,8-hexahydro[1,2 ,4]triazolo[4,3-a]pyridine-5-carboxylic acid (racemate)

[0687] Methyl (5RS)-2-[(3-methyl-1,2-oxazol-5-yl)methyl]-3-oxo-2,3,5,6,7,8-hexahydro[1 ,2,4]triazolo[4,3-a]pyridine-5-carboxylate (racemate) (259 mg, 86% purity, 762 μmol) was initially loaded into THF (7.7 mL) and lithium hydroxide was added. (91.2 mg, 3.81 mmol) dissolved in water. After stirring at room temperature overnight, the reaction mixture was concentrated under reduced pressure and then mixed with water, 1N aqueous hydrochloric acid and saturated aqueous sodium chloride solution. The aqueous phase was extracted three times with ethyl acetate. The combined organic phases were dried over sodium sulfate and filtered, and the filtrate was concentrated. 101 mg (90% purity, 43% possibility) of the title compound was obtained. LC-MS (Method 3): Rt = 0.64 min; MS (ESIpos): m /z = 279 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.008 (1.37), 0.008 (1.35), 1.157 (0.64), 1.175 ( 1.32), 1.192 (0.66), 1.812 (0.53), 1.823 (0.54), 1.834 (0.46), 1.845 (0.44), 1.908 (0.48), 1.988 (2.37), 2.071 (0.84), 2.084 (1.48), 2.093 ( 1.42), 2.100 (1.31), 2.113 (0.67), 2.201 (16.00), 2.226 (0.83), 2.524 (0.85), 2.567 (0.76), 2.580 (0.76), 2.594 (0.61), 2.621 (0.61), 2.633 ( 0.96), 2.644 (0.67), 2.664 (0.43), 2.674 (0.56), 4.020 (0.57), 4.038 (0.55), 4.455 (1.00), 4.467 (1.96), 4.479 (1.00), 4.495 (0.61), 4.509 ( 0.60), 4.636 (0.43), 4.973 (4.04), 4.978 (4.07), 6.210 (0.49), 6.234 (3.48). Intermediate 168 (5RS)-2-[2-Fluoro-3-(trifluoromethyl)benzyl]-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4 ,3-a]pyridine-5-carboxylic acid (racemate)

[0688] Methyl (5RS)-2-[2-fluoro-3-(trifluoromethyl)benzyl]-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazole [4,3-a]pyridine-5-carboxylate (racemate) (184 mg, 493 μmol) was initially loaded into THF (3.0 mL) and lithium hydroxide (59.0 mg, 2.46 mmol) was added. dissolved in water. After stirring at room temperature for 72 hours, the reaction mixture was concentrated under reduced pressure and then mixed with water, 1N aqueous hydrochloric acid and saturated aqueous sodium chloride solution. The aqueous phase was extracted three times with ethyl acetate. The combined organic phases were dried over sodium sulfate and filtered, and the filtrate was concentrated. 166 mg (94% chance) of the title compound was obtained. LC-MS (Method 3): Rt = 1.35 min; MS (ESIpos): m /z = 360 [M+H]+ Intermediate 169 (5RS)-2-[3-Fluoro-5-(trifluoromethyl)benzyl]-3-oxo-2,3,5,6,7 ,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylic acid (racemate)

[0689] Methyl (5RS)-2-[3-fluoro-5-(trifluoromethyl)benzyl]-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazole [4,3-a]pyridine-5-carboxylate (racemate) (154 mg, 413 μmol) was initially loaded into THF (3.0 mL) and lithium hydroxide (49.4 mg, 2.06 mmol) was added. dissolved in water. After stirring at room temperature overnight, the reaction mixture was concentrated under reduced pressure and then mixed with water, 1N aqueous hydrochloric acid and saturated aqueous sodium chloride solution. The aqueous phase was extracted three times with ethyl acetate. The combined organic phases were dried over sodium sulfate and filtered, and the filtrate was concentrated. 124 mg (84% chance) of the title compound was obtained. LC-MS (Method 3): Rt = 1.39 min; MS (ESIpos): m /z = 360 [M+H]+ Intermediate 170 (5RS)-3-Oxo-2-[(3,5,6-trimethylpyrazin-2-yl)methyl]-2,3,5 ,6,7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylic acid (racemate)

[0690] Methyl (5RS)-3-oxo-2-[(3,5,6-trimethylpyrazin-2-yl)methyl]- 2,3,5,6,7,8-hexahydro[1,2 ,4]triazolo[4,3-a]pyridine-5-carboxylate (racemate) (179 mg, 540 μmol) was initially loaded into THF (5.0 mL) and lithium hydroxide (64.7 mg, 2 .70 mmol) dissolved in water. After stirring at room temperature overnight, the reaction mixture was concentrated under reduced pressure and then mixed with water, 1N aqueous hydrochloric acid and saturated aqueous sodium chloride solution. The aqueous phase was extracted three times with ethyl acetate. The combined organic phases were dried over sodium sulfate and filtered, and the filtrate was concentrated. 80.0 mg (47% chance) of the title compound was obtained. LC-MS (Method 1): Rt = 0.65 min; MS (ESIpos): m /z = 318 [M+H]+ Intermediate 171 (5RS)-2-[(1-Methyl-1H-1,2,4-triazol-3-yl)methyl]-3-oxo -2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylic acid (racemate)

[0691] Methyl (5RS)-2-[(1-methyl-1H-1,2,4-triazol-3-yl)methyl]-3-oxo- 2,3,5,6,7,8-hexa -hydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylate (racemate) (176 mg, 74% purity, 446 μmol) was initially loaded into THF (4.5 mL) and was added lithium hydroxide (53.4 mg, 2.23 mmol) dissolved in water. After stirring at room temperature overnight, the reaction mixture was concentrated under reduced pressure and then mixed with water, 1N aqueous hydrochloric acid and saturated aqueous sodium chloride solution. The aqueous phase was extracted three times with ethyl acetate. The aqueous phase was concentrated and 268 mg (76% purity, > 100%) of the title compound were obtained. LC-MS (Method 9): Rt = 3.37 min; MS (ESIpos): m /z = 279 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (0.54), -0.008 (3.90), 0.146 (0.46), 1.592 (0.57), 1705 (0.76), 1857 (0.54), 2119 (0.81), 2166 (3.04), 2329 (0.89), 2368 (0.50), 2452 (1.14), 2670 (0.80), 2712 (0.42), 3041 (1.56) (1.03), 4,815 (2.91), 4,854 (1.76), 8,345 (0.57), 8,360 (3.83), 8,675 (0.64), 11,177 (0.50). Intermediate 172 (5RS)-3-Oxo-2-{[2-(trifluoromethyl)pyridin-4-yl]methyl}-2,3,5,6,7,8-hexahydro[1,2,4] triazolo[4,3-a]pyridine-5-carboxylic acid (enantiomer 1)

[0692] Methyl (5RS)-3-oxo-2-{[2-(trifluoromethyl)pyridin-4-yl]methyl}-2,3,5,6,7,8-hexahydro[1,2, 4]triazolo[4,3-a]pyridine-5-carboxylate (enantiomer 1) (279 mg, 783 μmol) was initially loaded into THF (5.0 mL) and lithium hydroxide (93.8 mg) was added. , 3.92 mmol) dissolved in water. After stirring at room temperature overnight, the reaction mixture was concentrated under reduced pressure and then mixed with water, 1N aqueous hydrochloric acid and saturated aqueous sodium chloride solution. The aqueous phase was extracted three times with ethyl acetate. The combined organic phases were dried over sodium sulfate and filtered, and the filtrate was concentrated. 180 mg (67% chance) of the title compound was obtained. LC-MS (Method 3): Rt = 0.95 min; MS (ESIpos): m /z = 343 [M+H]+ The (5S) configuration was assigned based on the elucidation of the crystal structure for Examples 26, 108, 113, 157, 237, 358 and 454. (5S) -3-Oxo-2-{[2-(trifluoromethyl)pyridin-4-yl]methyl}-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3 -a]pyridine-5-carboxylic acid Intermediate 173 (5RS)-2-{[3-Fluoro-2-(trifluoromethyl)pyridin-4-yl]methyl}-3-oxo-2,3,5,6,7 ,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylic acid (enantiomer 1)

[0693] Methyl (5rs)-2-{[3-fluoro-2-(Trifluoromethyl)Pyridin-4-yl]Methyl}-3-Oxo-2,3,5,6,7,8-hexahydro[ 1,2,4]Triazolo[4,3-a]Pyridine-5-carboxylate (Enantiomer 1) (181 Mg, 484 µmol) Was Initially Loaded In Thf (3.0 Ml) And Lithium Hydroxide (57.0 Ml) Was Added 9 Mg, 2.42 Mmol) Dissolved In Water. After stirring at room temperature for 72 hours, the reaction mixture was concentrated under reduced pressure and then mixed with water, 1 N aqueous hydrochloric acid and saturated aqueous sodium chloride solution. The Aqueous Phase Was Extracted Three Times With Ethyl Acetate. The combined organic phases were dried over sodium sulfate and filtered, and the filtrate was concentrated. 150 Mg (86% Possibility) Of The Title Compound Was Obtained. Lc-ms (Method 1): Rt = 0.89 Min; Ms (Epipos): M /Z = 361 [M+h]+

[0694] Configuration (5s) Was Assigned Based On Elucidation Of The Crystal Structure For Examples 26, 108, 113, 157, 237, 358 AND 454. (5s)-2-{[3-fluoro-2-(Trifluoromethyl )Pyridin-4-yl]Methyl}-3-oxo-2,3,5,6,7,8- Hexahydro[1,2,4]Triazolo[4,3-a]Pyridine-5-Carboxylic Acid Intermediate 174 (5rs)-3-oxo-2-{[2-(Trifluoromethyl)Quinolin-4-yl]Methyl}-2,3,5,6,7,8-hexa- Hydro[1,2,4] Triazolo[4,3-a]Pyridine-5-Carboxylic Acid (Enantiomer 1)

[0695] Methyl (5RS)-3-oxo-2-{[2-(trifluoromethyl)quinolin-4-yl]methyl}- 2,3,5,6,7,8-hexahydro[1,2, 4]triazolo[4,3-a]pyridine-5-carboxylate (enantiomer 1) (111 mg, 273 μmol) was initially loaded into THF (3.0 mL) and lithium hydroxide (32.7 mg) was added. , 1.37 mmol) dissolved in water. After stirring at room temperature for 72 hours, the reaction mixture was concentrated under reduced pressure and then mixed with water, 1N aqueous hydrochloric acid and saturated aqueous sodium chloride solution. The aqueous phase was extracted three times with ethyl acetate. The combined organic phases were dried over sodium sulfate and filtered, and the filtrate was concentrated. 94.0 mg (88% chance) of the title compound was obtained. LC-MS (Method 4): Rt = 0.76 min; MS (ESIpos): m /z = 393 [M+H]+

[0696] The (5S) configuration was assigned based on the elucidation of the crystal structure for Examples 26, 108, 113, 157, 237, 358 and 454. (5S)-3-Oxo-2-{[2-(trifluoromethyl )quinolin-4-yl]methyl}-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylic acid Intermediate 175 (5RS )-2-{[5-Chloro-4-(trifluoromethyl)pyridin-2-yl]methyl}-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4] triazolo[4,3-a]pyridine-5-carboxylic acid (enantiomer 1)

[0697] Methyl (5RS)-2-{[5-chloro-5-(trifluoromethyl)pyridin-2-yl]methyl}-3-oxo-2,3,5,6,7,8-hexahydro[ 1,2,4]triazolo[4,3-a]pyridine-5-carboxylate (enantiomer 1) (269 mg, 688 μmol) was initially loaded into THF (3.0 mL) and lithium hydroxide (82, 4 mg, 3.44 mmol) dissolved in water. After stirring at room temperature for 72 hours, the reaction mixture was concentrated under reduced pressure and then mixed with water, 1N aqueous hydrochloric acid and saturated aqueous sodium chloride solution. The aqueous phase was extracted three times with ethyl acetate. The combined organic phases were dried over sodium sulfate and filtered, and the filtrate was concentrated. 100 mg (39% chance) of the title compound was obtained. LC-MS (Method 3): Rt = 1.29 min; MS (ESIpos): m /z = 377 [M+H]+

[0698] The (5S) configuration was assigned based on the elucidation of the crystal structure for Examples 26, 108, 113, 157, 237, 358 and 454. (5S)-2-{[5-Chloro-2-(trifluoromethyl )pyridin-2-yl]methyl}-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylic acid Intermediate 176 (5RS)-3-Oxo-2-[(3,5,6-trimethylpyrazin-2-yl)methyl]-2,3,5,6,7,8-hexahydro[1,2,4 ]triazolo[4,3-a]pyridine-5-carboxylic acid (enantiomer 1)

[0699] Methyl (5RS)-3-oxo-2-[(3,5,6-trimethylpyrazin-2-yl)methyl]- 2,3,5,6,7,8-hexahydro[1,2 ,4]triazolo[4,3-a]pyridine-5-carboxylate (enantiomer 1) (261 mg, 788 μmol) was initially loaded into THF (5.0 mL) and lithium hydroxide (94.3 mg, 3.94 mmol) dissolved in water. After stirring at room temperature for 72 hours, the reaction mixture was concentrated under reduced pressure and then mixed with water, 1N aqueous hydrochloric acid and saturated aqueous sodium chloride solution. The aqueous phase was extracted three times with ethyl acetate. The combined organic phases were dried over sodium sulfate and filtered, and the filtrate was concentrated. 124 mg (50% chance) of the title compound was obtained. LC-MS (Method 3): Rt = 0.77 min; MS (ESIpos): m /z = 318 [M+H]+ Intermediate 177 (5RS)-2-{[3-Chloro-5-(trifluoromethyl)pyridin-2-yl]methyl}-3-oxo-2, 3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylic acid (enantiomer 1)

[0700] Methyl (5RS)-2-{[3-chloro-5-(trifluoromethyl)pyridin-2-yl]methyl}-3-oxo-2,3,5,6,7,8-hexahydro[ 1,2,4]triazolo[4,3-a]pyridine-5-carboxylate (enantiomer 1) (216 mg, 553 μmol) was initially loaded into THF (4.0 mL) and lithium hydroxide (66, 2 mg, 2.76 mmol) dissolved in water. After stirring at room temperature for 72 hours, the reaction mixture was concentrated under reduced pressure and then mixed with water, 1N aqueous hydrochloric acid and saturated aqueous sodium chloride solution. The aqueous phase was extracted three times with ethyl acetate. The combined organic phases were dried over sodium sulfate and filtered, and the filtrate was concentrated. 181 mg (87% chance) of the title compound was obtained. LC-MS (Method 3): Rt = 1.21 min; MS (ESIpos): m /z = 377 [M+H]+ Intermediate 178 (5RS)-3-Oxo-2-{[4-(trifluoromethyl)pyridin-2-yl]methyl}-2,3,5, 6,7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylic acid (enantiomer 1)

[0701] Methyl (5RS)-3-oxo-2-{[4-(trifluoromethyl)pyridin-2-yl]methyl}-2,3,5,6,7,8-hexahydro[1,2, 4]triazolo[4,3-a]pyridine-5-carboxylate (enantiomer 1) (275 mg, 770 μmol) was initially loaded into THF (10 mL) and lithium hydroxide (92.2 mg, 3.85 mmol) dissolved in water. After stirring at room temperature for 5 hours, the reaction mixture was concentrated under reduced pressure and then mixed with water, 1N aqueous hydrochloric acid and saturated aqueous sodium chloride solution. The aqueous phase was extracted three times with ethyl acetate. The combined organic phases were dried over sodium sulfate and filtered, and the filtrate was concentrated. 247 mg (94% chance) of the title compound was obtained. LC-MS (Method 4): Rt = 0.59 min; MS (ESIpos): m /z = 343 [M+H]+

[0702] The (5S) configuration was assigned based on the elucidation of the crystal structure for Examples 26, 108, 113, 157, 237, 358 and 454. (5S)-3-Oxo-2-{[4-(trifluoromethyl )pyridin-2-yl]methyl}-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylic acid Intermediate 179 (5RS )-3-Oxo-2-{[2-(trifluoromethyl)pyrimidin-4-yl]methyl}-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4, 3-a]pyridine-5-carboxylic acid (enantiomer 1)

[0703] Methyl (5RS)-3-oxo-2-{[2-(trifluoromethyl)pyrimidin-4-yl]methyl}-2,3,5,6,7,8-hexahydro[1,2, 4]triazolo[4,3-a]pyridine-5-carboxylate (enantiomer 1) (49.5 mg, 139 μmol) was initially loaded into THF (2.0 mL) and lithium hydroxide (16.6 mg) was added , 693 μmol) dissolved in water. After stirring at room temperature for 5 hours, the reaction mixture was concentrated under reduced pressure and then mixed with water, 1N aqueous hydrochloric acid and saturated aqueous sodium chloride solution. The aqueous phase was extracted three times with ethyl acetate. The combined organic phases were dried over sodium sulfate and filtered, and the filtrate was concentrated. 45.0 mg (95% chance) of the title compound was obtained. LC-MS (Method 4): Rt = 0.55 min; MS (ESIpos): m /z = 344 [M+H]+

[0704] The (5S) configuration was assigned based on the elucidation of the crystal structure for Examples 26, 108, 113, 157, 237, 358 and 454. (5S)-3-Oxo-2-{[2-(trifluoromethyl )pyrimidin-4-yl]methyl}-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylic acid Intermediate 180 (5RS )-3-Oxo-2-(2,4,5-trimethylbenzyl)-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine- 5-carboxylic acid (enantiomer 1)

[0705] Methyl (5RS)-3-oxo-2-(2,4,5-trimethylbenzyl)-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4, 3-a]pyridine-5-carboxylate (enantiomer 1) (198 mg, 601 μmol) was initially loaded into THF (2.0 mL) and lithium hydroxide (72.0 mg, 3.01 mmol) dissolved in water. After stirring at room temperature for 72 hours, the reaction mixture was concentrated under reduced pressure and then mixed with water, 1N aqueous hydrochloric acid and saturated aqueous sodium chloride solution. The aqueous phase was extracted three times with ethyl acetate. The combined organic phases were dried over sodium sulfate and filtered, and the filtrate was concentrated. 189 mg (99% chance) of the title compound was obtained. LC-MS (Method 1): Rt = 1.05 min; MS (ESIpos): m /z = 316 [M+H]+

[0706] The (5S) configuration was assigned based on the elucidation of the crystal structure for Examples 26, 108, 113, 157, 237, 358 and 454. (5S)-3-Oxo-2-(2,4,5 -trimethylbenzyl)-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylic acid Intermediate 181 (5RS)-2-(4 -Methylbenzyl)-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3- a]pyridine-5-carboxylic acid (enantiomer 1)

[0707] Methyl (5RS)-2-(4-methylbenzyl)-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a] Pyridine-5-carboxylate (enantiomer 1) (1.05 g, 3.48 mmol) was initially loaded into THF (29 mL) and lithium hydroxide (417 mg, 17.4 mmol) dissolved in water was added. After stirring overnight, the reaction mixture was mixed at room temperature with water, 1 N aqueous hydrochloric acid, and saturated aqueous sodium chloride solution. The organic phase was removed and the aqueous phase was extracted three times with ethyl acetate. The combined organic phases were dried over sodium sulfate and filtered, and the filtrate was concentrated. 733 mg (73% chance) of the title compound was obtained. Alternative synthesis:

[0708] tert-Butyl (5RS)-2-(4-methylbenzyl)-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3- a]pyridine-5-carboxylate (enantiomer 1) (2.65 g, 7.72 mmol) was dissolved in dichloromethane (45 mL), and trifluoroacetic acid (45 mL, 580 mmol) was added at room temperature. After the reaction mixture was stirred at room temperature overnight, the solvent was removed under reduced pressure. The residue was taken up in dichloromethane and mixed with water. The organic phase was removed and the aqueous phase was extracted twice with dichloromethane. The combined organic phases were dried over magnesium sulfate and filtered, and the filtrate was concentrated. 2.16 g (97% chance) of the title compound was obtained. LC-MS (Method 1): Rt = 0.91 min; MS (ESIpos): m /z = 288 [M+H]+ 1H-NMR (500 MHz, DMSO-d6) δ [ppm]: 1.356 (0.56), 2.065 (0.43), 2.072 (0.54), 2.076 (0.79 ), 2.082 (0.79), 2.089 (0.76), 2.100 (0.41), 2.271 (8.20), 2.526 (0.56), 2.612 (0.50), 3.321 (0.68), 4.449 (0.65), 4.458 (1.21), 4.468 (0.62 ), 4,770 (2.95), 7,128 (16.00).

[0709] The (5S) configuration was assigned based on the elucidation of the crystal structure for Examples 26, 108, 113, 157, 237, 358 and 454. (5S)-2-(4-Methylbenzyl)-3-oxo- 2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylic acid Intermediate 182 (5RS)-5-Methyl-2-(4 -methylbenzyl)-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylic acid (racemate)

[0710] Methyl (5RS)-5-methyl-2-(4-methylbenzyl)-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4, 3-a]pyridine-5-carboxylate (racemate) (32.0 mg, 101 μmol) was initially loaded into THF (1.0 mL) and lithium hydroxide (12.1 mg, 507 μmol) dissolved in water was added . After stirring at room temperature for 72 hours, the reaction mixture was concentrated under reduced pressure at room temperature for and then mixed with water, 1N aqueous hydrochloric acid and saturated aqueous sodium chloride solution. The aqueous phase was extracted three times with ethyl acetate. The combined organic phases were dried over sodium sulfate and filtered, and the filtrate was concentrated. 30.0 mg (98% chance) of the title compound was obtained. LC-MS (Method 1): Rt = 0.98 min; MS (ESIpos): m /z = 302 [M+H]+ Intermediate 183 (5RS,7RS)-7-Methyl-2-(4-methylbenzyl)-3-oxo-2,3,5,6,7, 8-hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylic acid (mixture of diastereomer; 4 isomers)

[0711] tert-Butyl (5RS,7RS)-7-methyl-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a] Pyridine-5-carboxylate (diastereomer mixture; 4 isomers) (150 mg, 592 μmol) was initially loaded into acetonitrile (6.0 mL). Cesium carbonate (289 mg, 888 μmol) and 1-(bromomethyl)-4-methylbenzene (115 mg, 622 μmol) were subsequently added. After stirring overnight, the reaction mixture was mixed with water and ethyl acetate at room temperature. The organic phase was removed and the aqueous phase was extracted three times with ethyl acetate. The combined organic phases were washed with saturated aqueous sodium chloride solution, dried over magnesium sulfate and filtered, and the filtrate was concentrated. The residue was dissolved in dichloromethane (5 ml) and trifluoroacetic acid (2.5 ml) was added at room temperature. After the reaction mixture was stirred at room temperature overnight, the solvent was removed under reduced pressure. The residue was purified via preparatory HPLC (Method 10). The fractions containing the product were concentrated under reduced pressure and 120 mg (67% possibility) of the title compound were obtained. LC-MS (Method 4): Rt = 0.73 min; MS (ESIpos): m /z = 302 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.008 (0.53), 0.008 (0.47), 1.004 (3.87), 1.021 ( 4.00), 1.438 (0.57), 1.471 (0.61), 1.785 (0.92), 1.861 (0.40), 2.133 (0.60), 2.162 (0.50), 2.174 (0.69), 2.202 (0.57), 2.244 (0.44), 2.270 ( 10.91), 2.602 (0.51), 2.609 (0.51), 2.642 (0.45), 2.649 (0.43), 4.233 (0.46), 4.249 (0.53), 4.258 (0.53), 4.275 (0.45), 4.746 (5.02), 4.780 ( 0.47), 4.795 (0.45), 7.132 (16.00). Intermediate 184 (5RS,7RS)-7-Methyl-3-oxo-2-{[6-(trifluoromethyl)pyridin-3-yl]methyl}-2,3,5,6,7,8-hexahydro[ 1,2,4]triazolo[4,3-a]pyridine-5-carboxylic acid (mixture of diastereomer; 4 isomers)

[0712] tert-Butyl (5S,7S)-7-methyl-3-oxo-2-{[6-(trifluoromethyl)pyridin-3-yl]methyl}-2,3,5,6,7,8- hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylate (mixture of diastereomer; 4 isomers) (383 mg, 929 μmol) was dissolved in dichloromethane (5.0 mL), and trifluoroacetic acid (5.0 mL, 65 mmol) was added at room temperature. After the reaction mixture was stirred at room temperature for 2.5 h, the solvent was removed under reduced pressure. The residue was dissolved in dichloromethane and washed with water. The aqueous phase was extracted with dichloromethane, saturated with sodium chloride and extracted again with dichloromethane. The combined organic phases were dried over magnesium sulfate and filtered, and the filtrate was concentrated. 325 mg (92% chance) of the title compound was obtained. LC-MS (Method 3): Rt = 1.18 min; MS (ESIpos): m /z = 357 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.008 (4.92), 0.008 (2.52), 1.015 (15.45), 1.032 ( 15.37), 1.237 (0.63), 1.324 (0.45), 1.407 (3.53), 1.444 (1.27), 1.471 (2.46), 1.499 (1.90), 1.504 (2.44), 1.532 (1.40), 1.920 (1.12), 1.927 ( 1.22), 1.936 (1.30), 1.946 (1.16), 1.954 (1.10), 2.181 (2.72), 2.209 (2.30), 2.221 (3.18), 2.250 (3.93), 2.265 (1.63), 2.282 (1.40), 2.298 ( 1.26), 2.328 (0.46), 2.519 (2.23), 2.524 (2.06), 2.637 (2.03), 2.643 (2.06), 2.673 (1.93), 2.683 (1.64), 3.566 (1.59), 3.686 (0.42), 4.306 ( 2.98), 4.322 (3.48), 4.332 (3.20), 4.348 (2.66), 4.835 (1.62), 5.016 (16.00), 5.040 (0.46), 5.754 (1.60), 7.899 (2.66), 7.918 (9.08), 7.919 ( 8.98), 7.931 (5.18), 7.936 (4.87), 7.952 (1.45), 7.956 (1.45), 8.670 (5.04). Intermediate 185 (5RS,6RS)-6-Methyl-2-(4-methylbenzyl)-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4, 3-a]pyridine-5-carboxylic acid (mixture of diastereomer; 4 isomers)

[0713] Ethyl (5RS,6RS)-6-methyl-2-(4-methylbenzyl)-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[ 4,3-a]pyridine-5-carboxylate (diastereomer mixture; 4 isomers) (108 mg, 328 μmol) was initially loaded into THF (1.5 mL) and hydroxide (19.6 mg, 820 μmol) was added of lithium (750 μl) dissolved in water. After stirring overnight, the reaction mixture was mixed at room temperature with saturated aqueous ammonium chloride solution and 1 N aqueous hydrochloric acid. The organic phase was removed and the aqueous phase was extracted three times with dichloromethane. The combined organic phases were dried over magnesium sulfate and filtered, and the filtrate was concentrated. 95.3 mg (67% purity, 65% possibility) of the title compound was obtained. LC-MS (Method 8): Rt = 1.88 min; MS (ESIpos): m /z = 302 [M+H]+ Intermediate 186 (5RS,7RS)-2-(4-Methylbenzyl)-3-oxo-7-(trifluoromethyl)-2,3,5,6, 7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylic acid (mixture of diastereomer; 4 isomers)

[0714] Ethyl (5RS, 7RS)2-(4-methylbenzyl)-3-oxo-7-(trifluoromethyl)- 2,3,5,6,7,8-hexahydro[1,2,4]triazole [4,3-a]pyridine-5-carboxylate (diastereomer; 4 isomers) (102 mg, 265 μmol) was initially loaded into THF (1.0 mL) and lithium hydroxide (15.9 mg, 663 μmol) was added ) dissolved in water (500 μl). After stirring overnight, the reaction mixture was mixed at room temperature with saturated aqueous ammonium chloride solution and 1/5 dichloromethane/i-propanol. The organic phase was removed and the aqueous phase was extracted twice with 1/5 dichloromethane/i-propanol. The aqueous phase was mixed with 1N aqueous hydrochloric acid and extracted three times with 1/5 dichloromethane/i-propanol. The combined organic phases were dried over magnesium sulfate and filtered, and the filtrate was concentrated. 98 mg (82% purity, 83% chance) of the title compound was obtained. LC-MS (Method 1): Rt = 1.06 min; MS (ESIpos): m /z = 356 [M+H]+ Intermediate 187 (5RS)-2-[2-(4-Methylphenyl)ethyl]-3-oxo-2,3,5,6,7,8 -hexa-hydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylic acid (racemate)

[0715] Methyl (5RS)-2-[-2-(4-methylphenyl)ethyl]-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[ 4,3-a]pyridine-5-carboxylate (racemate) (90.0 mg, 285 μmol) was initially loaded into THF (3.0 mL) and lithium hydroxide (34.2 mg, 1.43 mmol) was added ) dissolved in water. After stirring at room temperature overnight, the reaction mixture was concentrated under reduced pressure at room temperature for and then mixed with water, 1N aqueous hydrochloric acid and saturated aqueous sodium chloride solution. The aqueous phase was extracted three times with ethyl acetate. The combined organic phases were dried over sodium sulfate and filtered, and the filtrate was concentrated. 82.0 mg (95% chance) of the title compound was obtained. LC-MS (Method 3): Rt = 1.27 min; MS (ESIpos): m /z = 302 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.150 (0.41), -0.008 (3.22), 0.008 (2.98), 0.146 (0.44), 1908 (1.11), 1988 (0.63), 2071 (0.92), 2256 (9.10), 2327 (0.53), 2523 (1.85), 2580 (0.53), 2643 (0.69), 2674 (0.63), 2862 (1.04) (16.00), 13.178 (0.58). Intermediate 188 (5RS)-3-Oxo-2-{[4-(trifluoromethyl)cyclohexyl]methyl}-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4, 3-a]pyridine-5-carboxylic acid (mixture of diastereomer; 4 isomers)

[0716] To a solution of tert-butyl (5RS)-3-oxo-2-[{4-(trifluoromethyl)cyclohexyl]methyl}-2,3,5,6,7,8-hexahydro[1, 2,4]triazolo[4,3- a]pyridine-5-carboxylate (mixture of diastereomer; 4 isomers) (465 mg, 1.15 mmol) into 20 mL of dichloromethane were added 2.0 mL (26 mmol) of trifluoroacetic acid, and the mixture was stirred at room temperature overnight. For elaboration, the mixture was adjusted to pH 3 with 3 N sodium hydroxide solution while cooling with an ice bath and vigorous stirring, diluted with dichloromethane/water and extracted. The aqueous phase was extracted twice more with dichloromethane. The combined organic phases were washed with saturated sodium chloride solution, dried over sodium sulfate and concentrated and dried under reduced pressure. 327 mg (82% possibility) of the title compound were obtained (as a racemic cis/trans mixture), which was further converted as such. LC-MS (Method 4): Rt = 0.78 min; MS (ESIpos): m /z = 348 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (1.44), -0.008 (12.24), 0.008 (10.19), 0.146 (1.37) (3.32) (4.88) (3.65), 1900 (1.95), 2079 (7.58), 2088 (6.79), 2100 (3.68), 2332 (2.09), 2366 (1.91), 2569 (2.93), 2583 (2.20), 2619 (2.31), 2630 (4.01) (1.12) (5.53), 4,435 (5.16), 4,447 (1.95), 13,170 (3.58). Intermediate 189 (5RS)-2-[(4,4-Difluorocyclohexyl)methyl]-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3 -a]pyridine-5-carboxylic acid (racemate)

[0717] To a solution of tert-butyl (5S)-2-[(4,4-difluorocyclohexyl)methyl]-3-oxo-2,3,5,6,7,8-hexahydro[1,2 ,4]triazolo[4,3-a]pyridine-5-carboxylate (racemate) (41.2 mg, 111 μmol) in 2.0 mL of dichloromethane were added 90 μL (1.2 mmol) of trifluoroacetic acid, and the mixture was stirred at room temperature for 5 hours. Subsequently, an additional 120 μl (1.6 mmol) of trifluoroacetic acid was stirred overnight (HPLC conversion monitoring). For elaboration, the mixture was adjusted to pH 3 with 3 N NaOH while cooling with an ice bath and vigorous stirring, diluted with dichloromethane/water and extracted. The aqueous phase was extracted twice more with dichloromethane. The combined organic phases were washed with saturated sodium chloride solution, dried over sodium sulfate and concentrated and dried under reduced pressure. In this way, 30.5 mg (87% possibility) of the title compound were obtained. LC-MS (Method 3): Rt = 1.08 min; MS (ESIpos): m /z = 316 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (1.97), -0.008 (16.00), 0.008 (14.35), 0.146 (1.78) (3.84) (3.25), 5,754 (1.60), 13,179 (2.88). Intermediate 190 [2-(Trifluoromethyl)-1,8-naphthyridin-3-yl]methanol

[0718] Ethyl 2-(trifluoromethyl)-1,8-naphthyridine-3-carboxylate (1.00 g, 3.70 mmol) was dissolved in THF (25 mL) and lithium aluminum hydride (1.9 mL, 2.4 M, 4.4 mmol) was added at -20°C. After stirring at -20°C for 2 hours, the reaction mixture was mixed with saturated aqueous ammonium chloride solution, and THF was removed under reduced pressure. The residue was mixed with ethyl acetate and water. The aqueous phase was extracted three times with ethyl acetate. The combined organic phases were dried over sodium sulfate and filtered, and the filtrate was concentrated. The residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/gradient water). The fractions containing the product were concentrated under reduced pressure and 230 mg (26% possibility) of the title compound were obtained. LC-MS (Method 3): Rt = 0.90 min; MS (ESIpos): m /z = 229 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (0.86), -0.008 (7.77), 0.008 (6.74), 0.146 (0.86) (7.51) (8.17), 8,868 (16.00), 9,204 (7.51), 9,209 (7.68), 9,214 (7.80), 9,219 (7.23). Intermediate 191 3-(Chloromethyl)-2-(trifluoromethyl)-1,8-naphthyridine

[0719] [2-(Trifluoromethyl)-1,8-naphthyridin-3-yl]methanol (46.0 mg, 202 μmol) was dissolved in dichloromethane (910 μl) and thionyl dichloride (29 μl, 400 μmol) was added at 0°C. The reaction mixture was stirred at room temperature for 2 hours and then the solvent was removed under reduced pressure. 46.0 mg (93% chance) of the title compound was obtained. 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.008 (1.81), 0.008 (1.26), 2.330 (0.40), 2.521 (1.58), 2.526 (1.33), 2.672 (0.57), 2.712 (0.43 ), 5.126 (16.00), 5.177 (0.78), 5.756 (1.49), 7.026 (0.49), 7.041 (0.66), 7.059 (0.57), 7.853 (3.44), 7.863 (3.55), 7.873 (3.64), 7.883 (3.67 ), 8.038 (0.42), 8.676 (3.22), 8.681 (3.30), 8.697 (3.06), 8.701 (3.04), 8.995 (9.01), 9.278 (3.59), 9.283 (3.64), 9.288 (3.68), 9.293 (3.40 ). Intermediate 192 1-[1-(Bromomethyl)cyclopropyl]-4-(trifluoromethyl)benzene

[0720] {1-[4-(Trifluoromethyl)phenyl]cyclopropyl}methanol (350 mg, 1.62 mmol) was dissolved in dichloromethane (10 mL) and N,N-diisopropylethylamine (560 μl, 3.2 mmol) and dibromo(triphenyl)phosphorane (854 mg, 96% purity, 1.94 mmol) was added at 0°C. The reaction mixture was stirred at room temperature overnight and dibromo(triphenyl)phosphorane (854 mg, 96% purity, 1.94 mmol) was added again. After stirring at room temperature overnight, the solvent was removed under reduced pressure, and the residue was purified via column chromatography (silica gel, dichloromethane/ethyl acetate). The fractions containing the product were concentrated under reduced pressure and 110 mg (23% possibility) of the title compound were obtained. 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: 1.129 (1.56), 1.136 (1.65), 1.144 (4.59), 1.148 (5.92), 1.157 (3.27), 1.169 (1.19), 1.191 (1.17) , 1,202 (3.09), 1,212 (5,74), 1,223 (1.45), 1,231 (1.56), 1,360 (1.16), 1,397 (5,40), 3,915 (16.00), 4,783 (0.41), 7,540 (4,22), 7,561 (5,81) , 7,664 (5.75), 7,685 (4.22). Intermediate 193 Methyl 1-(6-chloropyridin-2-yl)cyclopropanecarboxylate

[0721] 1-(6-Chloropyridin-2-yl) cyclopropanecarboxylic acid (1.00 g, 5.06 mmol) was dissolved in methanol (10 mL) and sulfuric acid (54 μl, 1.0 mmol) was added. The reaction mixture was stirred at 60°C overnight. The reaction mixture was concentrated under reduced pressure and the residue was dissolved in ethyl acetate and washed with saturated sodium hydrogen carbonate solution. The organic phase was dried over sodium sulfate and filtered, and the filtrate was concentrated. 947 mg (87% chance) of the title compound was obtained. LC-MS (Method 4): Rt = 0.83 min; MS (ESIpos): m /z = 212 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: 1.394 (4.13), 1.405 (10.89), 1.414 (14.44), 1.422 (6.17 ), 1,461 (0.81), 1,484 (0.89), 1,521 (6.34), 1,530 (14.64), 1,539 (10,67), 1,550 (4,00), 2,732 (1.03), 2,892 (1.17), 3.314 (16.00), 3,798 (0.65 ), 7,384 (6.75), 7,404 (7.47), 7,558 (7.35), 7,577 (8.61), 7,803 (5.32), 7,823 (9.19), 7,842 (4.27). Intermediate 194 [1-(6-Chloropyridin-2-yl)cyclopropyl]methanol

[0722] Methyl 1-(6-chloropyridin-2-yl)cyclopropanecarboxylate (947 mg, 4.47 mmol) was dissolved in THF (15 mL) and lithium aluminum hydride (2.2 mL, 2.4 M, 5.4 mmol) was added at -78°C. The reaction mixture was stirred at room temperature for 2 hours, and then saturated aqueous ammonium chloride solution was added. The solvent was removed under reduced pressure and the residue was mixed with ethyl acetate and water. The aqueous phase was extracted three times with ethyl acetate. The combined organic phases were dried over sodium sulfate and filtered, and the filtrate was concentrated. 603 mg (92% purity, 68% possibility) of the title compound were obtained. LC-MS (Method 4): Rt = 0.68 min; MS (ESIpos): m /z = 184 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: 0.918 (3.81), 0.928 (11.67), 0.933 (14.82), 0.980 (0.54 ) 6 ), 4,800 (8.73), 4,814 (4.16), 7,229 (5.90), 7,248 (6.45), 7,495 (6.83), 7,515 (8.03), 7,695 (0.49), 7,725 (3.88), 7,744 (6.81), 7,764 (3.12 ), 7,853 (0.40), 9,297 (0.99). Intermediate 195 2-[1-(Bromomethyl)cyclopropyl]-6-chloropyridine

[0723] [1-(6-Chloropyridin-2-yl)cyclopropyl]methanol (300 mg, 1.63 mmol) was dissolved in dichloromethane (10 mL) and N,N-diisopropylethylamine (570 μl, 3.3 mmol) and dibromo(triphenyl)phosphorane (862 mg, 96% purity, 1.96 mmol) were added at 0°C. The reaction mixture was stirred at room temperature overnight and then concentrated under reduced pressure. The residue was purified by column chromatography (silica gel, dichloromethane/ethyl acetate). The fractions containing the product were concentrated under reduced pressure and 141 mg (34% possibility) of the title compound were obtained. GC-MS (Method 2): Rt = 5.32 min; MS (ESIpos): m /z = 213 [M+H]+ Intermediate 196 Ethyl 6-chloro-3-(trifluoromethyl)pyridine-2-carboxylate

[0724] 6-Chloro-3-(trifluoromethyl)pyridine-2-carboxylic acid (2.50 g, 11.1 mmol) was dissolved in ethanol (29 mL), sulfuric acid (710 μl, 13 mmol) was added and the reaction mixture was stirred under reflux overnight. The reaction mixture was concentrated under reduced pressure and the residue was dissolved in ethyl acetate and washed with saturated sodium hydrogen carbonate solution. The organic phase was dried over sodium sulfate and filtered, and the filtrate was concentrated. 2.24 g (88% possibility, 70% possibility) of the title compound was obtained and directly converted. Intermediate 197 3-Azabicyclo[2.1.1]hexane:trifluoroacetic acid

[0725] tert-Butyl 2-azabicyclo[2.1.1]hexane-2-carboxylate (70.0 mg, 382 μmol) was dissolved in dichloromethane (10 mL) and trifluoroacetic acid (590 μl, 7.6 mmol) was added at room temperature. After the reaction mixture was stirred at room temperature overnight, the solvent was removed under reduced pressure. The title compound was obtained. The compound was converted more directly. Intermediate 198 Ethyl 6-{1-[(benzyloxy)carbonyl]hydrazino}-3-(trifluoromethyl)pyridine-2-carboxylate

[0726] Under argon, ethyl 6-chloro-3-(trifluoromethyl)pyridine-2-carboxylate (2.24 g, 88% purity, 7.77 mmol) and benzyl hydrazinecarboxylate (1.42 g, 8.55 mmol ) were dissolved in toluene (20 mL), and tris(dibenzylideneacetone)dipalladium-chloroform complex (402 mg, 389 μmol), 1,1'-bis(diphenylphosphine)ferrocene (441 mg, 777 μmol), and cesium carbonate (3 .04 g, 9.33 mmol) were added. The reaction mixture was stirred at 80°C for 3 hours, and then water and ethyl acetate were added. The organic phase was removed and the aqueous phase was extracted with ethyl acetate. The combined organic phases were dried over sodium sulfate and filtered, and the filtrate was concentrated. The residue was purified by column chromatography (silica gel; eluent: isocratic, ethyl acetate/dichloromethane). The fractions containing the product were concentrated under reduced pressure and 1.80 g (60% possibility) of the title compound were obtained. LC-MS (Method 4): Rt = 1.05 min; MS (ESIpos): m /z = 384 [M+H]+ Intermediate 199 Ethyl 6-hydrazino-3-(trifluoromethyl)pyridine-2-carboxylate

[0727] Ethyl 6-{1-[(benzyloxy)carbonyl]hydrazino}-3-(trifluoroethyl)pyridine2-carboxylate (1.80 g, 4.69 mmol) was dissolved in ethanol (10 mL) and converted using an apparatus hydrogenation (H-Cube®, Pd/C 10% palladium, 1 bar, 50°C, flow rate: 1 ml/min). 1.03 g (88% possibility) of the title compound was obtained. LC-MS (Method 1): Rt = 0.94 min; MS (ESIpos): m /z = 250 [M+H]+ Intermediate 200 Ethyl 3-oxo-6-(trifluoromethyl)-2,3-dihydro[1,2,4]triazolo[4,3-a ]pyridine-5-carboxylate

[0728] Ethyl 6-hydrazino-3-(trifluoromethyl)pyridine-2-carboxylate (1.11 g, 4.45 mmol) was mixed in THF (15 mL) and di-1H-imidazol-1-ylmethanone (866 mg , 5.34 mmol) was added. The reaction mixture was stirred at room temperature overnight. The reaction mixture was mixed with water and dichloromethane, and mixed with saturated aqueous sodium chloride solution. The organic phase was washed with saturated aqueous sodium chloride solution. The aqueous phase was extracted with dichloromethane. The combined organic phases were dried over sodium sulfate and filtered, and the filtrate was concentrated. 1.22 g (100% chance) of the title compound was obtained. LC-MS (Method 4): Rt = 0.74 min; MS (ESIpos): m /z = 276 [M+H]+ Intermediate 201 Ethyl (5RS,6RS)-3-oxo-6-(trifluoromethyl)-2,3,5,6,7,8-hexahydro [1,2,4]triazolo[4,3-a]pyridine-5-carboxylate (mixture of diastereomer; 4 isomers)

[0729] Ethyl 3-oxo-6-(trifluoromethyl)-2,3-dihydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylate (1.22 g, 4.45 mmol) was dissolved in ethanol (10 mL) and converted using a hydrogenation apparatus (H-Cube®, Pd/C 10% palladium, 1 bar, 80°C, flow rate: 1 ml/min). 1.24 g (100% chance) of the title compound was obtained. LC-MS (Method 1): Rt = 0.88 min; MS (ESIpos): m /z = 280 [M+H]+ Intermediate 202 Methyl 6-{1-[(benzyloxy)carbonyl]hydrazino}-5-(trifluoromethyl)pyridine-2-carboxylate

[0730] Methyl 6-chloro-5-(trifluoromethyl)pyridine-2-carboxylate (3.00 g, 12.5 mmol), benzyl hydrazinecarboxylate (2.29 g, 13.8 mmol) and tris(dibenzylideneacetone)dipalladium ( 573 mg, 626 μmol) were suspended in toluene (60 mL) under argon. 1,1'-Bis(diphenylphosphine)ferrocene (694 mg, 1.25 mmol) and cesium carbonate (4.90 g, 15.0 mmol) were added, and the reaction mixture was stirred at 80°C for 3 H. The reaction mixture was mixed with water and ethyl acetate, and the organic phase was removed, washed with water and saturated aqueous sodium chloride solution, dried over sodium sulfate, filtered and concentrated. The residue was purified via column chromatography (silica gel; eluent: cyclohexane/ethyl acetate 9:1, 0:1). The product-containing fractions were concentrated under reduced pressure and 1.87 g (86% purity, 35% possibility) of the title compound were obtained. LC-MS (Method 1): Rt = 1.23 min; MS (ESIneg): m /z = 368 [MH]- 1H-NMR (500 MHz, DMSO-d6) δ [ppm]: -0.007 (1.19), 0.006 (0.87), 1.160 (2.79), 1.174 (5.66) , 1,189 (2.80), 1,398 (1.98), 1,988 (10.25), 2,518 (0.42), 3,038 (0.55), 3,051 (0.56), 3,852 (16.00), 4,008 (0.77), 4,022 (2.29), 4,037 (2.24 ) , 4.051 (0.73), 4.484 (1.47), 4.496 (1.51), 4.998 (0.87), 5.036 (1.06), 5.085 (0.93), 5.125 (7.85), 5.134 (1.18), 5.146 (1.34), 5.157 (0.63) , 7.107 (0.52), 7.195 (0.84), 7.221 (0.64), 7.232 (0.48), 7.238 (0.48), 7.271 (0.56), 7.287 (0.79), 7.309 (5.08), 7.316 (2.18), 7.319 (2.37) , 7,326 (1.95), 7,340 (1.80), 7,364 (2.08), 7,380 (3.95), 7,394 (6.93), 7,409 (1.97), 7,416 (1.42), 7,422 (1.02), 7,482 (1.90), 7,498 (2.13) , 7,532 (0.42), 8,085 (2.06), 8,101 (1.89), 8,765 (2.66), 8,849 (0.45), 9,009 (0.47), 9,367 (2.77). Intermediate 203 Methyl 6-hydrazino-5-(trifluoromethyl)pyridine-2-carboxylate

[0731] Methyl 6-{1-[(benzyloxy)carbonyl]hydrazino}-5-(trifluoromethyl)pyridine-2-carboxylate (1.87 g, 86% purity, 4.35 mmol) and palladium on charcoal (100 mg, 10% palladium) were suspended in methanol (100 mL) under argon, and the mixture was stirred at room temperature in a hydrogen atmosphere (1 bar) overnight. The reaction mixture was filtered through Celite and washed with methanol. The filtrate was concentrated under reduced pressure and 1.09 g (75% purity, 80% chance) of the title compound were obtained. LC-MS (Method 3): Rt = 0.86 min; MS (ESIpos): m /z = 236 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: 3.849 (0.45), 3.875 (16.00), 4.491 (0. 97), 4.590 (0.43), 7.244 (0.61), 7.260 (0.47), 7.277 (0.47), 7.291 (1.32), 7.308 (3.01), 7.326 (2.14 ), 7.956 (2.10), 7.975 (2.01), 8.058 (1.29). Intermediate 204 Methyl 3-oxo-8-(trifluoromethyl)-2,3-dihydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylate

[0732] Methyl 6-hydrazino-5-(trifluoromethyl)pyridine-2-carboxylate (1.09 g, 75% purity, 3.48 mmol) was dissolved in THF (30 mL), and 1,1-carbonyldiimidazole ( 1.01 g, 6.26 mmol) was added at room temperature while stirring. The reaction mixture was stirred at room temperature overnight. The reaction mixture was mixed with water and ethyl acetate, and the organic phase was removed, washed with water and saturated aqueous sodium chloride solution, dried over sodium sulfate, filtered and concentrated. 1.38 g (>100% chance) of the title compound was obtained. LC-MS (Method 3): Rt = 1.07 min; MS (ESIpos): m /z = 262 [M+H]+ Intermediate 205 tert-Butyl 6-chloro-5-methylpyridine-2-carboxylate

[0733] 6-Chloro-5-methylpyridine-2-carboxylic acid (2.10 g, 12.2 mmol) was dissolved in pyridine (8.4 mL) and tert-butanol (42 mL, 440 mmol), and 4 -methylbenzenesulfonyl chloride (4.67 g, 24.5 mmol) was added. The reaction mixture was stirred at room temperature for 3 hours and diluted with saturated aqueous sodium hydrogen carbonate solution. The organic phase was removed and the aqueous phase was extracted with dichloromethane. The combined organic phases were washed with saturated aqueous sodium chloride solution, dried over sodium sulfate and filtered, and the filtrate was concentrated. 2.50 g (> 100%) of the title compound were obtained. 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: 1.552 (16.00), 7.901 (0.52), 7.920 (1.04), 7.959 (0.77), 7.978 (0.43). Intermediate 206 tert-Butyl 6-{1-[(benzyloxy)carbonyl]hydrazino}-5-methylpyridine-2-carboxylate

[0734] Under argon, tert-butyl 6-chloro-5-methylpyridine-2-carboxylate (2.50 g, 11.0 mmol) and benzyl hydrazinecarboxylate (3.28 g, 19.8 mmol) were dissolved in toluene ( 50 mL), and tris(dibenzylideneacetone)dipalladium-chloroform complex (568 mg, 549 μmol), cesium carbonate (4.29 g, 13.2 mmol) and 1,1'-bis(diphenylphosphine)ferrocene (609 mg, 1.10 mmol) were added. The reaction mixture was stirred at 80°C for 4 hours and water and ethyl acetate were added. The organic phase was removed and the aqueous phase was extracted three times with ethyl acetate. The combined organic phases were washed with saturated aqueous sodium chloride solution, dried over magnesium sulfate and filtered, and the filtrate was concentrated. The residue was purified via column chromatography (SiO2; eluent: isocratic, ethyl acetate/cyclohexane 30/70). The fractions containing the product were concentrated under reduced pressure and 1.81 g (46% possibility) of the title compound were obtained. LC-MS (Method 3): Rt = 1.91 min; MS (ESIpos): m /z = 358 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: 1.514 (16.00), 2.157 (1.85), 5.112 (1.13), 7.292 (0.85 ), 7,310 (1.16), 7,377 (0.57), 7,396 (0.48), 7,408 (0.70), 7,446 (0.50), 8,196 (0.45), 9,097 (0.44). Intermediate 207 tert-Butyl 6-hydrazino-5-methylpyridine-2-carboxylate

[0735] To an initial charge of palladium on charcoal (195 mg, 10% palladium) under argon was added tert-butyl 6-{1-[(benzyloxy)carbonyl]hydrazino}-5-methylpyridine-2-carboxylate (1, 30 g, 3.64 mmol) in methanol (60 mL). The reaction mixture was stirred in a hydrogen atmosphere (1 bar) at room temperature for 5 hours. The suspension was diluted with methanol and filtered through kieselguhr and washed with methanol. The solvent was removed under reduced pressure and 837 mg (99% chance) of the title compound were obtained. LC-MS (Method 4): Rt = 0.50 min; MS (ESIpos): m /z = 224 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: 1.527 (16.00), 1.548 (1.20), 2.080 (4.20), 4.258 (1.00 ), 7,174 (0.76), 7,193 (0.93), 7,343 (0.70), 7,361 (0.59), 7,420 (0.64). Intermediate 208 tert-Butyl 8-methyl-3-oxo-2,3-dihydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylate

[0736] tert-Butyl 6-6-hydrazino-5-methylpyridine-2-carboxylate (1.18 g, 5.27 mmol) was dissolved in THF (100 mL), and 1,1-carbonyldiimidazole (1.03 g , 6.32 mmol) was added at room temperature while stirring. The reaction mixture was heated under reflux for 1.5 hours. The reaction mixture was mixed with water and ethyl acetate, and basified with saturated aqueous sodium hydrogen carbonate solution. The organic phase was removed and the aqueous phase was extracted three times with ethyl acetate. The combined organic phases were washed with saturated aqueous sodium chloride solution, dried over magnesium sulfate and filtered. The filtrate was concentrated and the residue was purified via column chromatography (SiO2; eluent: cyclohexane/ethyl acetate 70:30 to 50:50). The fractions containing the product were concentrated under reduced pressure and 800 mg (61% possibility) of the title compound were obtained. LC-MS (Method 4): Rt = 0.71 min; MS (ESIneg): m /z = 248 [MH]- 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: 1.529 (16.00), 2.245 (3.28), 6.683 (0.78), 6.700 (0.88), 6,940 (0.50), 6,943 (0.51), 6,957 (0.46), 6,960 (0.46), 12,505 (0.46). Intermediate 209 tert-Butyl (5RS,8RS)-8-methyl-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine -5-carboxylate (mixture of diastereomer; 4 isomers)

[0737] tert-Butyl 8-methyl-3-oxo-2,3-dihydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylate (200 mg, 802 μmol) and palladium in charcoal (40 mg, 10% palladium) were suspended in methanol (12 mL), and the mixture was stirred at room temperature in a hydrogen atmosphere (3 bar) for 24 h. The reaction mixture was filtered through kieselguhr and washed with 9/1 dichloromethane/methanol. The filtrate was concentrated and the residue was stirred with ethyl acetate for 30 minutes, then filtered and concentrated. The residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/gradient water). The product-containing fractions were concentrated under reduced pressure and 150 mg (74% possibility) of the title compound was obtained as a mixture of diastereomers. LC-MS (Method 4): Rt = 0.67 min; MS (ESIpos): m /z = 254 [M]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: 1.184 (2.53), 1.201 (2.50), 1.396 (16.00), 1.409 (0.40), 2,096 (0.48), 2,103 (0.44), 2,108 (0.52), 4,363 (0.46), 11,396 (0.58). Intermediate 210 Methyl (5S)-2-{[3-fluoro-2-(trifluoromethyl)pyridin-4-yl]methyl}-3-oxo-2,5,6,7-tetrahydro-3H-pyrrolo[2 ,1-c][1,2,4]triazol-5-carboxylate

[0738] Methyl (5S)-3-oxo-2,5,6,7-tetrahydro-3H-pyrrolo[2,1- c][1,2,4]triazol-5-carboxylate (150 mg, 819 μmol) was initially loaded into acetonitrile (8.2 mL). Cesium carbonate (400 mg, 1.23 mmol) and 4-(chloromethyl)-3-fluoro-2-(trifluoromethyl)pyridine hydrochloride (231 mg, 860 μmol) were subsequently added. After stirring at room temperature overnight, water and ethyl acetate were added to the reaction mixture. The organic phase was removed, washed with saturated aqueous sodium chloride solution, dried over sodium sulfate and filtered, and the filtrate was concentrated. 318 mg (75% purity, 81% chance) of the title compound was obtained. LC-MS (Method 3): Rt = 1.39 min; MS (ESIpos): m /z = 361 [M+H]+ Intermediate 211 tert-Butyl (5S)-2-(cyclopropylmethyl)-3-oxo-2,3,5,6,7,8-hexahydro [1,2,4]triazolo[4,3-a]pyridine-5-carboxylate

[0739] tert-Butyl(5S)-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylate ( 150 mg, 627 μmol) was initially loaded into acetonitrile (9.0 mL). Cesium carbonate (633 mg, 1.94 mmol) and (bromomethyl) cyclopropane (130 μl, 1.4 mmol) were subsequently added. After stirring at room temperature over the weekend, the reaction mixture was concentrated under reduced pressure. Water and ethyl acetate were added to the residue. The organic phase was removed and the aqueous phase was extracted three times with ethyl acetate. The combined organic phases were dried over sodium sulfate and filtered, and the filtrate was concentrated. 175 mg (95% chance) of the title compound was obtained. LC-MS (Method 4): Rt = 0.81 min; MS (ESIpos): m /z = 294 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: 0.261 (0.23), 0.273 (0.89), 0.286 (0.95), 0.298 (0.30 ), 0.323 (0.07), 0.427 (0.26), 0.437 (0.75), 0.441 (0.75), 0.457 (0.80), 0.461 (0.73), 0.472 (0.20), 0.527 (0.08), 0.545 (0.08), 1.055 (0.19 ), 1.072 (0.29), 1.091 (0.18), 1.241 (0.08), 1.402 (16.00), 1.416 (1.49), 1.491 (0.17), 1.526 (0.18), 1.558 (0.11), 1.807 (0.21), 1.830 (0.18 ), 1.841 (0.19), 1.988 (0.08), 2.048 (0.56), 2.060 (0.53), 2.070 (0.37), 2.082 (0.20), 2.089 (0.20), 2.097 (0.19), 2.500 (5.48), 2.565 (0.30 ), 2.578 (0.30), 2.592 (0.24), 2.628 (0.24), 2.639 (0.41), 2.651 (0.25), 2.670 (0.16), 2.681 (0.19), 3.485 (1.60), 3.502 (1.57), 4.379 (0.39 ), 4,389 (0.43), 4,394 (0.55), 4,404 (0.39). Intermediate 212 Ethyl (5RS,7RS)-2-[(6-chloropyridin-3-yl)methyl]-3-oxo-7-(trifluoromethyl)- 2,3,5,6,7,8-hexahydro[ 1,2,4]triazolo[4,3-a]pyridine-5-carboxylate (mixture of diastereomer; 4 isomers)

[0740] Ethyl (5RS,7RS)-3-oxo-7-(trifluoromethyl)-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a] Pyridine-5-carboxylate (diastereomer mixture, 4 isomers) (1.07 g, 3.83 mmol) was initially loaded into acetonitrile (40 mL). Cesium carbonate (1.87 g, 5.75 mmol) and 2-chloro-5-(chloromethyl)pyridine (652 mg, 4.02 mmol) were subsequently added. After stirring at room temperature overnight, the reaction mixture was filtered and ethyl acetate was added. The filtrate was washed with saturated aqueous sodium chloride solution, dried over sodium sulfate and filtered, and the filtrate was concentrated. The residue was purified via column chromatography (silica gel, eluent: cyclohexane/ethyl acetate gradient 7/1, 0/1). The product-containing fractions were concentrated under reduced pressure and 604 mg (89% purity, 34% possibility) of the title compound were obtained. LC-MS (Method 3): Rt = 1.67 min; MS (ESIpos): m /z = 405 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.008 (1.54), 0.008 (1.04), 1.164 (7.65), 1.182 ( 16.00), 1.194 (4.45), 1.199 (8.79), 1.212 (7.15), 1.229 (3.56), 1.305 (0.41), 1.398 (0.87), 1.797 (0.72), 1.828 (0.72), 1.988 (0.50), 2.256 ( 0.50), 2.275 (1.17), 2.291 (1.41), 2.304 (1.85), 2.318 (3.16), 2.346 (0.60), 2.523 (2.04), 2.678 (1.08), 2.708 (2.69), 2.743 (2.49), 2.760 ( 1.08), 2.768 (1.27), 2.778 (1.30), 2.808 (1.12) ), 3.059 (0.41), 4.114 (0.58), 4.132 (1.58), 4.141 (1.19), 4.150 (1.82), 4.159 (3.29), 4.168 (1.29), 4.177 (3.81), 4.191 (2.65), 4.196 (2.34 ), 4.208 (3.20), 4.215 (0.99), 4.226 (2.75), 4.235 (1.45), 4.243 (0.95), 4.252 (1.31), 4.270 (0.44), 4.509 (0.78), 4.524 (0.89), 4.537 (0.85 ), 4.551 (0.71), 4.816 (1.74), 4.822 (2.13), 4.829 (1.91), 4.836 (1.64), 4.910 (1.22), 4.922 (5.15), 4.950 (6.09), 4.959 (5.78), 4.999 (0.74 ), 5.754 (2.32), 7.521 (4.68), 7.541 (5.67), 7.713 (2.49), 7.719 (2.49), 7.734 (2.52), 7.740 (2.40), 7.751 (0.94), 7.758 (0.91), 8.315 (2.85 ), 8,321 (2.72), 8,333 (1.28), 8,339 (1.26). Intermediate 213 Ethyl (5RS,7RS)-3-oxo-7-(trifluoromethyl)-2-{[6-(trifluoromethyl)pyridin-3-yl]methyl}-2,3,5,6,7,8-hexa -hydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylate (mixture of diastereomer; 4 isomers)

[0741] Ethyl (5RS,7RS)-3-oxo-7-(trifluoromethyl)-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a] Pyridine-5-carboxylate (diastereomer mixture, 4 isomers) (570 mg, 2.04 mmol) was initially loaded into acetonitrile (20 mL). Cesium carbonate (998 mg, 3.06 mmol) and 5-(chloromethyl)-2-(trifluoromethyl)pyridine (419 mg, 2.14 mmol) were subsequently added. After stirring at room temperature overnight, ethyl acetate was added to the reaction mixture. The organic phase was washed with water and saturated aqueous sodium chloride solution, dried over sodium sulfate and filtered, and the filtrate was concentrated. The residue was purified via column chromatography (silica gel, eluent: gradient cyclohexane/ethyl acetate 4/1, 1/1). The fractions containing the product were concentrated under reduced pressure and 809 mg (86% possibility) of the title compound were obtained. LC-MS (Method 1): Rt = 1.25 min; MS (ESIpos): m /z = 439 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.008 (1.17), 0.008 (1.20), 1.159 (7.54), 1.177 ( 16.00), 1,192 (8.78), 1,194 (10.17), 1,210 (11.69), 1,228 (5.67), 1,398 (1.08), 1,776 (0.63), 1,806 (1.30), 1,838 (1.33), 4,144 (0.92), ( 1.52), 4.161 (3.26), 4.176 (3.33), 4.181 (4.21), 4.194 (3.83), 4.199 (3.26), 4.211 (3.58), 4.217 (1.14), 4.229 (2.63), 4.238 (1.36), 4.247 ( 0.82), 4.256 (1.27), 4.274 (0.41), 4.521 (1.33), 4.536 (1.55), 4.549 (1.52), 4.563 (1.33), 4.831 (1.68), 4.838 (2.12), 4.853 (1.68), 4.931 ( 2.38), 5.036 (1.05), 5.048 (8.17), 5.077 (5.51), 5.087 (5.39), 5.127 (0.67), 7.913 (1.93), 7.933 (12.67), 7.950 (2.57), 7.954 (2.63), 7.974 ( 0.82), 8.661 (3.58), 8.679 (2.53). Intermediate 214 Ethyl (5RS,7RS)-2-{[3-fluoro-2-(trifluoromethyl)pyridin-4-yl]methyl}-3-oxo-7-(trifluoromethyl)-2,3,5,6,7 ,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylate (diastereomer mixture; 4 isomers)

[0742] Ethyl (5RS,7RS)-3-oxo-7-(trifluoromethyl)-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a] Pyridine-5-carboxylate (diastereomer mixture, 4 isomers) (500 mg, 83% purity, 1.49 mmol) was initially loaded into acetonitrile (15 mL). Cesium carbonate (1.21 g, 3.72 mmol) and 4-(chloromethyl)-3-fluoro-2-(trifluoromethyl)pyridine hydrochloride (420 mg, 1.56 mmol) were subsequently added. After stirring at room temperature overnight, ethyl acetate was added to the reaction mixture. The organic phase was washed with water and saturated aqueous sodium chloride solution, dried over sodium sulfate and filtered, and the filtrate was concentrated. The residue was purified via column chromatography (silica gel, eluent: gradient cyclohexane/ethyl acetate 7/1, 1/16). The fractions containing the product were concentrated under reduced pressure and 440 mg (65% possibility) of the title compound were obtained. LC-MS (Method 3): Rt = 1.92 min; MS (ESIpos): m /z = 457 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: 0.008 (2.05), 1.157 (4.28), 1.170 (8.73), 1.175 (8.65 ), 1.187 (16.00), 1.192 (6.64), 1.205 (7.99), 1.210 (4.00), 1.228 (1.75), 1.398 (2.75), 1.819 (0.47), 1.850 (0.50), 1.988 (13.53), 2.253 (0.43 ), 2.269 (0.50), 2.288 (1.23), 2.303 (1.42), 2.317 (1.87), 2.332 (3.90), 2.365 (0.95), 2.523 (2.37), 2.670 (0.46), 2.696 (0.97), 2.709 (0.48 ), 2.726 (2.59), 2.762 (2.99), 2.798 (1.01), 2.828 (0.73), 2.908 (0.46), 2.999 (2.03), 3.028 (1.70), 4.003 (1.18), 4.021 (3.36), 4.038 (3.28 ), 4.056 (1.09), 4.123 (0.48), 4.140 (1.43), 4.149 (1.10), 4.158 (1.74), 4.167 (2.84), 4.175 (1.44), 4.185 (2.86), 4.192 (1.17), 4.199 (1.96 ), 4.216 (2.83), 4.226 (0.79), 4.234 (2.59), 4.243 (1.39), 4.252 (0.88), 4.261 (1.25), 4.532 (0.48), 4.547 (0.51), 4.560 (0.50), 4.574 (0.43 ), 4.848 (2.48), 4.857 (2.20), 5.098 (2.28), 5.134 (12.28), 7.594 (1.95), 7.607 (3.49), 7.620 (1.88), 7.638 (0.47), 7.650 (0.81), 7.663 (0.44 ), 8,581 (4.60), 8,593 (4.39). Intermediate 215 tert-Butyl (5S)-2-{[6-(difluoromethyl)pyridin-3-yl]methyl}-3-oxo-2,3,5,6,7,8-hexahydro[1,2 ,4]triazolo[4,3-a]pyridine-5-carboxylate

[0743] tert-Butyl(5S)-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylate ( 239 mg, 999 μmol) was initially loaded into acetonitrile (10 mL). Subsequently, cesium carbonate (488 mg, 1.50 mmol) and 5-(chloromethyl)-2-(difluoromethyl)pyridine (186 mg, 1.05 mmol) were added. The reaction mixture was stirred at room temperature overnight. Cesium carbonate (326 mg, 999 μmol) was added again and the mixture was stirred at room temperature overnight. The reaction mixture was mixed with water and ethyl acetate, and the organic phase was removed. The organic phase was washed with saturated aqueous sodium chloride solution, dried over sodium sulfate and filtered, and the filtrate was concentrated. 395 mg (83% purity, 86% chance) of the title compound was obtained. LC-MS (Method 3): Rt = 1.58 min; MS (ESIpos): m /z = 381 [M+H]+ Intermediate 216 Ethyl (5RS,7RS)-2-[(5-chloro-3-fluoropyridin-2-yl)methyl]-3-oxo-7- (trifluoromethyl)-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylate (mixture of diastereomer; 4 isomers)

[0744] Ethyl (5RS,7RS)-3-oxo-7-(trifluoromethyl)-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a] Pyridine-5-carboxylate (diastereomer mixture, 4 isomers) (100 mg, 358 μmol) was initially loaded into acetonitrile (4.0 mL). Cesium carbonate (175 mg, 537 μmol) and 5-chloro-2-(chloromethyl)-3-fluoropyridine (67.7 mg, 376 μmol) were subsequently added. After stirring at room temperature overnight, ethyl acetate was added to the reaction mixture. The organic phase was washed with water and saturated aqueous sodium chloride solution, dried over sodium sulfate and filtered, and the filtrate was concentrated. 135 mg (89% chance) of the title compound was obtained. LC-MS (Method 4): Rt = 0.91 min; MS (ESIpos): m /z = 423 [M+H]+ Intermediate 217 Ethyl (5RS,7RS)-2-[(5-chloropyridin-3-yl)methyl]-3-oxo-7-(trifluoromethyl)- 2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylate (mixture of diastereomer; 4 isomers)

[0745] Ethyl (5RS,7RS)-3-oxo-7-(trifluoromethyl)-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a] Pyridine-5-carboxylate (diastereomer mixture, 4 isomers) (100 mg, 358 μmol) was initially loaded into acetonitrile (4.0 mL). Cesium carbonate (175 mg, 537 μmol) and 3-chloro-5-(chloromethyl)pyridine (60.9 mg, 376 μmol) were subsequently added. After stirring at room temperature overnight, ethyl acetate was added to the reaction mixture. The organic phase was washed with water and saturated aqueous sodium chloride solution, dried over sodium sulfate and filtered, and the filtrate was concentrated. 128 mg (72% purity, 64% chance) of the title compound was obtained. LC-MS (Method 4): Rt = 0.86 min; MS (ESIpos): m /z = 405 [M+H]+ Intermediate 218 tert-Butyl (5S)-2-(4-bromobenzyl)-3-oxo-2,3,5,6,7,8-hexa - hydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylate

[0746] tert-Butyl(5S)-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylate ( 150 mg, 627 μmol) was initially loaded into acetonitrile (8.0 mL). Cesium carbonate (306 mg, 940 μmol) and 1-bromo-4-(chloromethyl)benzene (135 mg, 658 μmol) were added subsequently. After stirring at room temperature overnight, ethyl acetate was added to the reaction mixture. The organic phase was washed with water and saturated aqueous sodium chloride solution, dried over sodium sulfate and filtered, and the filtrate was concentrated. 201 mg (74% chance) of the title compound was obtained. LC-MS (Method 3): Rt = 1.94 min; MS (ESIpos): m /z = 408 [M+H]+ Intermediate 219 tert-Butyl (5S)-2-(3-bromobenzyl)-3-oxo-2,3,5,6,7,8-hexa - hydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylate

[0747] tert-Butyl(5S)-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylate ( 150 mg, 627 μmol) was initially loaded into acetonitrile (8.0 mL). Cesium carbonate (306 mg, 940 μmol) and 1-bromo-3-(chloromethyl)benzene (84 μl, 660 μmol) were subsequently added. After stirring at room temperature overnight, ethyl acetate was added to the reaction mixture. The organic phase was washed with water and saturated aqueous sodium chloride solution, dried over sodium sulfate and filtered, and the filtrate was concentrated. 256 mg (94% chance) of the title compound was obtained. LC-MS (Method 3): Rt = 1.94 min; MS (ESIpos): m /z = 408 [M+H]+ Intermediate 220 tert-Butyl (5S)-2-(4-bromo-2-fluorobenzyl)-3-oxo-2,3,5,6,7 ,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylate

[0748] tert-Butyl(5S)-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylate ( 150 mg, 627 μmol) was initially loaded into acetonitrile (8.0 mL). Cesium carbonate (306 mg, 940 μmol) and 4-bromo-1-(chloromethyl)-2-fluorobenzene (147 mg, 658 μmol) were subsequently added. The reaction mixture was stirred at room temperature overnight. 4-Bromo-1-(chloromethyl)-2-fluorobenzene (30 mg, 132 μmol) and cesium carbonate (41 mg, 125 μmol) were added again and the mixture was stirred for another 6 hours. Ethyl acetate was added to the reaction mixture, the organic phase was washed with water and saturated aqueous sodium chloride solution, dried over sodium sulfate and filtered, and the filtrate was concentrated. The residue was purified via column chromatography (silica gel, eluent: cyclohexane/ethyl acetate gradient 19/1, 0/1). The fractions containing the product were concentrated under reduced pressure and 135 mg (51% possibility) of the title compound were obtained. LC-MS (Method 3): Rt = 2.01 min; MS (ESIpos): m /z = 426 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.174 (0.09), -0.033 (0.69), - 0.017 (0.63), 0.121 (0.08), 1.132 (0.07), 1.150 (0.14), 1.167 (0.07), 1.208 (0.08), 1.368 (16.00), 1.445 (0.17), 1.480 (0.18), 1.773 (0.20), 1.795 (0.17), 1.807 (0.17), 1.963 (0.26), 2.029 (0.55), 2.037 (0.48), 2.063 (0.18), 2.071 (0.16), 2.303 (0.07), 2.578 (0.22), 2.589 (0.38), 2.601 (0.24), 2,620 (0.13), 2,631 (0.19), 2,644 (0.16), 3,995 (0.06), 4,013 (0.06), 4,391 (0.38), 4,406 (0.58), 4,416 (0.37), 4,785 (0.08), 4,826 (1.67), 4.867 (0.08), 7.187 (0.37), 7.208 (0.80), 7.228 (0.46), 7.380 (0.50), 7.384 (0.51), 7.401 (0.41), 7.405 (0.42), 7.522 (0.46), 7.527 (0.43), 7,546 (0.47), 7,550 (0.44). Intermediate 221 tert-Butyl (5S)-3-oxo-2-{(1RS)-1-[6-(trifluoromethyl)pyridin-3-yl]ethyl}- 2,3,5,6,7,8-hexa -hydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylate (isomer 1)

[0749] tert-Butyl(5S)-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylate ( 201 mg, 840 μmol) was initially loaded into acetonitrile (10 mL). Cesium carbonate (410 mg, 1.26 mmol) and 5-[(1RS)-1-bromomethyl]-2-(trifluoromethyl)pyridine (320 mg, 70% purity, 882 μmol) were subsequently added. After stirring at room temperature overnight, ethyl acetate was added to the reaction mixture. The organic phase was washed with water and saturated aqueous sodium chloride solution, dried over sodium sulfate and filtered, and the filtrate was concentrated. The residue was purified via column chromatography (silica gel, eluent: gradient cyclohexane/ethyl acetate 9/1, 0/1). After separation, 86.9 mg (24% possibility) of isomer 1, which elutes first, and 97.7 mg (26% possibility) of isomer 2, which elutes later, were isolated. Isomer 1: LC-MS (Method 3): Rt = 1.84 min; MS (ESIpos): m /z = 413 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (0.21), -0.024 (0.08), - 8.015 (0.45), 8,019 (0.46), 8,040 (0.33), 8,699 (0.63), 8,703 (0.63). Intermediate 222 tert-Butyl (5S)-3-oxo-2-{(1RS)-1-[6-(trifluoromethyl)pyridin-3-yl]ethyl}- 2,3,5,6,7,8-hexa -hydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylate (isomer 2)

[0750] tert-Butyl(5S)-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylate ( 201 mg, 840 μmol) was initially loaded into acetonitrile (10 mL). Cesium carbonate (410 mg, 1.26 mmol) and 5-[(1RS)-1-bromomethyl]-2-(trifluoromethyl)pyridine (320 mg, 70% purity, 882 μmol) were subsequently added. After stirring at room temperature overnight, ethyl acetate was added to the reaction mixture. The organic phase was washed with water and saturated aqueous sodium chloride solution, dried over sodium sulfate and filtered, and the filtrate was concentrated. The residue was purified via column chromatography (silica gel, eluent: gradient cyclohexane/ethyl acetate 9/1, 0/1). After separation, 86.9 mg (24% possibility) of isomer 1, which elutes first, and 97.7 mg (26% possibility) of isomer 2, which elutes later, were isolated. Isomer 2: LC-MS (Method 3): Rt = 1.86 min; MS (ESIpos): m /z = 413 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.014 (0.28), 1.152 (0.06), 1.169 (0.13), 1.187 ( 0.06), 1.240 (0.07), 1.372 (0.22), 1.401 (16.00), 1.480 (0.16), 1.503 (0.17), 1.515 (0.18), 1.529 (0.13), 1.557 (0.09), 1.680 (2.33), 1.698 ( 2.34), 1.809 (0.19), 1.820 (0.18), 1.831 (0.17), 1.842 (0.17), 1.983 (0.16), 2.049 (0.56), 2.061 (0.46), 2.089 (0.16), 2.322 (0.06), 2.518 ( 0.24), 2.560 (0.34), 2.575 (0.24), 2.587 (0.25), 2.602 (0.20), 2.659 (0.23), 2.670 (0.39), 2.682 (0.22), 2.712 (0.19), 2.724 (0.10), 3.093 ( 0.08), 4.399 (0.37), 4.414 (0.62), 4.424 (0.36), 4.635 (0.06), 4.650 (0.07), 5.511 (0.14), 5.529 (0.53), 5.547 (0.48), 5.564 (0.14), 7.881 ( 0.67), 7.901 (0.90), 8.011 (0.48), 8.016 (0.48), 8.037 (0.36), 8.723 (0.69). Intermediate 223 tert-Butyl (5S)-3-oxo-2-{[cis/trans-4-(trifluoromethyl)cyclohexyl]methyl}- 2,3,5,6,7,8-hexahydro[1,2 ,4]triazolo[4,3-a]pyridine-5-carboxylate (mixture of diastereomer; 2 isomers)

[0751] tert-Butyl(5S)-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylate ( 450 mg, 1.88 mmol) was initially loaded into acetonitrile (20 mL). Cesium carbonate (1.90 g, 5.83 mmol) and cis/trans-1-(bromomethyl)-4-(trifluoromethyl)cyclohexane (660 μl, 4.1 mmol) were subsequently added, and the reaction mixture was stirred at room temperature overnight. cis/trans-1-(Bromomethyl)-4-(trifluoromethyl)cyclohexane (660 μl, 4.1 mmol) and cesium carbonate (613 mg, 1.88 mmol) were added again, and the reaction mixture was stirred for the weekend. The reaction mixture was filtered and ethyl acetate was added. The organic phase was washed with water and saturated aqueous sodium chloride solution, dried over sodium sulfate and filtered, and the filtrate was concentrated. The residue was purified via column chromatography (silica gel; eluent: dichloromethane/methanol 99/1, 9/1). Purification was carried out once again via column chromatography (silica gel; eluent: cyclohexane/ethyl acetate 11:1, 1:2). The fractions containing the product were concentrated under reduced pressure and 112 mg (14% possibility) of the title compound were obtained. LC-MS (Method 3): Rt = 2.08 min; MS (ESIpos): m /z = 404 [M+H]+ Intermediate 224 (5S)-5-{[(2S)-2-(Hydroxymethyl)pyrrolidin-1-yl]carbonyl}-2-(4-methylbenzyl )- 5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one

[0752] (5S)-2-(4-Methylbenzyl)-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a ]pyridine-5-carboxylic acid (100 mg, 348 μmol) was initially loaded into dichloromethane (2.0 mL) and DMF (4.0 mL) at room temperature. Subsequently, 1-[bis(dimethylamino)methylene]-1H-benzotriazol-1-ium 3-oxide hexafluorophosphate (172 mg, 452 μmol) and N,N-diisopropylethylamine (85 μl, 490 μmol) were added. After stirring for 15 min, (2S)-pyrrolidin-2-ylmethanol (41 μl, 420 μmol) was added, and the reaction mixture was stirred at room temperature for 1.5 h. The solvent was removed under reduced pressure, and the residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/water gradient). HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/gradient water). The fractions containing the product were concentrated under reduced pressure and 83.1 mg (64% possibility) of the title compound were obtained. LC-MS (Method 3): Rt = 0.93 min; MS (ESIpos): m /z = 371 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (1.74), -0.008 (16.00), 0.008 ( 12.83), 0.146 (1.58), 2.271 (2.57), 2.327 (2.72), 2.366 (2.42), 2.523 (7.55), 2.669 (2.57), 2.709 (2 .42), 4.741 (1.13), 5.753 (3.40), 7.122 (1.66). Intermediate 225 2-[(2S)-1-{[(5S)-2-(4-Methylbenzyl)-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4 ]triazolo[4,3-a]pyridin-5-yl]carbonyl}pyrrolidin-2-yl]-2-oxoethyl acetate

[0753] tert-Butyl (2S)-2-(acetoxyacetyl)pyrrolidine-1-carboxylate (189 mg, 696 μmol) was dissolved in dichloromethane (1 mL), trifluoroacetic acid (1 mL) was added, and the mixture was stirred at room temperature for 1 h, then the volatile organic compounds were removed under reduced pressure. The crude product of (2S)-2-(acetoxyacetyl)pyrrolidine was directly converted in the next stage.

[0754] (5S)-2-(4-Methylbenzyl)-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a ]pyridine-5-carboxylic acid (100 mg, 348 μmol) was dissolved in dichloromethane (2 mL) and cooled to 0°C. 1-Chloro-N,N,2-trimethylprop-1-en-1-amine (64 μl, 490 μmol) was added, and the mixture was stirred at 0°C for an additional 20 min. (2S)-2-(Acetoxyacetyl)pyrrolidine (crude product) was dissolved in dichloromethane (1 mL) and slowly added dropwise to the reaction mixture at 0°C, followed by N,N-diisopropylethylamine (180 μl, 1.0 mmol). After 5 min, the solvent was removed under reduced pressure, and the residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/water gradient). HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/gradient water). The fractions containing the product were concentrated under reduced pressure and 112 mg (73% possibility) of the title compound were obtained. LC-MS (Method 1): Rt = 1.05 min; MS (ESIpos): m /z = 441 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.008 (2.75), 0.008 (1.89), 1.580 (0.46), 1.594 ( 0.46), 1.726 (0.58), 1.759 (0.48), 1.799 (0.53), 1.814 (0.75), 1.832 (0.76), 1.847 (0.76), 1.862 (0.49), 1.912 (0.68), 1.928 (1.30), 1.947 ( 1.68), 1.960 (1.27), 2.040 (1.43), 2.080 (16.00), 2.096 (4.78), 2.100 (1.50), 2.162 (0.56), 2.183 (0.63), 2.193 (0.66), 2.214 (0.65), 2.269 ( 11.51), 2.323 (0.52), 2.327 (0.68), 2.366 (0.59), 2.518 (2.35), 2.523 (2.26), 2.567 (1.05), 2.580 (0.71), 2.669 (0.65), 2.710 (0.55), 3.575 ( 0.79), 3.582 (0.56), 3.599 (0.99), 3.617 (0.43), 3.690 (0.46), 3.750 (0.45), 3.766 (0.94), 3.783 (0.53), 3.791 (0.71), 4.545 (1.05), 4.559 ( 1.17), 4.566 (1.15), 4.581 (1.01), 4.733 (4.26), 4.766 (0.86), 4.774 (0.45), 4.809 (4.21), 4.822 (5.23), 4.830 (1.60), 4.840 (0.86), 4.865 ( 1.73), 4.951 (1.12), 4.995 (0.62), 7.093 (0.92), 7.114 (7.45), 7.120 (6.87), 7.141 (0.89). Intermediate 226 Methyl 3-oxo-8-(trifluoromethyl)-2-{[6-(trifluoromethyl)pyridin-3-yl]methyl}-2,3-dihydro[1,2,4]triazolo[4,3 -a]pyridine-5-carboxylate

[0755] Methyl 3-oxo-8-(trifluoromethyl)-2,3-dihydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylate (50.0 mg, 191 μmol) it was initially loaded in acetonitrile (2.0 mL). Cesium carbonate (93.6 mg, 287 μmol) and 5-(chloromethyl)-2-(trifluoromethyl)pyridine (39.3 mg, 201 μmol) were subsequently added. After stirring at room temperature overnight, ethyl acetate was added to the reaction mixture. The organic phase was washed with water and saturated aqueous sodium chloride solution, dried over sodium sulfate and filtered, and the filtrate was concentrated. 86.9 mg (77% purity, 83% possibility) of the title compound was obtained. LC-MS (Method 3): Rt = 1.80 min; MS (ESIpos): m /z = 421 [M+H]+ Intermediate 227 Methyl 2-[(5-chloro-3-fluoropyridin-2-yl)methyl]-3-oxo-8-(trifluoromethyl)-2, 3-dihydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylate

[0756] Methyl 3-oxo-8-(trifluoromethyl)-2,3-dihydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylate (150 mg, 574 μmol) was initially charged in acetonitrile (5.0 mL). Cesium carbonate (281 mg, 862 μmol) and 5-chloro-2-(chloromethyl)-3-fluoropyridine (109 mg, 603 μmol) were subsequently added. After stirring at room temperature overnight, ethyl acetate was added to the reaction mixture. The organic phase was washed with water and saturated aqueous sodium chloride solution, dried over sodium sulfate and filtered, and the filtrate was concentrated. The residue was purified via column chromatography (silica gel, eluent: cyclohexane/ethyl acetate gradient 7/1, 0/1). The fractions containing the product were concentrated under reduced pressure and 87.5 mg (38% possibility) of the title compound were obtained. LC-MS (Method 3): Rt = 1.77 min; MS (ESIpos): m /z = 405 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.150 (0.63), -0.008 (5.70), 0.008 (5.37), 0.146 (0.68) (4.66) (1.50). Intermediate 228 tert-Butyl (5RS,8RS)-8-methyl-2-(4-methylbenzyl)-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazole [4,3-a]pyridine-5-carboxylate (mixture of diastereomer; 4 isomers)

[0757] tert-Butyl (5RS,8RS)-8-methyl-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a] Pyridine-5-carboxylate (diastereomer mixture, 4 isomers) (33.4 mg, 132 μmol) was initially loaded into acetonitrile (5 mL). Cesium carbonate (51.6 mg, 158 μmol) and 1-(bromomethyl)-4-methylbenzene (25.6 mg, 138 μmol) were subsequently added. The reaction mixture was stirred at room temperature overnight, then 1-(bromomethyl)-4-methylbenzene (5 mg, 2.6 μmol) was added and the mixture was stirred for 2 hours. Water and ethyl acetate were added to the reaction mixture. The organic phase was removed and the aqueous phase was extracted three times with ethyl acetate. The combined organic phases were washed with saturated aqueous sodium chloride solution, dried over sodium sulfate and filtered, and the filtrate was concentrated. 39.5 mg (79% possibility) of the title compound was obtained as a mixture of diastereomers. LC-MS (Method 3): Rt = 2.02 min; MS (ESIpos): m /z = 358 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.008 (1.06), 0.008 (0.92), 1.153 (0.40), 1.164 ( 2.69), 1.181 (2.84), 1.194 (0.43), 1.201 (0.63), 1.236 (0.88), 1.259 (0.60), 1.298 (0.42), 1.344 (0.64), 1.350 (0.72), 1.355 (1.41), 1.386 ( 16.00), 1.396 (3.32), 1.417 (0.68), 1.424 (0.49), 1.428 (0.55), 1.510 (0.69), 1.548 (0.87), 1.562 (0.66), 2.120 (0.63), 2.130 (0.54), 2.272 ( 5.05), 2.294 (0.49), 2.523 (0.91), 4.447 (0.54), 4.790 (1.10), 4.820 (1.08), 7.129 (6.94). Intermediate 229 tert-Butyl (5RS,8RS)-8-methyl-3-oxo-2-{[6-(trifluoromethyl)pyridin-3-yl]methyl}-2,3,5,6,7,8-hexa -hydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylate (mixture of diastereomer, 4 isomers)

[0758] tert-Butyl (5RS,8RS)-8-methyl-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a] Pyridine-5-carboxylate (diastereomer mixture, 4 isomers) (503 mg, 1.98 mmol) was initially loaded into acetonitrile (20 mL). Cesium carbonate (970 mg, 2.98 mmol) and 5-(bromomethyl)-2-(trifluoromethyl)pyridine (500 mg, 2.08 mmol) were subsequently added. After stirring at room temperature overnight, the reaction mixture was stirred under reflux for 1 hour. Water and ethyl acetate were added to the reaction mixture. The organic phase was removed and the aqueous phase was extracted three times with ethyl acetate. The combined organic phases were washed with saturated aqueous sodium chloride solution, dried over magnesium sulfate and filtered, and the filtrate was concentrated. 854 mg (90% purity, 94% possibility) of the title compound was obtained as a mixture of diastereomers. LC-MS (Method 4): Rt = 1.00 min; MS (ESIpos): m /z = 413 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: 1.157 (0.41), 1.177 (3.04), 1.194 (3.00), 1.367 (16.00 ), 1.548 (0.40), 1.988 (0.72), 2.135 (0.73), 2.145 (0.70), 2.154 (0.41), 4.466 (0.44), 4.475 (0.69), 4.487 (0.44), 5.067 (1.61), 5.074 (1.56 ), 7,926 (1.76), 8,659 (0.86). Intermediate 230 tert-Butyl (5S)-2-[(E)-2-(4-fluorophenyl)vinyl]-3-oxo-2,3,5,6,7,8-hexahydro[1,2, 4]triazolo[4,3-a]pyridine-5-carboxylate (enantiomer 1)

[0759] Molecular sieve (4Â, 20.0 mg) and [(E)-2-(4-fluorophenyl)vinyl]boric acid (139 mg, 836 μmol) were initially loaded into dichloromethane (2.0 mL) at room temperature. Subsequently, triethylamine (120 μl, 840 μmol), copper(II) acetate (85.4 mg, 460 μmol), tert-butyl (5S)-3-oxo-2,3,5,6,7,8- hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylate (100 mg, 418 μmol) and 2,2,6,6-tetramethylpiperidin-1-yloxy (71.8 mg, 460 μmol) were added. The reaction mixture was stirred at room temperature overnight. 2 N ammonia in methanol (50 μl) was added to the reaction mixture, which was concentrated. The residue was purified via column chromatography (silica gel, eluent: cyclohexane/ethyl acetate gradient 7/1, 0/1). The fractions containing the product were concentrated under reduced pressure and 53.1 mg (35% possibility) of the title compound were obtained. LC-MS (Method 3): Rt = 2.10 min; MS (ESIpos): m /z = 360 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ 1.014 (0.21), 1.098 (0.22), 1.423 2.086 (0.17), 2.097 (0.45), 2.107 2.141 (0.17), 2.323 (0.20), 2.327 2.523 (1.07), 2.636 (0.18), 2.665 2.679 (0.38), 2.691 (0.28), 2.710 2.762 (0.24), 2.792 (0.17), 4.502 4. 526 (0.35), 6,753 (0.74), 6.789 7.165 (0.75), 7.393 (0.98), 7.429 7.565 (0.75), 7.574 (0.30), 7.579 (0 Intermediate 231 Ethyl (5RS,6RS)-2-{[3-fluoro-2-(trifluoromethyl )pyridin-4-yl]methyl}-3-oxo-6-(trifluoromethyl)-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a] pyridine-5-carboxylate (mixture of diastereomer; 4 isomers)

[0760] Ethyl (5RS,6RS)-3-oxo-6-(trifluoromethyl)-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a] pyridine-5-carboxylate diastereomer, 4 isomers) (400 mg, 62% purity, 888 μmol) was initially loaded into acetonitrile (6.2 mL). Cesium carbonate (579 mg, 1.78 mmol) and 4-(chloromethyl)-3-fluoro-2-(trifluoromethyl)pyridine (199 mg, 933 μmol) were subsequently added. After stirring at room temperature for 48 hours, the reaction mixture was mixed with water and ethyl acetate. The organic phase was removed and the aqueous phase was extracted three times with ethyl acetate. The combined organic phases were washed with saturated aqueous sodium chloride solution, dried over sodium sulfate and filtered, and the filtrate was concentrated. The residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/gradient water). The product-containing fractions were concentrated under reduced pressure and 231 mg (73% purity, 42% chance) of the title compound were obtained. LC-MS (Method 3): Rt = 1.82 min; MS (ESIpos): m /z = 457 [M+H]+ and Rt = 1.85 min; MS (ESIpos): m /z = 457 [M+H]+ Intermediate 232 Ethyl (5RS,6RS)-3-oxo-6-(trifluoromethyl)-2-{[6-(trifluoromethyl)pyridin-3-yl] methyl}-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylate (mixture of diastereomer, 4 isomers)

[0761] Ethyl (5RS,6RS)-3-oxo-6-(trifluoromethyl)-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a] Pyridine-5-carboxylate (diastereomer mixture, 4 isomers) (250 mg, 62% purity, 555 μmol) was initially loaded into acetonitrile (3.9 mL). Cesium carbonate (362 mg, 1.11 mmol) and 5-(chloromethyl)-2-(trifluoromethyl)pyridine (114 mg, 583 μmol) were subsequently added. After stirring overnight, the reaction mixture was mixed with water and ethyl acetate at room temperature. The organic phase was removed and the aqueous phase was extracted three times with ethyl acetate. The combined organic phases were washed with saturated aqueous sodium chloride solution, dried over sodium sulfate and filtered, and the filtrate was concentrated. The residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/gradient water). The fractions containing the product were concentrated under reduced pressure and 131 mg (54% possibility) of the title compound were obtained. LC-MS (Method 1): Rt = 1.23 min; MS (ESIpos): m /z = 439 [M+H]+ and Rt = 1.24 min; MS (ESIpos): m /z = 439 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (1.37), -0.008 (13.25), 0.008 (11.69), 0.146 (1.37) (2.19) (1.44) (1.50), 4.829 (1.62), 5.010 (0.63), 5.058 (9.50), 5.099 (0.69), 7.927 (14.25), 7.930 (11.12), 8.642 (1.69), 8.655 (3.81). Intermediate 233 Ethyl (5RS,6RS)-2-[(3,5-dichloropyridin-2-yl)methyl]-3-oxo-6-(trifluoromethyl)- 2,3,5,6,7,8-hexa- hydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylate (mixture of diastereomer, 4 isomers)

[0762] Ethyl (5RS,6RS)-3-oxo-6-(trifluoromethyl)-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a] Pyridine-5-carboxylate (diastereomer mixture, 4 isomers) (566 mg, 2.03 mmol) was initially loaded into acetonitrile (15 mL). Cesium carbonate (1.32 g, 4.05 mmol) and 3,5-dichloro-2-(chloromethyl)pyridine (418 mg, 2.13 mmol) were subsequently added. After stirring overnight, the reaction mixture was mixed with water and ethyl acetate at room temperature. The organic phase was removed and the aqueous phase was extracted three times with ethyl acetate. The combined organic phases were washed with saturated aqueous sodium chloride solution, dried over sodium sulfate and filtered, and the filtrate was concentrated. The residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/gradient water). The product-containing fractions were concentrated under reduced pressure and 235 mg (86% purity, 23% chance) of the title compound were obtained. LC-MS (Method 8): Rt = 2.82 min; MS (ESIpos): m /z = 439 [M+H]+ and Rt = 2.87 min; MS (ESIpos): m /z = 439 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (1.83), -0.008 (16.00), 0.008 (12.50), 0.146 (1.68) (1.22) (1.07) (4.11) (4.11), 8,557 (4.27), 8,562 (4.11). Intermediate 234 Ethyl (5RS,6RS)-2-[(5-chloro-3-fluoropyridin-2-yl)methyl]-3-oxo-6- (trifluoromethyl)-2,3,5,6,7,8- hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylate (mixture of diastereomer, 4 isomers)

[0763] Ethyl (5RS,6RS)-3-oxo-6-(trifluoromethyl)-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a] Pyridine-5-carboxylate (diastereomer mixture, 4 isomers) (432 mg, 1.55 mmol) was initially loaded into acetonitrile (10 mL). Cesium carbonate (1.01 g, 3.09 mmol) and 5-chloro-2-(chloromethyl)-3-fluoropyridine (292 mg, 1.62 mmol) were subsequently added. After stirring overnight, the reaction mixture was mixed with water and ethyl acetate at room temperature. The organic phase was removed and the aqueous phase was extracted three times with ethyl acetate. The combined organic phases were washed with saturated aqueous sodium chloride solution, dried over sodium sulfate and filtered, and the filtrate was concentrated. The residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/gradient water). The fractions containing the product were concentrated under reduced pressure and 235 mg (36% possibility) of the title compound were obtained. LC-MS (Method 4): Rt = 0.90 min; MS (ESIpos): m /z = 423 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (1.95), -0.008 (16.00), 0.008 (15.09), 0.146 (1.90) (0.95) (0.61) (0.86), 4,607 (1.43), 4,620 (1.43), 4,793 (1.08), 4,807 (1.08), 5,008 (2.68), 5,017 (2.64), 8,104 (1.30), 8,129 (1.38), 8,476 (1.86). Intermediate 235 Ethyl (5RS,6RS)-2-[(5-chloropyridin-2-yl)methyl]-3-oxo-6-(trifluoromethyl)- 2,3,5,6,7,8-hexahydro[ 1,2,4]triazolo[4,3-a]pyridine-5-carboxylate (mixture of diastereomer, 4 isomers)

[0764] Ethyl (5RS,6RS)-3-oxo-6-(trifluoromethyl)-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a] Pyridine-5-carboxylate (mixture of diastereomer, 4 isomers) (400 mg, 1.43 mmol) was initially loaded into acetonitrile (7.1 mL). Cesium carbonate (934 mg, 2.87 mmol) and 5-chloro-2-(chloromethyl)pyridine (244 mg, 1.50 mmol) were subsequently added. After stirring overnight, the reaction mixture was mixed with water and ethyl acetate at room temperature. The organic phase was removed and the aqueous phase was extracted three times with ethyl acetate. The combined organic phases were washed with saturated aqueous sodium chloride solution, dried over sodium sulfate and filtered, and the filtrate was concentrated. The residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/gradient water). The fractions containing the product were concentrated under reduced pressure and 135 mg (23% possibility) of the title compound were obtained. LC-MS (Method 3): Rt = 1.65 min; MS (ESIpos): m /z = 405 [M+H]+ and Rt = 1.68 min; MS (ESIpos): m /z = 405 [M+H]+ Intermediate 236 tert-Butyl (5RS,7RS)-2-{[3-fluoro-2-(trifluoromethyl)pyridin-4-yl]methyl}-7 - methyl-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylate (mixture of diastereomer, 4 isomers)

[0765] tert-Butyl (5RS,7RS)-7-methyl-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a] Pyridine-5-carboxylate (diastereomer mixture, 4 isomers) (300 mg, 1.18 mmol) was initially loaded into acetonitrile (6.0 mL). Cesium carbonate (965 mg, 2.96 mmol) and 4-(chloromethyl)-3-fluoro-2-(trifluoromethyl)pyridine (266 mg, 1.24 mmol) were subsequently added. After stirring at 60°C overnight, the reaction mixture was mixed with water and ethyl acetate. The organic phase was removed and the aqueous phase was extracted three times with ethyl acetate. The combined organic phases were washed with saturated aqueous sodium chloride solution, dried over sodium sulfate and filtered, and the filtrate was concentrated. The residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/gradient water). The fractions containing the product were concentrated under reduced pressure and 374 mg (73% possibility) of the title compound were obtained. LC-MS (Method 4): Rt = 1.02 min; MS (ESIpos): m /z = 431 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: 1.018 (2.06), 1.035 (2.12), 1.354 (5.48), 1.393 (0.48 ), 1.410 (16.00), 1.911 (0.98), 2.228 (0.46), 2.241 (0.62), 2.269 (0.49), 2.650 (0.42), 4.303 (0.47), 4.313 (0.45), 5.067 (1.13), 5.079 (1.12 ), 5,133 (0.72), 7,619 (0.77), 7,632 (0.57), 8,569 (0.89), 8,581 (0.89). Intermediate 237 tert-Butyl (5RS,7RS)-7-methyl-3-oxo-2-{[6-(trifluoromethyl)pyridin-3-yl]methyl}-2,3,5,6,7,8-hexa -hydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylate (mixture of diastereomer, 4 isomers)

[0766] tert-Butyl (5RS,7RS)-7-methyl-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a] Pyridine-5-carboxylate (diastereomer mixture, 4 isomers) (247 mg, 975 μmol) was initially loaded into acetonitrile (5.0 mL). Cesium carbonate (794 mg, 2.44 mmol) and 5-(chloromethyl)-2-(trifluoromethyl)pyridine (200 mg, 1.02 mmol) were subsequently added. After stirring at 60°C overnight, the reaction mixture was mixed with water and ethyl acetate. The organic phase was removed and the aqueous phase was extracted three times with ethyl acetate. The combined organic phases were washed with saturated aqueous sodium chloride solution, dried over sodium sulfate and filtered, and the filtrate was concentrated. The residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/gradient water). The fractions containing the product were concentrated under reduced pressure and 274 mg (68% possibility) of the title compound were obtained. LC-MS (Method 4): Rt = 0.98 min; MS (ESIpos): m /z = 413 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: 1.011 (2.18), 1.028 (2.23), 1.337 (5.62), 1.385 (0.63 ), 1.406 (16.00), 1.905 (1.13), 2.217 (0.52), 2.230 (0.66), 2.258 (0.53), 2.641 (0.48), 4.279 (0.40), 4.295 (0.47), 4.305 (0.45), 5.019 (2.49 ), 5.077 (0.86), 7.921 (1.40), 7.931 (0.85), 7.936 (0.83), 8.667 (0.73). Intermediate 238 tert-Butyl (5RS,7RS)-2-(3-chloro-4-fluorobenzyl)-7-methyl-3-oxo-2,3,5,6,7,8-hexahydro[1,2 ,4]triazolo[4,3-a]pyridine-5-carboxylate (mixture of diastereomer, 4 isomers)

[0767] tert-Butyl (5RS,7RS)-7-methyl-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a] Pyridine-5-carboxylate (diastereomer mixture, 4 isomers) (300 mg, 1.18 mmol) was initially loaded into acetonitrile (6.0 mL). Cesium carbonate (965 mg, 2.96 mmol) and 4-(bromomethyl)-2-chloro-1-fluorobenzene (278 mg, 1.24 mmol) were subsequently added. After stirring overnight, the reaction mixture was mixed with water and ethyl acetate at room temperature. The organic phase was removed and the aqueous phase was extracted three times with ethyl acetate. The combined organic phases were washed with saturated aqueous sodium chloride solution, dried over sodium sulfate and filtered, and the filtrate was concentrated. The residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/gradient water). The fractions containing the product were concentrated under reduced pressure and 327 mg (70% possibility) of the title compound were obtained. LC-MS (Method 3): Rt = 2.09 min; MS (ESIpos): m /z = 396 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.008 (0.46), 1.011 (2.15), 1.027 (2.14), 1.348 ( 0.46), 1.381 (0.71), 1.411 (16.00), 2.186 (0.41), 2.214 (0.51), 2.227 (0.60), 2.255 (0.51), 4.275 (0.41), 4.291 (0.48), 4.302 (0.45), 4.834 ( 1.64), 7.376 (0.59), 7.399 (0.79), 7.421 (0.44), 7.448 (0.45), 7.453 (0.42), 7.466 (0.45). Intermediate 239 Ethyl (5RS,7RS)-2-[(5-chloropyridin-2-yl)methyl]-3-oxo-7-(trifluoromethyl)- 2,3,5,6,7,8-hexahydro[ 1,2,4]triazolo[4,3-a]pyridine-5-carboxylate (mixture of diastereomer, 4 isomers)

[0768] Ethyl (5RS,7RS)-3-oxo-7-(trifluoromethyl)-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a] Pyridine-5-carboxylate (mixture of diastereomer, 4 isomers) (500 mg, 1.70 mmol) was initially loaded into acetonitrile (20 mL). Cesium carbonate (1.39 g, 4.25 mmol) and 5-chloro-2-(chloromethyl)pyridine hydrochloride (355 mg, 1.79 mmol) were subsequently added. After stirring overnight, the reaction mixture was concentrated by half and mixed with water and ethyl acetate at room temperature. The organic phase was removed and the aqueous phase was extracted three times with ethyl acetate. The combined organic phases were washed with saturated aqueous sodium chloride solution, dried over sodium sulfate and filtered, and the filtrate was concentrated. The residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/gradient water). The fractions containing the product were concentrated under reduced pressure and 248 mg (36% possibility) of the title compound were obtained. LC-MS (Method 4): Rt = 0.89 min; MS (ESIpos): m /z = 405 [M+H]+ ¹H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (0.41), 0.146 (0.41), 1.183 (4.99), 1.201 ( 15.06), 1,217 (16.00), 1,234 (6.56), 1,780 (0.75), 1,810 (1.63), 1,841 (1.78), 1,871 (0.84), 2,296 (0.77), 2,324 (2.75), 2,336 (2.13), 2.366 ( 0.42), 2.670 (0.49), 2.686 (0.67), 2.716 (1.72), 2.740 (1.79), 2.753 (1.97), 2.770 (1.78), 2.780 (2.11), 2.810 (2.19), 2.888 (1.32), 2.895 ( 1.52), 2.929 (0.83), 2.935 (0.84), 2.986 (1.41), 3.015 (1.12), 3.082 (0.72), 4.148 (0.92), 4.162 (2.00), 4.179 (5.57), 4.197 (5.43), 4.217 ( 2.69), 4.235 (1.82), 4.245 (0.93), 4.253 (0.62), 4.262 (0.85), 4.531 (1.67), 4.546 (1.90), 4.559 (1.81), 4.573 (1.61), 4.824 (1.22), 4.831 ( 1.64) 3.59), 7,956 (3.73), 8,579 (4.25), 8,584 (4.25). Intermediate 240 tert-Butyl (5RS,8RS)-2-{[3-fluoro-2-(trifluoromethyl)pyridin-4-yl]methyl}-8-methyl-3-oxo-2,3,5,6,7 ,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylate (mixture of diastereomer, 4 isomers)

[0769] tert-Butyl (5RS,8RS)-8-methyl-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a] Pyridine-5-carboxylate (diastereomer mixture; 4 isomers) (300 mg, 1.18 mmol) was initially loaded into acetonitrile (10 mL). Cesium carbonate (424 mg, 1.30 mmol) and 4-(chloromethyl)-3-fluoro-2-(trifluoromethyl)pyridine (266 mg, 1.24 mmol) were subsequently added. After stirring overnight, the reaction mixture was mixed with water and ethyl acetate at room temperature. The organic phase was removed and the aqueous phase was extracted three times with ethyl acetate. The combined organic phases were washed with saturated aqueous sodium chloride solution, dried over sodium sulfate and filtered, and the filtrate was concentrated. 456 mg (89% chance) of the title compound was obtained. LC-MS (Method 1): Rt = 2.09 min; MS (ESIpos): m /z = 429 [MH]+ Intermediate 241 tert-Butyl (5RS,8RS)-2-(3-chloro-4-fluorobenzyl)-8-methyl-3-oxo- 2,3,5 ,6,7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylate (mixture of diastereomer, 4 isomers)

[0770] tert-Butyl (5RS,8RS)-8-methyl-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a] Pyridine-5-carboxylate (diastereomer mixture; 4 isomers) (300 mg, 1.18 mmol) was initially loaded into acetonitrile (10 mL). Cesium carbonate (772 mg, 2.37 mmol) and 2-chloro-4-(chloromethyl)-1-fluorobenzene (223 mg, 1.24 mmol) were subsequently added. After stirring overnight, the reaction mixture was mixed with water and ethyl acetate at room temperature. The organic phase was removed and the aqueous phase was extracted three times with ethyl acetate. The combined organic phases were washed with saturated aqueous sodium chloride solution, dried over sodium sulfate and filtered, and the filtrate was concentrated. The residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/gradient water). The fractions containing the product were concentrated under reduced pressure and 450 mg (87% possibility) of the title compound were obtained. LC-MS (Method 3): Rt =.08 min; MS (ESIpos): m /z = 340 [M-tBu+H]+ Intermediate 242 tert-Butyl (5RS,8RS)-2-(2,4-difluorobenzyl)-8-methyl-3-oxo-2,3 ,5,6,7,8- hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylate (mixture of diastereomer, 4 isomers)

[0771] tert-Butyl (5RS,8RS)-8-methyl-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a] Pyridine-5-carboxylate (diastereomer mixture; 4 isomers) (300 mg, 1.18 mmol) was initially loaded into acetonitrile (10 mL). Cesium carbonate (772 mg, 2.37 mmol) and 1-(chloromethyl)-2,4-difluorobenzene (202 mg, 1.24 mmol) were subsequently added. After stirring overnight, the reaction mixture was mixed with water and ethyl acetate at room temperature. The organic phase was removed and the aqueous phase was extracted three times with ethyl acetate. The combined organic phases were washed with saturated aqueous sodium chloride solution, dried over sodium sulfate and filtered, and the filtrate was concentrated. 400 mg (84% purity, 75% possibility) of the title compound was obtained. LC-MS (Method 3): Rt = 1.44 min; MS (ESIpos): m /z = 380 [M+H]+ Intermediate 243 Methyl (5S)-2-(2-chloro-4-fluorobenzyl)-3-oxo-2,3,5,6,7,8 -hexa-hydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylate

[0772] Methyl(5S)-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylate (110 mg , 559 μmol) was initially loaded into acetonitrile (2.0 mL, 38 mmol). Cesium carbonate (273 mg, 838 μmol) and 2-chloro-4-(chloromethyl)-1-fluorobenzene (105 mg, 587 μmol) were subsequently added. After stirring overnight, the reaction mixture was mixed with water and refluxing ethyl acetate. The organic phase was removed and the aqueous phase was extracted three times with ethyl acetate. The combined organic phases were washed with saturated aqueous sodium chloride solution, dried over sodium sulfate and filtered, and the filtrate was concentrated. 58.5 mg (30% chance) of the title compound was obtained. LC-MS (Method 1): Rt = 1.11 min; MS (ESIpos): m /z = 340 [M+H]+ Intermediate 244 Methyl (5S)-3-oxo-2-[3-(trifluoromethyl)benzyl]-2,3,5,6,7,8- hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylate

[0773] Methyl(5S)-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylate (300 mg , 1.52 mmol) was initially loaded into acetonitrile (6.0 mL). Cesium carbonate (744 mg, 2.28 mmol) and 1-(bromomethyl)-3-(trifluoromethyl)benzene (382 mg, 1.60 mmol) were subsequently added. After stirring overnight, the reaction mixture was mixed under reflux with water, 1N aqueous hydrochloric acid and ethyl acetate. The organic phase was removed and the aqueous phase was extracted three times with ethyl acetate. The combined organic phases were washed with saturated aqueous sodium chloride solution, dried over sodium sulfate and filtered, and the filtrate was concentrated. The residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/gradient water). The fractions containing the product were concentrated under reduced pressure and 345 mg (64% possibility) of the title compound were obtained. LC-MS (Method 1): Rt = 1.15 min; MS (ESIpos): m /z = 356 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: 1.196 (2.01), 1.212 (3.72), 1.226 (2.33), 1.502 (0.44 ), 1.530 (0.49), 1.802 (0.57), 1.826 (0.49), 1.835 (0.51), 2.078 (0.89), 2.093 (0.89), 2.120 (0.57), 2.131 (0.51), 2.139 (0.55), 2.147 (0.53 ), 2.328 (0.59), 2.562 (1.35), 2.577 (0.99), 2.589 (0.99), 2.603 (0.80), 2.629 (0.74), 2.641 (1.31), 2.653 (0.76), 2.671 (1.02), 2.711 (0.51 ), 2.891 (0.42), 3.702 (16.00), 4.622 (1.08), 4.631 (1.23), 4.637 (1.44), 4.647 (1.10), 4.960 (4.25), 4.965 (4.25), 7.101 (5.21), 7.519 (1.04 ), 7,538 (1.71), 7,584 (0.95), 7,603 (2.01), 7,615 (2.41), 7,658 (1.63), 7,676 (0.87). Intermediate 245 Methyl (5S)-3-oxo-2-{[5-(trifluoromethyl)pyridin-2-yl]methyl}-2,3,5,6,7,8-hexahydro[1,2,4 ]triazolo[4,3-a]pyridine-5-carboxylate

[0774] Methyl(5S)-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylate (187 mg , 947 μmol) was initially loaded into acetonitrile (4.0 mL). Cesium carbonate (463 mg, 1.42 mmol) and 2-(bromomethyl)-5-(trifluoromethyl)pyridine (250 mg, 1.04 mmol) were subsequently added. After stirring overnight, the reaction mixture was mixed at room temperature with water, 1 N aqueous hydrochloric acid, and ethyl acetate. The organic phase was removed and the aqueous phase was extracted three times with ethyl acetate. The combined organic phases were washed with saturated aqueous sodium chloride solution, dried over sodium sulfate and filtered, and the filtrate was concentrated. The residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/gradient water). The fractions containing the product were concentrated under reduced pressure and 185 mg (55% possibility) of the title compound were obtained. LC-MS (Method 3): Rt = 1.34 min; MS (ESIpos): m /z = 357 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: 1.560 (0.40), 1.827 (0.50), 1.841 (0.44), 1.851 (0.42 ), 2.083 (0.45), 2.092 (0.76), 2.106 (0.76), 2.126 (0.45), 2.135 (0.53), 2.147 (0.47), 2.155 (0.52), 2.163 (0.48), 2.559 (0.44), 2.575 (0.90 ), 2.589 (0.77), 2.601 (0.78), 2.615 (0.64), 2.637 (0.60), 2.649 (1.13), 2.661 (0.72), 2.691 (0.47), 3.715 (16.00), 4.631 (1.05), 4.641 (1.16 ), 4,647 (1.36), 4,657 (1.01), 5,063 (5.88), 7,396 (1.64), 7,416 (1.71), 8,223 (1.06), 8,228 (1.09), 8,243 (1.02), 8,249 (1.04), 8,935 (1.74 ). Intermediate 246 Methyl (5S)-2-[(5-methyl-1H-pyrazol-3-yl)methyl]-3-oxo-2,3,5,6,7,8-hexahydro[1,2, 4]triazolo[4,3-a]pyridine-5-carboxylate

[0775] Methyl(5S)-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylate (200 mg , 1.01 mmol) was initially loaded into acetonitrile (5.0 mL). Cesium carbonate (364 mg, 1.12 mmol) and 3-(chloromethyl)-5-methyl-1H-pyrazole hydrochloride (178 mg, 1.06 mmol) were subsequently added. After stirring overnight, the reaction mixture was mixed at room temperature with water, 1 N aqueous hydrochloric acid, and ethyl acetate. The organic phase was removed and the aqueous phase was extracted three times with ethyl acetate. The combined organic phases were washed with saturated aqueous sodium chloride solution, dried over sodium sulfate and filtered, and the filtrate was concentrated. The residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/gradient water). The fractions containing the product were concentrated under reduced pressure and 60.7 mg (21% possibility) of the title compound were obtained. LC-MS (Method 3): Rt = 0.85 min; MS (ESIpos): m /z = 292 [M+H]+ Intermediate 247 Methyl (5S)-2-{[3-chloro-4-(trifluoromethyl)pyridin-2-yl]methyl}-3-oxo- 2 ,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylate

[0776] Methyl(5S)-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylate (150 mg , 761 μmol) was initially loaded into acetonitrile (5.0 mL). Cesium carbonate (273 mg, 837 μmol) and 3-chloro-2-(chloromethyl)-4-(trifluoromethyl)pyridine hydrochloride (532 mg, 40% purity, 799 μmol) were subsequently added. After stirring overnight, the reaction mixture was mixed at room temperature with water, 1 N aqueous hydrochloric acid, and ethyl acetate. The organic phase was removed and the aqueous phase was extracted three times with ethyl acetate. The combined organic phases were washed with saturated aqueous sodium chloride solution, dried over sodium sulfate and filtered, and the filtrate was concentrated. The residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/gradient water). The fractions containing the product were concentrated under reduced pressure and 137 mg (46% possibility) of the title compound were obtained. LC-MS (Method 1): Rt = 1.06 min; MS (ESIpos): m /z = 391 [M+H]+ Intermediate 248 Methyl (5S)-2-[4-fluoro-3-(trifluoromethyl)benzyl]-3-oxo-2,3,5,6, 7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylate

[0777] Methyl(5S)-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylate (200 mg , 1.01 mmol) was initially loaded into acetonitrile (5.0 mL). Cesium carbonate (826 mg, 2.54 mmol) and 4-(bromomethyl)-1-fluoro-2-(trifluoromethyl)benzene (287 mg, 1.12 mmol) were subsequently added. After stirring overnight, the reaction mixture was mixed at room temperature with water, 1 N aqueous hydrochloric acid, and ethyl acetate. The organic phase was removed and the aqueous phase was extracted three times with ethyl acetate. The combined organic phases were washed with saturated aqueous sodium chloride solution, dried over sodium sulfate and filtered, and the filtrate was concentrated. The residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/gradient water). The fractions containing the product were concentrated under reduced pressure and 370 mg (98% possibility) of the title compound were obtained. LC-MS (Method 4): Rt = 0.88 min; MS (ESIpos): m /z = 374 [M+H]+ Intermediate 249 Methyl (5S)-3-oxo-2-{[6-(trifluoromethyl)pyridin-3-yl]methyl}-2,3,5 ,6,7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylate

[0778] Methyl(5S)-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylate (400 mg , 2.03 mmol) was initially loaded into acetonitrile (10 mL). Cesium carbonate (991 mg, 3.04 mmol) and 5-(bromomethyl)-2-(trifluoromethyl)pyridine (511 mg, 2.13 mmol) were subsequently added. After stirring overnight, the reaction mixture was mixed with water and ethyl acetate at room temperature. The organic phase was removed and the aqueous phase was extracted three times with ethyl acetate. The combined organic phases were washed with saturated aqueous sodium chloride solution, dried over sodium sulfate and filtered, and the filtrate was concentrated. 622 mg (79% possibility) of the title compound was obtained. LC-MS (Method 4): Rt = 0.73 min; MS (ESIpos): m /z = 357 [M+H]+ Intermediate 250 Methyl (5S)-2-{[6-fluoro-2-(trifluoromethyl)quinolin-4-yl]methyl}-3-oxo- 2 ,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylate

[0779] Methyl(5S)-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylate (200 mg , 1.01 mmol) was initially loaded into acetonitrile. Cesium carbonate (826 mg, 2.54 mmol) and 4-(chloromethyl)-6-fluoro-2-(trifluoromethyl)quinoline (453 mg, 62% purity, 1.06 mmol) were subsequently added. After stirring overnight, the reaction mixture was mixed with water and ethyl acetate at room temperature. The organic phase was removed and the aqueous phase was extracted three times with ethyl acetate. The combined organic phases were washed with saturated aqueous sodium chloride solution, dried over sodium sulfate and filtered, and the filtrate was concentrated. The residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/gradient water). The fractions containing the product were concentrated under reduced pressure and 59.0 mg (14% possibility) of the title compound were obtained. LC-MS (Method 1): Rt = 1.24 min; MS (ESIpos): m /z = 425 [M+H]+ Intermediate 251 Methyl (5S)-2-(6,7-dihydro-5H-cyclopenta[c]pyridin-3-ylmethyl)-3-oxo - 2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylate

[0780] Methyl(5S)-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylate (85, 5 mg, 433 μmol) was initially loaded into acetonitrile (10 mL). Cesium carbonate (353 mg, 1.08 mmol) and 3-(chloromethyl)-6,7-dihydro-5H-cyclopenta[b]pyridine hydrochloride (115 mg, 563 μmol) were subsequently added. After stirring at room temperature overnight and under reflux for a further 3 hours, the reaction mixture was cooled and mixed with water and ethyl acetate. The organic phase was removed and the aqueous phase was extracted three times with ethyl acetate. The combined organic phases were washed with saturated aqueous sodium chloride solution, dried over sodium sulfate and filtered, and the filtrate was concentrated. The residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/gradient water). The fractions containing the product were concentrated under reduced pressure and 106 mg (90% purity, 67% possibility) of the title compound were obtained. LC-MS (Method 3): Rt = 0.75 min; MS (ESIpos): m /z = 329 [M+H]+ Intermediate 252 Methyl (5S)-3-oxo-2-{[5-(trifluoromethyl)pyridin-3-yl]methyl}-2,3,5 ,6,7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylate

[0781] Methyl(5S)-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylate (90, 0 mg, 456 μmol) was initially loaded into acetonitrile (10 mL). Cesium carbonate (372 mg, 1.14 mmol) and 3-(chloromethyl)-5-(trifluoromethyl)pyridine (116 mg, 593 μmol) were subsequently added. The reaction mixture was stirred under reflux for 3 hours at room temperature overnight and then under reflux for a further 4 hours. The reaction mixture was cooled to room temperature, and water and ethyl acetate were added. The organic phase was removed and the aqueous phase was extracted three times with ethyl acetate. The combined organic phases were washed with saturated aqueous sodium chloride solution, dried over sodium sulfate and filtered, and the filtrate was concentrated. The residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/gradient water). The fractions containing the product were concentrated under reduced pressure and 40.9 mg (25% possibility) of the title compound were obtained. LC-MS (Method 3): Rt = 1.29 min; MS (ESIpos): m /z = 357 [M+H]+ Intermediate 253 Methyl (5S)-3-oxo-2-{[2-(trifluoromethyl)-1,8-naphthyridin-3-yl]methyl}- 2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylate

[0782] Methyl(5S)-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylate (28, 3 mg, 143 μmol) was initially loaded into acetonitrile (3.0 mL). Cesium carbonate (187 mg, 574 μmol) and 3-(chloromethyl)-2-(trifluoromethyl)-1,8-naphthyridine (46.0 mg, 187 μmol) were subsequently added. After stirring under reflux for 3 hours, the reaction mixture was cooled to room temperature and mixed with water and ethyl acetate. The organic phase was removed and the aqueous phase was extracted three times with ethyl acetate. The combined organic phases were washed with saturated aqueous sodium chloride solution, dried over sodium sulfate and filtered, and the filtrate was concentrated. The residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/gradient water). The fractions containing the product were concentrated under reduced pressure and 9.70 mg (17% possibility) of the title compound were obtained. LC-MS (Method 3): Rt = 1.23 min; MS (ESIpos): m /z = 408 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.008 (2.26), 0.008 (1.74), 1.572 (0.46), 1.832 ( 0.55), 1.843 (0.53), 1.857 (0.48), 1.867 (0.48), 2.111 (0.58), 2.135 (1.21), 2.144 (0.85), 2.152 (0.66), 2.164 (0.53), 2.172 (0.55), 2.179 ( 0.48), 2.327 (0.61), 2.366 (0.52), 2.523 (2.03), 2.561 (0.52), 2.589 (0.90), 2.604 (0.78), 2.616 (0.79), 2.630 (0.66), 2.656 (0.65), 2.667 ( 1.51), 2.679 (0.84), 2.709 (0.92), 3.732 (16.00), 4.672 (1.05), 4.682 (1.15), 4.688 (1.44), 4.697 (1.01), 5.239 (5.10), 7.818 (1.42), 7.828 ( 1.44), 7.838 (1.45), 7.849 (1.49), 8.434 (3.29), 8.583 (1.49), 8.588 (1.59), 8.604 (1.46), 8.609 (1.43), 9.248 (1.43), 9.253 (1.53), 9.258 ( 1.53), 9.263 (1.42). Intermediate 254 tert-Butyl (5S)-2-[(6-methoxypyridin-3-yl)methyl]-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4] triazolo[4,3-a]pyridine-5-carboxylate

[0783] tert-Butyl(5S)-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylate ( 1.33 g, 5.55 mmol) was initially charged into acetonitrile (30 mL). Cesium carbonate (4.52 g, 13.9 mmol), 5-(chloromethyl)-2-methoxypyridine (963 mg, 6.11 mmol) and sodium iodide (5.00 mg, 0.03 mmol) were added subsequently. After stirring for 4 days, the reaction mixture was mixed with water and ethyl acetate at room temperature. The organic phase was removed and the aqueous phase was extracted three times with ethyl acetate. The combined organic phases were washed with saturated aqueous sodium chloride solution, dried over sodium sulfate and filtered, and the filtrate was concentrated. The residue was purified via column chromatography (silica gel, eluent: cyclohexane/ethyl acetate gradient). The fractions containing the product were concentrated under reduced pressure and 751 mg (37% possibility) of the title compound were obtained. LC-MS (Method 3): Rt = 1.56 min; MS (ESIpos): m /z = 361 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: 1.385 (16.00), 2.048 (0.54), 2.058 (0.48), 2.525 (0.41 ), 3.825 (6.81), 4.424 (0.60), 4.791 (2.68), 6.785 (0.78), 6.807 (0.84), 7.574 (0.51), 7.580 (0.52), 7.595 (0.49), 7.602 (0.50), 8.074 (0.67 ), 8,080 (0.65). Intermediate 255 tert-Butyl (5S)-3-oxo-2-{[5-(trifluoromethyl)pyrazin-2-yl]methyl}-2,3,5,6,7,8-hexahydro[1,2 ,4]triazolo[4,3-a]pyridine-5-carboxylate

[0784] tert-Butyl(5S)-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylate ( 300 mg, 1.25 mmol) was initially loaded into acetonitrile (4.1 mL). Cesium carbonate (1.02 g, 3.13 mmol) and 2-(chloromethyl)-5-(trifluoromethyl)pyrazine (259 mg, 1.32 mmol) were subsequently added. After stirring overnight, the reaction mixture was mixed with water and ethyl acetate at room temperature. The organic phase was removed and the aqueous phase was extracted three times with ethyl acetate. The combined organic phases were washed with saturated aqueous sodium chloride solution, dried over sodium sulfate and filtered, and the filtrate was concentrated. The residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/gradient water). The fractions containing the product were concentrated under reduced pressure and 111 mg (22% possibility) of the title compound were obtained. LC-MS (Method 1): Rt = 0.83 min; MS (ESIneg): m /z = 457 [M-tBu+H]+ Intermediate 256 tert-Butyl (5S)-2-{[3-fluoro-2-(trifluoromethyl)pyridin-4-yl]methyl}-3 -oxo- 2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylate

[0785] tert-Butyl(5S)-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylate ( 970 mg, 4.05 mmol) was initially loaded into acetonitrile (20 mL). Cesium carbonate (3.30 g, 10.1 mmol) and 4-(chloromethyl)-3-fluoro-2-(trifluoromethyl)pyridine (978 mg, 93% purity, 4.26 mmol) were subsequently added. After stirring under reflux for 2 hours and stirring overnight, the reaction mixture was mixed with water and ethyl acetate at room temperature. The organic phase was removed and the aqueous phase was extracted three times with ethyl acetate. The combined organic phases were washed with saturated aqueous sodium chloride solution, dried over sodium sulfate and filtered, and the filtrate was concentrated. 1.37 g (80% possibility) of the title compound was obtained. LC-MS (Method 3): Rt = 1.92 min; MS (ESIpos): m /z = 417 [M+H]+ Intermediate 257 tert-Butyl (5S)-2-[(1RS)-1-(4-methylphenyl)ethyl]-3-oxo-2,3, 5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylate (mixture of diastereomer, 2 isomers)

[0786] tert-Butyl(5S)-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylate ( 200 mg, 836 μmol) was initially loaded into acetonitrile (5.5 mL). Cesium carbonate (681 mg, 2.09 mmol) and 1-[(1RS)-1-chloroethyl]-4-methylbenzene (142 mg, 919 μmol) were subsequently added. After stirring overnight, the reaction mixture was mixed at room temperature with water, 1 N aqueous hydrochloric acid, and ethyl acetate. The organic phase was removed and the aqueous phase was extracted three times with ethyl acetate. The combined organic phases were washed with saturated aqueous sodium chloride solution, dried over sodium sulfate and filtered, and the filtrate was concentrated. The residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/gradient water). The fractions containing the product were concentrated under reduced pressure and 69.8 mg (23% possibility) of the title compound were obtained. LC-MS (Method 1): Rt = 1.35 min; MS (ESIpos): m /z = 302 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: 1.322 (0.75), 1.341 (16.00), 1.587 (2.31), 1.605 (2.28 ), 2.048 (0.49), 2.059 (0.49), 2.266 (4.00), 2.518 (0.52), 4.407 (0.57), 5.271 (0.49), 5.288 (0.48), 7.111 (0.75), 7.131 (1.46), 7.173 (1.69 ), 7,193 (0.87). Intermediate 258 tert-Butyl (5S)-2-[2-(4-methylphenyl)ethyl]-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[ 4,3-a]pyridine-5-carboxylate

[0787] tert-Butyl(5S)-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylate ( 250 mg, 1.04 mmol) was initially loaded into acetonitrile (8.0 mL). Cesium carbonate (851 mg, 2.61 mmol) and 1-(2-bromoethyl)-4-methylbenzene (180 μl, 1.1 mmol) were subsequently added. After stirring overnight, the reaction mixture was mixed at room temperature with water, 1 N aqueous hydrochloric acid, and ethyl acetate. The organic phase was removed and the aqueous phase was extracted three times with ethyl acetate. The combined organic phases were washed with saturated aqueous sodium chloride solution, dried over sodium sulfate and filtered, and the filtrate was concentrated. The residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/gradient water). The fractions containing the product were concentrated under reduced pressure and 238 mg (64% possibility) of the title compound were obtained. LC-MS (Method 1): Rt = 1.35 min; MS (ESIpos): m /z = 302 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: 1.394 (16.00), 2.041 (0.53), 2.051 (0. 48), 2.255 (4.71), 2.864 (0.59), 2.883 (1.12), 2.902 (0.64), 3.778 (0.43), 3.783 (0.44), 3.796 (0.81 ), 3.803 (0.81), 4.373 (0.59), 7.089 (6.23). Intermediate 259 tert-Butyl (5S)-2-{[3-chloro-4-(trifluoromethyl)pyridin-2-yl]methyl}-3-oxo-2,3,5,6,7,8-hexahydro [1,2,4]triazolo[4,3-a]pyridine-5-carboxylate

[0788] tert-Butyl(5S)-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylate ( 991 mg, 4.14 mmol) was initially loaded into acetonitrile (19 mL). Cesium carbonate (1.48 g, 4.55 mmol) and 3-chloro-2-(chloromethyl)-4-(trifluoromethyl)pyridine (1.00 g, 4.35 mmol) were subsequently added. After stirring overnight, the reaction mixture was mixed with water and ethyl acetate under reflux. The organic phase was removed and the aqueous phase was extracted three times with ethyl acetate. The combined organic phases were washed with saturated aqueous sodium chloride solution, dried over sodium sulfate and filtered, and the filtrate was concentrated. The residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/gradient water). The fractions containing the product were concentrated under reduced pressure and 794 mg (42% possibility) of the title compound were obtained. LC-MS (Method 1): Rt = 1.28 min; MS (ESIpos): m /z = 377 [M-tBu+H]+ Intermediate 260 tert-Butyl (5S)-2-{[1-(4-methylphenyl)cyclopropyl]methyl}-3-oxo-2,3 ,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylate

[0789] tert-Butyl(5S)-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylate ( 120 mg, 500 μmol) was initially loaded into acetonitrile (3.0 mL). Cesium carbonate (408 mg, 1.25 mmol) and 1-[1-(bromomethyl)cyclopropyl]-4-methylbenzene (124 mg, 550 μmol) were subsequently added. After stirring overnight, the reaction mixture was mixed with water and ethyl acetate at room temperature. The organic phase was removed and the aqueous phase was extracted three times with ethyl acetate. The combined organic phases were washed with saturated aqueous sodium chloride solution, dried over sodium sulfate and filtered, and the filtrate was concentrated. 167 mg (90% purity, 78% chance) of the title compound was obtained. LC-MS (Method 3): Rt = 2.13 min; MS (ESIpos): m /z = 384 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: 0.752 (0.63), 0.772 (0.71), 0.977 (1.55), 1.157 (0.59 ), 1.175 (1.19), 1.192 (0.62), 1.344 (1.25), 1.378 (16.00), 1.405 (1.99), 1.417 (0.84), 1.988 (2.18), 2.016 (0.51), 2.027 (0.54), 2.037 (0.43 ), 2.232 (4.19), 2.249 (0.42), 2.519 (0.47), 3.755 (0.54), 3.792 (0.96), 3.866 (1.00), 3.902 (0.51), 4.020 (0.51), 4.038 (0.51), 4.322 (0.42 ), 4.333 (0.42), 4.337 (0.59), 4.347 (0.44), 7.025 (0.89), 7.045 (1.39), 7.119 (1.76), 7.139 (1.14). Intermediate 261 tert-Butyl (5S)-3-oxo-2-{[2-(trifluoromethyl)-1,8-naphthyridin-3-yl]methyl}- 2,3,5,6,7,8-hexa- hydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylate

[0790] tert-Butyl(5S)-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylate ( 208 mg, 868 μmol) was initially loaded into acetonitrile (20 mL). Cesium carbonate (1.13 g, 3.47 mmol) and 3-(chloromethyl)-2-(trifluoromethyl)-1,8-naphthyridine (278 mg, 1.13 mmol) were subsequently added. After stirring for 48 hours, the reaction mixture was mixed with water and ethyl acetate at room temperature. The organic phase was removed and the aqueous phase was extracted three times with ethyl acetate. The combined organic phases were washed with saturated aqueous sodium chloride solution, dried over sodium sulfate and filtered, and the filtrate was concentrated. The residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/gradient water). The fractions containing the product were concentrated under reduced pressure and 146 mg (38% possibility) of the title compound were obtained. LC-MS (Method 3): Rt = 1.65 min; MS (ESIpos): m /z = 450 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: 1.421 (16.00), 2.113 (0.64), 2.125 (0.64), 2.665 (0.41 ), 4.520 (0.73), 5.235 (1.07), 7.820 (0.54), 7.830 (0.56), 7.840 (0.56), 7.851 (0.57), 8.449 (1.25), 8.564 (0.56), 8.569 (0.57), 8.585 (0.55 ), 8,589 (0.52), 9,245 (0.61), 9,250 (0.64), 9,256 (0.63), 9,261 (0.57). Intermediate 262 tert-Butyl (5S)-2-[(6-chloropyridin-3-yl)methyl]-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4] triazolo[4,3-a]pyridine-5-carboxylate

[0791] tert-Butyl(5S)-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylate ( 552 mg, 2.31 mmol) was initially loaded into acetonitrile (11 mL). Cesium carbonate (1.13 g, 3.46 mmol) and 5-(bromomethyl)-2-chloropyridine (500 mg, 2.42 mmol) were subsequently added. After stirring overnight, the reaction mixture was mixed with water and ethyl acetate at room temperature. The organic phase was removed and the aqueous phase was extracted three times with ethyl acetate. The combined organic phases were washed with saturated aqueous sodium chloride solution, dried over sodium sulfate and filtered, and the filtrate was concentrated. The residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/gradient water). The product-containing fractions were concentrated under reduced pressure and 509 mg (93% purity, 56% possibility) of the title compound were obtained. LC-MS (Method 1): Rt = 1.13 min; MS (ESIpos): m /z = 365 [M+H]+ Intermediate 263 tert-Butyl (5S)-3-oxo-2-{[6-(trifluoromethyl)pyridin-3-yl]methyl}-2,3 ,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylate

[0792] tert-Butyl(5S)-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylate ( 1.00 g, 4.18 mmol) was initially loaded into acetonitrile (21 mL). Cesium carbonate (2.04 g, 6.27 mmol) and 5-(chloromethyl)-2-(trifluoromethyl)pyridine (858 mg, 4.39 mmol) were subsequently added. After stirring overnight, the reaction mixture was mixed with water and ethyl acetate at room temperature. The organic phase was removed and the aqueous phase was extracted three times with ethyl acetate. The combined organic phases were washed with saturated aqueous sodium chloride solution, dried over sodium sulfate and filtered, and the filtrate was concentrated. 1.71 g (100% possibility) of the title compound was obtained. LC-MS (Method 3): Rt = 1.73 min; MS (ESIpos): m /z = 399 [M+H]+ Intermediate 264 tert-Butyl (5S)-2-{[5-chloro-6-(trifluoromethyl)pyridin-3-yl]methyl}-3-oxo - 2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylate

[0793] tert-Butyl(5S)-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylate ( 163 mg, 682 μmol) was initially loaded into acetonitrile (5.0 mL). Cesium carbonate (555 mg, 1.70 mmol) and 3-chloro-5-(chloromethyl)-2-(trifluoromethyl)pyridine (549 mg, 30% purity, 716 μmol) were subsequently added. After stirring overnight, the reaction mixture was mixed with water and ethyl acetate at room temperature. The organic phase was removed and the aqueous phase was extracted three times with ethyl acetate. The combined organic phases were washed with saturated aqueous sodium chloride solution, dried over sodium sulfate and filtered, and the filtrate was concentrated. The residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/gradient water). The product-containing fractions were concentrated under reduced pressure and 156 mg (72% purity, 38% possibility) of the title compound were obtained. LC-MS (Method 1): Rt = 1.35 min; MS (ESIpos): m /z = 377 [M-tBu+H]+ Intermediate 265 tert-Butyl (5S)-2-{2-[3-chloro-5-(trifluoromethyl)pyridin-2-yl]ethyl} -3-oxo- 2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylate

[0794] tert-Butyl(5S)-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylate ( 95.0 mg, 397 μmol) was initially loaded into acetonitrile (3.0 mL). Cesium carbonate (323 mg, 992 μmol) and 3-chloro-2-(2-chloroethyl)-5-(trifluoromethyl)pyridine (113 mg, 94% purity, 437 μmol) were subsequently added. After stirring overnight, the reaction mixture was mixed with water and ethyl acetate at room temperature. The organic phase was removed and the aqueous phase was extracted three times with ethyl acetate. The combined organic phases were washed with saturated aqueous sodium chloride solution, dried over sodium sulfate and filtered, and the filtrate was concentrated. The residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/gradient water). The fractions containing the product were concentrated under reduced pressure and 74.5 mg (42% possibility) of the title compound were obtained. LC-MS (Method 1): Rt = 1.36 min; MS (ESIpos): m /z = 391 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.008 (2.40), 0.008 (1.82), 1.389 (16.00), 2.034 ( 0.55), 2.619 (0.43), 2.669 (0.51), 4.058 (0.75), 4.077 (1.16), 4.094 (0.66), 4.361 (0.59), 8.407 (0.85), 8.871 (0.84). Intermediate 266 tert-Butyl (5S)-3-oxo-2-[3-(trifluoromethyl)benzyl]-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4, 3-a]pyridine-5-carboxylate

[0795] tert-Butyl(5S)-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylate ( 400 mg, 1.67 mmol) was initially loaded into acetonitrile (6.0 mL). Cesium carbonate (817 mg, 2.51 mmol) and 1-(bromomethyl)-3-(trifluoromethyl)benzene (420 mg, 1.76 mmol) were subsequently added. After stirring overnight, the reaction mixture was mixed with water and ethyl acetate at room temperature. The organic phase was removed and the aqueous phase was extracted three times with ethyl acetate. The combined organic phases were washed with saturated aqueous sodium chloride solution, dried over sodium sulfate and filtered, and the filtrate was concentrated. 581 mg (87% chance) of the title compound was obtained. LC-MS (Method 3): Rt = 1.98 min; MS (ESIpos): m /z = 398 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.008 (0.69), 0.008 (0.57), 1.384 (16.00), 1.400 ( 0.78), 2.068 (0.55), 2.077 (0.49), 2.523 (0.41), 4.460 (0.57), 4.949 (1.19), 4.965 (1.15), 7.558 (0.62), 7.575 (0.40), 7.594 (0.64), 7.629 ( 0.79), 7.652 (0.50). Intermediate 267 tert-Butyl (5S)-3-oxo-2-(2,4,5-trifluorobenzyl)-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4 ,3-a]pyridine-5-carboxylate

[0796] tert-Butyl(5S)-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylate ( 400 mg, 1.67 mmol) was initially loaded into acetonitrile (10 mL). Cesium carbonate (572 mg, 1.76 mmol) and 1-(chloromethyl)-2,4,5-trifluorobenzene (317 mg, 1.76 mmol) were subsequently added. After stirring overnight, the reaction mixture was mixed with water and ethyl acetate at room temperature. The organic phase was removed and the aqueous phase was extracted three times with ethyl acetate. The combined organic phases were washed with saturated aqueous sodium chloride solution, dried over sodium sulfate and filtered, and the filtrate was concentrated. 523 mg (80% chance) of the title compound was obtained. LC-MS (Method 3): Rt = 1.87 min; MS (ESIpos): m /z = 328 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: 1.175 (0.64), 1.394 (16.00), 1.988 (1.17), 2.060 (0.65 ), 2,069 (0.65), 2,072 (0.65), 2,627 (0.44), 4,428 (0.44), 4,442 (0.62), 4,864 (2.33). Intermediate 268 tert-Butyl (5S)2-(3,4-difluorobenzyl)-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3- a]pyridine-5-carboxylate

[0797] tert-Butyl(5S)-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylate ( 500 mg, 2.09 mmol) was initially loaded into acetonitrile (10 mL). Cesium carbonate (1.70 g, 5.22 mmol) and 4-(bromomethyl)-1,2-difluorobenzene (454 mg, 2.19 mmol) were subsequently added. After stirring overnight, the reaction mixture was mixed with water and ethyl acetate at room temperature. The organic phase was removed and the aqueous phase was extracted three times with ethyl acetate. The combined organic phases were washed with saturated aqueous sodium chloride solution, dried over sodium sulfate and filtered, and the filtrate was concentrated. 900 mg (78% purity, 92% chance) of the title compound was obtained. LC-MS (Method 1): Rt = 0.83 min; MS (ESIpos): m /z = 310 [M-tBu+H]+ Intermediate 269 tert-Butyl (5S)-2-[3-chloro-4-(trifluoromethyl)benzyl]-3-oxo-2,3, 5,6,7,8- hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylate

[0798] tert-Butyl(5S)-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylate ( 400 mg, 1.67 mmol) was initially loaded into acetonitrile (8.0 mL). Cesium carbonate (1.36 g, 4.18 mmol) and 2-chloro-4-(chloromethyl)-1-(trifluoromethyl)benzene (402 mg, 1.76 mmol) were subsequently added. After stirring overnight, the reaction mixture was mixed with water and ethyl acetate at room temperature. The organic phase was removed and the aqueous phase was extracted three times with ethyl acetate. The combined organic phases were washed with saturated aqueous sodium chloride solution, dried over sodium sulfate and filtered, and the filtrate was concentrated. The residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/gradient water). The fractions containing the product were concentrated under reduced pressure and 190 mg (26% possibility) of the title compound were obtained. LC-MS (Method 3): Rt = 2.12 min; MS (ESIpos): m /z = 454 [M+Na]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.008 (0.90), 0.008 (0.82), 1.390 (16.00), 2.075 ( 0.55), 4.466 (0.60), 4.970 (1.54), 7.404 (0.46), 7.425 (0.49), 7.584 (0.94), 7.844 (0.81), 7.865 (0.75). Intermediate 270 tert-Butyl (5S)-2-(3-chloro-4-fluorobenzyl)-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4 ,3-a]pyridine-5-carboxylate

[0799] tert-Butyl(5S)-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylate ( 500 mg, 2.09 mmol) was initially loaded into acetonitrile (10 mL). Cesium carbonate (1.70 g, 5.22 mmol) and 4-(bromomethyl)-2-chloro-1-fluorobenzene (490 mg, 2.19 mmol) were subsequently added. After stirring overnight, the reaction mixture was mixed with water and ethyl acetate at room temperature. The organic phase was removed and the aqueous phase was extracted three times with ethyl acetate. The combined organic phases were washed with saturated aqueous sodium chloride solution, dried over sodium sulfate and filtered, and the filtrate was concentrated. The residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/gradient water). The fractions containing the product were concentrated under reduced pressure and 600 mg (75% possibility) of the title compound were obtained. LC-MS (Method 4): Rt = 1.01 min; MS (ESIpos): m /z = 382 [M+H]+ Intermediate 271 tert-Butyl (5S)-2-[3-fluoro-4-(trifluoromethyl)benzyl]-3-oxo-2,3,5, 6,7,8- hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylate

[0800] tert-Butyl(5S)-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylate ( 500 mg, 2.09 mmol) was initially loaded into acetonitrile (10 mL). Cesium carbonate (1.70 g, 5.22 mmol) and 4-(chloromethyl)-2-fluoro-1-(trifluoromethyl)benzene (466 mg, 2.19 mmol) were subsequently added. After stirring for 72 hours, the reaction mixture was mixed with water and ethyl acetate at room temperature. The organic phase was removed and the aqueous phase was extracted three times with ethyl acetate. The combined organic phases were washed with saturated aqueous sodium chloride solution, dried over sodium sulfate and filtered, and the filtrate was concentrated. 707 mg (91% purity, 74% possibility) of the title compound were obtained. LC-MS (Method 1): Rt = 0.83 min; MS (ESIpos): m /z = 360 [M-tBu+H]+ Intermediate 272 tert-Butyl (5S)-2-{[3-fluoro-2-(trifluoromethyl)pyridin-4-yl]methyl}-3 -oxo- 2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylate

[0801] tert-Butyl(5S)-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylate ( 371 mg, 1.55 mmol) was initially loaded into acetonitrile (7.0 mL). Cesium carbonate (1.11 g, 3.41 mmol) and 4-(chloromethyl)-3-fluoro-2-(trifluoromethyl)pyridine (348 mg, 1.63 mmol) were subsequently added. After stirring overnight, the reaction mixture was mixed with water and ethyl acetate at room temperature. The organic phase was removed and the aqueous phase was extracted three times with ethyl acetate. The combined organic phases were washed with saturated aqueous sodium chloride solution, dried over sodium sulfate and filtered, and the filtrate was concentrated. The residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/gradient water). The fractions containing the product were concentrated under reduced pressure and 420 mg (65% possibility) of the title compound were obtained. LC-MS (Method 3): Rt = 1.83 min; MS (ESIpos): m /z = 417 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: 1.228 (0.06), 1.359 (0.10), 1.388 (16.00), 1.471 (0.11 ), 1.484 (0.16), 1.497 (0.15), 1.506 (0.16), 1.518 (0.17), 1.531 (0.12), 1.545 (0.15), 1.815 (0.19), 1.825 (0.18), 1.837 (0.16), 1.849 (0.16 ), 2.068 (0.55), 2.081 (0.45), 2.106 (0.17), 2.114 (0.16), 2.322 (0.04), 2.361 (0.04), 2.568 (0.26), 2.581 (0.27), 2.595 (0.21), 2.630 (0.21 ), 2.641 (0.36), 2.653 (0.23), 2.672 (0.13), 2.683 (0.17), 2.695 (0.09), 4.447 (0.39), 4.461 (0.60), 4.471 (0.37), 4.942 (0.11), 5.083 (2.35 ), 7,596 (0.35), 7,609 (0.64), 7,622 (0.35), 8,566 (0.73), 8,578 (0.71). Intermediate 273 tert-Butyl (5S)-2-{[1-(6-chloropyridin-2-yl)cyclopropyl]methyl}-3-oxo-2,3,5,6,7,8-hexahydro[1 ,2,4]triazolo[4,3-a]pyridine-5-carboxylate

[0802] tert-Butyl(5S)-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylate ( 129 mg, 541 μmol) was initially loaded into acetonitrile (3.0 mL). Cesium carbonate (441 mg, 1.35 mmol) and 2-[1-(bromomethyl)cyclopropyl]-6-chloropyridine (140 mg, 568 μmol) were subsequently added. After stirring overnight, the reaction mixture was mixed with water and ethyl acetate at room temperature. The organic phase was removed and the aqueous phase was extracted three times with ethyl acetate. The combined organic phases were washed with saturated aqueous sodium chloride solution, dried over sodium sulfate and filtered, and the filtrate was concentrated. 224 mg (96% chance) of the title compound was obtained. LC-MS (Method 3): Rt = 1.94 min; MS (ESIpos): m /z = 405 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: 1.157 (2.03), 1.161 (1.97), 1.175 (3.58), 1.192 (1.29 ), 1.253 (0.99), 1.331 (0.71), 1.376 (16.00), 1.406 (3.62), 1.988 (4.27), 2.023 (0.56), 2.036 (0.59), 2.046 (0.41), 2.520 (0.43), 4.020 (0.99 ), 4.038 (1.01), 4.056 (0.41), 4.096 (2.12), 4.388 (0.40), 4.393 (0.56), 7.245 (0.76), 7.265 (0.83), 7.606 (0.68), 7.625 (0.99), 7.696 (0.72 ), 7,715 (1.13), 7,735 (0.49). Intermediate 274 tert-Butyl (5S)-2-{[1-(4-fluorophenyl)cyclopropyl]methyl}-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4 ]triazolo[4,3-a]pyridine-5-carboxylate

[0803] tert-Butyl(5S)-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylate ( 344 mg, 1.44 mmol) was initially loaded into acetonitrile (10 mL). Cesium carbonate (1.17 g, 3.59 mmol) and 1-[1-(bromomethyl)cyclopropyl]-4-fluorobenzene (346 mg, 1.51 mmol) were subsequently added. After stirring overnight, the reaction mixture was mixed with water and ethyl acetate at room temperature. The organic phase was removed and the aqueous phase was extracted three times with ethyl acetate. The combined organic phases were washed with saturated aqueous sodium chloride solution, dried over sodium sulfate and filtered, and the filtrate was concentrated. 557 mg (100% chance) of the title compound was obtained. LC-MS (Method 3): Rt = 2.04 min; MS (ESIpos): m /z = 388 [M+H]+ Intermediate 275 tert-Butyl (5S)-2-{[1-(4-methoxyphenyl)cyclopropyl]methyl}-3-oxo-2,3,5 ,6,7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylate

[0804] tert-Butyl(5S)-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylate ( 172 mg, 717 μmol) was initially loaded into acetonitrile (4.8 mL). Cesium carbonate (584 mg, 1.79 mmol) and 1-[1-(bromomethyl)cyclopropyl]-4-methoxybenzene (190 mg, 789 μmol) were subsequently added. After stirring overnight, the reaction mixture was mixed with water and ethyl acetate at room temperature. The organic phase was removed and the aqueous phase was extracted three times with ethyl acetate. The combined organic phases were washed with saturated aqueous sodium chloride solution, dried over sodium sulfate and filtered, and the filtrate was concentrated. The residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/gradient water). The fractions containing the product were concentrated under reduced pressure and 222 mg (73% possibility) of the title compound were obtained. LC-MS (Method 3): Rt = 1.95 min; MS (ESIpos): m /z = 344 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: 0.699 (0.14), 0.724 (0.72), 0.743 (0.79), 0.766 (0.18 ), 0.839 (0.08), 0.931 (0.17), 0.949 (1.72), 0.971 (0.15), 1.219 (0.07), 1.354 (1.10), 1.380 (16.00), 1.512 (0.20), 1.537 (0.16), 1.780 (0.22 ), 1.802 (0.20), 1.814 (0.20), 2.019 (0.54), 2.030 (0.56), 2.040 (0.39), 2.327 (0.07), 2.469 (0.14), 2.525 (0.43), 2.595 (0.25), 2.606 (0.42 ), 2.618 (0.25), 2.637 (0.15), 2.648 (0.21), 2.660 (0.13), 2.709 (0.06), 3.698 (6.61), 3.711 (0.51), 3.726 (0.56), 3.762 (1.00), 3.831 (1.00 ), 3.867 (0.53), 4.286 (0.06), 4.319 (0.40), 4.334 (0.59), 4.344 (0.39), 6.776 (1.42), 6.798 (1.61), 6.818 (0.10), 6.840 (0.10), 7.142 (1.66 ), 7,163 (1.47), 7,227 (0.10), 7,248 (0.09). Intermediate 276 tert-Butyl (5S)-2-{[1-(2,4-difluorophenyl)cyclopropyl]methyl}-3-oxo-2,3,5,6,7,8-hexahydro[1,2 ,4]triazolo[4,3-a]pyridine-5-carboxylate

[0805] tert-Butyl(5S)-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylate ( 313 mg, 1.31 mmol) was initially loaded into acetonitrile (8.7 mL). Cesium carbonate (1.06 g, 3.27 mmol) and 1-[1-(bromomethyl)cyclopropyl]-2,4-difluorobenzene (355 mg, 1.44 mmol) were subsequently added. After stirring for 72 hours, the reaction mixture was mixed with water and ethyl acetate at room temperature. The organic phase was removed and the aqueous phase was extracted three times with ethyl acetate. The combined organic phases were washed with saturated aqueous sodium chloride solution, dried over sodium sulfate and filtered, and the filtrate was concentrated. The residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/gradient water). The fractions containing the product were concentrated under reduced pressure and 256 mg (48% possibility) of the title compound were obtained. LC-MS (Method 1): Rt = 1.38 min; MS (ESIpos): m /z = 350 [M-tBu]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: 0.007 (0.24), 0.747 (0.38), 0.759 (1.23), 0.774 (0.45 ), 0.996 (0.45), 1.007 (1.20), 1.023 (0.37), 1.375 (16.00), 1.466 (0.16), 1.501 (0.17), 1.527 (0.11), 1.764 (0.19), 1.786 (0.17), 1.798 (0.16 ) .278 6.882 (0.18), 6.898 (0.37), 6.903 7.082 (0.23), 7.089 (0.24), 7.111 7.160 (0.46), 7.177 (0.46), 7.198 (0 Intermediate 277 tert-Butyl (5S)-3-oxo-2- ({1-[4-(trifluoromethyl)phenyl]cyclopropyl}methyl)- 2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine-5 -carboxylate

[0806] tert-Butyl(5S)-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylate ( 80.4 mg, 336 μmol) was initially loaded into acetonitrile (2.0 mL). Cesium carbonate (274 mg, 840 μmol) and 1-[1-(bromomethyl)cyclopropyl]-4-(trifluoromethyl)benzene (110 mg, 94% purity, 370 μmol) were subsequently added. After stirring overnight, the reaction mixture was mixed with water and ethyl acetate at room temperature. The organic phase was removed and the aqueous phase was extracted three times with ethyl acetate. The combined organic phases were washed with saturated aqueous sodium chloride solution, dried over sodium sulfate and filtered, and the filtrate was concentrated. The residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/gradient water). The fractions containing the product were concentrated under reduced pressure and 113 mg (74% possibility) of the title compound were obtained. LC-MS (Method 1): Rt = 1.47 min; MS (ESIpos): m /z = 382 [M-tBu]+ Intermediate 278 tert-Butyl (5S)2-(2,4-difluorobenzyl)-3-oxo-2,3,5,6,7,8- hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylate

[0807] tert-Butyl(5S)-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylate ( 300 mg, 1.25 mmol) was initially loaded into acetonitrile (8.0 mL). Cesium carbonate (1.02 g, 3.13 mmol) and 1-(chloromethyl)-2,4-difluorobenzene (214 mg, 1.32 mmol) were subsequently added. After stirring overnight, the reaction mixture was mixed with water and ethyl acetate at room temperature. The organic phase was removed and the aqueous phase was extracted three times with ethyl acetate. The combined organic phases were washed with saturated aqueous sodium chloride solution, dried over sodium sulfate and filtered, and the filtrate was concentrated. 423 mg (92% chance) of the title compound was obtained. LC-MS (Method 3): Rt = 1.81 min; MS (ESIpos): m /z = 366 [M+H]+ Intermediate 279 tert-Butyl (5S)-2-(2-chloro-4-fluorobenzyl)-3-oxo-2,3,5,6,7 ,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylate

[0808] tert-Butyl(5S)-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylate ( 250 mg, 1.04 mmol) was initially loaded into acetonitrile (6.0 mL). Cesium carbonate (851 mg, 2.61 mmol) and 1-(bromomethyl)-2-chloro-4-fluorobenzene (245 mg, 1.10 mmol) were subsequently added. After stirring overnight, the reaction mixture was mixed with water and ethyl acetate at room temperature. The organic phase was removed and the aqueous phase was extracted three times with ethyl acetate. The combined organic phases were washed with saturated aqueous sodium chloride solution, dried over sodium sulfate and filtered, and the filtrate was concentrated. 370 mg (88% chance) of the title compound was obtained. LC-MS (Method 3): Rt = 0.83 min; MS (ESIpos): m /z = 326 [M-tBu+H]+ Intermediate 280 tert-Butyl (5S)-2-[(5-chloro-6-methoxypyridin-3-yl)methyl]-3-oxo- 2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylate

[0809] tert-Butyl(5S)-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylate ( 664 mg, 2.78 mmol) was initially loaded into acetonitrile (10 mL). Cesium carbonate (1.36 g, 4.17 mmol) and 3-chloro-5-(chloromethyl)-2-methoxypyridine (560 mg, 2.92 mmol) were subsequently added. After stirring overnight, the reaction mixture was mixed with water and ethyl acetate at room temperature. The organic phase was removed and the aqueous phase was extracted three times with ethyl acetate. The combined organic phases were washed with saturated aqueous sodium chloride solution, dried over sodium sulfate and filtered, and the filtrate was concentrated. The residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/gradient water). The fractions containing the product were concentrated under reduced pressure and 718 mg (90% purity, 59% chance) of the title compound were obtained. LC-MS (Method 1): Rt = 1.25 min; MS (ESIpos): m /z = 395 [M+H]+ Intermediate 281 tert-Butyl (5S)2-(4-fluorobenzyl)-3-oxo-2,3,5,6,7,8-hexa- hydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylate

[0810] tert-Butyl(5S)-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylate ( 250 mg, 1.04 mmol) was initially loaded into acetonitrile (6.0 mL). Cesium carbonate (851 mg, 2.61 mmol) and 1-(bromomethyl)-4-fluorobenzene (207 mg, 1.10 mmol) were subsequently added. After stirring overnight, the reaction mixture was mixed with water and ethyl acetate at room temperature. The organic phase was removed and the aqueous phase was extracted three times with ethyl acetate. The combined organic phases were washed with saturated aqueous sodium chloride solution, dried over sodium sulfate and filtered, and the filtrate was concentrated. The residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/gradient water). The fractions containing the product were concentrated under reduced pressure and 299 mg (82% possibility) of the title compound were obtained. LC-MS (Method 3): Rt = 1.75 min; MS (ESIpos): m /z = 348 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: 1.334 (0.45), 1.392 (16.00), 2.057 (0.50), 2.067 (0.46 ), 2.073 (0.41), 4.435 (0.57), 4.823 (2.34), 7.143 (0.57), 7.165 (1.32), 7.188 (0.83), 7.276 (0.70), 7.290 (0.77), 7.298 (0.62), 7.312 (0.51 ). Intermediate 282 tert-Butyl (5S)-2-[(6-chloropyridin-2-yl)methyl]-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4] triazolo[4,3-a]pyridine-5-carboxylate

[0811] tert-Butyl(5S)-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylate ( 266 mg, 1.11 mmol) was initially loaded into acetonitrile (10 mL). Cesium carbonate (904 mg, 2.77 mmol) and 2-chloro-6-(chloromethyl)pyridine (189 mg, 1.17 mmol) were subsequently added. After stirring overnight, the reaction mixture was mixed with water and ethyl acetate at room temperature. The organic phase was removed and the aqueous phase was extracted three times with ethyl acetate. The combined organic phases were washed with saturated aqueous sodium chloride solution, dried over sodium sulfate and filtered, and the filtrate was concentrated. 372 mg (92% chance) of the title compound was obtained. LC-MS (Method 3): Rt = 1.65 min; MS (ESIpos): m /z = 365 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.009 (0.09), 0.007 (0.09), 0.786 (0.01), 0.805 ( 0.03), 0.828 (0.02), 0.846 (0.04), 0.865 (0.02), 1.139 (0.04), 1.156 (0.65), 1.174 (1.28), 1.191 (0.66), 1.248 (0.07), 1.372 (0.24), 1.409 ( 16.00), 1.456 (0.05), 1.469 (0.08), 1.482 (0.12), 1.495 (0.17), 1.507 (0.16), 1.517 (0.17), 1.529 (0.18), 1.542 (0.13), 1.556 (0.10), 1.566 ( 0.12), 1.823 (0.21), 1.832 (0.19), 1.844 (0.18), 1.856 (0.17), 1.867 (0.13), 1.987 (2.34), 2.044 (0.07), 2.055 (0.08), 2.072 (0.92), 2.081 ( 0.55), 2.090 (0.52), 2.098 (0.37), 2.109 (0.21), 2.116 (0.19), 2.124 (0.17), 2.136 (0.06), 2.145 (0.05), 2.152 (0.05), 2.160 (0.04), 2.327 ( 0.02), 2.365 (0.02), 2.573 (0.27), 2.585 (0.28), 2.599 (0.22), 2.630 (0.22), 2.641 (0.38), 2.653 (0.24), 2.672 (0.13), 2.683 (0.18), 2.695 ( 0.10), 2.808 (0.01), 4.002 (0.19), 4.020 (0.56), 4.037 (0.55), 4.055 (0.18), 4.451 (0.39), 4.461 (0.41), 4.465 (0.58), 4.475 (0.38), 4.737 ( 0.02), 4.771 (0.08), 4.872 (0.06), 4.915 (2.29), 4.957 (0.06), 5.154 (0.03), 5.169 (0.03), 5.392 (0.02), 5.405 (0.02), 7.163 (0.72), 7.182 ( 0.77), 7.332 (0.02), 7.350 (0.02), 7.437 (0.62), 7.456 (0.69), 7.482 (0.03), 7.502 (0.03), 7.515 (0.01), 7.558 (0.01), 7.577 (0.01), 7.842 ( 0.58), 7.861 (1.02), 7.881 (0.51), 7.904 (0.03), 7.918 (0.02). Intermediate 283 Methyl (5S)-2-[2-(4-fluorophenyl)ethyl]-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4, 3-a]pyridine-5-carboxylate

[0812] Methyl(5S)-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylate (224 mg , 1.13 mmol) was initially loaded into acetonitrile (8.0 mL). Cesium carbonate (923 mg, 2.83 mmol) and 1-(2-chloroethyl)-4-fluorobenzene (189 mg, 1.19 mmol) were subsequently added. After stirring overnight, the reaction mixture was mixed with water and ethyl acetate at room temperature. The organic phase was removed and the aqueous phase was extracted three times with ethyl acetate. The combined organic phases were washed with saturated aqueous sodium chloride solution, dried over sodium sulfate and filtered, and the filtrate was concentrated. 221 mg (61% chance) of the title compound was obtained. LC-MS (Method 3): Rt = 1.43 min; MS (ESIpos): m /z = 320 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (1.81), -0.008 (16.00), 0.008 (13.92), 0.146 (1.74) (1.94), 2710 (1.27), 2910 (0.54), 2929 (0.87), 2947 (0.54), 3677 (5.42), 3687 (1.41), 3808 (0.67), 3826 (1.00), 3844 (0.60), 4021 (0.60), 4.038 (0.60), 4.533 (0.47), 7.067 (0.47), 7.090 (1.14), 7.112 (0.74), 7.208 (0.67), 7.222 (0.74), 7.243 (0.54). Intermediate 284 tert-Butyl (5S)2-(4-methoxybenzyl)-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a] pyridine-5-carboxylate

[0813] tert-Butyl(5S)-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylate ( 100 mg, 418 μmol) was initially loaded into acetonitrile (4.0 mL). Cesium carbonate (272 mg, 836 μmol) and 1-(bromomethyl)-4-methoxybenzene (88.2 mg, 439 μmol) were subsequently added. After stirring overnight, the reaction mixture was mixed with water and ethyl acetate at room temperature. The organic phase was removed and the aqueous phase was extracted three times with ethyl acetate. The combined organic phases were washed with saturated aqueous sodium chloride solution, dried over sodium sulfate and filtered, and the filtrate was concentrated. 129 mg (90% purity, 77% chance) of the title compound was obtained. LC-MS (Method 1): Rt = 1.21 min; MS (ESIpos): m /z = 304 [M-tBu+H]+ Intermediate 285 tert-Butyl (5S)-2-[(5-chloro-3-fluoropyridin-2-yl)methyl]-3-oxo- 2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylate

[0814] tert-Butyl(5S)-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylate ( 300 mg, 1.25 mmol) was initially loaded into acetonitrile (12 mL, 230 mmol). Cesium carbonate (817 mg, 2.51 mmol) and 5-chloro-2-(chloromethyl)-3-fluoropyridine (237 mg, 1.32 mmol) were subsequently added. After stirring overnight, the reaction mixture was mixed with water and ethyl acetate at room temperature. The organic phase was removed and the aqueous phase was extracted three times with ethyl acetate. The combined organic phases were washed with saturated aqueous sodium chloride solution, dried over sodium sulfate and filtered, and the filtrate was concentrated. 465 mg (95% chance) of the title compound was obtained. LC-MS (Method 4): Rt = 0.88 min; MS (ESIpos): m /z = 383 [M+H]+ Intermediate 286 tert-Butyl (5S)-2-[(5-fluoropyridin-2-yl)methyl]-3-oxo-2,3,5, 6,7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylate

[0815] tert-Butyl(5S)-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylate ( 275 mg, 1.15 mmol) was initially loaded into acetonitrile (10 mL). Cesium carbonate (936 mg, 2.87 mmol) and 2-(chloromethyl)-5-fluoropyridine hydrochloride (220 mg, 1.21 mmol) were subsequently added. After stirring for 72 hours, the reaction mixture was mixed with water and ethyl acetate at room temperature. The organic phase was removed and the aqueous phase was extracted three times with ethyl acetate. The combined organic phases were washed with saturated aqueous sodium chloride solution, dried over sodium sulfate and filtered, and the filtrate was concentrated. 345 mg (83% chance) of the title compound was obtained. LC-MS (Method 3): Rt = 1.45 min; MS (ESIpos): m /z = 349 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: 1.156 (0.20), 1.174 (0.36), 1.191 (0.20), 1.353 (0.26 ), 1.408 (16.00), 1.487 (0.22), 1.499 (0.22), 1.510 (0.24), 1.521 (0.25), 1.534 (0.19), 1.814 (0.28), 1.824 (0.28), 1.836 (0.24), 1.847 (0.24 ), 1.858 (0.18), 1.987 (0.66), 2.049 (0.18), 2.072 (0.93), 2.083 (0.69), 2.107 (0.24), 2.115 (0.20), 2.557 (0.30), 2.570 (0.30), 2.584 (0.24 ), 2.617 (0.29), 2.628 (0.49), 2.639 (0.29), 2.670 (0.26), 4.440 (0.45), 4.453 (0.67), 4.465 (0.42), 4.928 (1.68), 4.934 (1.63), 7.255 (0.43 ), 7.266 (0.44), 7.277 (0.49), 7.288 (0.46), 7.701 (0.26), 7.708 (0.25), 7.723 (0.49), 7.730 (0.47), 7.745 (0.24), 7.752 (0.24), 8.513 (0.78 ), 8,519 (0.73). Intermediate 287 tert-Butyl (5S)-2-[2-(4-fluorophenyl)ethyl]-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[ 4,3-a]pyridine-5-carboxylate

[0816] tert-Butyl(5S)-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylate ( 250 mg, 1.04 mmol) was initially loaded into acetonitrile (10 mL). Cesium carbonate (851 mg, 2.61 mmol) and 1-(2-bromoethyl)-4-fluorobenzene (223 mg, 1.10 mmol) were subsequently added. After stirring overnight, the reaction mixture was mixed with water and ethyl acetate at room temperature. The organic phase was removed and the aqueous phase was extracted three times with ethyl acetate. The combined organic phases were washed with saturated aqueous sodium chloride solution, dried over sodium sulfate and filtered, and the filtrate was concentrated. 340 mg (83% chance) of the title compound was obtained. LC-MS (Method 4): Rt = 0.98 min; MS (ESIpos): m /z = 362 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: 1.364 (0.43), 1.391 (16.00), 1.406 (2.02), 1.414 (0.60 ), 2.039 (0.72), 2.049 (0.64), 2.638 (0.44), 2.909 (0.64), 2.927 (1.21), 2.946 (0.68), 3.807 (0.87), 3.825 (1.29), 3.843 (0.76), 4.352 (0.47 ), 4.366 (0.64), 4.376 (0.41), 7.062 (0.61), 7.084 (1.28), 7.106 (0.77), 7.219 (0.78), 7.233 (0.93), 7.240 (0.73), 7.254 (0.57). Intermediate 288 tert-Butyl (5S)-2-[(5-chloropyridin-3-yl)methyl]-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4] triazolo[4,3-a]pyridine-5-carboxylate

[0817] tert-Butyl(5S)-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylate ( 300 mg, 1.25 mmol) was initially loaded into acetonitrile (10 mL). Cesium carbonate (1.02 g, 3.13 mmol) and 3-chloro-5-(chloromethyl)pyridine (213 mg, 1.32 mmol) were subsequently added. After stirring overnight, the reaction mixture was mixed again with 3-chloro-5-(chloromethyl)pyridine (213 mg, 1.32 mmol) and stirred at 60 ° C for 4 hours. The reaction mixture was mixed with water and ethyl acetate. The organic phase was removed and the aqueous phase was extracted three times with ethyl acetate. The combined organic phases were washed with saturated aqueous sodium chloride solution, dried over sodium sulfate and filtered, and the filtrate was concentrated. 450 mg (98% chance) of the title compound was obtained. LC-MS (Method 4): Rt = 0.84 min; MS (ESIpos): m /z = 365 [M+H]+ Intermediate 289 tert-Butyl (5S)-2-(4-chloro-3-fluorobenzyl)-3-oxo-2,3,5,6,7 ,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylate

[0818] tert-Butyl(5S)-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylate ( 300 mg, 1.25 mmol) was initially loaded into acetonitrile (5.0 mL). Cesium carbonate (449 mg, 1.38 mmol) and 4-(bromomethyl)-1-chloro-2-fluorobenzene (294 mg, 1.32 mmol) were subsequently added. After stirring overnight, the reaction mixture was mixed with water and ethyl acetate at room temperature. The organic phase was removed and the aqueous phase was extracted three times with ethyl acetate. The combined organic phases were washed with saturated aqueous sodium chloride solution, dried over sodium sulfate and filtered, and the filtrate was concentrated. The residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/gradient water). The fractions containing the product were concentrated under reduced pressure and 363 mg (76% possibility) of the title compound were obtained. LC-MS (Method 8): Rt = 3.17 min; MS (ESIpos): m /z = 382 [M+H]+ Intermediate 290 tert-Butyl (5S)-2-[(5-methoxypyridin-2-yl)methyl]-3-oxo-2,3,5, 6,7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylate

[0819] tert-Butyl(5S)-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylate ( 200 mg, 836 μmol) was initially loaded into acetonitrile (1.3 mL). Cesium carbonate (545 mg, 1.67 mmol) and 2-(chloromethyl)-5-methoxypyridine (138 mg, 878 μmol) were subsequently added. After stirring overnight, the reaction mixture was mixed with water and ethyl acetate at room temperature. The organic phase was removed and the aqueous phase was extracted three times with ethyl acetate. The combined organic phases were washed with saturated aqueous sodium chloride solution, dried over sodium sulfate and filtered, and the filtrate was concentrated. The residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/gradient water). The fractions containing the product were concentrated under reduced pressure and 196 mg (64% possibility) of the title compound were obtained. LC-MS (Method 3): Rt = 1.52 min; MS (ESIpos): m /z = 361 [M+H]+ Intermediate 291 tert-Butyl (5S)-2-[(3,5-dichloropyridin-2-yl)methyl]-3-oxo-2,3, 5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylate

[0820] tert-Butyl(5S)-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylate ( 300 mg, 1.25 mmol) was initially loaded into acetonitrile (5.0 mL). Cesium carbonate (449 mg, 1.38 mmol) and 3,5-dichloro-2-(chloromethyl)pyridine (271 mg, 1.38 mmol) were subsequently added. After stirring overnight, the reaction mixture was mixed with water and ethyl acetate at room temperature. The organic phase was removed and the aqueous phase was extracted three times with ethyl acetate. The combined organic phases were washed with saturated aqueous sodium chloride solution, dried over sodium sulfate and filtered, and the filtrate was concentrated. The residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/gradient water). The fractions containing the product were concentrated under reduced pressure and 260 mg (52% possibility) of the title compound were obtained. LC-MS (Method 4): Rt = 0.93 min; MS (ESIpos): m /z = 399 [M+H]+ Intermediate 292 tert-Butyl (5S)-2-[2-(4-methoxyphenyl)ethyl]-3-oxo-2,3,5,6, 7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylate

[0821] tert-Butyl(5S)-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylate ( 250 mg, 1.04 mmol) was initially loaded into acetonitrile (10 mL). Cesium carbonate (851 mg, 2.61 mmol) and 1-(2-bromoethyl)-4-methoxybenzene (170 μl, 1.1 mmol) were subsequently added. After stirring for 4 hours, the reaction mixture was mixed with water and ethyl acetate at room temperature. The organic phase was removed and the aqueous phase was extracted three times with ethyl acetate. The combined organic phases were washed with saturated aqueous sodium chloride solution, dried over sodium sulfate and filtered, and the filtrate was concentrated. 369 mg (87% chance) of the title compound was obtained. LC-MS (Method 3): Rt = 1.86 min; MS (ESIpos): m /z = 374 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: 1.395 (16.00), 1.405 (1.18), 1.417 (0.64), 2.043 (0.56 ), 2.052 (0.51), 2.844 (0.59), 2.863 (1.09), 2.882 (0.63), 3.713 (6.85), 3.727 (0.83), 3.764 (0.44), 3.768 (0.48), 3.781 (0.80), 3.788 (0.83 ), 3.801 (0.41), 4.359 (0.41), 4.373 (0.62), 6.827 (1.37), 6.848 (1.63), 7.113 (1.43), 7.135 (1.23). Intermediate 293 tert-Butyl (5S)-3-oxo-2-{[3-(trifluoromethyl)-1,2,4-oxadiazol-5-yl]methyl}- 2,3,5,6,7,8- hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylate

[0822] tert-Butyl (5S)-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylate ( 300 mg, 1.25 mmol) was dissolved in acetonitrile (10 mL), and cesium carbonate (1.02 g, 3.13 mmol) was added at room temperature. The reaction mixture was stirred at room temperature overnight and at 50°C for 1 hour. 5-(Chloromethyl)-3-(trifluoromethyl)-1,2,4-oxadiazole (258 mg, 95% purity, 1.32 mmol) was added, and the mixture was stirred at 50°C for 5 hours and then room temperature overnight. 5-(Chloromethyl)-3-(trifluoromethyl)-1,2,4-oxadiazole (94 mg, 95% purity, 0.48 mmol) was added, and the mixture was stirred at 50°C overnight. 5-(Chloromethyl)-3-(trifluoromethyl)-1,2,4-oxadiazole (94 mg, 95% purity, 0.48 mmol) was added again, and the mixture was stirred at 50°C for 5 hours. The solvent was removed under reduced pressure. The residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/gradient water). The fractions containing the product were concentrated under reduced pressure and 322 mg (66% possibility) of the title compound were obtained. LC-MS (Method 3): Rt = 1.82 min; MS (ESIpos): m /z = 334 [M-tBu]+ Intermediate 294 tert-Butyl (5S)-2-[(1-methyl-1H-pyrazolo[3,4-b]pyridin-3-yl)methyl ]-3-oxo- 2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylate

[0823] tert-Butyl(5S)-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylate ( 199 mg, 833 μmol) was initially loaded into acetonitrile (7.0 mL). Cesium carbonate (815 mg, 2.50 mmol) and 3-(chloromethyl)-1-methyl-1H-pyrazol[3,4-b]pyridine (167 mg, 917 μmol) were subsequently added. After stirring overnight, the reaction mixture was mixed with water and ethyl acetate at room temperature. The organic phase was removed and the aqueous phase was extracted three times with ethyl acetate. The combined organic phases were washed with saturated aqueous sodium chloride solution, dried over sodium sulfate and filtered, and the filtrate was concentrated. The residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/gradient water). The product-containing fractions were concentrated under reduced pressure and 203 mg (88% purity, 56% chance) of the title compound were obtained. LC-MS (Method 4): Rt = 0.78 min; MS (ESIpos): m /z = 385 [M+H]+ ¹H-NMR (400 MHz, DMSO-d6) δ [ppm]: 0.008 (1.19), 1.175 (0.42), 1.372 (16.00), 1.406 (0.56 ), 1.988 (0.75), 2.033 (0.53), 2.041 (0.56), 2.524 (0.57), 2.579 (0.42), 4.007 (0.86), 4.028 (5.82), 4.433 (0.40), 4.443 (0.43), 4.448 (0.59 ), 5.124 (1.50), 5.142 (1.48), 7.178 (0.58), 7.189 (0.61), 7.198 (0.64), 7.209 (0.62), 8.193 (0.63), 8.197 (0.64), 8.213 (0.61), 8.217 (0.60 ), 8,546 (0.68), 8,550 (0.68), 8,557 (0.64), 8,561 (0.60). Intermediate 295 tert-Butyl (5S)-2-[(3,5-difluoropyridin-2-yl)methyl]-3-oxo-2,3,5,6,7,8-hexahydro[1,2, 4]triazolo[4,3-a]pyridine-5-carboxylate

[0824] tert-Butyl(5S)-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylate ( 258 mg, 1.08 mmol) was initially loaded into acetonitrile (10 mL). Cesium carbonate (879 mg, 2.70 mmol) and 2-(chloromethyl)-3,5-difluoropyridine (218 mg, 89% purity, 1.19 mmol) were subsequently added. The reaction mixture was stirred at room temperature for 4 hours, at 50°C for 8 hours and at room temperature overnight, and then water and ethyl acetate were added. The organic phase was removed and the aqueous phase was extracted three times with ethyl acetate. The combined organic phases were washed with saturated aqueous sodium chloride solution, dried over sodium sulfate and filtered, and the filtrate was concentrated. The residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/gradient water). The fractions containing the product were concentrated under reduced pressure and 90.1 mg (22% possibility) of the title compound were obtained. LC-MS (Method 1): Rt = 1.10 min; MS (ESIpos): m /z = 312 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: 1.404 (16.00), 2.048 (0.56), 2.059 (0. 56), 2.517 (0.51), 2.588 (0.42), 4.411 (0.42), 4.421 (0.44), 4.426 (0.58), 4.974 (0.83), 4.977 (0.82 ), 4.989 (0.82), 8.461 (0.78), 8.467 (0.74). Intermediate 296 tert-Butyl (5S)-2-[(3-chloropyridin-2-yl)methyl]-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4] triazolo[4,3-a]pyridine-5-carboxylate

[0825] tert-Butyl(5S)-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylate ( 352 mg, 1.47 mmol) was initially loaded into acetonitrile (10 mL). Cesium carbonate (1.20 g, 3.68 mmol) and 3-chloro-2-(chloromethyl)pyridine (262 mg, 1.62 mmol) were subsequently added. The reaction mixture was stirred at room temperature for 4 hours, at 50°C for 4 hours and at room temperature overnight, and then water and ethyl acetate were added. The organic phase was removed and the aqueous phase was extracted three times with ethyl acetate. The combined organic phases were washed with saturated aqueous sodium chloride solution, dried over sodium sulfate and filtered, and the filtrate was concentrated. The residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/gradient water). The product-containing fractions were concentrated under reduced pressure and 269 mg (88% purity, 44% chance) of the title compound were obtained. LC-MS (Method 1): Rt = 1.10 min; MS (ESIpos): m /z = 311 [M+H]+ Intermediate 297 tert-Butyl (5S)-3-oxo-2-{[6-(trifluoromethyl)pyridin-2-yl]methyl}-2,3 ,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylate

[0826] tert-Butyl(5S)-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylate ( 176 mg, 737 μmol) was initially loaded into acetonitrile (5.0 mL, 95 mmol). Cesium carbonate (601 mg, 1.84 mmol) and 2-(chloromethyl)-6-(trifluoromethyl)pyridine (159 mg, 811 μmol) were subsequently added. After stirring overnight, the reaction mixture was mixed with water and ethyl acetate at room temperature. The organic phase was removed and the aqueous phase was extracted three times with ethyl acetate. The combined organic phases were washed with saturated aqueous sodium chloride solution, dried over sodium sulfate and filtered, and the filtrate was concentrated. 256 mg (88% purity, 76% possibility) of the title compound were obtained. LC-MS (Method 4): Rt = 0.94 min; MS (ESIpos): m /z = 399 [M+H]+ Intermediate 298 tert-Butyl (5S)-3-oxo-2-{[5-(trifluoromethyl)-1,3,4-oxadiazol-2-yl ]methyl}- 2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylate

[0827] tert-Butyl(5S)-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylate ( 300 mg, 1.25 mmol) was initially loaded into acetonitrile (5.0 mL). Cesium carbonate (817 mg, 2.51 mmol) and 2-(chloromethyl)-5-(trifluoromethyl)-1,3,4-oxadiazole (257 mg, 1.38 mmol) were subsequently added. After stirring overnight, the reaction mixture was mixed with water and ethyl acetate at room temperature. The organic phase was removed and the aqueous phase was extracted three times with ethyl acetate. The combined organic phases were washed with saturated aqueous sodium chloride solution, dried over sodium sulfate and filtered, and the filtrate was concentrated. The residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/gradient water). The fractions containing the product were concentrated under reduced pressure and 735 mg (66% purity, 99% chance) of the title compound were obtained. LC-MS (Method 1): Rt = 1.18 min; MS (ESIpos): m /z = 334 [M-tBu+H]+ Intermediate 299 tert-Butyl (5S)-2-{[1-ethyl-3-(trifluoromethyl)-1H-pyrazol-5-yl]methyl }-3-oxo- 2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylate

[0828] tert-Butyl(5S)-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylate ( 174 mg, 725 μmol) was initially loaded into acetonitrile (3.0 mL). Cesium carbonate (473 mg, 1.45 mmol) and 5-(chloromethyl)-1-ethyl-3-(trifluoromethyl)-1H-pyrazole (170 mg, 798 μmol) were subsequently added. After stirring overnight, the reaction mixture was mixed with water and ethyl acetate at room temperature. The organic phase was removed and the aqueous phase was extracted three times with ethyl acetate. The combined organic phases were washed with saturated aqueous sodium chloride solution, dried over sodium sulfate and filtered, and the filtrate was concentrated. 283 mg (89% purity, 84% chance) of the title compound was obtained. LC-MS (Method 1): Rt = 1.30 min; MS (ESIpos): m /z = 360 [M+H]+ Intermediate 300 tert-Butyl (5S)-2-[(5-chloropyridin-2-yl)methyl]-3-oxo-2,3,5, 6,7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylate

[0829] tert-Butyl(5S)-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylate ( 300 mg, 1.25 mmol) was initially loaded into acetonitrile (5.0 mL). Cesium carbonate (817 mg, 2.51 mmol) and 5-chloro-2-(chloromethyl)pyridine (223 mg, 1.38 mmol) were subsequently added. After stirring overnight, the reaction mixture was mixed with water and ethyl acetate at room temperature. The organic phase was removed and the aqueous phase was extracted three times with ethyl acetate. The combined organic phases were washed with saturated aqueous sodium chloride solution, dried over sodium sulfate and filtered, and the filtrate was concentrated. 450 mg (98% chance) of the title compound was obtained. LC-MS (Method 3): Rt = 1.61 min; MS (ESIpos): m /z = 365 [M+H]+ Intermediate 301 tert-Butyl (5S)-3-oxo-2-{[2-(trifluoromethyl)-1,3-thiazol-4-yl]methyl }- 2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylate

[0830] tert-Butyl(5S)-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylate ( 300 mg, 1.25 mmol) was initially loaded into acetonitrile (10 mL). Cesium carbonate (817 mg, 2.51 mmol) and 4-(chloromethyl)-2-(trifluoromethyl)-1,3-thiazole (276 mg, 96% purity, 1.32 mmol) were subsequently added. After stirring overnight, the reaction mixture was mixed with water and ethyl acetate at room temperature. The organic phase was removed and the aqueous phase was extracted three times with ethyl acetate. The combined organic phases were washed with saturated aqueous sodium chloride solution, dried over sodium sulfate and filtered, and the filtrate was concentrated. 500 mg (98% chance) of the title compound was obtained. Intermediate 302 tert-Butyl (5S)-2-{[1-methyl-5-(trifluoromethyl)-1H-pyrazol-3-yl]methyl}-3-oxo- 2,3,5,6,7,8- hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylate

[0831] tert-Butyl(5S)-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylate ( 234 mg, 978 μmol) was initially loaded into acetonitrile (5.0 mL). Cesium carbonate (638 mg, 1.96 mmol) and 3-(chloromethyl)-1-methyl-5-(trifluoromethyl)-1H-pyrazole (204 mg, 1.03 mmol) were subsequently added. After stirring overnight, the reaction mixture was mixed with water and ethyl acetate at room temperature. The organic phase was removed and the aqueous phase was extracted three times with ethyl acetate. The combined organic phases were washed with saturated aqueous sodium chloride solution, dried over sodium sulfate and filtered, and the filtrate was concentrated. The residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/gradient water). The fractions containing the product were concentrated under reduced pressure and 91.0 mg (23% possibility) of the title compound were obtained. LC-MS (Method 3): Rt = 1.75 min; MS (ESIpos): m /z = 402 [M+H]+ Intermediate 303 tert-Butyl (5S)-2-{[1-benzyl-5-(trifluoromethyl)-1H-pyrazol-3-yl]methyl}- 3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylate

[0832] tert-Butyl(5S)-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylate ( 548 mg, 2.29 mmol) was initially loaded into acetonitrile (20 mL). Cesium carbonate (1.49 g, 4.58 mmol) and 1-benzyl-3-(chloromethyl)-5-(trifluoromethyl)-1H-pyrazole (728 mg, 95% purity, 2.52 mmol) were added subsequently. After stirring overnight, the reaction mixture was mixed with water and ethyl acetate at room temperature. The organic phase was removed and the aqueous phase was extracted three times with ethyl acetate. The combined organic phases were washed with saturated aqueous sodium chloride solution, dried over sodium sulfate and filtered, and the filtrate was concentrated. The residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/gradient water). The product-containing fractions were concentrated under reduced pressure and 781 mg (76% purity, 54% chance) of the title compound were obtained. LC-MS (Method 3): Rt = 2.12 min; MS (ESIpos): m /z = 478 [M+H]+ Intermediate 304 tert-Butyl (5S)-2-[(5-bromopyridin-3-yl)methyl]-3-oxo-2,3,5, 6,7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylate

[0833] tert-Butyl(5S)-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylate ( 396 mg, 1.66 mmol) was initially loaded into acetonitrile (6.6 mL). Cesium carbonate (1.08 g, 3.31 mmol) and 3-bromo-5-(chloromethyl)pyridine (376 mg, 1.82 mmol) were subsequently added. After stirring overnight, the reaction mixture was mixed with water and ethyl acetate at room temperature. The organic phase was removed and the aqueous phase was extracted three times with ethyl acetate. The combined organic phases were washed with saturated aqueous sodium chloride solution, dried over sodium sulfate and filtered, and the filtrate was concentrated. The residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/gradient water). The fractions containing the product were concentrated under reduced pressure and 146 mg (22% possibility) of the title compound were obtained. LC-MS (Method 3): Rt = 1.64 min; MS (ESIpos): m /z = 409 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: 1.390 (16.00), 2.066 (0.53), 2.075 (0.53), 2.640 (0.40 ), 4,458 (0.61), 4,926 (1.27), 4,939 (1.25), 7,915 (0.87), 8,468 (0.83), 8,472 (0.90), 8,643 (0.71), 8,649 (0.75). Intermediate 305 tert-Butyl (5S)-2-[(5-bromopyridin-2-yl)methyl]-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4] triazolo[4,3-a]pyridine-5-carboxylate

[0834] tert-Butyl(5S)-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylate ( 309 mg, 1.29 mmol) was initially charged into dichloromethane (7.3 mL). Cesium carbonate (1.05 g, 3.23 mmol) and 5-bromo-2-(chloromethyl)pyridine (347 mg, 1.68 mmol) were subsequently added. After stirring for 5 hours, the reaction mixture was mixed with water and ethyl acetate at room temperature. The organic phase was removed and the aqueous phase was extracted three times with ethyl acetate. The combined organic phases were washed with saturated aqueous sodium chloride solution, dried over sodium sulfate and filtered, and the filtrate was concentrated. The residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/gradient water). The fractions containing the product were concentrated under reduced pressure and 580 mg (> 100% possibility) of the title compound were obtained. LC-MS (Method 3): Rt = 1.68 min; MS (ESIpos): m /z = 409 [M+H]+ Intermediate 306 tert-Butyl (5S)-2-[2-(4-methylphenyl)-2-oxoethyl]-3-oxo-2,3,5 ,6,7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylate

[0835] tert-Butyl(5S)-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylate ( 645 mg, 2.70 mmol) was initially loaded into acetonitrile (17 mL). Cesium carbonate (2.20 g, 6.74 mmol) and 2-chloro-1-(4-methylphenyl)ethanone (500 mg, 2.97 mmol) were subsequently added. After stirring overnight, the reaction mixture was mixed at room temperature with water, 1 N aqueous hydrochloric acid, and ethyl acetate. The organic phase was removed and the aqueous phase was extracted three times with ethyl acetate. The combined organic phases were washed with saturated aqueous sodium chloride solution, dried over sodium sulfate and filtered, and the filtrate was concentrated. The residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/gradient water). The fractions containing the product were concentrated under reduced pressure and 605 mg (60% possibility) of the title compound were obtained. LC-MS (Method 1): Rt = 1.23 min; MS (ESIpos): m /z = 316 [M+H]+ Intermediate 307 (5RS,6RS)-2-{[3-fluoro-2-(trifluoromethyl)pyridin-4-yl]methyl}-3-oxo- 6-(trifluoromethyl)-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylic acid (mixture of diastereomer; 4 isomers)

[0836] Ethyl (5RS, 6RS)-2-{[3-fluoro-2-(trifluoromethyl)pyridin-4-yl]methyl}-oxo-6-(trifluoromethyl)-2,3,5,6,7, 8-hexahydro[1,2,4]triazolo[4,3- a]pyridine-5-carboxylate (diastereomer, 4 isomers) (231 mg, 506 μmol) was initially loaded into THF (5.0 mL) and lithium hydroxide (48.5 mg, 2.02 mmol) dissolved in water was added. After stirring at room temperature overnight, the reaction mixture was concentrated under reduced pressure and then mixed with water, 1N aqueous hydrochloric acid and saturated aqueous sodium chloride solution. The aqueous phase was extracted three times with ethyl acetate. The combined organic phases were dried over sodium sulfate and filtered, and the filtrate was concentrated. 193 mg (89% chance) of the title compound was obtained. LC-MS (Method 3): Rt = 1.38 min; MS (ESIpos): m /z = 429 [M+H]+ Intermediate 308 (5RS,6RS)-3-oxo-6-(trifluoromethyl)-2-{[6-(trifluoromethyl)pyridin-3-yl]methyl }- 2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylic acid (mixture of diastereomer, 4 isomers)

[0837] Ethyl (5RS, 5RS)-3-oxo-6-(trifluoromethyl)-2-{[6-(trifluoromethyl)pyridin-3-yl]methyl}-2,3,5,6,7,8- hexahydro[1,2,4]triazolo[4,3- a]pyridine-5-carboxylate (mixture of diastereomer, 4 isomers) (131 mg, 299 μmol) was initially loaded into THF (2.0 mL) and lithium hydroxide (28.6 mg, 1.20 mmol) dissolved in water was added. After stirring at room temperature overnight, the reaction mixture was concentrated under reduced pressure and then mixed with water, 1N aqueous hydrochloric acid and saturated aqueous sodium chloride solution. The aqueous phase was extracted three times with ethyl acetate. The combined organic phases were dried over sodium sulfate and filtered, and the filtrate was concentrated. 109 mg (89% chance) of the title compound was obtained. LC-MS (Method 3): Rt = 1.35 min; MS (ESIpos): m /z = 411 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (0.95), -0.008 (7.81), 0.008 (7.27), 0.146 (0.98) (1.33) (3.35) (1.26) (5.50), 5.015 (1.30), 5.056 (8.73), 5.069 (7.91), 5.109 (1.30), 7.900 (0.66), 7.920 (16.00), 8.646 (5.88). Intermediate 309 (5RS,6RS)-2-[(3,5-Dichloropyridin-2-yl)methyl]-3-oxo-6-(trifluoromethyl)- 2,3,5,6,7,8-hexahydro [1,2,4]triazolo[4,3-a]pyridine-5-carboxylic acid (mixture of diastereomer, 4 isomers)

[0838] Ethyl (5RS,6RS)-2-[(3,5-dichloropyridin-2-yl)methyl-3-oxo-6- (trifluoromethyl)-2,3,5,6,7,8-hexa- hydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylate (diastereomer, 4 isomers) (235 mg, 535 μmol) was initially loaded into THF (2.0 mL) and hydrogen hydroxide was added. lithium (51.3 mg, 2.14 mmol) dissolved in water. After stirring at room temperature overnight, the reaction mixture was concentrated under reduced pressure and then mixed with water, 1N aqueous hydrochloric acid and saturated aqueous sodium chloride solution. The aqueous phase was extracted three times with ethyl acetate. The combined organic phases were dried over sodium sulfate and filtered, and the filtrate was concentrated. 218 mg (99% chance) of the title compound was obtained. LC-MS (Method 4): Rt = 0.69 min; MS (ESIpos): m /z = 411 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (0.94), -0.008 (13.63), 0.008 (8.92), 0.146 (0.97) 99), 2,603 2,670 (0.94) (5RS, 6RS)-2-[(5-Chloro-3-fluoropyridin-2-yl)methyl]-3-oxo-6-(trifluoromethyl)- 2,3,5,6,7,8-hexahydro[1, 2,4]triazolo[4,3-a]pyridine-5-carboxylic acid (mixture of diastereomer, 4 isomers)

[0839] Ethyl (5RS, 6RS)-2-[(5-chloro-3-fluoropyridin-2-yl)methyl]-oxo-6-(trifluoromethyl)-2,3,5,6,7,8-hexa -hydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylate (diastereomer, 4 isomers) (235 mg, 556 μmol) was initially loaded into THF (3.0 mL) and hydroxide was added lithium (53.2 mg, 2.22 mmol) dissolved in water. After stirring at room temperature overnight, the reaction mixture was concentrated under reduced pressure and then mixed with water, 1N aqueous hydrochloric acid and saturated aqueous sodium chloride solution. The aqueous phase was extracted three times with ethyl acetate. The combined organic phases were dried over sodium sulfate and filtered, and the filtrate was concentrated. 202 mg (92% chance) of the title compound was obtained. LC-MS (Method 3): Rt = 1.17 min; MS (ESIpos): m /z = 395 [M+H]+ Intermediate 311 (5RS,6RS)-2-[(-5-Chloropyridin-2-yl)methyl]-3-oxo-6-(trifluoromethyl)- 2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylic acid (mixture of diastereomer, 4 isomers)

[0840] Ethyl (5RS, 6RS)-2-[(5-chloropyridin-2-yl)methyl]-oxo-6-(trifluoromethyl)-2,3,5,6,7,8-hexahydro[1 ,2,4]triazolo[4,3-a]pyridine-5-carboxylate (diastereomer, 4 isomers) (150 mg, 371 μmol) was initially loaded into THF (3.0 mL) and lithium hydroxide was added (35 .5 mg, 1.48 mmol) dissolved in water. After stirring at room temperature overnight, the reaction mixture was concentrated under reduced pressure and then mixed with water, 1N aqueous hydrochloric acid and saturated aqueous sodium chloride solution. The aqueous phase was extracted three times with ethyl acetate. The combined organic phases were dried over sodium sulfate and filtered, and the filtrate was concentrated. 139 mg (100% chance) of the title compound was obtained. LC-MS (Method 3): Rt = 1.13 min; MS (ESIpos): m /z = 377 [M+H]+ Intermediate 312 (5RS,7RS)-2-{[3-Fluoro-2-(trifluoromethyl)pyridin-4-yl]methyl}-7-methyl- 3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylic acid (mixture of diastereomer, 4 isomers)

[0841] tert-Butyl (5RS,7RS)-2-{[3-fluoro-2-(trifluoromethyl)pyridin-4-yl]methyl}-7-methyl-3-oxo-2,3,5,6, 7,8-hexahydro[1,2,4]triazolo[4,3- a]pyridine-5-carboxylate (diastereomer mixture; 4 isomers) (375 mg, 870 μmol) was dissolved in dichloromethane (10 mL) , and trifluoroacetic acid (1.3 mL, 17 mmol) was added at room temperature. After the reaction mixture was stirred at room temperature overnight, the solvent was removed under reduced pressure. 422 mg (90% purity, >100% possibility) of the title compound was obtained. LC-MS (Method 4): Rt = 0.71 min; MS (ESIpos): m /z = 375 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (0.49), -0.008 (6.45), 0.008 (2.97), 0.146 (0.43), 1022 (14.53), 1039 (14.32), 1111 (1.07), 1354 (5.64), 1385 (0.49), 1410 1.27) , 1949 2223 (2.20), 2235 4,316 4,358 (2.54) , 4.782 (1.33), 4.801 5.134 (3.28), 5.153 (2.60), 5.195 6.149 (1.64), 7.567 (0.74), 7.580 7.625 (2.75), 8.548 (1.57), 8.564 (5 Intermediate 313 (5RS, 7RS)- 7-Methyl-3-oxo-2-{[6-(trifluoromethyl)pyridin-3-yl]methyl}-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[ 4,3-a]pyridine-5-carboxylic acid (mixture of diastereomer, 4 isomers)

[0842] tert-Butyl (5RS,7RS)-7-methyl-3-oxo-2-{[6- (trifluoromethyl)pyridin-3-yl]methyl}-2,3,5,6,7,8- hexahydro[1,2,4]triazolo[4,3- a]pyridine-5-carboxylate (mixture of diastereomer, 4 isomers) (274 mg, 664 μmol) was dissolved in dichloromethane (8.0 mL), and trifluoroacetic acid (1.0 mL, 13 mmol) was added at room temperature. After the reaction mixture was stirred at room temperature overnight, the solvent was removed under reduced pressure. 438 mg (>100% chance) of the title compound was obtained. LC-MS (Method 4): Rt = 0.66 min; MS (ESIpos): m /z = 357 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (0.46), 0.008 (3.92), 0.146 (0.46), 1.016 ( 14.93), 1,032 (15.11), 1,111 (1.31), 1,337 (0.57), 1,407 (2.26), 1,444 (1.19), 1,471 (2.41), 1.504 (2.44), 1,532 (1.43), 1,833 (0.54), 1.904 ( 7.33), 1.927 (1.28), 1.937 (1.34), 1.988 (0.61), 2.073 (0.93), 2.181 (2.59), 2.209 (2.18), 2.222 (3.05), 2.250 (3.80), 2.266 (1.58), 2.283 ( 1.37), 2.298 (1.24), 2.329 (0.52), 2.367 (0.47), 2.524 (3.38), 2.638 (2.93), 2.642 (2.91), 2.677 (2.32), 2.684 (2.91), 2.711 (0.61), 2.953 ( 0.46), 2.974 (0.47), 4.306 (2.84), 4.322 (3.29), 4.333 (3.06), 4.348 (2.60), 4.764 (1.36), 4.783 (1.34), 5.016 (16.00), 5.083 (5.43), 5.754 ( 1.00), 6.132 (2.18), 7.889 (1.01), 7.899 (2.82), 7.909 (3.67), 7.919 (10.17), 7.932 (5.19), 7.936 (5.01), 7.952 (1.48), 8.670 (4.96). Intermediate 314 (5RS,7RS)-2-(3-Chloro-4-fluorobenzyl)-7-methyl-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4] triazolo[4,3-a]pyridine-5-carboxylic acid (mixture of diastereomer, 4 isomers)

[0843] tert-Butyl (5RS,7RS)-2-(3-chloro-4-fluorobenzyl)-7-methyl-3-oxo-2,3,5,6,7,8-hexahydro[1, 2,4]triazolo[4,3-a]pyridine-5-carboxylate (mixture of diastereomer, 4 isomers) (327 mg, 827 μmol) was dissolved in dichloromethane (10 mL), and trifluoroacetic acid (1.3 mL , 17 mmol) was added at room temperature. After the reaction mixture was stirred at room temperature overnight, the solvent was removed under reduced pressure. 465 mg (>100% chance) of the title compound was obtained. LC-MS (Method 1): Rt = 1.06 min; MS (ESIpos): m /z = 340 [M+H]+ Intermediate 315 (5RS,7RS)-2-[(-5-Chloropyridin-2-yl)methyl]-3-oxo-7-(trifluoromethyl)- 2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylic acid (mixture of diastereomer, 4 isomers) Ethyl (5RS,7RS)-2-[(5-chloropyridin-2-yl)methyl]-3-oxo-7-(trifluoromethyl)- 2,3,5,6,7,8-hexahydro[1, 2,4]triazolo[4,3-a]pyridine-5-carboxylate (mixture of diastereomer, 4 isomers)

[0844] (248 mg, 612 μmol) was dissolved in THF (8.0 mL) and sodium ethoxide (367 mg, 21% by weight, 1.13 mmol) was added at 0 ° C. After stirring at 0°C for 20 minutes and at room temperature overnight, the reaction mixture was mixed with water, 1N aqueous hydrochloric acid, and ethyl acetate. The organic phase was removed and the aqueous phase was extracted three times with ethyl acetate. The combined organic phases were washed with saturated aqueous sodium chloride solution, dried over sodium sulfate and filtered, and the filtrate was concentrated. 206 mg (89% chance) of the title compound was obtained. LC-MS (Method 3): Rt = 1.15 min; MS (ESIpos): m /z = 377 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (1.11), 0.146 (1.07), 1.157 (1.49), 1.169 ( 3.71), 1.174 (3.55), 1.192 (1.45), 1.235 (0.59), 1.270 (0.59), 1.356 (1.21), 1.371 (0.50), 1.413 (0.52), 1.801 (0.42), 1.908 (2.00), 1.988 ( 5.04), 2.244 (0.83), 2.279 (2.20), 2.295 (2.52), 2.308 (3.01), 2.327 (7.89), 2.366 (2.38), 2.675 (2.62), 2.705 (6.74), 2.730 (6.62), 2.879 ( 0.40), 2.954 (0.93), 2.984 (4.62), 3.012 (3.79), 3.039 (0.65), 4.002 (0.44), 4.020 (1.25), 4.038 (1.19), 4.441 (0.42), 4.701 (5.49), 4.711 ( 4.94), 4,924 (2.18), 4,946 (2.82), 4,965 (16.00), 4,976 (15.98), 5,016 (2.18), 6,578 (0.50), 7,261 (9,87), 7,277 (0.95), 7,298 ( 0.83), 7,911 (5.79), 7,917 (6.17), 7,932 (5.93), 7,938 (6.01), 8,579 (7.32), 8,585 (7.57), 13,685 (0.99). Intermediate 316 (5RS,8RS)-2-{[3-Fluoro-2-(trifluoromethyl)pyridin-4-yl]methyl}-8-methyl-3-oxo- 2,3,5,6,7,8- hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylic acid (mixture of diastereomer, 4 isomers)

[0845] tert-Butyl (5RS,8RS)-2-{[3-fluoro-2-(trifluoromethyl)pyridin-4-yl]methyl}-8-methyl-3-oxo-2,3,5,6, 7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylate (diastereomer mixture; 4 isomers) (546 mg, 1.27 mmol) was dissolved in dichloromethane (10 mL), and trifluoroacetic acid (2.0 mL, 25 mmol) was added at room temperature. After the reaction mixture was stirred at room temperature overnight, the solvent was removed under reduced pressure. 474 mg (94% chance) of the title compound was obtained. LC-MS (Method 3): Rt = 1.29 min; MS (ESIpos): m /z = 375 [M+H]+ Intermediate 317 (5RS,8RS)-2-(3-Chloro-4-fluorobenzyl)-8-methyl-3-oxo-2,3,5, 6,7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylic acid (mixture of diastereomer, 4 isomers)

[0846] tert-Butyl (5RS,8RS)-2-(3-chloro-4-fluorobenzyl)-8-methyl-3-oxo-2,3,5,6,7,8-hexahydro[1, 2,4]triazolo[4,3-a]pyridine-5-carboxylate (mixture of diastereomer, 4 isomers) (450 mg, 1.14 mmol) was dissolved in dichloromethane (10 mL), and trifluoroacetic acid (1. 8 mL, 23 mmol) was added at room temperature. After the reaction mixture was stirred at room temperature overnight, the solvent was removed under reduced pressure. 470 mg (79% purity, 96% possibility) of the title compound was obtained. LC-MS (Method 3): Rt = 1.41 min; MS (ESIpos): m /z = 340 [M+H]+ Intermediate 318 (5RS,8RS)-2-(2,4-Difluorobenzyl)-8-methyl-3-oxo-2,3,5,6, 7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylic acid (mixture of diastereomer, 4 isomers)

[0847] tert-Butyl (5RS,8RS)-2-(2,4-difluorobenzyl)-8-methyl-3-oxo-2,3,5,6,7,8-hexahydro[1,2, 4]triazolo[4,3-a]pyridine-5-carboxylate (mixture of diastereomer; 4 isomers) (400 mg, 1.05 mmol) was dissolved in dichloromethane (10 mL), and trifluoroacetic acid (1.6 mL , 21 mmol) was added at room temperature. After the reaction mixture was stirred at room temperature overnight, the solvent was removed under reduced pressure. 578 mg (87% purity, 148% possibility) of the title compound was obtained. LC-MS (Method 3): Rt = 1.26 min; MS (ESIpos): m /z = 324 [M+H]+ Intermediate 319 (5RS,8RS)-8-Methyl-3-oxo-2-{[6-(trifluoromethyl)pyridin-3-yl]methyl}- 2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylic acid (mixture of diastereomer; 4 isomers)

[0848] tert-Butyl (5RS,8RS)-8-methyl-3-oxo-2-{[6-(trifluoromethyl)pyridin-3-yl]methyl}-2,3,5,6,7, 8-hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylate (mixture of diastereomer, 4 isomers) (854 mg, 2.07 mmol) was dissolved in dichloromethane (10 mL) , and trifluoroacetic acid (10 mL, 130 mmol) was added at room temperature. After the reaction mixture was stirred at room temperature for 2 h, the solvent was removed under reduced pressure. The residue was mixed with water and dichloromethane. The organic phase was removed and the aqueous phase was extracted three times with dichloromethane. The combined organic phases were washed with saturated aqueous sodium chloride solution, dried over sodium sulfate and filtered, and the filtrate was concentrated. 727 mg (99% chance) of the title compound was obtained. LC-MS (Method 3): Rt = 1.20 min; MS (ESIpos): m /z = 357 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.008 (2.12), 0.008 (1.76), 1.142 (0.42), 1.175 ( 15.73), 1,192 (16.00), 1,206 (1.64), 1,228 (2.06), 1,239 (1.49), 1,259 (0.64), 1,270 (0.63), 1,320 (0.68), 1,886 (1.20), 1,898 (1.32), 1.908 ( 1.05), 1.920 (1.15), 2.106 (0.43), 2.119 (1.06), 2.126 (1.10), 2.135 (1.16), 2.142 (1.21), 2.151 (2.06), 2.162 (3.13), 2.168 (3.21), 2.197 ( 0.61), 2.328 (0.44), 2.524 (1.33), 2.670 (0.41), 2.717 (1.01), 2.731 (1.49), 2.747 (1.88), 2.763 (1.41), 2.778 (0.89), 3.568 (3.56), 4.501 ( 2.48), 4.507 (3.45), 4.517 (2.38), 4.522 (2.56), 5.023 (1.32), 5.064 (6.79), 5.081 (6.73), 5.122 (1.30), 7.892 (0.60), 7.910 (13.13), 7.912 ( 13.01), 7.936 (0.51), 8.645 (4.58). Intermediate 320 (5S)-2-(3-Chloro-4-fluorobenzyl)-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3- a]pyridine-5-carboxylic acid

[0849] Methyl (5S)-2-(3-chloro-4-methylbenzyl)-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4, 3-a]pyridine-5-carboxylate (58.5 mg, 172 μmol) was initially loaded into THF (570 μl) and lithium hydroxide (20.6 mg, 861 μmol) dissolved in water was added. After stirring at room temperature overnight, the reaction mixture was concentrated under reduced pressure and then mixed with water, 1N aqueous hydrochloric acid and saturated aqueous sodium chloride solution. The aqueous phase was extracted three times with ethyl acetate. The combined organic phases were dried over sodium sulfate and filtered, and the filtrate was concentrated. 55.0 mg (98% chance) of the title compound was obtained. LC-MS (Method 4): Rt = 0.70 min; MS (ESIpos): m /z = 326 [M+H]+ Intermediate 321 (5S)-3-Oxo-2-[3-(trifluoromethyl)benzyl]-2,3,5,6,7,8-hexa - hydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylic acid

[0850] Methyl (5S)-3-oxo-2-[3-(trifluoromethyl)benzyl]-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3 -a]pyridine-5-carboxylate (336 mg, 947 μmol) was dissolved in THF (10 mL), and trifluoroacetic acid (113 mg, 4.73 mmol) was added at room temperature. After the reaction mixture was stirred at room temperature for 5 hours, the solvent was removed under reduced pressure. 218 mg (67% chance) of the title compound was obtained. LC-MS (Method 1): Rt = 1.01 min; MS (ESIpos): m /z = 342 [M+H]+ Intermediate 322 (5S)-3-Oxo-2-{[4-(trifluoromethyl)pyridin-2-yl]methyl}-2,3,5, 6,7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylic acid

[0851] Methyl (5S)-3-oxo-2-{[4-(trifluoromethyl)pyridin-2-yl]methyl}-2,3,5,6,7,8-hexahydro[1,2, 4]triazolo[4,3-a]pyridine-5-carboxylate (275 mg, 770 μmol) was initially loaded into THF (10 mL) and lithium hydroxide (92.2 mg, 3.85 mmol) dissolved in water. After stirring at room temperature for 5 hours, the reaction mixture was concentrated under reduced pressure and then mixed with water, 1N aqueous hydrochloric acid and saturated aqueous sodium chloride solution. The aqueous phase was extracted three times with ethyl acetate. The combined organic phases were dried over sodium sulfate and filtered, and the filtrate was concentrated. 247 mg (94% chance) of the title compound was obtained. LC-MS (Method 4): Rt = 0.59 min; MS (ESIpos): m /z = 343 [M+H]+ Intermediate 323 (5S)-3-Oxo-2-{[2-(trifluoromethyl)pyrimidin-4-yl]methyl}-2,3,5, 6,7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylic acid

[0852] Methyl (5S)-3-oxo-2-{[2-(trifluoromethyl)pyrimidin-4-yl]methyl}-2,3,5,6,7,8-hexahydro[1,2, 4]triazolo[4,3-a]pyridine-5-carboxylate (49.5 mg, 139 μmol) was initially loaded into THF (2.0 mL) and lithium hydroxide (16.6 mg, 693 μmol) was added. dissolved in water. After stirring at room temperature for 5 hours, the reaction mixture was concentrated under reduced pressure and then mixed with water, 1N aqueous hydrochloric acid and saturated aqueous sodium chloride solution. The aqueous phase was extracted three times with ethyl acetate. The combined organic phases were dried over sodium sulfate and filtered, and the filtrate was concentrated. 45.0 mg (95% chance) of the title compound was obtained. LC-MS (Method 4): Rt = 0.55 min; MS (ESIpos): m /z = 344 [M+H]+ Intermediate 324 (5S)-3-Oxo-2-{[5-(trifluoromethyl)pyridin-2-yl]methyl}-2,3,5, 6,7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylic acid

[0853] Methyl (5S)-3-oxo-2-{[5-(trifluoromethyl)pyridin-2-yl]methyl}-2,3,5,6,7,8-hexahydro[1,2, 4]triazolo[4,3-a]pyridine-5-carboxylate (175 mg, 491 μmol) was initially loaded into THF (7.0 mL) and lithium hydroxide (58.8 mg, 2.46 mmol) was added. dissolved in water. After stirring at room temperature for 5 hours, the reaction mixture was concentrated under reduced pressure and then mixed with water, 1N aqueous hydrochloric acid and saturated aqueous sodium chloride solution. The aqueous phase was extracted three times with ethyl acetate. The combined organic phases were dried over sodium sulfate and filtered, and the filtrate was concentrated. 156 mg (93% chance) of the title compound was obtained. LC-MS (Method 3): Rt = 1.04 min; MS (ESIpos): m /z = 343 [M+H]+ Intermediate 325 (5S)-2-[(5-Methyl-1H-pyrazol-3-yl)methyl]-3-oxo-2,3,5 ,6,7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylic acid

[0854] Methyl (5RS)-2-[(5-methyl-1H-pyrazol-3-yl)methyl]-3-oxo- 2,3,5,6,7,8-hexahydro[1,2 ,4]triazolo[4,3-a]pyridine-5-carboxylate (60.0 mg, 206 μmol) was initially loaded into THF (3.0 mL) and lithium hydroxide (24.7 mg, 1.0 mL) was added. 03 mmol) dissolved in water. After stirring at room temperature overnight, the reaction mixture was concentrated under reduced pressure and then mixed with water, 1N aqueous hydrochloric acid and saturated aqueous sodium chloride solution. The aqueous phase was extracted three times with ethyl acetate. The combined organic phases were dried over sodium sulfate and filtered, and the filtrate was concentrated. 38.0 mg (67% chance) of the title compound was obtained. LC-MS (Method 3): Rt = 0.57 min; MS (ESIpos): m /z = 278 [M+H]+ Intermediate 326 (5S)-2-{[3-Chloro-2-(trifluoromethyl)pyridin-2-yl]methyl}-3-oxo-2, 3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylic acid

[0855] Methyl (5S)-2-{[3-chloro-4-(trifluoromethyl)pyridin-2-yl]methyl}-3-oxo-2,3,5,6,7,8-hexahydro[ 1,2,4]triazolo[4,3-a]pyridine-5-carboxylate (137 mg, 351 μmol) was initially loaded into THF (2.0 mL) and lithium hydroxide (42.0 mg, 1 .75 mmol) dissolved in water. After stirring at room temperature for 72 hours, the reaction mixture was concentrated under reduced pressure and then mixed with water, 1N aqueous hydrochloric acid and saturated aqueous sodium chloride solution. The aqueous phase was extracted three times with ethyl acetate. The combined organic phases were dried over sodium sulfate and filtered, and the filtrate was concentrated. 107 mg (81% chance) of the title compound was obtained. LC-MS (Method 3): Rt = 1.18 min; MS (ESIpos): m /z = 377 [M+H]+ Intermediate 327 (5S)-2-[4-Fluoro-3-(trifluoromethyl)benzyl]-3-oxo-2,3,5,6,7 ,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylic acid

[0856] Methyl (5S)-2-[4-fluoro-3-(trifluoromethyl)benzyl]-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazole [4,3-a]pyridine-5-carboxylate (370 mg, 991 μmol) was initially loaded into THF (5.0 mL) and lithium hydroxide (119 mg, 4.96 mmol) dissolved in water was added. After stirring overnight, the reaction mixture was mixed at room temperature with water, 1 N aqueous hydrochloric acid, and saturated aqueous sodium chloride solution. The organic phase was removed and the aqueous phase was extracted three times with ethyl acetate. The combined organic phases were dried over sodium sulfate and filtered, and the filtrate was concentrated. 133 mg (37% chance) of the title compound was obtained. LC-MS (Method 1): Rt = 1.03 min; MS (ESIpos): m /z = 360 [M+H]+ Intermediate 328 (5S)-3-Oxo-2-{[6-(trifluoromethyl)pyridin-3-yl]methyl}-2,3,5, 6,7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylic acid

[0857] Methyl (5S)-3-oxo-2-{[6-(trifluoromethyl)pyridin-3-yl]methyl}-2,3,5,6,7,8-hexahydro[1,2, 4]triazolo[4,3-a]pyridine-5-carboxylate (442 mg, 75% purity, 930 μmol) was initially loaded into THF (2.7 mL) and lithium hydroxide (111 mg, 4.0 mL) was added. 65 mmol) dissolved in water. After stirring for 72 hours, the reaction mixture was mixed at room temperature with water, 1N aqueous hydrochloric acid and saturated aqueous sodium chloride solution. The organic phase was removed and the aqueous phase was extracted three times with ethyl acetate. The combined organic phases were dried over sodium sulfate and filtered, and the filtrate was concentrated. 316 mg (90% chance) of the title compound was obtained. LC-MS (Method 1): Rt = 0.83 min; MS (ESIpos): m /z = 343 [M+H]+ Alternative synthesis:

[0858] tert-Butyl (5S)-3-oxo-2-{[6-(trifluoromethyl)pyridin-3-yl]methyl}-2,3,5,6,7,8-hexahydro[1, 2,4]triazolo[4,3-a]pyridine-5-carboxylate (411 mg, 1.03 mmol) was dissolved in dichloromethane (5.0 mL), and trifluoroacetic acid (1.6 mL, 21 mmol) was added at 0°C. After the reaction mixture was stirred at room temperature overnight, the solvent was removed under reduced pressure. 798 mg (90% purity, >100% chance) of the title compound was obtained. LC-MS (Method 4): Rt = 0.60 min; MS (ESIpos): m /z = 343 [M+H]+ Intermediate 329 (5S)-2-{[6-Fluoro-2-(trifluoromethyl)quinolin-4-yl]methyl}-3-oxo-2, 3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylic acid

[0859] Methyl (5S)-2-{[6-fluoro-2-(trifluoromethyl)quinolin-4-yl]methyl}-3-oxo-2,3,5,6,7,8-hexahydro[ 1,2,4]triazolo[4,3-a]pyridine-5-carboxylate (59.0 mg, 139 μmol) was initially loaded into THF (2.0 mL) and lithium hydroxide (16.6 mg) was added , 695 μmol) dissolved in water. After stirring at room temperature for 72 hours, the reaction mixture was concentrated under reduced pressure and then mixed with water, 1N aqueous hydrochloric acid and saturated aqueous sodium chloride solution. The aqueous phase was extracted three times with ethyl acetate. The combined organic phases were dried over sodium sulfate and filtered, and the filtrate was concentrated. 44.0 mg (77% chance) of the title compound was obtained. LC-MS (Method 3): Rt = 1.46 min; MS (ESIpos): m /z = 411 [M+H]+ Intermediate 330 (5S)-2-(6,7-Dihydro-5H-cyclopenta[c]pyridin-3-ylmethyl)-3-oxo- 2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylic acid

[0860] Methyl (5S)-2-(6,7-dihydro-5H-cyclopenta[c]pyridin-3-ylmethyl)- 3-oxo-2,3,5,6,7,8-hexa- hydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylate (109 mg, 90% purity, 299 μmol) was initially loaded into THF (4.0 mL) and lithium hydroxide was added (35.8 mg, 1.50 mmol) dissolved in water. After stirring at room temperature overnight, the reaction mixture was concentrated under reduced pressure and then mixed with water, 1N aqueous hydrochloric acid and saturated aqueous sodium chloride solution. The aqueous phase was extracted three times with ethyl acetate. The combined organic phases were dried over sodium sulfate and filtered, and the filtrate was concentrated. 72.0 mg (43% purity, 33% chance) of the title compound was obtained. LC-MS (Method 3): Rt = 0.48 min; MS (ESIpos): m /z = 315 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: 1.645 (7.08), 2.036 (7.44), 2.158 (4.32), 2.859 (16.00 ), 3,974 (4.21), 4,762 (9.00), 7,462 (5.14), 8,192 (4.78). Intermediate 331 (5S)-3-Oxo-2-{[5-(trifluoromethyl)pyridin-3-yl]methyl}-2,3,5,6,7,8-hexahydro[1,2,4] triazolo[4,3-a]pyridine-5-carboxylic acid

[0861] Methyl (5S)-3-oxo-2-{[5-(trifluoromethyl)pyridin-3-yl]methyl}-2,3,5,6,7,8-hexahydro[1,2, 4]triazolo[4,3-a]pyridine-5-carboxylate (40.9 mg, 115 μmol) was initially loaded into THF (3.0 mL, 37 mmol) and lithium hydroxide (13.7 mg, 574 μmol) dissolved in water. After stirring at room temperature overnight, the reaction mixture was concentrated under reduced pressure and then mixed with water, 1N aqueous hydrochloric acid and saturated aqueous sodium chloride solution. The aqueous phase was extracted three times with ethyl acetate. The combined organic phases were dried over sodium sulfate and filtered, and the filtrate was concentrated. 35.4 mg (90% chance) of the title compound was obtained. LC-MS (Method 3): Rt = 0.99 min; MS (ESIpos): m /z = 343 [M+H]+ Intermediate 332 (5S)-2-[(6-Methoxypyridin-3-yl)methyl]-3-oxo-2,3,5,6,7 ,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylic acid

[0862] tert-Butyl (5S)-2-[(6-methoxypyridin-3-yl)methyl]-3-oxo- 2,3,5,6,7,8-hexahydro[1,2,4 ]triazolo[4,3-a]pyridine-5-carboxylate (761 mg, 2.11 mmol) was dissolved in dichloromethane (30 mL), and trifluoroacetic acid (3.3 mL, 42 mmol) was added at room temperature . After the reaction mixture was stirred at room temperature overnight, the solvent was removed under reduced pressure. 1.97 g (97% chance) of the title compound was obtained. LC-MS (Method 3): Rt = 0.99 min; MS (ESIpos): m /z = 305 [M+H]+ Intermediate 333 (5S)-2-{[3-Fluoro-2-(trifluoromethyl)pyridin-4-yl]methyl}-3-oxo-2, 3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylic acid

[0863] tert-Butyl (5S)-2-{[3-fluoro-2-(trifluoromethyl)pyridin-4-yl]methyl}-3-oxo-2,3,5,6,7,8-hexa- hydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylate (1.37 g, 3.29 mmol) was dissolved in dichloromethane (25 mL), and trifluoroacetic acid (5.1 mL , 66 mmol) was added at room temperature. After the reaction mixture was stirred at room temperature overnight, the solvent was removed under reduced pressure. 2.07 g (>100% chance) of the title compound was obtained. LC-MS (Method 3): Rt = 1.11 min; MS (ESIpos): m /z = 361 [M+H]+ Intermediate 334 (5S)-2-[2-(4-Methylphenyl)ethyl]-3-oxo-2,3,5,6,7,8 -hexa-hydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylic acid

[0864] tert-Butyl (5S)-2-[2-(-4-methylphenyl)ethyl]-3-oxo--2,3,5,6,7,8-hexahydro[1,2,4 ]triazolo[4,3-a]pyridine-5-carboxylate (238 mg, 665 μmol) was dissolved in dichloromethane (6.7 mL), and trifluoroacetic acid (800 μl, 10 mmol) was added at room temperature. After the reaction mixture was stirred at room temperature overnight, the solvent was removed under reduced pressure. 325 mg (>100% chance) of the title compound was obtained. LC-MS (Method 1): Rt = 0.98 min; MS (ESIpos): m /z = 302 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: 0.008 (1.06), 1.111 (0.44), 1.228 (0.60), 1.534 (1.02 ), 1.805 (0.42), 1.816 (0.43), 2.066 (1.03), 2.072 (1.19), 2.082 (1.11), 2.094 (0.64), 2.257 (9.22), 2.524 (0.71), 2.568 (0.54), 2.580 (0.54 ), 2.594 (0.41), 2.633 (0.41), 2.645 (0.71), 2.656 (0.54), 2.863 (1.16), 2.882 (2.43), 2.900 (1.28), 3.766 (0.67), 3.784 (1.69), 3.804 (1.53 ), 3,824 (0.62), 4,390 (0.71), 4,402 (1.44), 4,415 (0.79), 7,084 (16.00), 7,093 (1.84). Intermediate 335 (5S)-2-[(1R)-1-(4-Methylphenyl)ethyl]-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazole [4,3-a]pyridine-5-carboxylic acid (mixture of diastereomer, 2 isomers)

[0865] tert-Butyl (5S)-2-[(1RS)-1-(4-methylphenyl)ethyl]-3-oxo-2,3,5,6,7,8-hexahydro[1,2 ,4]triazolo[4,3-a]pyridine-5-carboxylate (69.8 mg, 195 μmol) was dissolved in dichloromethane (2.5 mL), and trifluoroacetic acid (300 μL, 3.9 mmol) was added at room temperature. After the reaction mixture was stirred at room temperature overnight, the solvent was removed under reduced pressure. 73.1 mg (>100% chance) of the title compound was obtained. LC-MS (Method 1): Rt = 0.98 min; MS (ESIneg): m /z = 300 [MH]- 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (0.62), -0.008 (6.44), 0.008 (6.37), 0.146 (0.65 ), 1.055 (0.44), 1.291 (0.56), 1.309 (1.08), 1.326 (0.54), 1.532 (0.71), 1.584 (8.87), 1.602 (8.75), 1.799 (0.87), 1.810 (0.79), 1.822 (0.73 ), 1.832 (0.73), 2.058 (1.44), 2.070 (2.60), 2.081 (2.58), 2.267 (16.00), 2.280 (1.58), 2.327 (1.15), 2.366 (0.85), 2.561 (1.98), 2.576 (1.25 ), 2.589 (1.21), 2.603 (0.87), 2.632 (0.94), 2.643 (1.50), 2.654 (1.08), 2.669 (1.40), 2.674 (1.37), 2.709 (0.87), 4.414 (0.56), 4.426 (1.52 ), 4,439 (2.79), 4,450 (1.65), 5,251 (0.56), 5,268 (1.98), 5,286 (1.92), 5,303 (0.54), 7,109 (2.96), 7,129 (5.87), 7,171 (6.58), 7,191 (3.38 ). Intermediate 336 (5S)-2-{[3-Chloro-2-(trifluoromethyl)pyridin-2-yl]methyl}-3-oxo-2,3,5,6,7,8-hexahydro[1, 2,4]triazolo[4,3-a]pyridine-5-carboxylic acid

[0866] tert-Butyl (5S)-2-{[3-chloro-4-(trifluoromethyl)pyridin-2-yl]methyl}-3-oxo-2,3,5,6,7,8-hexa- hydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylate (794 mg, 94% purity, 1.72 mmol) was dissolved in dichloromethane (28 mL), and trifluoroacetic acid (2 .7 mL, 34 mmol) was added at room temperature. After the reaction mixture was stirred at room temperature for 72 hours, the solvent was removed under reduced pressure. 800 mg (78% purity, 96% chance) of the title compound was obtained. LC-MS (Method 1): Rt = 0.91 min; MS (ESIpos): m /z = 377 [M+H]+ Intermediate 337 (5S)-2-{[1-(4-Methylphenyl)cyclopropyl]methyl}-3-oxo-2,3,5,6, 7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylic acid

[0867] tert-Butyl (5S)-2-{[1-(-4-methylphenyl)cyclopropyl]methyl}-3-oxo-2,3,5,6,7,8-hexahydro[1,2 ,4]triazolo[4,3-a]pyridine-5-carboxylate (167 mg, 436 μmol) was dissolved in dichloromethane (10 mL), and trifluoroacetic acid (670 μL, 8.7 mmol) was added at room temperature. . After the reaction mixture was stirred at room temperature overnight, the solvent was removed under reduced pressure. 228 mg (83% purity, >100% possibility) of the title compound was obtained. LC-MS (Method 1): Rt = 1.06 min; MS (ESIpos): m /z = 328 [M+H]+ ¹H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.008 (2.90), 0.008 (2.46), 0.708 (0.68), 0.729 ( 1.89), 0.756 (0.50), 0.783 (2.19), 0.806 (0.89), 0.978 (5.27), 1.110 (1.47), 1.175 (0.42), 1.378 (1.96), 1.406 (0.45), 1.535 (3.25), 1.782 ( 0.88), 1.988 (0.80), 2.051 (2.35), 2.063 (2.37), 2.074 (1.57), 2.206 (0.47), 2.235 (16.00), 2.328 (0.54), 2.524 (2.40), 2.606 (1.64), 2.615 ( 0.98), 2.646 (0.76), 2.671 (0.54), 3.729 (2.03), 3.765 (3.10), 3.877 (3.00), 3.913 (1.98), 4.363 (1.59), 4.374 (3.00), 4.387 (1.53), 5.754 ( 0.48), 7.024 (3.37), 7.044 (5.39), 7.106 (6.44), 7.126 (3.93), 11.356 (0.45). Intermediate 338 (5S)-3-Oxo-2-{[2-(trifluoromethyl)-1,8-naphthyridin-3-yl]methyl}-2,3,5,6,7,8-hexahydro[1 ,2,4]triazolo[4,3-a]pyridine-5-carboxylic acid

[0868] tert-Butyl (5S)-3-oxo-2-{[2-(trifluoromethyl)-1,8-naphthyridin-3-yl]methyl}-2,3,5,6,7,8-hexa -hydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylate (146 mg, 326 μmol) was dissolved in dichloromethane (7.0 mL) and trifluoroacetic acid (500 μl, 6.5 mmol ) was added at 0°C. After the reaction mixture was stirred at room temperature overnight, trifluoroacetic acid (500 μl, 6.5 mmol) was added again, and the mixture was stirred at room temperature overnight. The solvent was removed under reduced pressure. 252 mg (>100% chance) of the title compound was obtained. LC-MS (Method 4): Rt = 0.56 min; MS (ESIpos): m /z = 394 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (0.50), -0.008 (3.97), 0.008 (3.74), 0.146 (0.43) (3.42) (3.95) (3.61), 8,570 (3.57), 8,575 (3.38), 9,247 (3.83), 9,252 (4.07), 9,257 (3.95), 9,262 (3.69). Intermediate 339 (5S)-2-[(6-Chloropyridin-3-yl)methyl]-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4 ,3-a]pyridine-5-carboxylic acid

[0869] tert-Butyl (5S)-2-[(6-chloropyridin-3-yl)methyl]-3-oxo- 2,3,5,6,7,8-hexahydro[1,2,4 ]triazolo[4,3-a]pyridine-5-carboxylate (509 mg, 93% purity, 1.30 mmol) was dissolved in dichloromethane (20 mL), and trifluoroacetic acid (2.0 mL, 26 mmol) was added at 0°C. After the reaction mixture was stirred at room temperature overnight, the solvent was removed under reduced pressure. 850 mg (>100% chance) of the title compound was obtained. LC-MS (Method 3): Rt = 0.85 min; MS (ESIpos): m /z = 309 [M+H]+ 2.669 (1.44), 2.710 (0.57), 4.461 (2.42), 4.473 (4.35), 4.486 (2.19), 4.827 (0.51), 4.909 (16.00) , 5.067 (0.79), 5.075 (0.79), 5.088 (0.82), 5.097 (0.79), 5.445 (0.78), 7.500 (4.15), 7.510 (0.76), 7.520 (5.05), 7.703 (3.14), 7.709 (3.08) , 7,723 (2.67), 7,730 (2.53), 8,309 (3.43), 8,314 (3.14). Intermediate 340 (5S)-2-{[5-Chloro-6-(trifluoromethyl)pyridin-3-yl]methyl}-3-oxo-2,3,5,6,7,8-hexahydro[1, 2,4]triazolo[4,3-a]pyridine-5-carboxylic acid

[0870] tert-Butyl (5S)-2-{[5-chloro-6-(trifluoromethyl)pyridin-3-yl]methyl}-3-oxo-2,3,5,6,7,8-hexa- hydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylate (156 mg, 360 μmol) was dissolved in dichloromethane (3.0 mL), and trifluoroacetic acid (560 μl, 7.2 mmol) was added at 0°C. After the reaction mixture was stirred at room temperature overnight, the solvent was removed under reduced pressure. 156 mg (66% purity, 76% chance) of the title compound was obtained. LC-MS (Method 1): Rt = 0.99 min; MS (ESIpos): m /z = 377 [M+H]+ Intermediate 341 (5S)-2-(3,4-Difluorobenzyl)-3-oxo-2,3,5,6,7,8-hexa- hydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylic acid

[0871] tert-Butyl (5S)-2-(3,4-difluorobenzyl)-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4, 3-a]pyridine-5-carboxylate (900 mg, 78% purity, 1.92 mmol) was dissolved in dichloromethane (10 mL), and trifluoroacetic acid (3.0 mL, 38 mmol) was added at 0°C . After the reaction mixture was stirred at room temperature overnight, the solvent was removed under reduced pressure. 590 mg (92% chance) of the title compound was obtained. LC-MS (Method 3): Rt = 1.14 min; MS (ESIpos): m /z = 310 [M+H]+ Intermediate 342 (5S)-3-Oxo-2-(2,4,5-trifluorobenzyl)-2,3,5,6,7,8- hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylic acid

[0872] tert-Butyl (5S)-3-oxo-2-(2,4,5-trifluorobenzyl)-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[ 4,3-a]pyridine-5-carboxylate (523 mg, 1.36 mmol) was dissolved in dichloromethane (10 mL), and trifluoroacetic acid (2.1 mL, 27 mmol) was added at 0°C. After the reaction mixture was stirred at room temperature overnight, the solvent was removed under reduced pressure. 774 mg (>100% chance) of the title compound was obtained. LC-MS (Method 3): Rt = 1.14 min; MS (ESIpos): m /z = 328 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.008 (0.82), 0.008 (0.68), 1.118 (6.81), 1.129 ( 0.42), 1.161 (2.13), 1.170 (0.42), 1.179 (4.32), 1.186 (0.44), 1.197 (2.17), 1.236 (1.91), 1.399 (0.56), 1.469 (0.47), 1.484 (1.04), 1.497 ( 1.48), 1.511 (1.77), 1.521 (2.46), 1.537 (2.89), 1.548 (2.11), 1.561 (1.23), 1.568 (1.17), 1.582 (0.67), 1.756 (0.53), 1.807 (2.09), 1.820 ( 2.94), 1.830 (2.93), 1.841 (2.39), 1.852 (2.37), 1.914 (1.15), 1.990 (7.81), 2.055 (0.59), 2.060 (0.54), 2.073 (1.51), 2.082 (3.23), 2.090 ( 5.04), 2.104 (8.58), 2.115 (7.88), 2.126 (4.11), 2.563 (3.78), 2.576 (3.69), 2.591 (2.87), 2.626 (3.11), 2.638 (4.92), 2.648 (3.42), 2.668 ( 1.70), 2.679 (2.33), 2.690 (1.39), 4.008 (0.60), 4.025 (1.83), 4.043 (1.80), 4.061 (0.58), 4.477 (5.29), 4.488 (10.00), 4.501 (5.14), 4.757 ( 1.78), 4,831 (1.52), 4,872 (16.00), 4,878 (15.58), 4,918 (1.43), 7,264 (6,52), 7,282 (7,05), 7,287 (7,36), 7,291 (7,18), 7,304 (7,27), 7,308 (7,27) (7,27) 7.32), 7.313 (6.92), 7.331 (6.44), 7.523 (4.17), 7.540 (4.34), 7.548 (5.42), 7.565 (5.28), 7.574 (4.10), 7.591 (3.71), 7.621 (1.61), 7.648 ( 1.44), 7.673 (1.15), 7.694 (1.09), 7.711 (1.06), 7.733 (1.00), 7.761 (0.87), 7.832 (0.71), 8.138 (0.92). Intermediate 343 (5S)-2-{2-[3-Chloro-5-(trifluoromethyl)pyridin-2-yl]ethyl}-3-oxo-2,3,5,6,7,8-hexahydro[ 1,2,4]triazolo[4,3-a]pyridine-5-carboxylic acid

[0873] tert-Butyl (5S)-2-{2-[3-chloro-5-(trifluoromethyl)pyridin-2-yl]ethyl}-3-oxo-2,3,5,6,7,8- hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylate (120 mg, 269 μmol) was dissolved in dichloromethane (4.0 mL) and trifluoroacetic acid (410 μl, 5.4 mmol) was added at 0°C. After the reaction mixture was stirred at room temperature overnight, trifluoroacetic acid (300 μl, 3.9 mmol) was added again, and the mixture was stirred at room temperature overnight. The solvent was removed under reduced pressure. 153 mg (>100% chance) of the title compound was obtained. LC-MS (Method 1): Rt = 0.99 min; MS (ESIpos): m /z = 391 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.150 (0.75), 0.146 (0.75), 0.833 (0.43), 1.038 ( 0.57), 1.056 (1.21), 1.073 (0.60), 1.110 (2.01), 1.157 (0.57), 1.176 (0.83), 1.236 (1.38), 1.291 (3.19), 1.309 (6.41), 1.327 (3.25), 1.390 ( 1.90), 1.538 (2.30), 1.566 (1.41), 1.783 (2.07), 1.793 (3.13), 1.805 (3.02), 1.815 (2.61), 1.827 (2.53), 2.047 (4.51), 2.060 (8.10), 2.076 ( 7.58) 30 ), 2.671 (3.02), 2.710 (1.35), 3.291 (7.47) 3.309 (16.00), 3.328 (8.53), 3.432 (0.63), 3.449 (0.69), 4.004 (1.58) 4.022 (2.90), 4.039 (5.49), 4,057 (9.91), 4,081 (9.13), 4,099 (5.34), 4,116 (2.82), 4,135 (1.58), 4,384 (6.49), 4,396 (12.67), 4,408 (6.69), 4,415 (4.71), 4,433 (4.22), 4,450 (2.56), 4,729 (2.82), 8,414 (9.91), 8,881 (10.08). Intermediate 344 (5S)-2-[3-Chloro-4-(trifluoromethyl)benzyl]-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3 -a]pyridine-5-carboxylic acid

[0874] tert-Butyl (5S)-2-[3-chloro-4-(trifluoromethyl)benzyl]-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4 ]triazolo[4,3-a]pyridine-5-carboxylate (523 mg, 1.21 mmol) was dissolved in dichloromethane (10 mL), and trifluoroacetic acid (1.9 mL, 24 mmol) was added at 0° W. After the reaction mixture was stirred at room temperature overnight, the solvent was removed under reduced pressure. 175 mg (37% chance) of the title compound was obtained. LC-MS (Method 1): Rt = 1.09 min; MS (ESIpos): m /z = 376 [M+H]+ ¹H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.008 (2.69), 0.008 (2.18), 0.018 (0.56), 0.837 ( 0.57), 1.227 (0.51), 1.235 (0.42), 1.460 (0.42), 1.515 (1.26), 1.527 (1.23), 1.543 (1.10), 1.822 (1.58), 1.834 (1.53), 1.844 (1.29), 1.855 ( 1.31), 2.108 (4.38), 2.118 (4.15), 2.130 (2.21), 2.328 (0.63), 2.366 (0.62), 2.524 (2.14), 2.558 (2.84), 2.573 (1.97), 2.586 (2.06), 2.600 ( 1.62), 2.631 (1.67), 2.643 (2.69), 2.653 (1.89), 2.674 (1.29), 2.683 (1.20), 2.695 (0.72), 2.710 (0.63), 4.107 (0.72), 4.322 (1.38), 4.490 ( 3.29), 4.501 (5.97), 4.514 (3.19), 4.588 (0.53), 4.973 (16.00), 7.391 (3.50), 7.412 (3.86), 7.561 (7.11), 7.835 (6.26), 7.855 (5.71). Intermediate 345 (5S)-2-[3-Fluoro-4-(trifluoromethyl)benzyl]-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3 -a]pyridine-5-carboxylic acid

[0875] tert-Butyl (5S)-2-[3-fluoro-4-(trifluoromethyl)benzyl]-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4 ]triazolo[4,3-a]pyridine-5-carboxylate (707 mg, 1.70 mmol) was dissolved in dichloromethane (10 mL), and trifluoroacetic acid (2.6 mL, 34 mmol) was added at 0°C . After the reaction mixture was stirred at room temperature overnight, the solvent was removed under reduced pressure. 611 mg (96% chance) of the title compound was obtained. LC-MS (Method 3): Rt = 1.42 min; MS (ESIpos): m /z = 360 [M+H]+ Intermediate 346 (5S)-2-{[1-(6-Chloropyridin-2-yl)cyclopropyl]methyl}-3-oxo-2,3, 5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylic acid

[0876] tert-Butyl (5S)-2-{[1-(6-chloropyridin-2-yl)cyclopropyl]methyl}-3-oxo-2,3,5,6,7,8-hexahydro[ 1,2,4]triazolo[4,3-a]pyridine-5-carboxylate (224 mg, 554 μmol) was dissolved in dichloromethane (3.0 mL), and trifluoroacetic acid (850 μL, 11 mmol) was added at 0°C. After the reaction mixture was stirred at room temperature overnight, the solvent was removed under reduced pressure. 330 mg (>100% chance) of the title compound was obtained. LC-MS (Method 3): Rt = 1.20 min; MS (ESIpos): m /z = 349 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: 0.008 (0.48), 1.113 (1.42), 1.143 (0.85), 1.164 (10.97 ), 1.176 (15.26), 1.194 (2.29), 1.231 (0.88), 1.278 (0.44), 1.299 (0.48), 1.379 (0.87), 1.450 (0.49), 1.468 (0.79), 1.485 (1.13), 1.499 (1.16 ), 1.513 (1.06), 1.536 (4.67), 1.545 (0.54), 1.600 (0.68), 1.762 (0.79), 1.770 (1.14), 1.779 (1.55), 1.793 (1.54), 1.803 (1.35), 1.815 (1.28 ), 1.825 (1.00), 1.989 (5.49), 2.063 (4.19), 2.073 (4.25), 2.470 (0.72), 2.484 (1.00), 2.590 (1.40), 2.600 (2.51), 2.612 (1.97), 2.622 (0.54 ), 2.631 (0.82), 2.642 (1.22), 2.654 (0.82), 3.784 (0.51), 4.005 (0.47), 4.023 (1.38), 4.040 (1.38), 4.058 (0.74), 4.091 (16.00), 4.369 (0.48 ), 4.381 (0.93), 4.394 (0.53), 4.419 (2.40), 4.431 (4.64), 4.444 (2.31), 7.239 (4.53), 7.259 (4.97), 7.312 (0.46), 7.582 (4.49), 7.601 (6.06 ), 7,696 (3.81), 7,716 (6.11), 7,735 (2.62), 11,361 (0.58), 12,173 (0.58). Intermediate 347 (5S)-2-{[1-(4-Fluorophenyl)cyclopropyl]methyl}-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[ 4,3-a]pyridine-5-carboxylic acid

[0877] tert-Butyl (5S)-2-{[1-(4-fluorophenyl)cyclopropyl]methyl}-3-oxo-2,3,5,6,7,8-hexahydro[1,2, 4]triazolo[4,3-a]pyridine-5-carboxylate (557 mg, 1.44 mmol) was dissolved in dichloromethane (10 mL), and trifluoroacetic acid (2.2 mL, 29 mmol) was added at 0 °C. After the reaction mixture was stirred at room temperature overnight, the solvent was removed under reduced pressure. 743 mg (>100% chance) of the title compound was obtained. LC-MS (Method 4): Rt = 0.73 min; MS (ESIpos): m /z = 332 [M+H]+ Intermediate 348 (5S)-2-{[1-(4-Methoxyphenyl)cyclopropyl]methyl}-3-oxo-2,3,5,6, 7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylic acid

[0878] tert-Butyl (5S)-2-{[1-(4-methoxyphenyl)cyclopropyl]methyl}-3-oxo-2,3,5,6,7,8-hexahydro[1,2, 4]triazolo[4,3-a]pyridine-5-carboxylate (222 mg, 555 μmol) was dissolved in dichloromethane (3.0 mL), and trifluoroacetic acid (850 μL, 11 mmol) was added at 0°C . After the reaction mixture was stirred at room temperature overnight, the solvent was removed under reduced pressure. 373 mg (70% purity, >100% chance) of the title compound was obtained. LC-MS (Method 1): Rt = 0.97 min; MS (ESIpos): m /z = 344 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (0.45), -0.008 (3.69), 0.008 (3.61), 0.146 (0.45) (14.15) (1.91) (0.63), 1775 (1.48), 1788 (2.14), 1798 (2.10), 1809 (1.73), 1820 (1.70), 2005 (0.41), 2032 (2.15), 2040 (3.48), 2054 (5.96), 2065 (5.63) (1.28) (0.58) (3.38) (16.00), 7,120 (1.81), 7,127 (15.91), 7,132 (5.25), 7,144 (4.97), 7,149 (14.17), 7,156 (2.15), 11,357 (0.40). Intermediate 349 (5S)-3-Oxo-2-({1-[4-(trifluoromethyl)phenyl]cyclopropyl}methyl)-2,3,5,6,7,8-hexahydro[1,2,4 ]triazolo[4,3-a]pyridine-5-carboxylic acid

[0879] tert-Butyl (5S)-3-oxo-2-{[1-[4-(trifluoromethyl)phenyl]cyclopropyl}methyl)-2,3,5,6,7,8-hexahydro[1 ,2,4]triazolo[4,3-a]pyridine-5-carboxylate (113 mg, 258 μmol) was dissolved in dichloromethane (1.5 mL), and trifluoroacetic acid (400 μL, 5.2 mmol) was added at 0°C. After the reaction mixture was stirred at room temperature overnight, the solvent was removed under reduced pressure. 115 mg (88% purity, >100% possibility) of the title compound was obtained. LC-MS (Method 1): Rt = 1.14 min; MS (ESIpos): m /z = 382 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.150 (0.78), 0.008 (6.17), 0.146 (0.86), 0.866 ( 2.35), 0.893 (4.18), 0.926 (4.29), 0.951 (2.69), 1.038 (1.78), 1.055 (3.61), 1.073 (1.88), 1.110 (8.13), 1.127 (14.72), 1.227 (4.55), 1.291 ( 7.84), 1.309 (16.00), 1.327 (8.00), 1.358 (1.25), 1.492 (1.75), 1.736 (1.44), 1.785 (2.20), 1.795 (2.14), 1.817 (1.83), 2.052 (6.41), 2.064 ( 5.80), 2.327 (1.59), 2.366 (0.94), 2.465 (1.52), 2.601 (3.82), 2.612 (2.54), 2.643 (1.86), 2.670 (1.75), 2.710 (0.97), 3.414 (0.65), 3.431 ( 1.86) ( 10.17), 4,433 (9.93), 4,451 (5.59), 7,438 (9.57), 7,459 (12.99), 7,569 (13.54), 7,589 (10.01). Intermediate 350 (5S)-2-{[1-(2,4-Difluorophenyl)cyclopropyl]methyl}-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4] triazolo[4,3-a]pyridine-5-carboxylic acid

[0880] tert-Butyl (5S)-2-{[1-(2,4-difluorophenyl)cyclopropyl]methyl}-3-oxo-2,3,5,6,7,8-hexahydro[1, 2,4]triazolo[4,3-a]pyridine-5-carboxylate (256 mg, 630 μmol) was dissolved in dichloromethane (3.7 mL), and trifluoroacetic acid (970 μL, 13 mmol) was added at 0 °C. After the reaction mixture was stirred at room temperature overnight, the solvent was removed under reduced pressure. 391 mg (81% purity, >100% chance) of the title compound was obtained. LC-MS (Method 1): Rt = 1.01 min; MS (ESIpos): m /z = 350 [M+H]+ Intermediate 351 (5S)-2-(2,4-Difluorobenzyl)-3-oxo-2,3,5,6,7,8-hexa- hydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylic acid

[0881] tert-Butyl (5S)-2-(2,4-difluorobenzyl)-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4, 3-a]pyridine-5-carboxylate (443 mg, 1.21 mmol) was dissolved in dichloromethane (10 mL), and trifluoroacetic acid (1.9 mL, 24 mmol) was added at room temperature. After the reaction mixture was stirred at room temperature overnight, the solvent was removed under reduced pressure. 530 mg (>100% chance) of the title compound was obtained. LC-MS (Method 3): Rt = 1.10 min; MS (ESIpos): m /z = 310 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (0.62), -0.008 (6.71), 0.008 (4.59), 0.146 (0.59) (6.97) (3.22), 1821 (2.85), 1832 (2.72), 1988 (0.80), 2063 (4.96), 2075 (8.83), 2084 (8.61), 2092 (8.01), 2104 (4.30), 2328 (0.73), 2367 (0.62) (0.44) (15.73), 4860 (16.00), 4899 (3.40), 5097 (1.19), 5127 (1.32), 5475 (1.65), 5753 (0.97), 7047 (2.49), 7052 (2.65), 7069 (5.60), 7074 (5.92) (4.64), 7,311 (7.06), 7,328 (6.95), 7,349 (3.11). Intermediate 352 (5S)-2-(2-Chloro-4-fluorobenzyl)-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a] pyridine-5-carboxylic acid

[0882] tert-Butyl (5S)-2-(2-chloro-4-fluorobenzyl)-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[ 4,3-a]pyridine-5-carboxylate (371 mg, 970 μmol) was dissolved in dichloromethane (10 mL), and trifluoroacetic acid (1.5 mL, 19 mmol) was added at room temperature. After the reaction mixture was stirred at room temperature overnight, the solvent was removed under reduced pressure. 580 mg (>100% chance) of the title compound was obtained. LC-MS (Method 3): Rt = 1.19 min; MS (ESIpos): m /z = 326 [M+H]+ ¹H-NMR (400 MHz, DMSO-d6) δ [ppm]: 1.110 (1.55), 1.157 (0.51), 1.175 (1.15), 1.192 (0.58 ), 1.227 (0.70), 1.404 (1.18), 1.520 (1.43), 1.534 (1.96), 1.548 (1.29), 1.561 (0.93), 1.580 (0.48), 1.802 (1.27), 1.813 (1.85), 1.824 (1.81 ), 1.836 (1.52), 1.847 (1.48), 1.988 (1.90), 2.073 (4.52), 2.092 (4.73), 2.099 (5.07), 2.108 (4.79), 2.119 (2.69), 2.328 (0.57), 2.366 (0.50 ), 2.585 (1.84), 2.617 (2.00), 2.628 (3.21), 2.639 (2.14), 2.659 (1.19), 2.670 (2.01), 2.681 (0.96), 2.710 (0.53), 4.021 (0.47), 4.038 (0.48 ), 4,470 (3.11), 4,482 (5.98), 4,495 (3.09), 4,857 (0.87), 4,898 (16.00), 4,940 (0.98), 5,144 (1.15), 5,158 (1.19), 5,398 (0.94), 5,504 (1.36 ), 5.753 (0.75), 7.190 (1.16), 7.196 (1.23), 7.211 (3.51), 7.217 (3.73), 7.232 (2.72), 7.238 (2.93), 7.250 (4.64), 7.266 (4.90), 7.287 (2.11 ), 7,459 (2.87), 7,465 (2.85), 7,481 (2.93), 7,487 (2.91). Intermediate 353 (5S)-2-[(5-Chloro-6-methoxypyridin-3-yl)methyl]-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazole [4,3-a]pyridine-5-carboxylic acid

[0883] tert-Butyl (5S)-2-[(5-chloro-6-methoxypyridin-3-yl)methyl]-3-oxo- 2,3,5,6,7,8-hexahydro[1 ,2,4]triazolo[4,3-a]pyridine-5-carboxylate (718 mg, 1.82 mmol) was dissolved in dichloromethane (10 mL), and trifluoroacetic acid (2.8 mL, 36 mmol) was added at room temperature. After the reaction mixture was stirred at room temperature overnight, the solvent was removed under reduced pressure. 781 mg (>100% chance) of the title compound was obtained. LC-MS (Method 3): Rt = 1.12 min; MS (ESIpos): m /z = 339 [M+H]+ Intermediate 354 (5S)-2-(4-Fluorobenzyl)-3-oxo-2,3,5,6,7,8-hexahydro[ 1,2,4]triazolo[4,3- a]pyridine-5-carboxylic acid

[0884] tert-Butyl (5S)-2-(4-fluorobenzyl)-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3- a]pyridine-5-carboxylate (299 mg, 862 μmol) was dissolved in dichloromethane (10 mL), and trifluoroacetic acid (1.3 mL, 17 mmol) was added at room temperature. After the reaction mixture was stirred at room temperature for 4 hours, the solvent was removed under reduced pressure. 397 mg (>100% chance) of the title compound was obtained. LC-MS (Method 3): Rt = 1.02 min; MS (ESIpos): m /z = 292 [M+H]+ Intermediate 355 (5S)-2-[(6-Chloropyridin-2-yl)methyl]-3-oxo-2,3,5,6,7 ,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylic acid

[0885] tert-Butyl (5S)-2-[(6-chloropyridin-2-yl)methyl]-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4 ]triazolo[4,3-a]pyridine-5-carboxylate (372 mg, 1.02 mmol) was dissolved in dichloromethane (10 mL), and trifluoroacetic acid (1.6 mL, 20 mmol) was added at room temperature . After the reaction mixture was stirred at room temperature overnight, the solvent was removed under reduced pressure. 554 mg (>100% chance) of the title compound was obtained. LC-MS (Method 1): Rt = 0.74 min; MS (ESIpos): m /z = 309 [M+H]+ Intermediate 356 (5S)-2-(4-Methoxybenzyl)-3-oxo-2,3,5,6,7,8-hexahydro[ 1,2,4]triazolo[4,3- a]pyridine-5-carboxylic acid

[0886] tert-Butyl (5S)2-(-4-methoxybenzyl]-3-oxo--2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3 -a]pyridine-5-carboxylate (129 mg, 359 μmol) was dissolved in dichloromethane (3.0 mL), and trifluoroacetic acid (550 μl, 7.2 mmol) was added at room temperature after mixing the reaction. After being stirred at room temperature overnight, the solvent was removed under reduced pressure. 58 min; MS (ESIpos): m /z = 304 [M+H]+ Intermediate 357 (5S)-2-[(5-Chloro-3-fluoropyridin-2-yl)methyl]-3-oxo-2, 3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylic acid

[0887] tert-Butyl (5S)-2-[(5-chloro-3-fluoropyridin-2-yl)methyl]-3-oxo-2,3,5,6,7,8-hexahydro[1 ,2,4]triazolo[4,3-a]pyridine-5-carboxylate (465 mg, 1.21 mmol) was dissolved in dichloromethane (10 mL), and trifluoroacetic acid (1.9 mL, 24 mmol) was added at room temperature. After the reaction mixture was stirred at room temperature overnight, trifluoroacetic acid (0.19 mL, 2.4 mmol) was added again, and the mixture was stirred at room temperature for 3 hours. The solvent was removed under reduced pressure. 813 mg (>100% chance) of the title compound was obtained. LC-MS (Method 3): Rt = 0.96 min; MS (ESIpos): m /z = 327 [M+H]+ Intermediate 358 (5S)-2-[(5-Fluoropyridin-2-yl)methyl]-3-oxo-2,3,5,6,7 ,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylic acid

[0888] tert-Butyl (5S)-2-[(5-fluoropyridin-2-yl)methyl]-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4 ]triazolo[4,3-a]pyridine-5-carboxylate (345 mg, 989 μmol) was dissolved in dichloromethane (10 mL), and trifluoroacetic acid (1.5 mL, 20 mmol) was added at room temperature. After the reaction mixture was stirred at room temperature overnight, the solvent was removed under reduced pressure. 549 mg (>100% chance) of the title compound was obtained. LC-MS (Method 4): Rt = 0.42 min; MS (ESIpos): m /z = 293 [M+H]+ Intermediate 359 (5S)-2-(4-Chloro-3-fluorobenzyl)-3-oxo-2,3,5,6,7,8- hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylic acid

[0889] tert-Butyl (5S)-2-(4-chloro-3-fluorobenzyl)-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[ 4,3-a]pyridine-5-carboxylate (363 mg, 951 μmol) was dissolved in dichloromethane (8.0 mL), and trifluoroacetic acid (1.5 mL, 19 mmol) was added at room temperature. After the reaction mixture was stirred at room temperature overnight, the solvent was removed under reduced pressure. 454 mg (>100% chance) of the title compound was obtained. LC-MS (Method 4): Rt = 0.72 min; MS (ESIpos): m /z = 326 [M+H]+ Intermediate 360 (5S)-2-[(5-Chloropyridin-3-yl)methyl]-3-oxo-2,3,5,6,7 ,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylic acid

[0890] tert-Butyl (5S)-2-[(5-chloropyridin-3-yl)methyl]-3-oxo- 2,3,5,6,7,8-hexahydro[1,2,4 ]triazolo[4,3-a]pyridine-5-carboxylate (450 mg, 1.23 mmol) was dissolved in dichloromethane (12 mL), and trifluoroacetic acid (1.9 mL, 25 mmol) was added at room temperature . After the reaction mixture was stirred at room temperature overnight, the solvent was removed under reduced pressure. 380 mg (100% chance) of the title compound was obtained. LC-MS (Method 4): Rt = 0.5 min; MS (ESIpos): m /z = 309 [M+H]+ Intermediate 361 (5S)-2-[2-(4-Fluorophenyl)ethyl]-3-oxo-2,3,5,6,7,8 -hexa-hydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylic acid

[0891] tert-Butyl (5S)-2-[-2-(4-fluorophenyl)ethyl]-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4] triazolo[4,3-a]pyridine-5-carboxylate (340 mg, 941 μmol) was dissolved in dichloromethane (10 mL), and trifluoroacetic acid (1.4 mL, 19 mmol) was added at room temperature. After the reaction mixture was stirred at room temperature overnight, the solvent was removed under reduced pressure. 484 mg (>100% chance) of the title compound was obtained. LC-MS (Method 3): Rt = 1.13 min; MS (ESIpos): m /z = 306 [M+H]+ Intermediate 362 (5S)-2-[(5-Methoxypyridin-2-yl)methyl]-3-oxo-2,3,5,6,7 ,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylic acid

[0892] tert-Butyl (5S)-2-[(5-methoxypyridin-2-yl)methyl]-3-oxo- 2,3,5,6,7,8-hexahydro[1,2,4 ]triazolo[4,3-a]pyridine-5-carboxylate (196 mg, 544 μmol) was dissolved in dichloromethane, and trifluoroacetic acid (420 μl, 5.5 mmol) was added at room temperature. After the reaction mixture was stirred at room temperature overnight, trifluoroacetic acid (840 μl, 11 added again, and the mixture was stirred for 6 solvent was removed under reduced pressure. 302 mg (> possibility) of the title compound was obtained. LC-MS (Method 1): Rt = 0.53 min; -yl)methyl]-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylic acid

[0893] tert-Butyl (5S)-2-[(3,5-dichloropyridin-2-yl)methyl]-3-oxo-2,3,5,6,7,8-hexahydro[1,2 ,4]triazolo[4,3-a]pyridine-5-carboxylate (563 mg, 1.41 mmol) was dissolved in dichloromethane (29 mL), and trifluoroacetic acid (2.2 mL, 28 mmol) was added in room temperature. After the reaction mixture was stirred at room temperature overnight, the solvent was removed under reduced pressure. 823 mg (72% purity, >100% chance) of the title compound was obtained. LC-MS (Method 4): Rt = 0.59 min; MS (ESIpos): m /z = 343 [M+H]+ ¹H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.008 (1.94), 0.008 (2.31), 1.110 (0.45), 1.228 ( 0.43), 1.341 (0.41), 1.412 (16.00), 1.522 (0.93), 1.535 (1.80), 1.796 (1.19), 1.807 (1.15), 1.818 (1.05), 1.829 (1.01), 1.988 (0.57), 2.071 ( 2.07), 2.082 (3.10), 2.092 (2.96), 2.561 (1.34), 2.588 (1.36), 2.599 (2.22), 2.611 (1.52), 2.630 (0.75), 2.641 (1.00), 2.653 (0.60), 2.671 ( 0.48), 3.914 (1.27), 4.438 (0.62), 4.453 (1.95), 4.466 (3.78), 4.478 (1.88), 4.618 (0.42), 4.855 (1.24), 4.991 (1.12), 5.030 (8.30), 5.041 ( 9.08), 5.081 (1.19), 6.473 (0.41), 8.250 (4.12), 8.256 (5.12), 8.560 (1.18), 8.567 (5.22), 8.572 (4.55). Intermediate 364 (5S)-2-[2-(4-Methoxyphenyl)ethyl]-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a ]pyridine-5-carboxylic acid

[0894] tert-Butyl (5S)-2-[-2-(4-methoxyphenyl)ethyl]-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4] triazolo[4,3-a]pyridine-5-carboxylate (369 mg, 987 μmol) was dissolved in dichloromethane (10 mL), and trifluoroacetic acid (1.5 mL, 20 mmol) was added at room temperature. After the reaction mixture was stirred at room temperature overnight, the solvent was removed under reduced pressure. 489 mg (85% purity, >100% possibility) of the title compound was obtained. LC-MS (Method 3): Rt = 1.11 min; MS (ESIpos): m /z = 318 [M+H]+ Intermediate 365 (5S)-2-[(1-Methyl-1H-pyrazol[3,4-b)pyridin-3-yl)methyl]-3 -oxo-2,3,5,6,7,8- hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylic acid

[0895] tert-Butyl (5S)-2-[(1-methyl-1H-pyrazolo[3,4-b)pyridin-3-yl)methyl-3-oxo-2,3,5,6,7, 8-hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylate (203 mg, 88% purity, 465 μmol) was dissolved in dichloromethane (5.0 mL), and the trifluoroacetic acid (720 μl, 9.3 mmol) was added at room temperature. After the reaction mixture was stirred at room temperature overnight, the solvent was removed under reduced pressure. 284 mg (89% purity, >100% possibility) of the title compound was obtained. LC-MS (Method 1): Rt = 0.68 min; MS (ESIpos): m /z = 329 [M+H]+ Intermediate 366 (5S)-3-Oxo-2-{[3-(trifluoromethyl)-1,2,4-oxadiazol-5-yl]methyl} -2,3,5,6,7,8- hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylic acid

[0896] tert-Butyl (5S)-3-oxo-2-{[3-(trifluoromethyl)-1,2, 4-oxadiazol-5-yl]methyl}-2,3,5,6,7,8 -hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylate (322 mg, 826 μmol) was dissolved in dichloromethane (7.0 mL), and trifluoroacetic acid (1.3 mL, 17 mmol) was added at room temperature. After the reaction mixture was stirred at room temperature overnight, the solvent was removed under reduced pressure. 344 mg (82% purity, >100% possibility) of the title compound was obtained. LC-MS (Method 1): Rt = 0.84 min; MS (ESIpos): m /z = 334 [M+H]+ Intermediate 367 (5S)-2-[(3-Chloropyridin-2-yl)methyl]-3-oxo-2,3,5,6,7 ,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylic acid

[0897] tert-Butyl (5S)-2-[(3-chloropyridin-2-yl)methyl]-3-oxo- 2,3,5,6,7,8-hexahydro[1,2,4 ]triazolo[4,3-a]pyridine-5-carboxylate (268 mg, 735 μmol) was dissolved in dichloromethane (6.0 mL), and trifluoroacetic acid (1.1 mL, 15 mmol) was added at room temperature . After the reaction mixture was stirred at room temperature overnight, the solvent was removed under reduced pressure. 409 mg (>100% chance) of the title compound was obtained. LC-MS (Method 3): Rt = 0.79 min; MS (ESIpos): m /z = 309 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.008 (2.47), 0.008 (2.02), 1.111 (1.99), 1.228 ( 0.41), 1.415 (2.49), 1.513 (1.50), 1.535 (7.93), 1.551 (1.72), 1.564 (1.47), 1.577 (1.09), 1.592 (0.52), 1.787 (1.50), 1.798 (2.36), 1.809 ( 2.25), 1.820 (2.06), 1.831 (1.96), 1.844 (1.39), 2.074 (3.75), 2.086 (6.76), 2.097 (6.56), 2.110 (3.53), 2.368 (0.55), 2.482 (1.65), 2.524 ( 4.66), 2.565 (2.75), 2.588 (2.68), 2.600 (4.31), 2.612 (2.90), 2.631 (1.42), 2.641 (1.91), 2.654 (1.08), 2.672 (0.46), 2.712 (0.64), 4.458 ( 4.22), 4,470 (8.12), 4,482 (4.10), 4,993 (3.18), 5,033 (15.85), 5,050 (16.00), 5,090 (3.22), 5,42), 6,764 (0.71), 7,378 (5,76), 7,389 ( 5.97) 5.78). Intermediate 368 (5S)-2-[(3,5-Difluoropyridin-2-yl)methyl]-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazole [4,3-a]pyridine-5-carboxylic acid

[0898] tert-Butyl (5S)-2-[(3,5-difluoropyridin-2-yl)methyl]-3-oxo-2,3,5,6,7,8-hexahydro[1,2 ,4]triazolo[4,3-a]pyridine-5-carboxylate (90.1 mg, 246 μmol) was dissolved in dichloromethane (2.0 mL), and trifluoroacetic acid (380 μL, 4.9 mmol) was added at room temperature. After the reaction mixture was stirred at room temperature overnight, the solvent was removed under reduced pressure. 103 mg (90% purity, >100% possibility) of the title compound was obtained. LC-MS (Method 1): Rt = 0.64 min; MS (ESIpos): m /z = 311 [M+H]+ Intermediate 369 (5S)-3-Oxo-2-{[6-(trifluoromethyl)pyridin-2-yl]methyl}-2,3,5, 6,7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylic acid

[0899] tert-Butyl (5S)-3-oxo-2-{[6-(trifluoromethyl)pyridin-2-yl]methyl}-2,3,5,6,7,8-hexahydro[1, 2,4]triazolo[4,3-a]pyridine-5-carboxylate (256 mg, 89% purity, 571 μmol) was dissolved in dichloromethane (5.0 mL), and trifluoroacetic acid (880 μl, 11 mmol ) was added at room temperature. After the reaction mixture was stirred at room temperature overnight, the solvent was removed under reduced pressure. 256 mg (85% purity, >100% possibility) of the title compound was obtained. LC-MS (Method 4): Rt = 0.61 min; MS (ESIpos): m /z = 343 [M+H]+ Intermediate 370 (5S)-3-Oxo-2-{[5-(trifluoromethyl)-1,3,4-oxadiazol-2-yl]methyl} -2,3,5,6,7,8- hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylic acid

[0900] tert-Butyl (5S)-3-oxo-2-{[5-(trifluoromethyl)-1,3, 4-oxadiazol-2-yl]methyl}-2,3,5,6,7,8 -hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylate (735 mg, 66% purity, 1.25 mmol) was dissolved in dichloromethane (10 mL), and the acid Trifluoroacetic acid (1.9 mL, 25 mmol) was added at room temperature. After the reaction mixture was stirred at room temperature for 4 days, the solvent was removed under reduced pressure. 415 mg (80% purity, 80% chance) of the title compound was obtained. LC-MS (Method 1): Rt = 0.71 min; MS (ESIpos): m /z = 334 [M+H]+ Intermediate 371 (5S)-2-{[1-Ethyl-3-(trifluoromethyl)-1H-pyrazol-5-yl]methyl}-3-oxo -2,3,5,6,7,8- hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylic acid

[0901] tert-Butyl (5S)-2-{[1-ethyl-3-(trifluoromethyl)-1H-pyrazol-5-yl]methyl}-3-oxo-2,3,5,6,7,8 -hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylate (283 mg, 89% purity, 606 μmol) was dissolved in dichloromethane (5.0 mL), and the acid Trifluoroacetic acid (930 μl, 12 mmol) was added at room temperature. After the reaction mixture was stirred at room temperature overnight, the solvent was removed under reduced pressure. 400 mg (>100% chance) of the title compound was obtained. LC-MS (Method 4): Rt = 0.68 min; MS (ESIpos): m /z = 360 [M+H]+ Intermediate 372 (5S)-2-[(5-Chloropyridin-2-yl)methyl]-3-oxo-2,3,5,6,7 ,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylic acid

[0902] tert-Butyl (5S)-2-[(5-chloropyridin-2-yl)methyl]-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4 ]triazolo[4,3-a]pyridine-5-carboxylate (450 mg, 1.23 mmol) was dissolved in dichloromethane (10 mL), and trifluoroacetic acid (1.9 mL, 25 mmol) was added at room temperature . After the reaction mixture was stirred at room temperature overnight, the solvent was removed under reduced pressure. 380 mg (66% purity, 66% chance) of the title compound was obtained. LC-MS (Method 4): Rt = 0.51 min; MS (ESIpos): m /z = 309 [M+H]+ Intermediate 373 (5S)-3-Oxo-2-{[2-(trifluoromethyl)-1,3-thiazol-4-yl]methyl}-2 ,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylic acid

[0903] tert-Butyl (5S)-3-oxo-2-{[2-(trifluoromethyl)-1,3-thiazol-4-yl]methyl}-2,3,5,6,7,8-hexa -hydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylate (500 mg, 1.24 mmol) was dissolved in dichloromethane (8.0 mL), and trifluoroacetic acid (1.9 mL, 25 mmol) was added at room temperature. After the reaction mixture was stirred at room temperature overnight, the solvent was removed under reduced pressure. 430 mg (73% purity, 73% chance) of the title compound was obtained. LC-MS (Method 4): Rt = 0.62 min; MS (ESIpos): m /z = 349 [M+H]+ Intermediate 374 (5S)-2-{[1-Methyl-5-(trifluoromethyl)-1H-pyrazol-3-yl]methyl}-3-oxo -2,3,5,6,7,8- hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylic acid

[0904] tert-Butyl (5S)-2-{[1-methyl-5-(trifluoromethyl)-1H-pyrazol-3-yl]methyl-3-oxo--2,3,5,6,7,8 -hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylate (92.0 mg, 229 μmol) was dissolved in dichloromethane (2.0 mL), and trifluoroacetic acid (350 μl, 4.6 mmol) was added at room temperature. After the reaction mixture was stirred at room temperature for 72 hours, the solvent was removed under reduced pressure. 79.0 mg (70% purity, 100% chance) of the title compound was obtained. LC-MS (Method 3): Rt = 1.07 min; MS (ESIpos): m /z = 346 [M+H]+ Intermediate 375 (5S)-2-{[1-Benzyl-5-(trifluoromethyl)-1H-pyrazol-3-yl]methyl}-3-oxo - 2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylic acid

[0905] tert-Butyl (5S)-2-{[1-benzyl-5-(trifluoromethyl)-1H-pyrazol-3-yl]methyl}-3-oxo-2,3,5,6,7,8 -hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylate (781 mg, 75% purity, 1.23 mmol) was dissolved in dichloromethane (10 mL), and the acid Trifluoroacetic acid (1.9 mL, 25 mmol) was added at room temperature. After the reaction mixture was stirred at room temperature for 72 hours, trifluoroacetic acid (1.0 mL, 12.4 mmol) was added again, and the reaction mixture was stirred at 40 ° C for 2 hours. The solvent was removed under reduced pressure. 976 mg (70% purity, >100% possibility) of the title compound was obtained. LC-MS (Method 1): Rt = 1.11 min; MS (ESIpos): m /z = 422 [M+H]+ Intermediate 376 (5S)-2-[(5-Bromopyridin-2-yl)methyl]-3-oxo-2,3,5,6,7 ,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylic acid

[0906] tert-Butyl (5S)-2-[(5-bromopyridin-2-yl)methyl]-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4 ]triazolo[4,3-a]pyridine-5-carboxylate (580 mg, 1.42 mmol) was dissolved in dichloromethane (91 μl), and trifluoroacetic acid (2.2 mL, 28 mmol) was added at room temperature . After the reaction mixture was stirred at room temperature overnight, the solvent was removed under reduced pressure. 1.01 g (>100% chance) of the title compound was obtained. LC-MS (Method 3): Rt = 0.90 min; MS (ESIpos): m /z = 353 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (1.03), 0.146 (1.10), 1.110 (0.61), 1.176 ( 0.61), 1.192 (0.61), 1.227 (0.49), 1.409 (2.10), 1.535 (2.52), 1.819 (2.50), 1.830 (2.38), 1.841 (2.08), 1.852 (2.01), 1.988 (0.79), 2.098 ( 6.34), 2.107 (6.48), 2.328 (1.12), 2.367 (0.79), 2.564 (3.17), 2.577 (3.13), 2.591 (2.47), 2.619 (2.64), 2.630 (4.34), 2.641 (2.94), 2.661 ( 1.68), 2.671 (2.99), 2.711 (0.82), 4.473 (4.15), 4.485 (8.00), 4.498 (4.10), 4.528 (0.72), 4.769 (4.73), 4.867 (2.29), 4.908 (15.70), 4.919 ( 16.00), 4960 (2.43), 5224 (0.98), 5831 (1.91), 7162 (8.61), 7183 (9.17), 7532 (0.89), 7552 (0.98), 8024 (5.67), 8030 (5.78), 8045 ( 5.62), 8.051 (5.67), 8.102 (0.70), 8.117 (0.65), 8.654 (7.14), 8.659 (7.02), 8.697 (0.63). Intermediate 377 (5S)-2-[(5-Bromopyridin-3-yl)methyl]-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4 ,3-a]pyridine-5-carboxylic acid

[0907] tert-Butyl (5S)-2-[(5-bromopyridin-3-yl)methyl]-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4 ]triazolo[4,3-a]pyridine-5-carboxylate (146 mg, 357 μmol) was dissolved in dichloromethane (2.9 mL), and trifluoroacetic acid (550 μL, 7.1 mmol) was added at room temperature . After the reaction mixture was stirred at room temperature overnight, the solvent was removed under reduced pressure. 199 mg (89% purity, >100% chance) of the title compound was obtained. LC-MS (Method 4): Rt = 0.52 min; MS (ESIpos): m /z = 353 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.008 (2.87), 0.008 (2.73), 1.111 (0.85), 1.226 ( 0.54), 1.244 (2.70), 1.260 (2.67), 1.274 (1.67), 1.391 (9.28), 1.509 (1.14), 1.522 (1.13), 1.535 (3.08), 1.815 (1.43), 1.825 (1.40), 1.836 ( 1.22), 1.847 (1.20), 2.093 (3.51), 2.100 (3.75), 2.109 (3.48), 2.121 (1.86), 2.328 (0.61), 2.524 (2.13), 2.568 (1.92), 2.581 (1.92), 2.595 ( 1.53), 2.627 (1.61), 2.639 (2.57), 2.650 (1.73), 2.670 (1.47), 2.679 (1.38), 2.692 (0.70), 4.479 (2.53), 4.491 (4.87), 4.503 (2.51), 4.893 ( 0.40), 4.934 (16.00), 4.974 (0.48), 5.839 (1.06), 7.703 (0.95), 7.893 (3.04), 7.897 (5.36), 7.903 (3.24), 7.919 (0.56), 8.465 (5.32), 8.469 ( 5.56), 8.643 (4.66), 8.649 (4.90), 9.090 (0.42). Intermediate 378 (5S)-2-[2-(4-Methylphenyl)-2-oxoethyl]-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[ 4,3-a]pyridine-5-carboxylic acid

[0908] tert-Butyl (5S)-2-[2-(-4-methylphenyl)-2-oxoethyl]-3-oxo-2,3,5,6,7,8-hexahydro[1,2 ,4]triazolo[4,3-a]pyridine-5-carboxylate (226 mg, 99% purity, 603 μmol) was dissolved in dichloromethane (9.0 mL), and trifluoroacetic acid (930 μL, 12 mmol) was added at room temperature. After the reaction mixture was stirred at room temperature overnight, the solvent was removed under reduced pressure. 190 mg (100% chance) of the title compound was obtained. LC-MS (Method 1): Rt = 0.86 min; MS (ESIpos): m /z = 316 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: 0.008 (2.13), 1.110 (1.66), 1.419 (0.45), 1.535 (2.08 ), 1.566 (0.73), 1.577 (0.67), 1.828 (0.81), 1.861 (0.67), 1.988 (0.60), 2.098 (1.30), 2.109 (2.54), 2.121 (2.51), 2.328 (0.50), 2.366 (0.49 ), 2.398 (16.00), 2.580 (1.52), 2.594 (1.27), 2.607 (1.36), 2.621 (1.07), 2.635 (1.10), 2.647 (1.65), 2.658 (1.19), 2.687 (0.71), 2.710 (0.63 ), 4,466 (1.43), 4,480 (2.76), 4,491 (1.53), 5,221 (11.53), 7,359 (4.46), 7,380 (5.04), 7,912 (5.54), 7,933 (5.39). Intermediate 379 (5RS,8RS)-8-Methyl-2-(4-methylbenzyl)-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4, 3-a]pyridine-5-carboxylic acid (mixture of diastereomer; 4 isomers)

[0909] tert-Butyl (5RS,8RS)-8-methyl-2-(4-methylbenzyl)-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4] triazolo[4,3-a]pyridine-5-carboxylate (mixture of diastereomer; 4 isomers) (39.5 mg, 111 μmol) was dissolved in dichloromethane (2.0 mL), and trifluoroacetic acid (2.0 mL , 26 mmol) was added at room temperature. After the reaction mixture was stirred at room temperature overnight, the solvent was removed under reduced pressure. The residue was mixed with water and dichloromethane. The organic phase was removed and the aqueous phase was extracted three times with dichloromethane. The combined organic phases were washed with saturated aqueous sodium chloride solution, dried over sodium sulfate and filtered, and the filtrate was concentrated. 27.2 mg (82% chance) of the title compound was obtained. LC-MS (Method 3): Rt = 1.33 min; MS (ESIpos): m /z = 302 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.008 (4.03), 0.008 (2.37), 0.854 (0.43), 1.162 ( 6.13), 1.179 (6.09), 1.194 (1.00), 1.200 (0.78), 1.210 (0.80), 1.235 (3.03), 1.259 (1.66), 1.298 (1.05), 1.878 (0.53), 1.888 (0.41), 1.900 ( 0.43), 2.074 (0.43), 2.110 (0.53), 2.141 (1.26), 2.148 (1.20), 2.245 (0.73), 2.271 (11.10), 2.327 (0.46), 2.518 (2.94), 2.523 (2.66), 2.669 ( 0.61), 2.674 (0.46), 2.685 (0.45), 2.700 (0.64), 2.709 (0.70), 2.716 (0.77), 2.731 (0.58), 4.471 (0.92), 4.478 (1.27), 4.487 (0.82), 4.492 ( 0.88), 4.739 (0.98), 4.778 (2.39), 4.825 (2.35), 4.864 (1.01), 5.754 (2.62), 7.105 (0.61), 7.127 (16.00), 7.145 (0.72). Intermediate 380 (5S)-2-(Cyclopropylmethyl)-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3- a]pyridine-5- carboxylic acid

[0910] tert-Butyl (5S)-2-(cyclopropylmethyl)-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a] Pyridine-5-carboxylate (174 mg, 593 μmol) was dissolved in dichloromethane (6.0 mL), and trifluoroacetic acid (3.0 mL, 39 mmol) was added while cooling with ice. After the reaction mixture was stirred at room temperature overnight, the solvent was removed under reduced pressure. 231 mg (>100% chance) of the title compound was obtained. LC-MS (Method 3): Rt = 0.73 min; MS (ESIpos): m /z = 238 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: 0.008 (2.18), 0.262 (1.91), 0.274 (8.08), 0.285 (8.53 ), 0.297 (2.52), 0.313 (0.57), 0.427 (1.63), 0.438 (8.30), 0.442 (7.40), 0.458 (8.82), 0.475 (1.47), 0.488 (0.45), 1.034 (0.65), 1.039 (0.94 ), 1.051 (1.82), 1.059 (1.78), 1.071 (2.90), 1.083 (1.70), 1.088 (1.77), 1.101 (0.92), 1.111 (3.14), 1.403 (1.07), 1.493 (0.71), 1.513 (1.50 ), 1,527 (1.76), 1,540 (1.95), 1,550 (1.73), 1,564 (1.44), 1,578 (1.34), 1,590 (0.60), 1,806 (2.26), 1,817 (2.13), 1,828 (2.01), 1,839 (1.90 ), 1,852 (1.35), 2,060 (3.96), 2,072 (7.12), 2,083 (6.87), 2,097 (3.54), 2,105 (1.98), 2,558 (4.03), 2,572 (2.98), 2,585 (3.06), 2,599 (2.54 ), 2.628 (2.55), 2.639 (4.08), 2.651 (2.76), 2.670 (1.62), 2.681 (1.95), 2.693 (1.10), 3.482 (16.00), 3.499 (15.83), 4.377 (0.51), 4.409 (3.82 ), 4,422 (7.29), 4,434 (3.82), 11,357 (0.41). Intermediate 381 (5S)-2-[(E)-2-(4-Fluorophenyl)vinyl]-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazole [4,3-a]pyridine-5-carboxylic acid

[0911] tert-Butyl (5S)-2-[(E)-2-(4-fluorophenyl)vinyl]-3-oxo-2,3,5,6,7,8-hexahydro[1,2 ,4]triazolo[4,3-a]pyridine-5-carboxylate (150 mg, 417 μmol) was dissolved in dichloromethane (5.0 mL), and trifluoroacetic acid (500 μL, 6.5 mmol) was added in room temperature. After the reaction mixture was stirred at room temperature overnight, the solvent was removed under reduced pressure. 198 mg (>100% chance) of the title compound was obtained. LC-MS (Method 3): Rt = 1.37 min; MS (ESIpos): m /z = 304 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (0.58), -0.008 (5.47), 0.008 (4.55), 0.146 (0.64) (1.31) (1.40) (4.21) (3.30) (11.48), 7,420 (10.23), 7,542 (8.09), 7,556 (9.16), 7,564 (8.52), 7,578 (7.27). Intermediate 382 (5S)-2-{[6-(Difluoromethyl)pyridin-3-yl]methyl}-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4] triazolo[4,3-a]pyridine-5-carboxylic acid

[0912] tert-Butyl (5S)-2-{[6-(difluoromethyl)pyridin-3-yl]methyl}-3-oxo-2,3,5,6,7,8-hexahydro[1, 2,4]triazolo[4,3-a]pyridine-5-carboxylate (200 mg, 86% purity, 452 μmol) was dissolved in dichloromethane (4.5 mL), and trifluoroacetic acid (2.0 mL, 26 mmol) was added at room temperature. After the reaction mixture was stirred at room temperature for 3.5 hours, the solvent was removed under reduced pressure. 615 mg (25% purity, >100% possibility) of the title compound was obtained. LC-MS (Method 3): Rt = 0.87 min; MS (ESIpos): m /z = 325 [M+H]+ Intermediate 383 (5S)-2-(4-Bromobenzyl)-3-oxo-2,3,5,6,7,8-hexahydro[ 1,2,4]triazolo[4,3- a]pyridine-5-carboxylic acid

[0913] tert-Butyl (5S)-2-(-4-bromobenzyl]-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3 -a]pyridine-5-carboxylate (201 mg, 74% purity, 365 μmol) was dissolved in dichloromethane (3.7 mL), and trifluoroacetic acid (500 μL, 6.5 mmol) was added at room temperature. After the reaction mixture was stirred at room temperature overnight, the solvent was removed under reduced pressure. 268 mg (47% purity, 98% possibility) of the title compound were obtained (Method 4): Rt = 0.69 min; MS (ESIpos): m /z = 352 [M+H]+ Intermediate 384 (5S)-2-(3-Bromobenzyl)-3-oxo-2,3,5,6,7 ,8-hexahydro[1,2,4]triazolo[4,3- a]pyridine-5-carboxylic acid

[0914] tert-Butyl (5S)2-(3-bromobenzyl)-3-oxo--2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3- a]pyridine-5-carboxylate (256 mg, 590 μmol) was dissolved in dichloromethane (4.5 mL), and trifluoroacetic acid (500 μL, 6.5 mmol) was added at room temperature. After the reaction mixture was stirred at room temperature overnight, the solvent was removed under reduced pressure. 346 mg (59% purity, 98% possibility) of the title compound were obtained. LC-MS (Method 4): Rt = 0.69 min; MS (ESIpos): m /z = 352 [M+H]+ Intermediate 385 (5S)-2-(4-Bromo-2-fluorobenzyl)-3-oxo-2,3,5,6,7,8- hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylic acid

[0915] tert-Butyl (5S)2-(-4-bromo-2-fluorobenzyl]-3-oxo-2,3,5,6,7,8-hexahydro[1,2, 4-bromo 4 ]triazolo[4,3-a]pyridine-5-carboxylate (135 mg, 317 μmol) was dissolved in dichloromethane (3.0 mL), and trifluoroacetic acid (300 μL, 3.9 mmol) was added at room temperature After the reaction mixture was stirred at room temperature overnight, the solvent was removed under reduced pressure: Rt = 1. .31 min; MS (ESIpos): m /z = 370 [M+H]+ Intermediate 386 (5S)-3-Oxo-2-{(1RS)-1-[6-(trifluoromethyl)pyridin-3-yl ]ethyl}-2,3,5,6,7,8- hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylic acid (isomer 1)

[0916] tert-Butyl (5S)-3-oxo-2-{(1RS)-1-[6-(trifluoromethyl)pyridin-3-yl]ethyl}-2,3,5,6,7,8- hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylate (isomer 1) (97.0 mg, 235 μmol) was dissolved in dichloromethane (2.0 mL), and trifluoroacetic acid (200 μl, 2.6 mmol) was added at room temperature. After the reaction mixture was stirred at room temperature overnight, the solvent was removed under reduced pressure. 154 mg (>100% chance) of the title compound was obtained. LC-MS (Method 3): Rt = 1.21 min; MS (ESIpos): m /z = 357 [M+H]+ Intermediate 387 (5S)-3-Oxo-2-{(1RS)-1-[6-(trifluoromethyl)pyridin-3-yl]ethyl}- 2,3,5,6,7,8- hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylic acid (isomer 2)

[0917] tert-Butyl (5S)-3-oxo-2-{(1RS)-1-[6-(trifluoromethyl)pyridin-3-yl]ethyl}-2,3,5,6,7,8- hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylate (isomer 2) (86.0 mg, 209 μmol) was dissolved in dichloromethane (2.0 mL), and the acid Trifluoroacetic acid (200 μl, 2.6 mmol) was added at room temperature. After the reaction mixture was stirred at room temperature overnight, the solvent was removed under reduced pressure. 133 mg (>100% chance) of the title compound was obtained. LC-MS (Method 3): Rt = 1.19 min; MS (ESIpos): m /z = 357 [M+H]+ Intermediate 388 (5S)-3-Oxo-2-{[cis/trans-4-(trifluoromethyl)cyclohexyl]methyl}-2,3,5, 6,7,8- hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylic acid (mixture of diastereomer; 2 isomers)

[0918] tert-Butyl (5S)-3-oxo-2-{[cis/trans-4-(trifluoromethyl)cyclohexyl]methyl}-2,3,5,6,7,8-hexahydro[1, 2,4]triazolo[4,3- a]pyridine-5-carboxylate (mixture of diastereomer, 2 isomers) (112 mg, 264 μmol) was dissolved in dichloromethane (5.0 mL), and trifluoroacetic acid (500 μl , 6.5 mmol) was added at room temperature. After the reaction mixture was stirred at room temperature overnight, the solvent was removed under reduced pressure. 153 mg (>100% chance) of the title compound was obtained. LC-MS (Method 3): Rt = 1.41 min; MS (ESIpos): m /z = 348 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.150 (1.53), -0.008 (16.00) 0.008 (13.04), 0.147 ( 1.83), 1.030 (2.72), 1.110 (9.48), 1.191 (2.96) 1.249 (3.95), 1.395 (3.01), 1.491 1.828 (5.53), 2.079 (9.98), 2.328 2.569 (4.20) 11), 2,631 3.474 (4.79), 3.609 (5.04), 3.622 4.436 (8.69), 4.448 (4.00), 4.970 (3 Intermediate 389 (5S)-2-{[3-Fluoro-2-(trifluoromethyl)pyridin-4-yl]methyl }-3-oxo-2,5,6,7-tetrahydro-3H-pyrrole[2,1-c][1,2,4]triazol-5-carboxylic acid

[0919] Methyl (5S)-2-{[3-fluoro-2-(trifluoromethyl)pyridin-4-yl]methyl}-3-oxo-2,5,6,7-tetrahydro-3H-pyrrolo[ 2,1-c][1,2,4]triazole-5-carboxylate (243 mg, 75% purity, 506 μmol) was initially loaded into THF (2.5 mL) and water (2.5 mL) and lithium hydroxide (60.6 mg, 2.53 mmol) was added. After stirring for 90 minutes, the reaction mixture was mixed with 1 N aqueous hydrochloric acid at room temperature. The solvent was concentrated and the aqueous phase was extracted three times with ethyl acetate. The combined organic phases were dried over sodium sulfate and filtered, and the filtrate was concentrated. 264 mg (>100% chance) of the title compound was obtained. LC-MS (Method 4): Rt = 0.60 min; MS (ESIpos): m /z = 347 [M+H]+ Intermediate 390 (5RS,7RS)-2-[(6-Chloropyridin-3-yl)methyl]-3-oxo-7-(trifluoromethyl)- 2 ,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylic acid (diastereomer mixture; 4 isomers)

[0920] Ethyl (5RS,7RS)-2-[(6-chloropyridin-3-yl)methyl]-3-oxo-7-(trifluoromethyl)-2,3,5,6,7,8-hexahydro [1,2,4]triazolo[4,3-a]pyridine-5-carboxylate (diastereomer mixture; 4 isomers) (500 mg, 1.24 mmol) was initially loaded into THF (10 mL), and was added sodium ethoxide (850 μl, 21% in ethanol, 2.3 mmol). The reaction mixture was stirred at 0°C for 15 minutes and overnight at room temperature. Water was added and the mixture was acidified with 1N aqueous hydrochloric acid. The aqueous phase was extracted with ethyl acetate and the organic phase was dried over sodium sulfate and filtered, and the filtrate was concentrated to 479 mg (> 100% possibility ) of the title compound were obtained. LC-MS (Method 4): Rt = 0.64 min; MS (ESIpos): m /z = 377 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: 1.094 (0.28), 1.157 (2.06), 1.170 (1.54), 1.175 (4.26 ), 1.193 (2.09), 1.240 (0.19), 1.271 (0.24), 1.786 (0.19), 1.817 (0.21), 1.908 (2.01), 1.988 (7.50), 2.224 (0.42), 2.240 (0.55), 2.259 (1.12 ), 2.275 (1.16), 2.288 (1.30), 2.304 (1.30), 2.319 (2.92), 2.352 (1.02), 2.667 (0.88), 2.696 (3.39), 2.720 (3.41), 2.749 (0.95), 2.874 (0.20 ), 2.951 (0.48), 2.977 (2.16), 3.005 (1.87), 3.034 (0.37), 4.002 (0.61), 4.021 (1.81), 4.038 (1.78), 4.056 (0.60), 4.394 (0.20), 4.409 (0.23 ), 4.421 (0.22), 4.437 (0.19), 4.689 (2.91), 4.700 (2.65), 4.921 (1.26), 4.948 (16.00), 7.507 (4.76), 7.515 (0.69), 7.527 (5.86), 7.715 (3.26 ), 7,721 (3.37), 7,735 (3.05), 7,742 (3.13), 7,756 (0.28), 8,317 (4.42), 8,322 (4.42), 8,336 (0.48), 13,683 (0.28). Intermediate 391 (5RS,7RS)-3-oxo-7-(trifluoromethyl)-2-{[6-(trifluoromethyl)pyridin-3-yl]methyl}- 2,3,5,6,7,8-hexa- hydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylic acid (mixture of diastereomer, 4 isomers)

[0921] Ethyl (5RS, 7RS)-3-oxo-7-(trifluoromethyl)-2-{[6-(trifluoromethyl)pyridin-3-yl]methyl}-2,3,5,6,7,8- hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylate (mixture of diastereomer; 4 isomers) (480 mg, 1.10 mmol) was initially loaded into THF (20 mL) and sodium ethoxide (760 μl, 21% in ethanol, 2.0 mmol) was added. The reaction mixture was stirred at 0°C for 20 minutes and at room temperature overnight. Ice water was added and the mixture was acidified with 1N aqueous hydrochloric acid. The aqueous phase was extracted with ethyl acetate and the organic phase was dried over sodium sulfate and filtered, and the filtrate was concentrated 577 mg (88% purity , > 100% chance) of the title compound were obtained. LC-MS (Method 4): Rt = 0.73 min; MS (ESIpos): m /z = 411 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ 1.157 (4.39), 1.169 (1.76), 1.175 1.988 (16.00), 2.266 (0.42), 2.283 2,328 (1.28), 2,366 (0.50), 2,524 2,729 (1.28), 2,986 (0.84), 3,014 4,038 (3.75), 4,056 (1.23), 4,701 5,047 (0.49), 5,076 (5.23), 7,900 7. 937 (1.59), 7,954 (0.60), 7.958 (0 Intermediate 392 (5RS,7RS)-2-{[3-fluoro-2-(trifluoromethyl)pyridin-4-yl]methyl}-3-oxo-7-(trifluoromethyl)-2.3 ,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylic acid (mixture of diastereomer; 4 isomers)

[0922] Ethyl (5RS, 7RS)-2-{[3-fluoro-2-(trifluoromethyl)pyridin-4-yl]methyl}-oxo-7-(trifluoromethyl)-2,3,5,6,7, 8-hexahydro[1,2,4]triazolo[4,3- a]pyridine-5-carboxylate (diastereomer, 4 isomers) (440 mg, 964 μmol) was initially loaded into THF (5.0 mL) and water (5.0 mL) and lithium hydroxide (69.3 mg, 2.89 mmol) was added. After stirring overnight, the reaction mixture was mixed at room temperature with 1N aqueous hydrochloric acid. The aqueous phase was extracted with ethyl acetate, and the organic phase was dried over sodium sulfate and filtered, and the filtrate was concentrated 372 mg (90% chance) of the title compound were obtained. LC-MS (Method 4): Rt = 0.78 min; MS (ESIpos): m /z = 429 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (0.91), -0.008 (8.08), 0.008 (7.23), 0.146 (0.98) (0.66) (1.29), 2718 (5.76), 2742 (5.61), 2770 (1.75), 2800 (0.73), 2896 (0.48), 2974 (0.81), 2999 (3.66), 3027 (3.18), 3055 (0.71), 3077 (0.89) (4.45) (0.54), 7,644 (0.87), 7,658 (0.46), 8,562 (7.88), 8,574 (8.27), 8,589 (1.12), 13,733 (0.56). Intermediate 393 (5RS,7RS)-2-[(5-Chloro-3-fluoropyridin-2-yl)methyl]-3-oxo-7-(trifluoromethyl)- 2,3,5,6,7,8-hexa -hydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylic acid (mixture of diastereomer; 4 isomers)

[0923] Ethyl (5RS, 7RS)-2-[(5-chloro-3-fluoropyridin-2-yl)methyl]-3-oxo-7-(trifluoromethyl)-2,3,5,6,7,8 -hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylate (mixture of diastereomer, 4 isomers) (133 mg, 315 μmol) was initially loaded into THF (1.5 mL) and water (1.5 mL) and lithium hydroxide (22.6 mg, 944 μmol) was added. After stirring overnight, the reaction mixture was mixed at room temperature with 1N aqueous hydrochloric acid. The aqueous phase was extracted with ethyl acetate, and the organic phase was dried over sodium sulfate and filtered, and the filtrate was concentrated 113 mg (91% chance) of the title compound were obtained. LC-MS (Method 3): Rt = 1.26 min; MS (ESIpos): m /z = 395 [M+H]+ Intermediate 394 (5RS,7RS)-2-[(5-Chloropyridin-3-yl)methyl]-3-oxo-7-(trifluoromethyl)- 2 ,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylic acid (diastereomer mixture; 4 isomers)

[0924] Ethyl (5RS, 7RS)-2-[(5-chloropyridin-3-yl)methyl]-3-oxo-7-(trifluoromethyl)-2,3,5,6,7,8-hexahydro [1,2,4]triazolo[4,3-a]pyridine-5-carboxylate (mixture of diastereomer, 4 isomers) (55.0 mg, 136 μmol) was initially loaded into THF (1.0 mL) and water (1.0 mL) and lithium hydroxide (9.76 mg, 408 μmol) was added. After stirring overnight, the reaction mixture was mixed at room temperature with 1N aqueous hydrochloric acid. The aqueous phase was extracted with ethyl acetate, and the organic phase was dried over sodium sulfate and filtered, and the filtrate was concentrated. .7 mg (75% purity, >100% chance) of the title compound was obtained. LC-MS (Method 4): Rt = 0.64 min; MS (ESIpos): m /z = 377 [M+H]+ Intermediate 395 3-Oxo-8-(trifluoromethyl)-2-{[6-(trifluoromethyl)pyridin-3-yl]methyl}-2,3- dihydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylic acid

[0925] Methyl 3-oxo-8-(trifluoromethyl)-2-{[6-(trifluoromethyl)pyridin-3-yl]methyl}-2,3-dihydro[1,2,4]triazolo[4, 3-a]pyridine-5-carboxylate (85.0 mg, 77% purity, 156 μmol) was initially loaded into THF (1.0 mL) and water (1.0 mL) and lithium hydroxide (7 .46 mg, 311 μmol). After stirring overnight, the reaction mixture was mixed at room temperature with 1N aqueous hydrochloric acid. The aqueous phase was extracted with ethyl acetate, and the organic phase was dried over sodium sulfate and filtered, and the filtrate was concentrated 113 mg (>100% chance) of the title compound were obtained. LC-MS (Method 1): Rt = 0.98 min; MS (ESIpos): m /z = 407 [M+H]+ Intermediate 396 2-[(5-Chloro-3-fluoropyridin-2-yl)methyl]-3-oxo-8-(trifluoromethyl)-2,3 -dihydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylic acid

[0926] Methyl 2-[(5-chloro-3-fluoropyridin-2-yl)methyl]-3-oxo-8-(trifluoromethyl)-2,3-dihydro[1,2,4]triazolo[4 ,3-a]pyridine-5-carboxylate (86.0 mg, 212 μmol) was initially loaded into THF (1.0 mL) and water (1.0 mL) and lithium hydroxide (10.2 mg, 425 μmol). After stirring overnight, the reaction mixture was mixed at room temperature with 1N aqueous hydrochloric acid. The aqueous phase was extracted with ethyl acetate, and the organic phase was dried over sodium sulfate and filtered, and the filtrate was concentrated 85 .4 mg (96% chance) of the title compound were obtained. LC-MS (Method 4): Rt = 0.68 min; MS (ESIpos): m /z = 391 [M+H]+ Intermediate 397 5-{[(3R,4S)-3,4-Difluoropyrrolidin-1-yl]carbonyl}-8-(trifluoromethyl)-2-{ [6-(trifluoromethyl)pyridin-3-yl]methyl}[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one

[0927] 3-Oxo-8-(trifluoromethyl)-2-{[6-(trifluoromethyl)pyridin-3-yl]methyl}-2,3-dihydro[1,2,4]triazolo[4,3 -a]pyridine-5-carboxylic acid (110 mg, 249 μmol) was initially loaded into THF (3.0 mL) at room temperature. Subsequently, HBTU (123 mg, 324 μmol) and N,N-diisopropylethylamine (220 μl, 1.2 mmol) were added. After stirring for 5 minutes, (3R, 4S)-3,4-difluoropyrrolidine hydrochloride (42.9 mg, 299 μmol) was added and the reaction mixture was stirred at room temperature for 4 hours. The reaction mixture was mixed with water and ethyl acetate, and the organic phase was removed. The organic phase was washed with 10% aqueous citric acid solution and saturated aqueous sodium chloride solution, dried over sodium sulfate and filtered, and the filtrate was concentrated. The residue was purified via column chromatography (silica gel, eluent: dichloromethane/methanol gradient 1/0, 98/2). The fractions containing the product were concentrated under reduced pressure and 23.0 mg (87% purity, 16% chance) of the title compound were obtained. LC-MS (Method 3): Rt = 1.71 min; MS (ESIpos): m /z = 496 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (0.99), -0.009 (8.81), 0.007 (7.55), 0.146 (0.99), 1.237 (0.90), 1.949 (0.36), 2.322 (1.80), 8.026 (0.81), 8.046 (0.63), 8.772 (0.99), 14.278 (0.27). Intermediate 398 5-{[(3S)-3-Fluoropyrrolidin-1-yl]carbonyl}-8-(trifluoromethyl)-2-{[6-(trifluoromethyl)pyridin-3-yl]methyl}[1,2,4 ]triazolo[4,3-a]pyridin-3(2H)-one

[0928] 3-Oxo-8-(trifluoromethyl)-2-{[6-(trifluoromethyl)pyridin-3-yl]methyl}-2,3-dihydro[1,2,4]triazolo[4,3 -a]pyridine-5-carboxylic acid (127 mg, 300 μmol) was initially loaded into THF (5.0 mL) at room temperature. Subsequently, HBTU (148 mg, 390 μmol) and N,N-diisopropylethylamine (260 μl, 1.5 mmol) were added. After stirring for 5 minutes, (3S)-3-fluoropyrrolidine hydrochloride (45.2 mg, 360 μmol) was added and the reaction mixture was stirred at room temperature overnight. The reaction mixture was mixed with water and ethyl acetate, and the organic phase was removed. The organic phase was washed with 10% aqueous citric acid solution and saturated aqueous sodium chloride solution, dried over sodium sulfate and filtered, and the filtrate was concentrated. 167 mg (60% purity, 70% chance) of the title compound was obtained. LC-MS (Method 3): Rt = 1.64 min; MS (ESIpos): m /z = 478 [M+H]+ Intermediate 399 2-[(5-Chloro-3-fluoropyridin-2-yl)methyl]-5-{[(3S)-3-fluoropyrrolidin-1 - yl]carbonyl}-8-(trifluoromethyl)[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one

[0929] 2-[(5-Chloro-3-fluoropyridin-2-yl)methyl]-3-oxo-8-(trifluoromethyl)- 2,3-dihydro[1,2,4]triazolo[4, 3-a]pyridine-5-carboxylic acid (42.0 mg, 100 μmol) was initially loaded into THF (2.0 mL) at room temperature. Subsequently, HBTU (49.3 mg, 130 μmol) and N,N-diisopropylethylamine (87 μl, 500 μmol) were added. After stirring for 5 minutes, (3S)-3-fluoropyrrolidine hydrochloride (15.1 mg, 120 μmol) was added and the reaction mixture was stirred at room temperature overnight. The reaction mixture was mixed with water and ethyl acetate, and the organic phase was removed. The organic phase was washed with 10% aqueous citric acid solution and saturated aqueous sodium chloride solution, dried over sodium sulfate and filtered, and the filtrate was concentrated. 51.2 mg (62% purity, 69% chance) of the title compound was obtained. LC-MS (Method 3): Rt = 1.65 min; MS (ESIpos): m /z = 462 [M+H]+ Intermediate 400 2-[(5-Chloro-3-fluoropyridin-2-yl)methyl]-5-{[(3R,4S)-3.4 -difluoropyrrolidin-1-yl]carbonyl}-8-(trifluoromethyl)[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one

[0930] 2-[(5-Chloro-3-fluoropyridin-2-yl)methyl]-3-oxo-8-(trifluoromethyl)- 2,3-dihydro[1,2,4]triazolo[4, 3-a]pyridine-5-carboxylic acid (42.0 mg, 100 μmol) was initially loaded into THF (2.0 mL) at room temperature. Subsequently, HBTU (49.3 mg, 130 μmol) and N,N-diisopropylethylamine (87 μl, 500 μmol) were added. After stirring for 5 minutes, (3R,4S)-3,4-difluoropyrrolidine hydrochloride (17.2 mg, 120 μmol) was added and the reaction mixture was stirred at room temperature overnight. The reaction mixture was mixed with water and ethyl acetate, and the organic phase was removed. The organic phase was washed with 10% aqueous citric acid solution and saturated aqueous sodium chloride solution, dried over sodium sulfate and filtered, and the filtrate was concentrated. 95.2 mg (47% purity, 92% chance) of the title compound was obtained. LC-MS (Method 3): Rt = 1.70 min; MS (ESIpos): m /z = 480 [M+H]+ Intermediate 401 (5S)-2-[(5-Chloropyridin-2-yl)methyl]-5-{[(3S)-3-fluoropyrrolidin-1 -yl]carbonyl}-6,7-dihydro[1,2,4]triazolo[4,3-a]pyridine-3,8(2H,5H)-dione

[0931] (5S,8RS)-2-[(5-Chloropyridin-2-yl)methyl]-5-{[(3S)-3-fluoropyrrolidin-1-yl]carbonyl}-8-hydroxy-5,6 ,7,8-tetrahydro[1,2,4]triazolo[4,3- a]pyridin-3(2H)-one (mixture of diastereomer; 2 isomers) (39.0 mg, 92.6 μmol) was initially loaded into dichloromethane (940 μl) at room temperature, and the reaction mixture was cooled to 0°C. Subsequently, Dess-Martin periodinane (98.2 mg, 232 μmol) was added, and the reaction mixture was stirred at 0 °C for 15 min. and at room temperature overnight. The reaction mixture was mixed with diethyl ether and a solution of sodium thiosulfate (350 mg) in saturated aqueous sodium hydrogen carbonate solution. The organic phase was removed and the aqueous phase was extracted with diethyl ether. The combined organic phases were dried over sodium sulfate and filtered, and the filtrate was concentrated. 12.7 mg (90% purity, 31% chance) of the title compound was obtained. LC-MS (Method 1): Rt = 0.86 min; MS (ESIpos): m /z = 394 [M+H]+ Intermediate 402 (5S)-2-[(5-Chloro-3-fluoropyridin-2-yl)methyl]-5-{[(3S)-3 -fluoropyrrolidin-1-yl]carbonyl}-6,7-dihydro[1,2,4]triazolo[4,3-a]pyridine-3,8(2H,5H)-dione

[0932] (5S,8RS)-2-[(-chloro 940 5-Chloro-3-fluoropyridin-2-yl)methyl]-5- {[(3S)-3-fluoropyrrolidin-1-yl]carbonyl}- 8-hydroxy-5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one (diastereomer mixture; 2 isomers) (51.7 mg, 86% purity, 107 μmol) was initially loaded into dichloromethane (1.1 mL) at room temperature, and the reaction mixture was cooled to 0 °C. Subsequently, Dess-Martin periodinane (114 mg, 269 μmol) was added, and the reaction mixture was stirred at 0°C for 15 min. and at room temperature overnight. The reaction mixture was mixed with diethyl ether and a solution of sodium thiosulfate (350 mg) in saturated aqueous sodium hydrogen carbonate solution and stirred. The organic phase was removed and the aqueous phase was extracted with diethyl ether and three times with ethyl acetate. The combined organic phases were dried over sodium sulfate and filtered, and the filtrate was concentrated. 25.8 mg (75% purity, 46% chance) of the title compound was obtained. LC-MS (Method 1): Rt = 0.89 min; MS (ESIpos): m /z = 412 [M+H]+ Intermediate 403 (5S)-2-[(6-Chloropyridin-3-yl)methyl]-5-[(3,3-difluoropyrrolidin-1-yl )carbonyl]-6,7-dihydro[1,2,4]triazolo[4,3-a]pyridine-3,8(2H,5H)-dione

[0933] (5S,8RS)-2-[(6-Chloropyridin-3-yl)methyl]-5-[(3,3-difluoropyrrolidin-1-yl)carbonyl]-8-hydroxy-5,6,7 ,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one (diastereomer mixture; 2 isomers) (66.9 mg, 90% purity, 146 μmol ) was dissolved in dichloromethane (6.0 mL, 94 mmol) and manganese(IV) oxide (254 mg, 2.92 mmol) was added at room temperature. The reaction mixture was stirred at room temperature overnight. The suspension was filtered through Celite and the filtrate was concentrated under reduced pressure. 47.3 mg (79% chance) of the title compound was obtained. LC-MS (Method 4): Rt = 0.69 min; MS (ESIpos): m /z = 412 [M+H]+ Intermediate 404 tert-Butyl (5S)-3-oxo-2-{[2-(trifluoromethyl)pyrimidin-5-yl]methyl}- 2.3 ,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylate

[0934] tert-Butyl(5S)-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylate ( 16.2 mg, 67.8 μmol) was initially loaded into acetonitrile (1.0 mL). Cesium carbonate (33.2 mg, 102 μmol) and 5-(chloromethyl)-2-(trifluoromethyl)pyrimidine (14.0 mg, 71.2 μmol) were subsequently added. After stirring at room temperature overnight, ethyl acetate was added to the reaction mixture. The organic phase was washed with water and saturated aqueous sodium chloride solution, dried over sodium sulfate and filtered, and the filtrate was concentrated. 22 mg (11% purity, 8% chance) of the title compound were obtained. LC-MS (Method 3): Rt = 1.88 min; MS (ESIpos): m /z = 400 [M+H]+ Intermediate 405 (5S)-3-Oxo-2-{[2-(trifluoromethyl)pyrimidin-5-yl]methyl}-2,3,5, 6,7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylic acid

[0935] tert-Butyl (5S)-3-oxo-2-{[2-(trifluoromethyl)pyrimidin-5-yl]methyl}-2,3,5,6,7,8-hexahydro[1, 2,4]triazolo[4,3-a]pyridine-5-carboxylate (22.0 mg, 11% purity, 6 μmol) was dissolved in 1,4-dioxane (200 μl), and dissolved hydrochloric acid was added in 1,4-dioxane (140 μl, 4.0 M, 550 μmol). After the reaction mixture was stirred at room temperature overnight, the solvent was removed under reduced pressure. 22 mg (11% purity, >100% chance) of the title compound was obtained. LC-MS (Method 3): Rt = 0.98 min; MS (ESIpos): m /z = 344 [M+H]+ Intermediate 406 Ethyl (5RS,7RS)-2-{[3-chloro-5-(trifluoromethyl)pyridin-2-yl]methyl}-3-oxo -7- (trifluoromethyl)-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylate (mixture of diastereomer; 4 isomers)

[0936] Ethyl (5S,7R)-3-oxo-7-(trifluoromethyl)-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a] Pyridine-5-carboxylate (diastereomer mixture, 4 isomers) (500 mg, 1.79 mmol) was initially loaded into acetonitrile (16 mL). Cesium carbonate (1.46 g, 4.48 mmol) and 3-chloro-2-(chloromethyl)-5-(trifluoromethyl)pyridine (432 mg, 1.88 mmol) were subsequently added. The reaction mixture was stirred at room temperature for 72 hours and then water and ethyl acetate were added. The organic phase was removed and the aqueous phase was extracted three times with ethyl acetate. The combined organic phases were washed with saturated aqueous sodium chloride solution, dried over sodium sulfate and filtered, and the filtrate was concentrated. 859 mg (96% chance) of the title compound was obtained. LC-MS (Method 4): Rt = 0.99 min; MS (ESIpos): m /z = 473 [M+H]+ Intermediate 407 tert-Butyl (5S)-2-[(5-chloro-3-fluoropyridin-2-yl)methyl]-3-oxo-2, 3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylate

[0937] tert-Butyl(5S)-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylate ( 500 mg, 2.09 mmol) was initially loaded into acetonitrile (15 mL). Cesium carbonate (1.36 g, 4.18 mmol) and 5-chloro-2-(chloromethyl)-3-fluoropyridine (395 mg, 2.19 mmol) were subsequently added. The reaction mixture was stirred at room temperature for 72 hours and then water and ethyl acetate were added. The organic phase was removed and the aqueous phase was extracted three times with ethyl acetate. The combined organic phases were washed with saturated aqueous sodium chloride solution, dried over sodium sulfate and filtered, and the filtrate was concentrated. 793 mg (99% chance) of the title compound was obtained. LC-MS (Method 4): Rt = 0.86 min; MS (ESIpos): m /z = 383 [M+H]+ Intermediate 408 tert-Butyl (5S)-2-[(3-chloro-5-fluoropyridin-2-yl)methyl]-3-oxo-2, 3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylate

[0938] tert-Butyl(5S)-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylate ( 452 mg, 1.89 mmol) was initially loaded into acetonitrile (41 mL). Cesium carbonate (1.54 g, 4.72 mmol) and 3-chloro-2-(chloromethyl)-5-fluoropyridine (476 mg, 2.65 mmol) were subsequently added. After stirring overnight, the reaction mixture was mixed with water and ethyl acetate at room temperature. The organic phase was removed and the aqueous phase was extracted three times with ethyl acetate. The combined organic phases were washed with saturated aqueous sodium chloride solution, dried over sodium sulfate and filtered, and the filtrate was concentrated. 842 mg (78% purity, 91% possibility) of the title compound were obtained. LC-MS (Method 3): Rt = 1.66 min; MS (ESIpos): m /z = 383 [M+H]+ Intermediate 409 (5RS,7RS)-2-{[3-Chloro-5-(trifluoromethyl)pyridin-2-yl]methyl}-3-oxo- 7- (trifluoromethyl)-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylic acid (mixture of diastereomer; 4 isomers)

[0939] Ethyl (5RS,7RS)-2-{[3-chloro-5-(trifluoromethyl)pyridin-2-yl]methyl}-3-oxo-7-(trifluoromethyl)-2,3,5,6, 7,8-hexahydro[1,2,4]triazolo[4,3- a]pyridine-5-carboxylate (mixture of diastereomer; 4 isomers) (859 mg, 1.82 mmol) was initially loaded into THF ( 21 mL), and sodium ethoxide solution (1.09 g, 3.36 mmol, 21% by weight) was added. The reaction mixture was stirred at 0°C for 20 minutes and at room temperature overnight. The reaction mixture was mixed with water, 1 N aqueous hydrochloric acid and ethyl acetate. The organic phase was removed and the aqueous phase was extracted three times with ethyl acetate. The combined organic phases were washed with saturated aqueous sodium chloride solution, dried over sodium sulfate and filtered, and the filtrate was concentrated. 846 mg (>100% chance) of the title compound was obtained. LC-MS (Method 3): Rt = 1.50 min; MS (ESIpos): m /z = 445 [M+H]+ Intermediate 410 (5S)-2-[(5-Chloro-3-fluoropyridin-2-yl)methyl]-3-oxo-2,3,5 ,6,7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylic acid

[0940] tert-Butyl (5S)-2-[(5-chloro-3-fluoropyridin-2-yl)methyl]-3-oxo-2,3,5,6,7,8-hexahydro[1 ,2,4]triazolo[4,3-a]pyridine-5-carboxylate (793 mg, 2.07 mmol) was dissolved in dichloromethane (15 mL), and trifluoroacetic acid (3.2 mL, 41 mmol) was added at room temperature. After the reaction mixture was stirred at room temperature overnight, trifluoroacetic acid (0.64 mL, 8.2 mmol) was added again, and the reaction mixture was stirred at room temperature for an additional 1.5 hours. The solvent was removed under reduced pressure. 676 mg (89% purity, 89% possibility) of the title compound was obtained. LC-MS (Method 4): Rt = 0.56 min; MS (ESIpos): m /z = 327 [M+H]+ Intermediate 411 (5S)-2-[(3-Chloro-5-fluoropyridin-2-yl)methyl]-3-oxo-2,3,5 ,6,7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylic acid

[0941] tert-Butyl (5S)-2-[(3-chloro-5-fluoropyridin-2-yl)methyl]-3-oxo-2,3,5,6,7,8-hexahydro[1 ,2,4]triazolo[4,3-a]pyridine-5-carboxylate (842 mg, 2.20 mmol) was dissolved in dichloromethane (14.1 mL), and trifluoroacetic acid (3.4 mL, 44 mmol ) was added at room temperature. After the reaction mixture was stirred at room temperature overnight, the solvent was removed under reduced pressure. 1.45 g (58% purity, 117% chance) of the title compound was obtained. LC-MS (Method 4): Rt = 0.53 min; MS (ESIpos): m /z = 327 [M+H]+ Intermediate 412 Ethyl -(5RS,7RS)-2-[(3-chloro-5-fluoropyridin-2-yl)methyl]-3-oxo-7 - (trifluoromethyl)-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylate (mixture of diastereomer; 4 isomers)

[0942] Ethyl-(5RS,7RS)-3-oxo-7-(trifluoromethyl)-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a ]pyridine-5-carboxylate (diastereomer mixture, 4 isomers) (300 mg, 1.07 mmol) was initially loaded into acetonitrile (10 mL). Cesium carbonate (700 mg, 2.15 mmol) and 3-chloro-2-(chloromethyl)-5-fluoropyridine hydrochloride (254 mg, 96% purity, 1.13 mmol) were subsequently added. The reaction mixture was stirred at room temperature overnight. Additional 3-chloro-2-(chloromethyl)-5-fluoropyridine hydrochloride (254 mg, 96% purity, 1.13 mmol) was then added and heated at 60°C overnight. To the reaction mixture, water and ethyl acetate were added and the organic phase was separated. The aqueous phase was extracted three times with ethyl acetate. The combined organic phases were washed with saturated aqueous sodium chloride solution, dried over sodium sulfate and filtered, and the filtrate was concentrated. The residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/gradient water). The fractions containing the product were concentrated under reduced pressure and 348 mg (75% possibility) of the title compound were obtained. LC-MS (Method 3): Rt = 1.67 min; MS (ESIpos): m /z = 423 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: 1.187 (1.01), 1.199 (7.45), 1.204 (2.57), 1.216 (16.00 ), 1.234 (7.55), 1.769 (0.74), 1.799 (1.54), 1.830 (1.61), 1.860 (0.83), 2.073 (0.42), 2.482 (0.94), 2.521 (0.84), 2.716 (1.04), 2.746 (1.26 ), 2.756 (1.70), 2.786 (1.98), 2.867 (1.23), 2.873 (1.39), 2.877 (1.27), 2.902 (0.68), 2.907 (0.77), 2.913 (0.75), 3.056 (0.40), 3.069 (0.55 ), 3.077 (0.63), 3.087 (0.58), 3.098 (0.57), 4.145 (0.51), 4.154 (1.19), 4.159 (1.36), 4.171 (3.77), 4.177 (3.81), 4.189 (3.90), 4.195 (3.66 ), 4.207 (1.35), 4.213 (1.28), 4.222 (0.43), 4.525 (1.71), 4.539 (1.98), 4.553 (1.89), 4.567 (1.64), 4.982 (1.78), 5.021 (4.32), 5.069 (5.20 ), 5,109 (1.75), 8,118 (2.64), 8,124 (2.83), 8,139 (2.69), 8,145 (2.80), 8,543 (0.91), 8,548 (5.70), 8,555 (5.07). Intermediate 413 Ethyl -(5RS,7RS)-2-[(3,5-difluoropyridin-2-yl)methyl]-3-oxo-7-(trifluoromethyl)-2,3,5,6,7,8-hexa -hydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylate (mixture of diastereomer; 4 isomers)

[0943] Ethyl-(5RS,7RS)-3-oxo-7-(trifluoromethyl)-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a ]pyridine-5-carboxylate (diastereomer mixture, 4 isomers) (600 mg, 2.15 mmol) was initially loaded into acetonitrile (10 mL). Cesium carbonate (1.75 g, 5.37 mmol) and 2-(chloromethyl)-3,5-difluoropyridine (387 mg, 2.36 mmol) were subsequently added. The reaction mixture was stirred at room temperature overnight and then at 60°C overnight. Additional 2-(chloromethyl)-3,5-difluoropyridine (100 mg, 0.61 mmol) was added, and the reaction mixture was heated to 60°C for 1 hour and then at room temperature for 48 hours. To the reaction mixture, water and ethyl acetate were added and the organic phase was separated. The aqueous phase was extracted three times with ethyl acetate. The combined organic phases were washed with saturated aqueous sodium chloride solution, dried over sodium sulfate and filtered, and the filtrate was concentrated. 734 mg (79% chance) of the title compound was obtained. LC-MS (Method 4): Rt = 0.82 min; MS (ESIpos): m /z = 407 [M+H]+ Intermediate 414 tert-Butyl-(5S)-3-oxo-2-{[5-(trifluoromethyl)pyridin-3-yl]methyl}-2, 3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylate

[0944] tert-Butyl-(5S)-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylate (154 mg, 645 μmol) was dissolved in acetonitrile (14 mL). Cesium carbonate (525 mg, 1.61 mmol) and 3-(chloromethyl)-5-(trifluoromethyl)pyridine (164 mg, 838 μmol) were added and stirred at 50°C for 5 hours and at room temperature overnight. Most of the solvent was removed under reduced pressure and water and ethyl acetate were added, and the organic phase was separated. The aqueous phase was extracted three times with ethyl acetate. The combined organic phases were washed with saturated aqueous sodium chloride solution, dried over sodium sulfate and filtered, and the filtrate was concentrated. The residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/gradient water). The fractions containing the product were concentrated under reduced pressure and 26.4 mg (83% purity, 9% chance) of the title compound were obtained. LC-MS (Method 3): Rt = 1.72 min; MS (ESIpos): m /z = 399 [M+H]+ Intermediate 415 (5RS,7RS)-2-[(3-Chloro-5-fluoropyridin-2-yl)methyl]-3-oxo-7-( trifluoromethyl)- 2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylic acid (mixture of diastereomer, 4 isomers)

[0945] Ethyl-(5RS,7RS)-2-[(3-chloro-5-fluoropyridin-2-yl)methyl]-3-oxo-7-(trifluoromethyl)-2,3,5,6,7, 8-hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylate (mixture of diastereomer; 4 isomers) (348 mg, 824 μmol) was initially loaded into THF (10 mL), and sodium ethoxide solution (494 mg, 1.52 mmol, 21% by weight in ethanol) was added. The reaction mixture was stirred at room temperature overnight. The reaction mixture was mixed with water, 1 N aqueous hydrochloric acid and ethyl acetate. The organic phase was removed and the aqueous phase was extracted three times with ethyl acetate. The combined organic phases were washed with saturated aqueous sodium chloride solution, dried over sodium sulfate and filtered, and the filtrate was concentrated. 289 mg (87% chance) of the title compound was obtained. LC-MS (Method 3): Rt = 1.14 min; MS (ESIpos): m /z = 395 [M+H]+ Intermediate 416 (5RS,7RS)-2-[(3,5-Difluoropyridin-2-yl)methyl]-3-oxo-7-(trifluoromethyl) - 2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylic acid (mixture of diastereomer; 4 isomers)

[0946] Ethyl-(5RS,7RS)-2-[(3,5-difluoropyridin-2-yl)methyl]-3-oxo-7- (trifluoromethyl)-2,3,5,6,7,8- hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylate (mixture of diastereomer; 4 isomers) (734 mg, 93% purity, 1.69 mmol) was initially loaded into THF (20 mL), and sodium ethoxide solution (1.01 g, 3.12 mmol, 21% by weight in ethanol) was added. The reaction mixture was stirred at 0°C for 20 minutes and then at room temperature overnight. The reaction mixture was mixed with water, 1 N aqueous hydrochloric acid and ethyl acetate. The organic phase was removed and the aqueous phase was extracted three times with ethyl acetate. The combined organic phases were washed with saturated aqueous sodium chloride solution, dried over sodium sulfate and filtered, and the filtrate was concentrated. 213 mg (32% chance) of the title compound was obtained. LC-MS (Method 3): Rt = 1.04 min; MS (ESIpos): m /z = 379 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: 1.309 (1.32), 1.324 (2.78), 1.341 (1.44), 1.774 (0.56 ), 1.804 (0.56), 2.064 (0.56), 2.072 (0.41), 2.096 (0.40), 2.169 (0.58), 2.224 (1.06), 2.240 (1.22), 2.259 (2.88), 2.275 (3.39), 2.301 (9.72 ), 2.332 (2.28), 2.455 (0.76), 2.636 (2.41), 2.666 (8.01), 2.701 (8.02), 2.743 (1.91), 2.785 (0.63), 2.849 (0.55), 2.949 (5.55), 2.979 (4.61 ), 3.848 (0.90), 4.073 (0.62), 4.090 (1.31), 4.108 (1.11), 4.113 (1.20), 4.391 (0.55), 4.405 (0.62), 4.418 (0.62), 4.433 (0.53), 4.665 (5.53 ), 4.671 (7.00), 4.680 (5.72), 4.685 (5.62), 4.836 (0.65), 4.857 (0.88), 4.874 (0.78), 4.898 (1.52), 4.964 (3.41), 4.998 (11.30), 5.030 (10.17 ), 5.066 (2.90), 7.468 (0.68), 7.495 (0.65), 7.937 (3.94), 7.943 (4.33), 7.962 (6.26), 7.966 (6.71), 7.984 (4.12), 7.990 (4.32), 8.051 (1.42 ), 8,420 (0.48), 8,468 (14.61), 8,473 (16.00), 13,619 (0.72). Intermediate 417 (5S)-3-Oxo-2-{[5-(trifluoromethyl)pyridin-3-yl]methyl}-2,3,5,6,7,8-hexahydro[1,2,4] triazolo[4,3-a]pyridine-5-carboxylic acid

[0947] tert-Butyl-(5S)-3-oxo-2-{[5-(trifluoromethyl)pyridin-3-yl]methyl}-2,3,5,6,7,8-hexahydro[1 ,2,4]triazolo[4,3-a]pyridine-5-carboxylate (1.13 g, 2.83 mmol) was dissolved in dichloromethane (180 μl), and trifluoroacetic acid (4.4 mL, 57 mmol) was added at room temperature. After the reaction mixture was stirred at room temperature overnight, the solvent was removed under reduced pressure. 980 mg (101% chance) of the title compound was obtained. LC-MS (Method 3): Rt = 1.01 min; MS (ESIpos): m /z = 343 [M+H]+ Intermediate 418 (5S)-2-{[3-Chloro-5-(trifluoromethyl)pyridin-2-yl]methyl}-5-[(3, 3-difluoropyrrolidin-1-yl)carbonyl]-6,7-dihydro[1,2,4]triazolo[4,3-a]pyridine-3,8(2H,5H)-dione

[0948] (5S,8RS)-2-{[3-Chloro-5-(trifluoromethyl)pyridin-2-yl]methyl}-5-[(3,3-difluoropyrrolidin-1-yl)carbonyl]-8- hydroxy-5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one (mixture of diastereomer; 2 isomers) (58.0 mg, 120 μmol) was dissolved in dichloromethane (10 mL), and manganese(IV) oxide (209 mg, 2.41 mmol) was added at room temperature. The reaction mixture was stirred at room temperature overnight. The suspension was filtered through Celite and the filtrate was concentrated under reduced pressure. 49.4 mg (86% chance) of the title compound was obtained. LC-MS (Method 3): Rt = 1.55 min; MS (ESIpos): m /z = 480 [M+H]+ Intermediate 419 (5S)-2-[(5-Chloropyridin-2-yl)methyl]-5-[(3,3-difluoropyrrolidin-1-yl )carbonyl]-6,7-dihydro[1,2,4]triazolo[4,3-a]pyridine-3,8(2H,5H)-dione

[0949] (5S,8RS)-2-[(5-Chloropyridin-2-yl)methyl]-5-[(3,3-difluoropyrrolidin-1-yl)carbonyl]-8-hydroxy-5,6,7 ,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one (diastereomer mixture; 2 isomers) (103 mg, 85% purity, 211 μmol) was dissolved in dichloromethane (8.7 mL), and manganese(IV) oxide (366 mg, 4.21 mmol) was added at room temperature. The reaction mixture was stirred at room temperature overnight. The suspension was filtered through Celite and the filtrate was concentrated under reduced pressure. 79.4 mg (88% purity, 81% chance) of the title compound was obtained. LC-MS (Method 3): Rt = 1.25 min; MS (ESIpos): m /z = 412 [M+H]+ Intermediate 420 (5S)-2-[(5-Chloropyridin-2-yl)methyl]-5-[(3-fluoroazetidin-1-yl)carbonyl ]-6,7-dihydro[1,2,4]triazolo[4,3-a]pyridine-3,8(2H,5H)-dione

[0950] (5S,8RS)-2-[(5-Chloropyridin-2-yl)methyl]-5-[(3-fluoroazetidin-1-yl)carbonyl]-8-hydroxy-5,6,7,8 -tetrahydro[1,2,4]triazolo[4,3-a]pyridin- 3(2H)-one (diastereomer mixture; 2 isomers) (48.1 mg, 86% purity, 108 μmol) was dissolved in dichloromethane (800 μl), and manganese(IV) oxide (188 mg, 2.17 mmol) was added at room temperature. The reaction mixture was stirred at room temperature overnight. The suspension was filtered through Celite and the filtrate was concentrated under reduced pressure. 37.1 mg (63% purity, 57% chance) of the title compound was obtained. LC-MS (Method 1): Rt = 0.83 min; MS (ESIpos): m /z = 380 [M+H]+ Intermediate 421 (5S)-2-[(3,5-Difluoropyridin-2-yl)methyl]-5-[(3,3-difluoropyrrolidin-1 -yl)carbonyl]-6,7-dihydro[1,2,4]triazolo[4,3-a]pyridine-3,8(2H,5H)-dione

[0951] (5S,8RS)-2-[(3,5-Difluoropyridin-2-yl)methyl]-5-[(3,3-difluoropyrrolidin-1-yl)carbonyl]-8-hydroxy-5,6 ,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one (mixture of diastereomer; 2 isomers) (112 mg, 270 μmol) was dissolved in dichloromethane (10 mL), and manganese(IV) oxide (469 mg, 5.39 mmol) was added at room temperature. The reaction mixture was stirred at room temperature overnight. The suspension was filtered through Celite and the filtrate was concentrated under reduced pressure. 61.3 mg (55% chance) of the title compound was obtained. LC-MS (Method 4): Rt = 0.64 min; MS (ESIpos): m /z = 414 [M+H]+ Intermediate 422 (5S)-5-{[(3S)-3-Fluoropyrrolidin-1-yl]carbonyl}-2-{[6-(trifluoromethyl) pyridin-3-yl]methyl}-6,7-dihydro[1,2,4]triazolo[4,3-a]pyridine-3,8(2H,5H)-dione (isomer 1)

[0952] (5S,8RS)-5-{[(3S)-3-Fluoropyrrolidin-1-yl]carbonyl}-8-hydroxy-2- {[6-(trifluoromethyl)pyridin-3-yl]methyl}- 5,6,7,8-tetrahydro[1,2,4]triazolo[4,3- a]pyridin-3(2H)-one (mixture of diastereomer; 2 isomers) (30.0 mg, 69, 9 μmol) was initially loaded into dichloromethane (180 μl) at room temperature, and the reaction mixture was cooled to 0°C. Subsequently, Dess-Martin periodinane (35.6 mg, 83.8 μmol) was added, and the reaction mixture was stirred at 0 °C for 15 min. and at room temperature for 2 hours. Dess-Martin periodinane (35.6 mg, 83.8 μmol) was added again and the mixture was stirred overnight. The reaction mixture was mixed with diethyl ether and a solution of sodium thiosulfate in saturated aqueous sodium hydrogen carbonate solution until the two phases were homogeneous. The organic phase was dried over sodium sulfate and filtered, and the filtrate was concentrated. The residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: gradient (acetonitrile/water with 0.1% formic acid). The fractions containing the product were concentrated under reduced pressure and 1. 60 mg (5% chance) of the title compound. LC-MS (Method 3): Rt = 1.28 min; MS (ESIpos): m / z = 428 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.150 (1.86), -0.044 (0.28), -0.035 (0.39), -0.033 (0.39), -0.029 (0.51), -0.027 (0.51), -0.024 (0.56) , - 0.022 (0.85), -0.020 (1.01), -0.016 (1.69), -0.009 (16.00), 0.007 (14.08), 0.013 (2.08), 0.015 (1.18), 0.018 (0.85), 0.020 (0.56), 0.023 (0.56), 0.025 (0.45), 0.029 (0.34), 0.146 (1.75), 2.113 (0.34), 2.135 (0.34), 2.151 (0.39), 2.193 (0.28), 2.238 (0.45), 2.266 (0.56), 2,292 (0.39), 2,323 (1.35), 2,327 (1.86), 2,331 (1.46), 2,366 (2.37), 2,396 (0.45), 2,424 (0.23), 2,431 (0.28), 2,453 (0.34), 2,523 (4.73), 2,525 (3.66), 2,558 (1.58), 2,612 (0.68), 2,622 (0.62), 2,646 (0.28), 2,664 (1.46), 2,669 (1.80), 2,674 (1.35), 2,709 (2.08), 3,364 (0.56), 3.391 (0.34), 3.400 (0.34), 3.418 (0.28), 3.435 (0.34), 3.507 (0.28), 3.534 (0.34), 3.544 (0.34), 3.651 (0.62), 3.673 (0.56), 3.681 (0.68), 3.702 (0.51), 3.711 (0.56), 3.749 (0.34), 3.792 (0.23), 3.815 (0.34), 3.841 (0.68), 3.889 (0.39), 3.919 (0.39), 3.948 (0.34), 5.029 (0.68), 5.068 (0.45), 5.081 (0.85), 5.185 (0.51), 5.224 (2.14), 5.239 (1.52), 5.245 (1.86), 5.285 (0.73), 5.417 (0.51), 5.541 (0.28), 7.928 (0.96), 7,948 (2.93), 7,965 (1.52), 7,987 (0.51), 8,535 (0.45), 8,699 (1.75). Intermediate 423 (5S)-2-{[3-Chloro-5-(trifluoromethyl)pyridin-2-yl]methyl}-5-{[(3S)-3-fluoropyrrolidin-1-yl]carbonyl}-6.7 -dihydro[1,2,4]triazolo[4,3-a]pyridine-3,8(2H,5H)-dione

[0953] (5S,8SR)-2-{[3-Chloro-5-(trifluoromethyl)pyridin-2-yl]methyl}-5-{[(3S)-3-fluoropyrrolidin-1-yl]carbonyl}- 8-hydroxy-5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one (diastereomer mixture; 2 isomers) (93.0 mg, 201 μmol) was dissolved in dichloromethane (2.0 mL), and manganese(IV) oxide (349 mg, 4.01 mmol) was added at room temperature. The reaction mixture was stirred at room temperature overnight. The suspension was filtered through Celite and the filtrate was concentrated under reduced pressure. 75.5 mg (82% chance) of the title compound was obtained. LC-MS (Method 3): Rt = 1.39 min; MS (ESIpos): m /z = 462 [M+H]+ Work-up examples: Example 1 (5RS)-5-(Pyrrolidin-1-ylcarbonyl)-2-[4-(trifluoromethyl)benzyl]-5.6 ,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one (racemate)

[0954] (5RS)-5-(Pyrrolidin-1-ylcarbonyl)-5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)- onena (racemate) (70.0 mg, 296 μmol) was dissolved in 5.0 mL of acetonitrile, then cesium carbonate (145 mg, 444 μmol) and 1-(bromomethyl)-4-(trifluoromethyl)benzene (85 .0 mg, 356 μmol) was added, and the mixture was stirred at room temperature overnight. For elaboration, the mixture was stirred with 1 mL of water and separated via preparatory HPLC (GromSila 120 ODS-4HE, 250x30mm 10μm. Flow rate: 50 ml/min. Gradient (A = water + 0.1% formic acid, B = acetonitrile): 0min 0% B, 6min 10%B, 27min 95% B, 38min 95% B, 40min 0%B. Run time per separation 40 min. The product fractions were combined, concentrated and lyophilized. In this way, 92 mg (79% possibility) of the title compound were obtained. LC-MS (Method 3): Rt = 1.52 min; MS (ESIpos): m /z = 395 [M+H]+ 1H-NMR (400MHz, DMSO-d6): δ [ppm]= 1.61 - 1.84 (m, 4H), 1.86 - 2.11 (m, 4H), 2.45 - 2.68 (m, 2H, partially covered by the solvent signal), 3.21 - 3.41 (m, 2H, partially overlapped by the water signal), 3.47 (dt, 1H), 3.62 (dt, 1H), 4.75 (dd, 1H), 4.92 (s, 2H), 7.41 - 7.47 (m, 2H), 7.68 - 7.74 (m, 2H). Example 2 (5RS)-2-(4-tert-Butylbenzyl)-5-(pyrrolidin-1-ylcarbonyl)-5,6,7,8-tetrahydro[1,2,4]triazolo[4,3- a]pyridin-3(2H)-one (racemate)

[0955] (5RS)-5-(Pyrrolidin-1-ylcarbonyl)-5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)- onena (racemate) (50.0 mg, 212 μmol) was dissolved in 3.0 mL of acetonitrile, then cesium carbonate (103 mg, 317 μmol) and 1-(bromomethyl)-4-butylbenzene (47 μl, 250 μmol) was added, and the mixture was stirred at room temperature overnight. For elaboration, the mixture was stirred with 1 mL of water and separated via preparatory HPLC (GromSila 120 ODS- 4HE, 250x30mm 10μm. Flow rate: 50 ml/min. Gradient (A = water + 0.1% formic acid, B = acetonitrile): 0min 0% B, 6min 10%B, 27min 95% B, 38min 95% B, 40min 0%B. Run time per separation 40 min. The product fractions were combined, concentrated and lyophilized. In this way, 63 mg (81% possibility) of the title compound were obtained. LC-MS (Method 3): Rt = 1.75 min; MS (ESIpos): m /z = 383 [M+H]+ 1H-NMR (400MHz, DMSO-d6): δ [ppm]= 1.26 (s, 9H), 1.61 - 1.84 (m, 4H), 1.87 - 2.10 (m, 4H), 2.46 - 2.65 (m, 2H, partially covered by solvent signal), 3.21 - 3.41 (m, 2H, partially overlapped by water signal), 3.47 (dt, 1H), 3.62 (dt, 1H), 4.70 - 4.73 (m, 3H), 7.13 - 7.18 (m, 2H), 7.31 - 7.37 (m, 2H). Example 3 (5RS)-2-[(1RS)-1-(4-Chlorophenyl)ethyl]-5-(pyrrolidin-1-ylcarbonyl)-5,6,7,8-tetrahydro[1,2,4 ]triazolo[4,3-a]pyridin-3(2H)-one (mixture of diastereomer; 4 isomers)

[0956] (5RS)-5-(Pyrrolidin-1-ylcarbonyl)-5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)- onena (racemate) (50.0 mg, 212 μmol) was dissolved in 3.0 mL of acetonitrile, then cesium carbonate (103 mg, 317 μmol) and 1-[(1RS)-1-bromoethyl]-4- chlorobenzene (racemate) (55.7 mg, 254 μmol) was added, and the mixture was stirred at room temperature overnight. For elaboration, the mixture was stirred with 1 mL of water and separated via preparatory HPLC (GromSila 120 ODS-4HE, 250x30mm 10μm. Flow rate: 50 ml/min. Gradient (A = water + 0.1% formic acid, B = acetonitrile): 0min 0% B, 6min 10%B, 27min 95% B, 38min 95% B, 40min 0%B. Run time per separation 40 min. The product fractions were combined, concentrated and lyophilized. In this way, 56 mg (71% possibility) of the title compound were obtained as a diastereomer mixture. LC-MS (Method 3): Rt = 1.52 min; MS (ESIpos): m /z = 375 [M+H]+ 1H-NMR (400MHz, DMSO-d6): δ [ppm]= 1.57 - 1.64 (m, 3H), 1.64 -1.82 (m, 4H), 1.86 - 2.10 (m, 4H), 2.50 - 2.69 (m, 2H, partially covered by solvent signal), 3.18 - 3.39 (m, 2H, partially overlapped by water signal), 3.41 - 3.50 (m, 1H), 3.56 - 3.65 (m, 1H), 4.67 - 4.75 (td, 1H), 5.25 - 5.33 (m, 1H), 7.28 - 7.41 (m, 4H).

[0957] In another batch of the same title compound, (5RS)-2-[(1RS)- 1-(4-chlorophenyl)ethyl]-3-oxo-2,3,5,6,7,8-hexa- hydro[1,2,4]triazolo[4,3- a]pyridine-5-carboxylic acid (mixture of diastereomer; 4 isomers) (392 mg, 90% purity, 1.10 mmol) were dissolved in 12 mL of THF. Triethylamine (310 μl, 2.2 mmol), HATU (542 mg, 1.43 mmol), and pyrrolidine (110 μl, 1.3 mmol) were added, and the mixture was stirred under argon at room temperature for 2 hours. For preparation, the mixture was diluted with water and then substantially concentrated under reduced pressure. The residue was mixed in ethyl acetate/water. After extraction and removal of the organic phase, the aqueous phase was extracted twice more with ethyl acetate. The organic phases were washed with saturated aqueous sodium chloride solution and dried over sodium sulfate. The residue that remained after concentration and drying under reduced pressure was dissolved in acetonitrile/water and separated into 2 batches via preparatory HPLC. (column: Kromasila C18, 125x30mm, 10μm, eluent: acetonitrile (B)/water + 0.1% TFA (A), gradient: 0min 90% A, 6min 90% A, 18min 5%A, 20min 5%A, 21min 90 %A, flow rate: 75ml/min, detector: 210nm). The combined fractions containing the product were concentrated under reduced pressure and dried. In this way, 293 mg 56 mg (98% purity, 70% possibility) of the title compound were obtained as a racemic diastereomer mixture. Example 4 (5RS)-2-[(1RS)-1-(4-Chlorophenyl)ethyl]-5-(pyrrolidin-1-ylcarbonyl)-5,6,7,8-tetrahydro[1,2,4 ]triazolo[4,3-a]pyridin-3(2H)-one (isomer 3)

[0958] (5RS)-2-[(1RS)-1-(4-Chlorophenyl)ethyl]-5-(pyrrolidin-1-ylcarbonyl)-5,6,7,8-tetrahydro[1,2, 4]triazolo[4,3-a]pyridin-3(2H)-one (diastereomer mixture; 4 isomers) was separated by two preparatory liquid chromatography runs into a chiral phase. First, stereoisomer 4 was separated by preparatory liquid chromatography in a chiral phase [sample preparation: 392 mg dissolved in 10 mL of ethanol; injection volume: 2.0 mL; column: Daicel Chiralcel® OX-H 5μm, 250 x 50 mm; eluent: ethanol, flow rate: 15.0 ml/min; temperature 50°C; UV detection: 220 nm]. This produced 61 mg of stereoisomer 4 which elutes last.

[0959] In the second step, the combined fractions of the three remaining stereoisomers were dissolved and separated again [sample in 10 mL of ethanol; injection volume: 0.4 mL; column: Daicel Chiralcel® OX-H 5μm, 250 x 50 mm; eluent: water/ethanol: isocratic 50% ethanol; flow rate: 15.0 ml/min; temperature 50°C; UV detection: 220 nm]. This produced, in the elution sequence, 51 mg of isomer 1, 62 mg of isomer 2 and 53 mg of isomer 3. Isomer 3: Specific rotation: -145.16 (589 nm, 0.2450 g/100 cm3 MeOH)

[0960] Analytical chiral HPLC: Rt = 4.74 min, de/ee = 100% [column: Daicel Chiralcel® OX-H 250 x 4.6 mm; eluent: ethanol; flow rate: 1 ml/min; 50°C; UV detection: 220 nm]. LC-MS (Method 4): Rt = 0.82 min; MS (ESIpos): m /z = 375 [M+H]+ 1H-NMR (500MHz, DMSO-d6): δ [ppm]= 1.61 (d, 3H), 1.68 - 1.74 (m, 2H); 1.74 - 1.83 (m, 2H), 1.87 - 1.98 (m, 3H), 1.98 - 2.07 (m, 1H), 2.50 - 2.59 (m, 1H, partially covered by solvent signal), 2.65 (dt, 1H), 3.21 - 3.39 (m, 2H, partially overlapped by water signal), 3.45 (dt, 1H), 3.60 (dt, 1H), 4.70 (dd, 1H), 5.28 (q, 1H), 7.30 - 7.34 (m, 2H), 7.36 - 7.40 (m, 2H). Example 5 (5RS)-2-[(1RS)-1-(4-Chlorophenyl)ethyl]-5-(pyrrolidin-1-ylcarbonyl)-5,6,7,8-tetrahydro[1,2,4 ]triazolo[4,3-a]pyridin-3(2H)-one (isomer 4)

[0961] (5RS)-2-[(1RS)-1-(4-Chlorophenyl)ethyl]-5-(pyrrolidin-1-ylcarbonyl)-5,6,7,8-tetrahydro[1,2, 4]triazolo[4,3-a]pyridin-3(2H)-one (diastereomer mixture; 4 isomers) was separated by two preparatory liquid chromatography runs into a chiral phase. First, stereoisomer 4 was separated by preparatory liquid chromatography in a chiral phase [sample preparation: 392 mg dissolved in 10 mL of ethanol; injection volume: 2.0 mL; column: Daicel Chiralcel® OX-H 5μm, 250 x 50 mm; eluent: ethanol, flow rate: 15.0 ml/min; temperature 50°C; UV detection: 220 nm]. This produced 61 mg of stereoisomer 4 which elutes last.

[0962] In the second step, the combined fractions of the three remaining stereoisomers were dissolved and separated again [sample in 10 mL of ethanol; injection volume: 0.4 mL; column: Daicel Chiralcel® OX-H 5μm, 250 x 50 mm; eluent: water/ethanol: isocratic 50% ethanol; flow rate: 15.0 ml/min; temperature 50°C; UV detection: 220 nm]. This produced, in the elution sequence, 51 mg of isomer 1, 62 mg of isomer 2 and 53 mg of isomer 3. Isomer 4:

[0963] Analytical chiral HPLC: Rt = 12.6 min, de/ee = 100% [column: Daicel Chiralcel® OX-H 250 x 4.6 mm; eluent: ethanol; flow rate: 1 ml/min; 50°C; UV detection: 220 nm]. Specific rotation: +134.80 (589 nm, 0.2500 g/100 cm3 MeOH) LC-MS (Method 4): Rt = 0.81 min; MS (ESIpos): m /z = 375 [M+H]+ 1H-NMR (500MHz, DMSO-d6): δ [ppm]= 1.60 (d, 3H), 1.63 - 1.82 (m, 4H), 1.85 - 2.09 (m, 4H), 2.50 - 2.61 (m, 1H, partially covered by solvent signal), 2.65 (dt, 1H), 3.23 (dt, 1H), 3.28 - 3.36 (m, 1H, partially overlapped by solvent signal water), 3.45 (dt, 1H), 3.60 (dt, 1H), 4.72 (dd, 1H), 5.29 (q, 1H), 7.29 - 7.33 (m, 2H), 7.37 - 7.41 (m, 2H). Example 6 (5RS)-2-[4-(Methylsulfonyl)benzyl]-5-(pyrrolidin-1-ylcarbonyl)-5,6,7,8-tetrahydro[1,2,4]triazolo[4,3 -a]pyridin-3(2H)-one (racemate)

[0964] (5RS)-5-(Pyrrolidin-1-ylcarbonyl)-5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)- onena (racemate) (50.0 mg, 212 μmol) was dissolved in 3.0 mL of acetonitrile, then cesium carbonate (103 mg, 317 μmol) and 1-(bromomethyl)-4-(methylsulfonyl)benzene ( 68 .5 mg, 275 μmol) was added, and the mixture was stirred at room temperature under argon overnight. For elaboration, the mixture was stirred with 1 mL of water and separated via preparatory HPLC (GromSila 120 ODS-4HE, 250x30mm 10μm. Flow rate: 50 ml/min. Gradient (A = water + 0.1% formic acid, B = acetonitrile): 0min 0% B, 6min 10%B, 27min 95% B, 38min 95% B, 40min 0%B. Run time per separation 40 min. The product fractions were combined, concentrated and lyophilized. In this way, 71 mg (82% possibility) of the title compound were obtained. LC-MS (Method 3): Rt = 0.96 min; MS (ESIpos): m /z = 405 [M+H]+ 1H-NMR (400MHz, DMSO-d6): δ [ppm]= 1.61 - 1.84 (m, 4H), 1.87 - 2.12 (m, 4H), 2.47 - 2.69 (m, 2H, partially covered by the solvent signal), 3.20 (s, 3H), 3.22 - 3.40 (m, 2H, partially overlapped by the water signal), 3.47 (dt, 1H), 3.62 (dt, 1H), 4.76 (dd, 1H), 4.94 (s, 2H), 7.45 - 7.51 (m, 2H), 7.87 - 7.92 (m, 2H). Example 7 (5RS)-2-[4-(Difluoromethoxy)benzyl]-5-(pyrrolidin-1-ylcarbonyl)-5,6,7,8-tetrahydro[1,2,4]triazolo[4,3 -a]pyridin-3(2H)-one (racemate)

[0965] (5RS)-5-(Pyrrolidin-1-ylcarbonyl)-5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)- onena (racemate) (50.0 mg, 212 μmol) was dissolved in 3.0 mL of acetonitrile, then cesium carbonate (103 mg, 317 μmol) and 1-(bromomethyl)-4-(difluoromethoxy)benzene (60 .2 mg, 254 μmol) was added, and the mixture was stirred at room temperature under argon overnight. For elaboration, the mixture was stirred with 1 mL of water and separated via preparatory HPLC (GromSila 120 ODS-4HE, 250x30mm 10μm. Flow rate: 50 ml/min. Gradient (A = water + 0.1% formic acid, B = acetonitrile): 0min 0% B, 6min 10%B, 27min 95% B, 38min 95% B, 40min 0%B. Run time per separation 40 min. The product fractions were combined, concentrated and lyophilized. The product obtained was purified a second time by preparatory HPLC as above. In this way, after reconcentration and lyophilization, 29 mg (35% possibility) of the title compound were obtained. LC-MS (Method 6): Rt = 1.39 min; MS (ESIpos): m /z = 393 [M+H]+ 1H-NMR (400MHz, DMSO-d6): δ [ppm]= 1.61 - 1.84 (m, 4H), 1.87 - 2.11 (m, 4H), 2.46 - 2.66 (m, 2H, partially covered by solvent signal), 3.21 - 3.40 (m, 2H, partially overlapped by water signal), 3.47 (dt, 1H), 3.62 (dt, 1H), 4.73 (dd, 1H), 4.80 (s, 2H), 7.11 - 7.17 (m, 2H), 7.20 (s, 1H) 7.25 - 7.31 (m, 2H). Example 8 (5RS)-2-(3-Methylbenzyl)-5-(pyrrolidin-1-ylcarbonyl)-5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a] pyridin-3(2H)-one (racemate)

[0966] (5RS)-5-(Pyrrolidin-1-ylcarbonyl)-5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)- onena (racemate) (45.0 mg, 190 μmol) and cesium carbonate (93.1 mg, 286 μmol) were suspended in 3.0 mL of acetonitrile, then 1-(bromomethyl)-3-methylbenzene (31 μl, 230 μmol) was added, and the mixture was stirred at room temperature first for 2 hours and then overnight. For elaboration, the mixture was diluted with ethyl acetate and water, and the organic phase was removed. The aqueous phase was extracted twice more with ethyl acetate. The combined organic phases were washed with saturated aqueous sodium chloride solution and then dried over sodium sulfate. The residue obtained after filtration and concentration under reduced pressure was dissolved in acetonitrile/water and separated by preparatory HPLC (column: Kromasila C18, 125x30mm, 10μm, eluent: acetonitrile (B)/water + 0.1% TFA (A), gradient: 0min 90%A, 6min 90%A, 18min 5%A, 20min 5%A, 21min 90%A, flow rate: 75ml/min, detector: 210nm). The product fractions were combined, concentrated and lyophilized, and subjected to further drying under reduced pressure. In this way, 35.1 mg (54% possibility) of the title compound were obtained. LC-MS (Method 4): Rt = 0.77 min; MS (ESIpos): m /z = 341 [M+H]+ 1H-NMR (500MHz, DMSO-d6): δ [ppm]= 1.63 - 1.84 (m, 4H), 1.88 - 2.09 (m, 4H), 2.28 (s, 3H), 2.45 - 2.65 (m, 2H, partially covered by solvent signal), 3.26 (dt, 1H) 3.36 (dt, 1H) 3.40 - 3.66 (m, 2H, partially overlapped by water signal) , 4.70 - 4.79 (m, 3H), 6.99 - 7.10 (m, 3H), 7.21 (t, 1H). Example 9 (5RS)-2-[4-(3-Methyl-1,2,4-oxadiazol-5-yl)benzyl]-5-(pyrrolidin-1-ylcarbonyl)-5,6,7,8-tetra -hydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one (racemate)

[0967] (5RS)-5-(Pyrrolidin-1-ylcarbonyl)-5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)- onena (racemate) (55.0 mg, 233 μmol) and cesium carbonate (114 mg, 349 μmol) were suspended in 3.0 mL of acetonitrile, then 5-[4-(bromomethyl)phenyl]-3- Methyl-1,2,4-oxadiazole (70.7 mg, 279 μmol) was added, and the mixture was stirred at room temperature initially for 2 hours, then overnight. For elaboration, the present precipitate was filtered with suction and washed with acetonitrile. The filtrate was concentrated, mixed in acetonitrile/water and separated by preparatory HPLC (column: Kromasila C18, 125x30mm, 10μm, eluent: acetonitrile (B)/water + 0.1% TFA (A), gradient: 0min 90% A, 6min 90 %A, 18min 5%A, 20min 5%A, 21min 90%A, flow rate: 75ml/min, detector: 210nm). The product fractions were combined, concentrated and dried under reduced pressure. In this way, 42.0 mg (44% possibility) of the title compound were obtained. LC-MS (Method 3): Rt = 1.26 min; MS (ESIpos): m /z = 409 [M+H]+ 1H-NMR (400MHz, DMSO-d6): δ [ppm]= 1.64 - 1.85 (m, 4H), 1.88 - 2.12 (m, 4H), 2.42 (s, 3H), 2.45 - 2.70 (m, 2H, partially covered by the solvent signal), 3.20 - 3.57 (m, 3H, partially overlapped by the water signal), 3.63 (dt, 1H), 4.73 - 4.78 ( m, 1H), 4.93 (s, 2H), 7.44 - 7.48 (m, 2H), 8.04 - 8.08 (m, 2H). Example 10 (5RS)-2-[4-(5-Methyl-1,2,4-oxadiazol-3-yl)benzyl]-5-(pyrrolidin-1-ylcarbonyl)-5,6,7,8-tetra -hydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one (racemate)

[0968] (5RS)-5-(Pyrrolidin-1-ylcarbonyl)-5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)- onena (racemate) (60.0 mg, 254 μmol) and cesium carbonate (124 mg, 381 μmol) were suspended in 3.0 mL of acetonitrile, then 5-[4-(bromomethyl)phenyl]-3- Methyl-1,2,4-oxadiazole (70.7 mg, 279 μmol) was added, and the mixture was stirred at room temperature over a weekend. For elaboration, the present precipitate was filtered with suction, and the filtrate was concentrated. Drying under reduced pressure was followed by purification by chromatography (instrument: Waters Prep LC/MS System, column: Phenomenex Kinetex C18 5μm 100x30 mm; eluent A: water, eluent B: acetonitrile, flow rate: 65 ml/min plus 5 mL of 2% formic acid in water, room temperature, wavelength 200-400 nm, in column injection (full injection): 0 to 2 min 10% eluent B, 2 to 2.2 min in; 20% eluent B, 2.2 to 7 min in 60% eluent B, 7 to 7.5 min in 92% eluent B, 7.5 to 9 min in 92% eluent B. The product fraction was lyophilized. This yielded 57.6 mg (54% chance) of the title compound. LC-MS (Method 3): Rt = 1.18 min; MS (ESIpos): m /z = 409 [M+H]+ 1H-NMR (400MHz, DMSO-d6): δ [ppm]= 1.62 - 1.85 (m, 4H), 1.88 - 2.12 (m, 4H), 2.48 - 2.72 (m, 2H, partially covered by the solvent signal), 2.86 (s, 3H), 3.22 - 3.41 (m, 2H, partially overlapped by the water signal), 3.47 (dt, 1H), 3.63 (dt, 1H), 4.76 (dd, 1H), 4.84 - 4.95 (m, 2H), 7.38 - 7.43 (m, 2H), 7.93 - 7.98 (m, 2H). Example 11 (5RS)-2-(2,3-Dihydro-1H-inden-5-ylmethyl)-5-(pyrrolidin-1-ylcarbonyl)-5,6,7,8-tetrahydro[1, 2,4]triazolo[4,3-a]pyridin-3(2H)-one (racemate)

[0969] (5RS)-5-(Pyrrolidin-1-ylcarbonyl)-5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)- onena (racemate) (75.4 mg, 316 μmol) and cesium carbonate (154 mg, 474 μmol) were suspended in 3.0 mL of acetonitrile, then 5-(bromomethyl)indan (100 mg, approximately 80% purity , approximately 379 μmol) was added, the mixture was stirred at room temperature for 1.5 h and then left to stand for a week at room temperature. For further conversion, cesium carbonate (206 mg, 632 μmol) and 5-(bromomethyl)indan (100 mg, approximately 80% purity, approximately 379 μmol) were added once again, and the mixture was stirred at room temperature. for 4 hours. For preparation, the precipitate present was filtered with suction and discarded. The filtrate was concentrated, mixed in acetonitrile/DMSO/water and separated by preparatory HPLC (column: Kromasila C18, 250x30mm, 10μm, eluent: acetonitrile (B)/water + 0.1% TFA (A), gradient: 0min 90% A, 6min90%A, 27min 5%A, 38min 5%A, 38min 5%A, 39min 90%A; flow rate: 50ml/min, detector: 210nm). The product-containing fractions were combined, concentrated and dried under reduced pressure. In this way, 77.2 mg (67% possibility) of the title compound were obtained. LC-MS (Method 4): Rt = 0.82 min; MS (ESIpos): m /z = 367 [M+H]+ 1H-NMR (400MHz, DMSO-d6): δ [ppm]= 1.64 - 1.74 (m, 2H), 1.79 (quint; 2H) 1.88 - 2.09 (m, 6H), 2.46 - 2.64 (m, 2H, partially covered by solvent signal), 2.81 (t, 4H), 3.25 (dt, 1H), 3.36 (dt, 1H), 3.42 - 3.68 (m, 2H, partially overlapped by the water signal), 4.67 - 4.79 (m, 3H), 6.99 (d, 1H), 7.09 (s, 1H), 7.16 (d, 1H). Example 12 (5RS)-2-[(5-Methyl-1,2,4-oxadiazol-3-yl)methyl]-5-(pyrrolidin-1-ylcarbonyl)-5,6,7,8-tetrahydro [1,2,4]triazolo[4,3-a]pyridin-3(2H)-one (racemate)

[0970] (5RS)-5-(Pyrrolidin-1-ylcarbonyl)-5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)- onena (racemate) (30.0 mg, 127 μmol) was initially loaded into acetonitrile (2.0 mL). Cesium carbonate (62.1 mg, 190 μmol) and 3-(bromomethyl)-5-methyl-1,2,4-oxadiazole (23.6 mg, 133 μmol) were subsequently added. After stirring overnight, the reaction mixture was mixed with water and ethyl acetate at room temperature. The organic phase was removed and the aqueous phase was extracted three times with ethyl acetate. The combined organic phases were washed with saturated aqueous sodium chloride solution, dried over sodium sulfate and filtered, and the filtrate was concentrated. The residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/gradient water). The fractions containing the product were concentrated under reduced pressure and 19.0 mg (45% possibility) of the title compound were obtained. LC-MS (Method 4): Rt = 0.48 min; MS (ESIpos): m /z = 333 [M+H]+ 1H-NMR (500 MHz, DMSO-d6) δ [ppm]: 1.701 (0.70), 1.713 (0.92), 1.717 (0.99), 1.727 (0.86 ), 1.776 (1.37), 1.789 (2.33), 1.803 (1.73), 1.817 (0.51), 1.899 (0.57), 1.913 (1.61), 1.926 (2.10), 1.940 (1.46), 1.952 (0.51), 1.969 (0.52 ), 1.979 (0.49), 2.023 (0.40), 2.040 (0.41), 2.052 (0.41), 2.518 (0.65), 2.522 (0.41), 2.568 (3.66), 2.573 (16.00), 2.590 (1.04), 2.598 (1.52 ), 2.866 (2.48), 3.247 (0.78), 3.256 (0.75), 3.260 (0.64), 3.270 (1.32), 3.284 (1.11), 3.310 (3.45), 3.324 (2.02), 3.338 (1.66), 3.348 (0.84 ), 3.352 (0.93), 3.362 (0.92), 3.376 (0.44), 3.460 (0.74), 3.466 (0.54), 3.474 (0.47), 3.480 (0.91), 3.494 (0.41), 3.599 (0.41), 3.613 (0.84 ), 3.619 (0.43), 3.626 (0.48), 3.633 (0.70), 4.494 (1.93), 4.720 (0.77), 4.727 (0.88), 4.732 (0.99), 4.740 (0.78), 4.857 (1.33), 4.889 (3.17 ), 4,928 (3.18), 4,960 (1.36). Example 13 (5RS)-2-[(3-Methyl-1,2-oxazol-5-yl)methyl]-5-(pyrrolidin-1-ylcarbonyl)-5,6,7,8-tetrahydro[1 ,2,4]triazolo[4,3-a]pyridin-3(2H)-one (racemate)

[0971] (5RS)-5-(Pyrrolidin-1-ylcarbonyl)-5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)- onena (racemate) (40.0 mg, 169 μmol) was initially loaded into acetonitrile (2.0 mL). Cesium carbonate (82.7 mg, 254 μmol) and 5-(bromomethyl)-3-methyl-1,2-oxazole (32.8 mg, 186 μmol) were subsequently added. After stirring at room temperature for 2 days, the reaction mixture was mixed with water and ethyl acetate. The organic phase was removed and the aqueous phase was extracted three times with ethyl acetate. The combined organic phases were washed with saturated aqueous sodium chloride solution, dried over sodium sulfate and filtered, and the filtrate was concentrated. 18.6 mg (33% chance) of the title compound was obtained. LC-MS (Method 3): Rt = 0.89 min; MS (ESIpos): m /z = 332 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.008 (0.87), 0.008 (0.76), 1.686 (0.49), 1.709 ( 0.99), 1.720 (1.17), 1.732 (0.87), 1.753 (0.57), 1.772 (1.53), 1.789 (2.62), 1.806 (2.01), 1.822 (0.60), 1.892 (0.62), 1.909 (1.85), 1.925 ( 2.33), 1.942 (1.50), 1.959 (0.66), 1.972 (0.52), 1.983 (0.78), 1.995 (0.71), 2.004 (0.63), 2.014 (0.50), 2.019 (0.48), 2.030 (0.68), 2.039 ( 0.56), 2.046 (0.46), 2.055 (0.49), 2.201 (16.00), 2.215 (0.69), 2.417 (0.49), 2.523 (1.09), 2.565 (0.86), 2.580 (0.74), 2.590 (0.68), 2.602 ( 1.21), 2.615 (0.66), 2.643 (0.48), 3.242 (0.75), 3.254 (0.74), 3.271 (1.33), 3.288 (0.70), 3.322 (0.97), 3.339 (1.33), 3.351 (0.50), 3.357 ( 0.70), 3.369 (0.78), 3.454 (0.86), 3.462 (0.63), 3.471 (0.53), 3.479 (1.08), 3.496 (0.47), 3.589 (0.50), 3.606 (1.03), 3.614 (0.52), 3.623 ( 0.59), 3.631 (0.79), 3.703 (0.42), 4.495 (0.41), 4.510 (0.41), 4.723 (0.92), 4.732 (1.05), 4.738 (1.20), 4.747 (0.90), 4.940 (4.70), 4.982 ( 0.54), 6.223 (3.16). Example 14 (5RS)-2-[3-Fluoro-4-(trifluoromethoxy)benzyl]-5-(pyrrolidin-1-ylcarbonyl)-5,6,7,8-tetrahydro[1,2,4]triazole [4,3-a]pyridin-3(2H)-one (racemate)

[0972] (5RS)-5-(Pyrrolidin-1-ylcarbonyl)-5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)- onena (racemate) (40.0 mg, 169 μmol) was initially loaded into acetonitrile (2.0 mL). Cesium carbonate (82.7 mg, 254 μmol) and 4-(bromomethyl)-2-fluoro-1-(trifluoromethyl)benzene (47.9 mg, 186 μmol) were subsequently added. After stirring for 48 hours, the reaction mixture was mixed with water and ethyl acetate at room temperature. The organic phase was removed and the aqueous phase was extracted three times with ethyl acetate. The combined organic phases were washed with saturated aqueous sodium chloride solution, dried over sodium sulfate and filtered, and the filtrate was concentrated. 48.9 mg (70% possibility) of the title compound was obtained. LC-MS (Method 3): Rt = 1.55 min; MS (ESIpos): m /z = 413 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.008 (3.00), 0.008 (1.79), 1.235 (0.49), 1.681 ( 1.63), 1.695 (1.81), 1.706 (1.87), 1.719 (2.35), 1.731 (2.76), 1.743 (2.21), 1.756 (2.58), 1.774 (5.53), 1.792 (8.57), 1.809 (6.54), 1.819 ( 2.30), 1.826 (3.06), 1.837 (3.80), 1.845 (1.54), 1.854 (1.49), 1.893 (2.04), 1.910 (5.29), 1.926 (6.37), 1.943 (3.93), 1.960 (1.38), 1.975 ( 1.13), 1.987 (1.15), 2.000 (1.81), 2.020 (3.43), 2.045 (1.84), 2.056 (1.54), 2.063 (1.50), 2.071 (1.41), 2.080 (0.76), 2.091 (0.52), 2.327 ( 0.60), 2.519 (4.26), 2.563 (2.70), 2.573 (2.53), 2.588 (2.17), 2.602 (2.17), 2.614 (3.60), 2.626 (2.07), 2.644 (1.03), 2.656 (1.47), 2.669 ( 1.30), 2.710 (0.51), 3.097 (1.58), 3.233 (1.25), 3.250 (2.51), 3.262 (2.74), 3.279 (4.78), 3.297 (3.97), 3.328 (2.43), 3.346 (4.21), 3.358 ( 1.68), 3.364 (2.26), 3.376 (2.38), 3.393 (1.08), 3.443 (1.37), 3.460 (2.81), 3.468 (2.17), 3.478 (1.79), 3.485 (3.40), 3.502 (1.52), 3.593 ( 1.77), 3.610 (3.23), 3.618 (1.80), 3.627 (1.95), 3.635 (2.43), 3.652 (1.15), 3.711 (0.75), 4.755 (3.09), 4.764 (3.43), 4.769 (4.01), 4.779 ( 2.85), 4.948 (16.00), 4.985 (0.48), 7.248 (3.78), 7.268 (4.07), 7.296 (3.67), 7.326 (3.62), 7.755 (2.93), 7.775 (5.28), 7.794 (2.72). Example 15 (5RS)-2-[(2-Methylpyridin-4-yl)methyl]-5-(pyrrolidin-1-ylcarbonyl)-5,6,7,8-tetrahydro[1,2,4]triazole [4,3-a]pyridin-3(2H)-one (racemate)

[0973] (5RS)-5-(Pyrrolidin-1-ylcarbonyl)-5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)- ona (40.0 mg, 169 μmol) was initially loaded into acetonitrile (2.0 mL). Cesium carbonate (82.7 mg, 254 μmol) and 4-(chloromethyl)-2-methylpyridine hydrochloride (33.2 mg, 186 μmol) were subsequently added. The reaction mixture was stirred at room temperature overnight and then at 85°C for 24 hours. After cooling to room temperature, water and ethyl acetate were added to the reaction mixture. The organic phase was removed and the aqueous phase was extracted three times with ethyl acetate. The aqueous phases were adjusted to pH 7 with sodium hydrogen carbonate. The solvent was removed under reduced pressure, and the residue was suspended in ethanol. The mixture was filtered, and the filtrate was concentrated. 51.6 mg (94% purity, 84% chance) of the title compound was obtained. LC-MS (Method 3): Rt = 0.51 min; MS (ESIpos): m /z = 342 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (1.03), -0.008 (8.61), 0.008 (8.84), 0.146 (0.99) (5.03) (1.26) (16.00) (2.36) (1.45) (0.46) (1.61), 7.575 (2.75), 7.833 (0.57), 8.664 (0.57), 8.679 (0.73), 8.703 (2.85), 8.717 (2.53). Example 16 (5RS)-2-(3-Fluorobenzyl)-5-(pyrrolidin-1-ylcarbonyl)-5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a] pyridin-3(2H)-one (racemate)

[0974] (5RS)-5-(Pyrrolidin-1-ylcarbonyl)-5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)- onena (racemate) (50.0 mg, 212 μmol) was initially loaded into acetonitrile (3.0 mL). Cesium carbonate (103 mg, 317 μmol) and 1-(bromomethyl)-3-fluorobenzene (42.0 mg, 222 μmol) were subsequently added. After stirring overnight, the reaction mixture was mixed with water and ethyl acetate at room temperature. The organic phase was removed and the aqueous phase was extracted three times with ethyl acetate. The combined organic phases were washed with saturated aqueous sodium chloride solution, dried over sodium sulfate and filtered, and the filtrate was concentrated. The residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/gradient water). The fractions containing the product were concentrated under reduced pressure and 48.0 mg (66% possibility) of the title compound were obtained. LC-MS (Method 4): Rt = 0.68 min; MS (ESIpos): m /z = 345 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (0.74), -0.008 (6.59), 0.008 (5.85), 0.146 (0.74) (6.30) (1.73), 2021 (1.22), 2036 (1.48), 2047 (1.06), 2053 (1.03), 2062 (1.06), 2072 (3.92), 2088 (0.42), 2322 (0.58), 2327 (0.84), 2332 (0.61), 2366 (0.64), 2518 (3.63), 2522 (3.05), 2564 (2.02), 2579 (1.61), 2593 (1.51), 2605 (2.80), 2617 (1.54), 2636 (0.71), 2647 (1.09) (2.38) (1.22) (2.47) (1.86), 7,110 (1.67), 7,124 (1.09), 7,131 (1.03), 7,356 (1.83), 7,372 (2.09), 7,376 (2.70), 7,391 (2.67), 7,396 (1.67), 7,411 (1.41). Example 17 (5RS)-2-(3,4-Difluorobenzyl)-5-(pyrrolidin-1-ylcarbonyl)-5,6,7,8-tetrahydro[1,2,4]triazolo[4,3- a]pyridin-3(2H)-one (racemate)

[0975] (5RS)-5-(Pyrrolidin-1-ylcarbonyl)-5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)- onena (racemate) (50.0 mg, 212 μmol) was initially loaded into acetonitrile (3.0 mL). Cesium carbonate (103 mg, 317 μmol) and 4-(bromomethyl)-1,2-difluorobenzene (46.0 mg, 222 μmol) were subsequently added. After stirring overnight, the reaction mixture was mixed at room temperature with water, 1 N aqueous hydrochloric acid, and ethyl acetate. The organic phase was removed and the aqueous phase was extracted three times with ethyl acetate. The combined organic phases were washed with saturated aqueous sodium chloride solution, dried over sodium sulfate and filtered, and the filtrate was concentrated. The residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/gradient water). The fractions containing the product were concentrated under reduced pressure and 51.4 mg (67% possibility) of the title compound were obtained. LC-MS (Method 3): Rt = 1.29 min; MS (ESIpos): m /z = 363 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.008 (1.10), 0.008 (0.79), 1.659 (0.87), 1.666 ( 0.94), 1.678 (1.26), 1.692 (1.49), 1.720 (2.53), 1.730 (1.97), 1.744 (1.22), 1.755 (1.63), 1.773 (4.14), 1.791 (6.91), 1.808 (5.24), 1.824 ( 1.51), 1.893 (1.74), 1.909 (4.73), 1.926 (5.77), 1.942 (3.55), 1.960 (1.63), 1.983 (1.35), 1.994 (2.27), 2.007 (2.54), 2.016 (1.71), 2.034 ( 1.69), 2.044 (1.27), 2.051 (1.22), 2.060 (1.18), 2.069 (0.65), 2.079 (0.40), 2.519 (2.58), 2.561 (2.09), 2.576 (1.78), 2.591 (1.72), 2.603 ( 3.08), 2.615 (1.71), 2.633 (0.78), 2.645 (1.17), 2.657 (0.59), 3.229 (1.01), 3.246 (2.10), 3.258 (2.34), 3.275 (4.13), 3.293 (3.31), 3.325 ( 2.59), 3.343 (3.64), 3.355 (1.42), 3.361 (1.92), 3.373 (2.02), 3.391 (0.93), 3.438 (1.10), 3.456 (2.33), 3.463 (1.76), 3.473 (1.45), 3.480 ( 2.91), 3.497 (1.27), 3.592 (1.40), 3.609 (2.74), 3.617 (1.46), 3.625 (1.61), 3.633 (2.09), 3.650 (0.96), 4.737 (2.62), 4.746 (2.87), 4.752 ( 3.26), 4761 (2.48), 4816 (16.00), 7061 (1.51), 7067 (1.55), 7072 (1.61), 7077 (1.78), 7083 (1.77), 7087 (1.69), 7093 (1.61), 7230 ( 1.48), 7.235 (1.43), 7.249 (1.57), 7.255 (1.72), 7.258 (1.78), 7.264 (1.49), 7.278 (1.47), 7.283 (1.38), 7.373 (1.70), 7.394 (3.23), 7.400 ( 1.93), 7.415 (1.77), 7.421 (3.17), 7.442 (1.48). Example 18 (5RS)-2-(3-Chloro-4-fluorobenzyl)-5-(pyrrolidin-1-ylcarbonyl)-5,6,7,8-tetrahydro[1,2,4]triazolo[4, 3-a]pyridin-3(2H)-one (racemate)

[0976] (5RS)-5-(Pyrrolidin-1-ylcarbonyl)-5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)- onena (racemate) (50.0 mg, 212 μmol) was initially loaded into acetonitrile (3.0 mL). Cesium carbonate (103 mg, 317 μmol) and 4-(bromomethyl)-2-chloro-1-fluorobenzene (49.7 mg, 222 μmol) were subsequently added. After stirring overnight, the reaction mixture was mixed with water and ethyl acetate at room temperature. The organic phase was removed and the aqueous phase was extracted three times with ethyl acetate. The combined organic phases were washed with saturated aqueous sodium chloride solution, dried over sodium sulfate and filtered, and the filtrate was concentrated. The residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/gradient water). The fractions containing the product were concentrated under reduced pressure and 57.0 mg (70% possibility) of the title compound were obtained. LC-MS (Method 3): Rt = 1.43 min; MS (ESIpos): m /z = 379 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.008 (1.11), 1.666 (0.83), 1.679 (1.17), 1.692 ( 1.58), 1.703 (2.12), 1.717 (2.65), 1.727 (2.06), 1.755 (1.33), 1.773 (4.00), 1.790 (6.78), 1.807 (5.21), 1.824 (1.52), 1.892 (1.58), 1.909 ( 4.70), 1926 (5.86), 1942 (3.78), 1960 (1.52), 1978 (1.20), 1989 (2.08), 2001 (2.02), 2016 (1.38), 2031 (1.61), 2042 (1.22), 2049 ( 1.16), 2.057 (1.13), 2.067 (0.64), 2.084 (0.41), 2.328 (0.44), 2.561 (2.11), 2.576 (1.68), 2.590 (1.62), 2.602 (3.04), 2.614 (1.70), 2.632 ( 0.75), 2.644 (1.17), 2.656 (0.60), 2.670 (0.54), 2.710 (0.50), 3.226 (0.91), 3.243 (1.93), 3.256 (1.96), 3.273 (3.44), 3.290 (2.06), 3.326 ( 2.63), 3.344 (3.57), 3.356 (1.39), 3.362 (1.83), 3.374 (2.03), 3.391 (0.92), 3.436 (1.07), 3.453 (2.27), 3.461 (1.71), 3.471 (1.36), 3.478 ( 2.85), 3.495 (1.24), 3.591 (1.30), 3.608 (2.66), 3.616 (1.36), 3.625 (1.55), 3.633 (2.06), 3.649 (0.94), 4.737 (2.43), 4.746 (2.77), 4.752 ( 3.15), 4761 (2.37), 4818 (16.00), 7219 (1.38), 7225 (1.49), 7231 (1.52), 7241 (2.09), 7246 (2.05), 7252 (1.89), 7258 (1.86), 7371 ( 3.67), 7,394 (4.98), 7,415 (2.94), 7,430 (2.84), 7,435 (2.61), 7,448 (2.75), 7,453 (2.63). Example 19 (5RS)-5-(Pyrrolidin-1-ylcarbonyl)-2-[3-(trifluoromethyl)benzyl]-5,6,7,8-tetrahydro[1,2,4]triazolo[4,3 -a]pyridin-3(2H)-one (racemate)

[0977] (5RS)-5-(Pyrrolidin-1-ylcarbonyl)-5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)- onena (racemate) (50.0 mg, 212 μmol) was initially loaded into acetonitrile (3.0 mL). Cesium carbonate (103 mg, 317 μmol) and 1-(bromomethyl)-3-(trifluoromethyl)benzene (53.1 mg, 222 μmol) were subsequently added. After stirring overnight, the reaction mixture was mixed at room temperature with water, 1 N aqueous hydrochloric acid, and ethyl acetate. The organic phase was removed and the aqueous phase was extracted three times with ethyl acetate. The combined organic phases were washed with saturated aqueous sodium chloride solution, dried over sodium sulfate and filtered, and the filtrate was concentrated. The residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/gradient water). The fractions containing the product were concentrated under reduced pressure and 60.6 mg (72% possibility) of the title compound were obtained. LC-MS (Method 3): Rt = 1.50 min; MS (ESIpos): m /z = 395 [M+H]+ 1H-NMR (600 MHz, DMSO-d6) δ [ppm]: 1.664 (0.98), 1.668 (0.95), 1.678 (1.17), 1.682 (1.23 ), 1.691 (0.96), 1.722 (1.76), 1.728 (1.61), 1.737 (1.14), 1.744 (0.88), 1.768 (1.18), 1.779 (4.61), 1.791 (7.62), 1.802 (5.64), 1.813 (1.54 ), 1,903 (1.45), 1,914 (4.15), 1,925 (5.43), 1,936 (3.45), 1,947 (0.98), 1,970 (0.90), 1,987 (1.15), 1,993 (1.84), 2,002 (1.65), 2,019 (0.96 ), 2.024 (1.13), 2.029 (1.12), 2.035 (1.30), 2.043 (1.30), 2.048 (1.39), 2.053 (1.22), 2.058 (0.65), 2.067 (0.45), 2.071 (0.45), 2.520 (1.58 ), 2,566 (1.45), 2,601 (1.51), 2,608 (2.81), 2,616 (1.71), 2,629 (0.89), 2,636 (1.43), 2,645 (0.69), 3,239 (1.12), 3,251 (2.30), 3,259 (1.97 ), 3.270 (3.23), 3.282 (1.50), 3.346 (3.70), 3.354 (1.55), 3.358 (1.83), 3.365 (2.29), 3.377 (1.04), 3.447 (1.17), 3.459 (2.47), 3.464 (1.70 ), 3.471 (1.50), 3.476 (2.81), 3.487 (1.25), 3.604 (1.37), 3.615 (2.62), 3.620 (1.48), 3.626 (1.60), 3.631 (2.16), 3.642 (1.05), 4.755 (2.69 ), 4,761 (2.92), 4,765 (3.15), 4,771 (2.50), 4,926 (16.00), 7,508 (2.83), 7,521 (3.83), 7,579 (2.39), 7,591 (4.65), 7,604 (2.52), 7,624 (5.77 ), 7,653 (3.72), 7,665 (2.53). Example 20 (5RS)-2-(3-Methoxybenzyl)-5-(pyrrolidin-1-ylcarbonyl)-5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a] pyridin-3(2H)-one (racemate)

[0978] (5RS)-5-(Pyrrolidin-1-ylcarbonyl)-5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)- onena (racemate) (50.0 mg, 212 μmol) was initially loaded into acetonitrile (2.0 mL). Cesium carbonate (72.4 mg, 222 μmol) and 1-(bromomethyl)-3-methoxybenzene (44.7 mg, 222 μmol) were subsequently added. After stirring overnight, the reaction mixture was mixed with water and ethyl acetate at room temperature. The organic phase was removed and the aqueous phase was extracted three times with ethyl acetate. The combined organic phases were washed with saturated aqueous sodium chloride solution, dried over sodium sulfate and filtered, and the filtrate was concentrated. The residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/gradient water). The fractions containing the product were concentrated under reduced pressure and 24.0 mg (32% possibility) of the title compound were obtained. LC-MS (Method 3): Rt = 1.21 min; MS (ESIpos): m /z = 357 [M+H]+ ¹H-NMR (400 MHz, DMSO-d6) δ [ppm]: 0.008 (0.70), 1.685 (0.46), 1.717 (0.93), 1.754 (0.42 ), 1.772 (1.40), 1.789 (2.40), 1.806 (1.85), 1.823 (0.54), 1.893 (0.57), 1.909 (1.70), 1.926 (2.17), 1.942 (1.40), 1.960 (0.57), 1.975 (0.43 ), 1.987 (0.75), 1.998 (0.72), 2.015 (0.49), 2.030 (0.61), 2.040 (0.43), 2.055 (0.41), 2.568 (0.61), 2.583 (0.58), 2.594 (1.13), 2.606 (0.61 ), 2.635 (0.43), 3.243 (0.68), 3.256 (0.69), 3.273 (1.24), 3.290 (0.66), 3.339 (1.29), 3.351 (0.48), 3.356 (0.66), 3.368 (0.71), 3.455 (0.80 ), 3.463 (0.58), 3.473 (0.48), 3.480 (1.01), 3.497 (0.45), 3.595 (0.46), 3.611 (0.97), 3.620 (0.49), 3.628 (0.56), 3.637 (0.76), 3.730 (16.00 ), 4.732 (0.91), 4.742 (1.03), 4.747 (1.21), 4.757 (1.02), 4.770 (6.44), 6.774 (3.04), 6.777 (2.99), 6.793 (1.49), 6.820 (0.90), 6.824 (0.92 ), 6,842 (1.08), 6,847 (0.91), 7,218 (1.07), 7,238 (2.10), 7,258 (1.08). Example 21 (5RS)-2-[(1-Methyl-1H-pyrazol-3-yl)methyl]-5-(pyrrolidin-1-ylcarbonyl)-5,6,7,8-tetrahydro[1,2 ,4]triazolo[4,3-a]pyridin-3(2H)-one (racemate)

[0979] (5RS)-5-(Pyrrolidin-1-ylcarbonyl)-5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)- onena (racemate) (50.0 mg, 212 μmol) was initially loaded into acetonitrile (2.0 mL). Cesium carbonate (72.4 mg, 222 μmol) and 3-(bromomethyl)-1-methyl-1H-pyrazole (38.9 mg, 222 μmol) were subsequently added. The reaction mixture was stirred at room temperature overnight and at 90°C for 1 hour. After cooling to room temperature, water, 1 N aqueous hydrochloric acid and ethyl acetate were added to the reaction mixture. The organic phase was removed and the aqueous phase was extracted three times with ethyl acetate. The combined organic phases were washed with saturated aqueous sodium chloride solution, dried over sodium sulfate and filtered, and the filtrate was concentrated. The residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/gradient water). The product-containing fractions were concentrated under reduced pressure and separated again by HPLC (Method 11). The fractions containing the product were concentrated under reduced pressure and 8.00 mg (11% possibility) of the title compound were obtained. LC-MS (Method 4): Rt = 0.48 min; MS (ESIpos): m /z = 331 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.008 (3.77), 0.008 (2.98), 1.705 (1.52), 1.717 ( 1.23), 1.751 (0.50), 1.770 (1.66), 1.787 (2.86), 1.804 (2.19), 1.821 (0.61), 1.891 (0.73), 1.908 (2.10), 1.924 (2.77), 1.941 (1.93), 1.965 ( 0.96), 2.000 (0.64), 2.011 (0.70), 2.021 (0.58), 2.036 (0.55), 2.327 (1.20), 2.366 (0.96), 2.523 (4.88), 2.574 (1.52), 2.586 (0.82), 2.616 ( 0.53), 2.669 (1.26), 2.709 (0.85), 3.220 (0.47), 3.236 (0.91), 3.249 (0.93), 3.266 (1.66), 3.334 (2.22), 3.351 (0.99), 3.363 (0.93), 3.380 ( 0.44), 3.434 (0.47), 3.451 (0.96), 3.458 (0.73), 3.476 (1.23), 3.493 (0.55), 3.590 (0.58), 3.607 (1.17), 3.624 (0.64), 3.633 (0.88), 3.649 ( 0.41), 3.774 (16.00), 3.796 (0.53), 4.646 (0.58), 4.685 (4.26), 4.696 (4.67), 4.706 (1.49), 4.715 (1.08), 4.735 (0.64), 6.034 (2.42), 6.039 ( 2.48), 7.569 (2.34), 7.574 (2.34). Example 22 (5RS)-2-(Pyridin-2-ylmethyl)-5-(pyrrolidin-1-ylcarbonyl)-5,6,7,8-tetrahydro[1,2,4]triazolo[4,3- a]pyridin-3(2H)-one (racemate)

[0980] (5RS)-5-(Pyrrolidin-1-ylcarbonyl)-5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)- ona (50.0 mg, 212 μmol) was initially loaded into acetonitrile (2.0 mL). Cesium carbonate (72.4 mg, 222 μmol) and 2-(bromomethyl)pyridine (38.2 mg, 222 μmol) were subsequently added. After stirring overnight, the reaction mixture was mixed with water and ethyl acetate at room temperature. The organic phase was removed and the aqueous phase was extracted three times with ethyl acetate. The combined organic phases were washed with saturated aqueous sodium chloride solution, dried over sodium sulfate and filtered, and the filtrate was concentrated. The residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/gradient water). The fractions containing the product were concentrated under reduced pressure and purified again via preparatory HPLC (Chromatorex C18, 10 μm, 125 mm x 30 mm; eluent: acetonitrile/water), and 3.00 mg (4% of theoretical value) were obtained. of the title compound. LC-MS (Method 4): Rt = 0.43 min; MS (ESIpos): m /z = 328 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (0.93), -0.008 (6.95), 0.008 (6.72), 0.146 (0.82) (3.45) (2.28) (1.75) (2.28) (2.69) (2.34), 7.332 (0.58), 7.748 (2.16), 7.753 (2.22), 7.767 (3.85), 7.772 (3.74), 7.787 (1.99), 7.791 (1.93), 8.506 (2.51), 8.520 (2.57). Example 23 (5RS)-5-(Pyrrolidin-1-ylcarbonyl)-2-{[5-(trifluoromethyl)pyridin-2-yl]methyl}-5,6,7,8-tetrahydro[1,2, 4]triazolo[4,3-a]pyridin-3(2H)-one (racemate)

[0981] (5RS)-5-(Pyrrolidin-1-ylcarbonyl)-5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)- onena (racemate) (40.0 mg, 169 μmol) was initially loaded into acetonitrile (2.0 mL). Cesium carbonate (82.7 mg, 254 μmol) and 2-(bromomethyl)-5-(trifluoromethyl)pyridine (44.7 mg, 186 μmol) were subsequently added. After stirring overnight, the reaction mixture was mixed at room temperature with water, 1 N aqueous hydrochloric acid, and ethyl acetate. The organic phase was removed and the aqueous phase was extracted three times with ethyl acetate. The combined organic phases were washed with saturated aqueous sodium chloride solution, dried over sodium sulfate and filtered, and the filtrate was concentrated. The residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/gradient water). The fractions containing the product were concentrated under reduced pressure and 44.6 mg (67% possibility) of the title compound were obtained. LC-MS (Method 3): Rt = 1.22 min; MS (ESIpos): m /z = 396 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (0.72), 0.147 (0.71), 1.726 (2.72), 1.738 ( 3.10), 1.775 (4.76), 1.792 (7.48), 1.809 (5.64), 2.625 (1.98), 2.655 (1.38), 2.669 (1.43), 2.710 (0.77), 3.236 (0.95), 3.253 (1.97), 3.265 ( 2.17), 3.282 (3.78), 3.329 (2.27), 3.347 (3.67), 3.364 (2.07), 3.377 (2.12), 3.395 (1.00), 3.450 (1.06), 3.467 (2.41), 3.492 (3.06), 3.509 ( 1.38), 3599 (1.44), 3615 (2.87), 3632 (1.84), 3640 (2.24), 3657 (1.00), 4760 (2.66), 4775 (3.67), 4784 (2.76), 5026 (16.00), 7383 ( 4.73), 7.403 (4.96), 8.212 (3.24), 8.233 (3.24), 8.929 (5.73). Example 24 (5RS)-2-[(5-Methyl-1H-imidazol-4-yl)methyl]-5-(pyrrolidin-1-ylcarbonyl)-5,6,7,8-tetrahydro[1,2 ,4]triazolo[4,3-a]pyridin-3(2H)-one (racemate)

[0982] (5RS)-5-(Pyrrolidin-1-ylcarbonyl)-5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)- onena (racemate) (30.0 mg, 127 μmol) was initially loaded into acetonitrile (2.0 mL). Cesium carbonate (165 mg, 508 μmol) and 4-(chloromethyl)-5-methyl-1H-imidazole hydrochloride (25.5 mg, 152 μmol) were subsequently added. After stirring under reflux overnight, the reaction mixture was concentrated under reduced pressure. The residue was purified via preparatory HPLC (Method 12). The fractions containing the product were concentrated under reduced pressure and 1.80 mg (4% possibility) of the title compound were obtained. LC-MS (Method 3): Rt = 0.46 min; MS (ESIpos): m /z = 331 [M+H]+ ¹H-NMR (600 MHz, METHANOL-d4) δ [ppm]: 1.814 (0.43), 1.823 (0.63), 1.828 (0.65), 1.833 (0.66 ), 1.839 (0.65), 1.849 (0.45), 1.856 (0.44), 1.864 (0.53), 1.867 (0.51), 1.872 (0.54), 1.880 (0.52), 1.889 (0.64), 1.895 (0.58), 1.902 (1.23 ), 1,906 (1.24), 1,913 (1.77), 1,917 (1.61), 1,925 (1.40), 1,928 (1.26), 1,939 (0.67), 2,019 (0.61), 2,029 (1.55), 2,040 (2.38), 2,052 (2.28 ), 2.063 (1.50), 2.072 (0.63), 2.137 (0.43), 2.143 (0.44), 2.148 (0.46), 2.154 (0.67), 2.161 (0.70), 2.166 (0.75), 2.171 (0.63), 2.178 (0.46 ), 2.189 (0.40), 2.195 (0.45), 2.217 (0.59), 2.228 (16.00), 2.575 (0.42), 2.584 (0.47), 2.590 (0.45), 2.603 (0.80), 2.613 (0.74), 2.619 (0.77 ), 2.628 (0.61), 2.681 (0.63), 2.690 (1.26), 2.699 (0.63), 2.709 (0.40), 2.718 (0.74), 3.363 (0.46), 3.374 (0.82), 3.383 (0.74), 3.394 (1.07 ), 3.406 (0.57), 3.504 (0.62), 3.516 (1.20), 3.524 (0.65), 3.528 (0.81), 3.531 (0.72), 3.536 (1.03), 3.543 (1.03), 3.548 (1.12), 3.554 (0.65 ), 3.560 (1.06), 3.571 (0.53), 3.756 (0.54), 3.767 (0.99), 3.772 (0.62), 3.778 (0.65), 3.784 (0.84), 3.795 (0.44), 4.630 (0.69), 4.770 (1.70 ), 4,785 (1.45), 4,796 (4.48), 4,802 (1.53), 4,862 (2.68), 5,491 (5.22), 7,477 (4.91). Example 25 (5RS)-2-(4-Methylbenzyl)-5-(pyrrolidin-1-ylcarbonyl)-5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridin- 3(2H)-one (racemate)

[0983] (5RS)-2-(4-Methylbenzyl)-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine -5-carboxylic acid (racemate) (436 mg, 1.52 mmol) was dissolved in 10 mL of THF. Triethylamine (420, 3.0 mmol), HATU (865 mg, 2.28 mmol) and pyrrolidine (150, 1.8 mmol) were added, and the mixture was stirred under argon at room temperature for 2 h. The reaction mixture was concentrated under reduced pressure, and the residue was dissolved in DMSO/acetonitrile/water and separated into 2 batches via preparatory HPLC (column: Kromasila C18, 250x30mm, 10μm, eluent: acetonitrile (B)/water + 0.1% TFA (A), gradient: 0min 90%A, 6min90%A, 27min 5%A, 38min 5%A, 38min 5%A, 39min 90%A; flow rate: 50ml/min, detector: 210nm) . The combined fractions containing the product were concentrated again and dried under reduced pressure. In this way, 430 mg (83% possibility) of the title compound were obtained. LC-MS (Method 4): Rt = 0.73 min; MS (ESIpos): m /z = 341 [M+H]+ 1H-NMR (400MHz, DMSO-d6): δ [ppm]= 1.61 - 1.83 (m, 4H), 1.86 - 2.10 (m, 4H), 2.27 (s, 3H), 2.42 - 2.65 (m, 2H, partially covered by solvent signal), 3.20 - 3.30 (m, 1H), 3.30 - 3.41 (m, 1H), 3.47 (dt, 1H), 3.62 ( dt, 1H), 4.68 - 4.79 (m, 3H), 7.07 - 7.16 (m, 4H). Example 26 (5RS)-2-(4-Methylbenzyl)-5-(pyrrolidin-1-ylcarbonyl)-5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a] pyridin-3(2H)-one (enantiomer 2)

[0984] (5RS)-2-(4-Methylbenzyl)-5-(pyrrolidin-1-ylcarbonyl)-5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a ]pyridin-3(2H)-one (racemate) was separated by chiral preparatory SFC [sample preparation: 1220 mg dissolved in 50 mL methanol/acetonitrile; injection volume: 2.0 mL; column: Daicel Chiralcel® OD-H 5μm, 250 x 50 mm; eluent: CO2/ethanol: isocratic 20% ethanol, flow rate: 80 ml/min; temperature 40°C; UV detection: 210 nm]. After separation, 494 mg of enantiomer 1, which eluted first, and 487 mg of enantiomer 2, which eluted later, were isolated. Enantiomer 2: Specific rotation: -25.70 (589 nm, 0.4150 g/100 cm3 MeOH)

[0985] Analytical chiral HPLC: Rt = 4.27 min, e.e. = 100% [column: Daicel Chiralcel® ID-3 3μm 50 x 4.6 mm; eluent: isohexane/isopropanol 1:1; flow rate: 1 ml/min; UV detection: 220 nm]. LC-MS (Method 3): Rt = 1.33 min; MS (ESIpos): m /z = 341 [M+H]+ 1H-NMR (400MHz, DMSO-d6): δ [ppm]= 1.61 - 1.83 (m, 4H), 1.87 - 2.10 (m, 4H), 2.27 (s, 3H), 2.47 - 2.70 (m, 2H, partially covered by solvent signal), 3.21 - 3.30 (m, 1H), 3.30 - 3.67 (m, 3H, partially overlapped by water signal), 4.69 - 4.81 (m, 3H), 7.08 - 7.16 (m, 4H).

[0986] The (5S) configuration was assigned based on the elucidation of the crystal structure for Example 26. (5S)-2-(4-Methylbenzyl)-5-(pyrrolidin-1-ylcarbonyl)-5,6,7, 8-tetrahydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one Example 27 (5RS)-2-(4-Chlorobenzyl)-5-(pyrrolidin-1-ylcarbonyl)-5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a] pyridin-3(2H)-one (racemate)

[0987] Methyl (5RS)-2-(4-chlorobenzyl)-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a] pyridine-5-carboxylate (racemate) (77.0 mg, 239 μmol) was initially loaded into 1 mL of THF/water, lithium hydroxide (28.7 mg, 1.20 mmol) was added, and the reaction mixture was stirred at room temperature over a weekend. For elaboration, THF was removed under reduced pressure, and the aqueous residue was lyophilized. In this way, 74 mg of the lithium salt of the carboxylic acid were obtained, which was converted more directly. For this purpose, the carboxylic acid was liberated with aqueous hydrochloric acid and dissolved in 3 mL of THF. Triethylamine (66 μl, 470 μmol), HATU (135 mg, 356 μmol), and pyrrolidine (24 μl, 280 μmol) were added and the mixture was stirred at room temperature under argon overnight. The reaction mixture was concentrated under reduced pressure and the residue was separated by preparatory HPLC (column: Chromatorex, 125x40mm 10μm. Flow rate: 50 ml/min. Gradient (A = water + 0.1% formic acid, B = acetonitrile): 0min 10%B, 5min 10%B, 27min 98%B, 35min 98%B, 35.01min 10%B, 38min 10%B. Run time per separation 38 min. The fractions containing the product were concentrated, lyophilized and freed from solvent residues under reduced pressure. In this way, 64.3 mg (75% possibility) of the title compound were obtained. LC-MS (Method 4): Rt = 0.76 min; MS (ESIpos): m /z = 361 [M+H]+ 1H-NMR (400MHz, DMSO-d6): δ [ppm]= 1.61 - 1.84 (m, 4H), 1.87 - 2.10 (m, 4H), 2.46 - 2.66 (m, 2H, partially covered by the solvent signal), 3.21 - 3.40 (m, 2H, partially overlapped by the water signal), 3.46 (dt, 1H), 3.62 (dt, 1H), 4.74 (dd, 1H), 4.75 - 4.85 (m, 2H), 7.22 - 7.28 (m, 2H), 7.37 - 7.43 (m, 2H). Example 28 tert-Butyl 4-{[(5RS)-3-oxo-5-(pyrrolidin-1-ylcarbonyl)-5,6,7,8-tetrahydro[1,2,4]triazolo[4,3 -a]pyridin-2(3H)-yl]methyl}benzoate (racemate)

[0988] (5RS)-2-[4-(tert-Butoxycarbonyl)benzyl]-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4, 3-a]pyridine-5-carboxylic acid (racemate) (246 mg, 88% purity, 580 μmol) was dissolved in 6.0 mL of THF. Triethylamine (240 μl, 1.7 mmol), HATU (287 mg, 754 μmol), and pyrrolidine (58 μl, 700 μmol) were added and the mixture was stirred at room temperature under argon overnight. For further conversion, triethylamine (81 μl, 580 μmol), HATU (66.1 mg, 174 μmol) and pyrrolidine (15 μl, 170 μmol) were added once more, and the mixture was stirred under the above conditions for another 2 .5h. For processing, the mixture was diluted with ethyl acetate/water. After extraction and removal of the organic phase, the aqueous phase was extracted twice more with ethyl acetate. The organic phases were washed with saturated aqueous sodium chloride solution and dried over sodium sulfate. The residue remaining after concentration under reduced pressure was dissolved in DMSO/acetonitrile/water and separated into 2 batches via preparatory HPLC. (column: Kromasila C18, 125x30mm, 10μm, eluent: acetonitrile (B)/water + 0.1% TFA (A), gradient: 0min 90% A, 6min 90% A, 18min 5%A, 20min 5%A, 21min 90 %A, flow rate: 75ml/min, detector: 210nm). The combined product-containing fractions were concentrated, and the crude product was again partitioned between water and ethyl acetate. From the organic phase, after drying, concentration and drying under reduced pressure, 235 mg (103% possibility) of the title compound were obtained. LC-MS (Method 4): Rt = 0.92 min; MS (ESIpos): m /z = 427 [M+H]+ 1H-NMR (400MHz, DMSO-d6): δ [ppm]= 1.54 (s, 9H), 1.62 - 1.85 (m, 4H), 1.87 - 2.10 (m, 4H), 2.47 - 2.67 (m, 2H, partially covered by solvent signal), 3.22 - 3.40 (m, 2H, partially overlapped by water signal), 3.47 (dt, 1H), 3.62 (dt, 1H), 4.75 (dd, 1H), 4.88 (s, 2H), 7.30 - 7.36 (m, 2H), 7.83 - 7.89 (m, 2H). Example 29 4-{[(5RS)-3-Oxo-5-(pyrrolidin-1-ylcarbonyl)-5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a] pyridin-2(3H)-yl]methyl}benzenesulfonamide (racemate)

[0989] (5RS)-3-Oxo-2-(4-sulfamoylbenzyl)-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine -5-carboxylic acid (racemate) (30.0 mg, 85.1 μmol) was dissolved in 2.0 mL of DMF. Triethylamine (24 μl, 170 μmol), HATU (48.6 mg, 128 μmol), and pyrrolidine (8.5 μl, 100 μmol) were added and the mixture was stirred at room temperature under argon overnight. For elaboration and purification, the mixture was separated directly via preparatory HPLC (column: Chromatorex, 125x30mm 10μm. Flow rate: 50 ml/min. Gradient (A = water + 0.1% formic acid, B = acetonitrile). Time of run for 38 min separation 0min 0%B, 6min 10%B, 27min 95%B, 38min 95%B, 40min 0%B). The combined fractions containing the product were lyophilized. In this way, 7.60 mg (22% possibility) of the title compound were obtained. LC-MS (Method 6): Rt = 0.99 min; MS (ESIpos): m /z = 406 [M+H]+ 1H-NMR (400MHz, DMSO-d6): δ [ppm]= 1.60 - 1.85 (m, 4H), 1.85 - 2.12 (m, 4H), 2.40 - 2.69 (m, 2H, partially covered by solvent signal), 3.20 - 3.31 (m, 1H), 3.31 - 3.58 (m, 2H, partially overlapped by water signal), 3.62 (dt, 1H), 4.75 ( dd, 1H), 4.89 (s, 2H), 7.32 (s, 2H), 7.40 (d, 2H), 7.78 (d, 2H). Example 30 (5RS)-2-[4-(Methylsulfanyl)benzyl]-5-(pyrrolidin-1-ylcarbonyl)-5,6,7,8-tetrahydro[1,2,4]triazolo[4,3 -a]pyridin-3(2H)-one (racemate)

[0990] (5RS)-2-[4-(Methylsulfanyl)benzyl]-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3- a]pyridine-5-carboxylic acid (racemate) (136 mg, 95% purity, 405 μmol) was dissolved in 4.0 mL of THF. Triethylamine (170 μl, 1.2 mmol), HATU (200 mg, 526 μmol), and pyrrolidine (41 μl, 490 μmol) were added and the mixture was stirred at room temperature under argon over a weekend. The reaction mixture was concentrated under reduced pressure, and the residue was mixed in acetonitrile/water and separated via preparatory HPLC (column: Kromasila C18, 125x30mm, 10μm, eluent: acetonitrile (B)/water + 0.1% TFA (A), gradient: 0min 90%A, 6min 90%A, 18min 5%A, 20min 5%A, 21min 90%A, flow rate: 75ml/min, detector: 210nm). The product-containing fractions were combined, concentrated and dried under reduced pressure. In this way, 85.0 mg (55% possibility) of the title compound were obtained. LC-MS (Method 4): Rt = 0.75 min; MS (ESIpos): m /z = 373 [M+H]+ 1H-NMR (400MHz, DMSO-d6): δ [ppm]= 1.61 - 1.84 (m, 4H), 1.88 - 2.10 (m, 4H), 2.45 (s, 3H), 2.47 - 2.67 (m, 2H, partially covered by solvent signal), 3.26 (dt, 1H), 3.36 (dt, 1H), 3.47 (dt, 1H), 3.65 (dt, 1H, partially overlapped by water signal), 4.70 - 4.80 (m, 3H), 7.15 - 7.25 (m, 4H). Example 31 (5RS)-2-[(6-Chloropyridin-3-yl)methyl]-5-(pyrrolidin-1-ylcarbonyl)-5,6,7,8-tetrahydro[1,2,4]triazole [4,3-a]pyridin-3(2H)-one (racemate)

[0991] (5RS)-2-[(6-Chloropyridin-3-yl)methyl]-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[ 4,3-a]pyridine-5-carboxylic acid (racemate) (1.59 g, 92% purity, 4.74 mmol) was dissolved in 25 mL of THF. Triethylamine (2.0 mL, 14 mmol), HATU (2.34 g, 6.16 mmol) and pyrrolidine (470 μL, 5.7 mmol) were added and the mixture was stirred at room temperature over a weekend. For preparation, the mixture was added to water, saturated with sodium chloride and extracted twice with ethyl acetate. The combined organic phases were dried over magnesium sulfate, filtered and concentrated. The residue was purified by silica gel chromatography (PuriFlash 100g silica gel cartridge dichloromethane/methanol 20:1, detector: 214 nm). In this way, 1.11 g (65% possibility) of the title compound were obtained. LC-MS (Method 3): Rt = 1.04 min; MS (ESIpos): m /z = 362 [M+H]+ 1H-NMR (400MHz, DMSO-d6): δ [ppm]= 1.59 - 1.86 (m, 4H), 1.86 - 2.10 (m, 4H), 2.53 - 2.71 (m, 2H, partially covered by the solvent signal), 3.21 - 3.41 (m, 2H, partially overlapped by the water signal), 3.47 (dt, 1H), 3.62 (dt, 1H), 4.74 (dd, 1H), 4.88 (s, 2H), 7.51 (d, 1H), 7.70 (dd, 1H), 8.30 (d, 1H). The spectrum shows broad signals for trimethylammonium ions at 1.15 ppm and 3.05 ppm. Example 32 (5RS)-2-[(6-Chloropyridin-3-yl)methyl]-5-(pyrrolidin-1-ylcarbonyl)-5,6,7,8-tetrahydro[1,2,4]triazole [4,3-a]pyridin-3(2H)-one (enantiomer 2)

[0992] (5RS)-2-[(6-Chloropyridin-3-yl)methyl]-5-(pyrrolidin-1-ylcarbonyl)- 5,6,7,8-tetrahydro[1,2,4] triazolo[4,3-a]pyridin-3(2H)-one (racemate) was separated by chiral preparatory SFC [sample preparation: 400 mg dissolved in 15 mL of ethanol; injection volume: 4.0 mL; column: Daicel Chiralpak® AD SFC 5μm, 250 x 50 mm; eluent: CO2/ethanol: isocratic 35% ethanol, flow rate: 80 ml/min; temperature 40°C; UV detection: 210 nm]. After separation and lyophilization of the products, 144 mg of enantiomer 1, which eluted first, and 138 mg of enantiomer 2, which eluted later, were isolated. Enantiomer 2:

[0993] Analytical chiral SFC: Rt = 3.41 min, ee = 100% [column: Daicel Chiralcel® AD; eluent: CO2/Ethanol 60:40; flow rate: 3 mL ethanol/min; UV detection: 210 nm]. LC-MS (Method 4): Rt = 0.60 min; MS (ESIpos): m /z = 362 [M+H]+ 1H-NMR (400MHz, DMSO-d6): δ [ppm]= 1.59 - 1.85 (m, 4H), 1.87 - 2.10 (m, 4H), 2.47 - 2.68 (m, 2H, partially covered by solvent signal), 3.22 - 3.31 (m, 1H), 3.31 - 3.40 (m, 1H), 3.47 (dt, 1H), 3.62 (dt, 1H), 4.74 ( dd, 1H), 4.88 (s, 2H), 7.51 (d, 1H), 7.70 (dd, 1H), 8.30 (d, 1H). Example 33 (5RS)-2-[(5-Chloropyridin-2-yl)methyl]-5-(pyrrolidin-1-ylcarbonyl)-5,6,7,8-tetrahydro[1,2,4]triazole [4,3-a]pyridin-3(2H)-one (racemate)

[0994] (5RS)-2-[(5-Chloropyridin-2-yl)methyl]-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[ 4,3-a]pyridine-5-carboxylic acid (racemate) (220 mg, 81% purity, 574 μmol) was dissolved in 3.0 mL of THF. Triethylamine (400 μl, 2.9 mmol), HATU (284 mg, 746 μmol), and pyrrolidine (57 μl, 690 μmol) were added and the mixture was stirred at room temperature overnight. For preparation, the mixture was added to water, saturated with sodium chloride and extracted twice with ethyl acetate. The combined organic phases were dried over magnesium sulfate, filtered and concentrated. The residue was separated via preparatory HPLC (column: Chromatorex, 125x30mm 10μm. Flow rate: 50 ml/min. Gradient (A = water + 0.1% formic acid, B = acetonitrile). Execution time per separation 38 min. Detection: 210 nm => 0min 0% B, 6min 10%B, 27min 95% B, 38min 95% B, 40min 0%B.). In this way, 177 mg (85% possibility) of the title compound were obtained. LC-MS (Method 3): Rt = 1.09 min; MS (ESIpos): m /z = 362 [M+H]+ 1H-NMR (500MHz, DMSO-d6): δ [ppm]= 1.64 - 1.83 (m, 4H), 1.87 - 2.11 (m, 4H), 2.46 - 2.66 (m, 2H, partially covered by the solvent signal), 3.22 - 3.43 (m, 2H, partially overlapped by the water signal), 3.48 (dt, 1H), 3.62 (dt, 1H), 4.76 (dd, 1H), 4.87 - 4.95 (m, 2H), 7.21 (d, 1H), 7.92 (dd, 1H), 8.57 (d, 1H). Example 34 (5RS)-2-[(5-Chloropyridin-2-yl)methyl]-5-(pyrrolidin-1-ylcarbonyl)-5,6,7,8-tetrahydro[1,2,4]triazole [4,3-a]pyridin-3(2H)-one (enantiomer 2)

[0995] (5RS)-2-[(5-Chloropyridin-2-yl)methyl]-5-(pyrrolidin-1-ylcarbonyl)- 5,6,7,8-tetrahydro[1,2,4] triazolo[4,3-a]pyridin-3(2H)-one (racemate) was separated by chiral preparatory liquid chromatography [sample preparation: 220 mg dissolved in 12 mL of isopropanol; injection volume: 0.5 mL; column: Daicel Chirapak® AS-H 5μm, 250 x 50 mm; eluent: isohexane/isopropanol: isocratic 50% isopropanol, flow rate: 15.0 ml/min; temperature 25°C; UV detection: 210 nm]. After separation, 69 mg of enantiomer 1, which eluted first, and 66 mg of enantiomer 2, which eluted later, were isolated. Enantiomer 2:

[0996] Analytical chiral HPLC: Rt = 1.40 min, ee = 100% [column: Daicel Chiralcel® AS-3 3μm 50 x 4.6 mm; eluent: isohexane/isopropanol 1:1; flow rate: 1 ml/min; UV detection: 220 nm]. LC-MS (Method 3): Rt = 1.06 min; MS (ESIpos): m /z = 362 [M+H]+ 1H-NMR (400MHz, DMSO-d6): δ [ppm]= 1.62 - 1.86 (m, 4H), 1.86 - 2.14 (m, 4H), 2.47 - 2.69 (m, 2H, partially covered by the solvent signal), 3.21 - 3.42 (m, 2H, partially overlapped by the water signal), 3.47 (dt, 1H), 3.62 (dt, 1H), 4.76 (dd, 1H), 4.86 - 4.96 (m, 2H), 7.21 (d, 1H), 7.92 (dd, 1H), 8.57 (d, 1H). Example 35 5-{[(5RS)-3-Oxo-5-(pyrrolidin-1-ylcarbonyl)-5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a] pyridin-2(3H)-yl]methyl}pyridine-2-carbonitrile (racemate)

[0997] (5RS)-2-[(6-Cyanopyridin-3-yl)methyl]-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[ 4,3-a]pyridine-5-carboxylic acid (racemate) (190 mg, 70% purity, 444 μmol) was dissolved in 4.0 mL of THF. Triethylamine (190 μl, 1.3 mmol), HATU (220 mg, 578 μmol), and pyrrolidine (45 μl, 530 μmol) were added and the mixture was stirred at room temperature over the weekend. For elaboration, the mixture was concentrated and the resulting residue was mixed in acetonitrile/water and separated via preparatory HPLC (column: Kromasila C18, 125x30mm, 10μm, eluent: acetonitrile (B)/water (A, neutral), gradient: 0min 90 %A, 6min 90%A, 18min 5%A, 20min 5%A, 21min 90%A, flow rate: 75ml/min, detector: 210nm). The fractions containing the product were combined, concentrated and dried. In this way, 80.0 mg (51% possibility) of the title compound were obtained. LC-MS (Method 4): Rt = 0.55 min; MS (ESIpos): m /z = 353 [M+H]+ 1H-NMR (400MHz, DMSO-d6): δ [ppm]= 1.59 - 1.84 (m, 4H), 1.86 - 2.11 (m, 4H), 2.46 - 2.69 (m, 2H, partially covered by the solvent signal), 3.22 - 3.40 (m, 2H, partially overlapped by the water signal), 3.47 (dt, 1H), 3.62 (dt, 1H), 4.76 (dd, 1H), 4.95 - 5.05 (m, 2H), 7.84 (dd, 1H), 8.04 (d, 1H), 8.62 (d, 1H). Example 36 (5RS)-2-(4-Methoxybenzyl)-5-(pyrrolidin-1-ylcarbonyl)-5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a] pyridin-3(2H)-one (racemate)

[0998] (5RS)-2-(4-Methoxybenzyl)-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine -5-carboxylic acid (racemate) (1.67 g, 80% purity, 4.40 mmol) was dissolved in DMF (10 mL). Triethylamine (1.2 mL, 8.8 mmol), HATU (2.51 g, 6.61 mmol) and pyrrolidine (440 μL, 5.3 mmol) were added and the mixture was stirred under argon at room temperature during night. For elaboration, the mixture was mixed with water, saturated sodium chloride and extracted three times with 30 mL each time with ethyl acetate. The combined organic phases were dried with magnesium sulfate, filtered and concentrated under reduced pressure. The remaining residue was separated into 3 injections via preparatory HPLC (column: Chromatorex, 125x40mm 10μm. Flow rate: 50 ml/min. Gradient (A = water + 0.1% formic acid, B = acetonitrile). Run time per separation 38 min. Detection: 210 nm => 0min 0% B, 6min 10%B, 27min 95% B, 38min 95% B, 40min 0%B =>). Concentrating the product-containing fractions, 830 mg (97% purity, 51% chance) of the title compound were obtained.

[0999] Most were used as intermediates without further purification.

[01000] About 15 mg was purified once again under the above conditions by preparatory HPLC to produce 33 mg of the title compound, 100% possibility according to LC-MS. LC-MS (Method 3): Rt = 1.16 min; MS (ESIpos): m /z = 357 [M+H]+ 1H-NMR (400MHz, DMSO-d6): δ [ppm]= 1.62 - 1.83 (m, 4H), 1.88 - 2.08 (m, 4H), 2.45 - 2.64 (m, 2H, partially covered by solvent signal), 3.21 - 3.40 (m, 2H, partially overlapped by water signal) 3.46 (dt, 1H), 3.62 (dt, 1H), 3.73 (s, 3H ), 4.66 - 4.77 (m, 3H), 6.85 - 6.91 (m, 2H), 7.13 - 7.20 (m, 2H). Example 37 (5RS)-2-[4-Chloro-3-(trifluoromethoxy)benzyl]-5-(pyrrolidin-1-ylcarbonyl)-5,6,7,8-tetrahydro[1,2,4]triazole [4,3-a]pyridin-3(2H)-one (racemate)

[01001] (5RS)-2-[4-Chloro-3-(trifluoromethyl)benzyl]-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[ 4,3-a]pyridine-5-carboxylic acid (racemate) (138 mg, 367 μmol) was dissolved in 4.0 mL of THF. Triethylamine (110 μl, 810 μmol), HATU (182 mg, 477 μmol), and pyrrolidine (37 μl, 440 μmol) were added and the mixture was stirred at room temperature overnight. For elaboration, the reaction mixture was concentrated and the resulting residue was mixed in acetonitrile/water and separated via preparatory HPLC (column: Kromasila C18, 125x30mm, 10μm, eluent: acetonitrile (B)/water + 0.1% TFA (A), gradient: 0min 90%A, 6min 90%A, 18min 5%A, 20min 5%A, 21min 90%A, flow rate: 75ml/min, detector: 210nm). The fractions containing the product were combined, concentrated and dried. In this way, 121 mg (77% possibility) of the title compound were obtained. LC-MS (Method 3): Rt = 1.66 min; MS (ESIpos): m /z = 429 [M+H]+ 1H-NMR (400MHz, DMSO-d6): δ [ppm]= 1.60 - 1.85 (m, 4H), 1.87 - 2.11 (m, 4H), 2.47 - 2.69 (m, 2H, partially covered by solvent signal), 3.21 - 3.57 (m, 3H, partially overlapped by water signal), 3.62 (dt, 1H), 4.75 (dd, 1H), 4.92 (s, 2H), 7.51 (dd, 1H), 7.72 (d, 1H), 7.76 (d, 1H). Example 38 (5RS)-2-(3-Chlorobenzyl)-5-(pyrrolidin-1-ylcarbonyl)-5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a] pyridin-3(2H)-one (racemate)

[01002] (5RS)-2-(3-Chlorobenzyl)-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine -5-carboxylic acid (racemate) (110 mg, 83% purity, 297 μmol) was dissolved in 3.5 mL of THF. Triethylamine (91 μl, 650 μmol), HATU (147 mg, 386 μmol), and pyrrolidine (30 μl, 360 μmol) were added and the mixture was stirred at room temperature overnight. For elaboration, the mixture was concentrated and the resulting residue was mixed in acetonitrile/water and separated via preparatory HPLC (column: Kromasila C18, 125x30mm, 10μm, eluent: acetonitrile (B)/water + 0.1% TFA (A), gradient: 0min 90%A, 6min 90%A, 18min 5%A, 20min 5%A, 21min 90%A, flow rate: 75ml/min, detector: 210nm). The fractions containing the product were combined, concentrated and dried. This yielded 80.3 mg (75% chance) of the title compound. LC-MS (Method 3): Rt = 1.39 min; MS (ESIpos): m /z = 361 [M+H]+ 1H-NMR (400MHz, DMSO-d6): δ [ppm]= 1.61 - 1.84 (m, 4H), 1.88 - 2.11 (m, 4H), 2.47 - 2.68 (m, 2H, partially covered by solvent signal), 3.26 (dt, 1H), 3.36 (dt, 1H), 3.47 (dt, 1H), 3.62 (dt, 1H, partially overlapped by water signal) , 4.75 (dd, 1H), 4.83 (s, 2H), 7.19 (br d, 1H), 7.29 (br s, 1H), 7.32 - 7.40 (m, 2H). Example 39 (5RS)-2-(3,4-Dichlorobenzyl)-5-(pyrrolidin-1-ylcarbonyl)-5,6,7,8-tetrahydro[1,2,4]triazolo[4,3- a]pyridin-3(2H)-one (racemate)

[01003] (5RS)-2-(3,4-Dichlorobenzyl)-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a ]pyridine-5-carboxylic acid (racemate) (120 mg, 80% purity, 281 μmol) was dissolved in 3.0 mL of THF. Triethylamine (86 μl, 620 μmol), HATU (139 mg, 365 μmol), and pyrrolidine (28 μl, 340 μmol) were added and the mixture was stirred at room temperature overnight. For elaboration, the mixture was concentrated and the resulting residue was mixed in acetonitrile/water and separated via preparatory HPLC (column: Kromasila C18, 125x30mm, 10μm, eluent: acetonitrile (B)/water + 0.1% TFA (A), gradient: 0min 90%A, 6min 90%A, 18min 5%A, 20min 5%A, 21min 90%A, flow rate: 75ml/min, detector: 210nm). The fractions containing the product were combined, concentrated and dried. This yielded 113 mg (97% chance) of the title compound. LC-MS (Method 4): Rt = 0.84 min; MS (ESIpos): m /z = 395 [M+H]+ 1H-NMR (400MHz, DMSO-d6): δ [ppm]= 1.60 - 1.84 (m, 4H), 1.85 - 2.10 (m, 4H), 2.45 - 2.67 (m, 2H, partially covered by solvent signal), 3.21 - 3.51 (m, 3H, partially overlapped by water signal), 3.62 (dt, 1H), 4.75 (dd, 1H), 4.83 (s, 2H), 7.22 (dd, 1H), 7.49 (d, 1H), 7.62 (d, 1H). Example 40 (5RS)-5-(Pyrrolidin-1-ylcarbonyl)-2-{[4-(trifluoromethyl)cyclohexyl]methyl}-5,6,7,8-tetrahydro[1,2,4]triazolo[ 4,3-a]pyridin-3(2H)-one (mixture of diastereomer; 4 isomers)

[01004] (5RS)-3-Oxo-2-{[4-(trifluoromethyl)cyclohexyl]methyl}-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4 ,3-a]pyridine-5-carboxylic acid (mixture of diastereomer; 4 isomers) (326 mg, 939 μmol) was dissolved in 10 mL of THF Triethylamine (260 μl, 1.9 mmol), HATU (464 mg, 1 .22 mmol) and pyrrolidine (94 μl, 1.1 mmol) were added and the mixture was stirred at room temperature overnight. For elaboration, the mixture was mixed with water and then concentrated, and the resulting residue was mixed in acetonitrile/water and separated via preparatory HPLC (column: Kromasila C18, 125x30mm, 10μm, eluent: acetonitrile (B)/water + 0.1% TFA (A), gradient: 0min 90%A, 6min 90%A, 18min 5%A, 20min 5%A, 21min 90%A, flow rate: 75ml/min, detector: 210nm). The fractions containing the product were combined, concentrated and dried. In this way, 90.2 mg (24% possibility) of the title compound were obtained as a racemic cis/trans mixture. LC-MS (Method 4): Rt = 0.90 min; MS (ESIpos): m /z = 401 [M+H]+ 1H-NMR (400MHz, DMSO-d6): δ [ppm]= 0.89 - 1.08 (m, 1H), 1.10 - 1.26 (m, 1H), 1.43 - 2.10 (m, 15H), 2.11 - 2.34 (m, 1H), 2.45 - 2.69 (m, 2H, partially covered by solvent signal), 3.20 - 3.29 (m, 1H), 3.29 - 3.72 (m, 5H , partially overlapped by the water sign), 4.67 - 4.74 (m, 1H). Example 41 (5RS)-2-[(4,4-Difluorocyclohexyl)methyl]-5-(pyrrolidin-1-ylcarbonyl)-5,6,7,8-tetrahydro[1,2,4]triazolo[4 ,3-a]pyridin-3(2H)-one (racemate)

[01005] (5RS)-2-[(4,4-Difluorocyclohexyl)methyl]-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4, 3-a]pyridine-5-carboxylic acid (racemate) (30.5 mg, 96.7 μmol) was dissolved in 1.0 mL of THF. Triethylamine (27 μl, 1.90 μmol), HATU (47.8 mg, 126 μmol), and pyrrolidine (9.7 μl, 120 μmol) were added and the mixture was stirred at room temperature overnight. For elaboration, the mixture was mixed with water and then concentrated, and the resulting residue was mixed in acetonitrile/water and separated via preparatory HPLC (column: Kromasila C18, 125x30mm, 10μm, eluent: acetonitrile (B)/water + 0.1% TFA (A), gradient: 0min 90%A, 6min 90%A, 18min 5%A, 20min 5%A, 21min 90%A, flow rate: 75ml/min, detector: 210nm). The fractions containing the product were combined, concentrated and dried. In this way, 17.6 mg (49% possibility) of the title compound were obtained. LC-MS (Method 4): Rt = 0.77 min; MS (ESIpos): m /z = 369 [M+H]+ 1H-NMR (400MHz, DMSO-d6): δ [ppm]= 1.12 - 1.27 (m, 2H), 1.61 - 2.09 (m, 15H), 2.47 - 2.68 (m, 2H, partially covered by solvent signal), 3.25 (dt, 1H), 3.34 (dt, 1H), 3.41 - ca. 3.70 (m, 4H, partially overlapped by water signal), 4.70 (dd, 1H). Example 42 (5RS)-5-[(3,3-Difluoropyrrolidin-1-yl)carbonyl]-2-(4-methylbenzyl)-5,6,7,8-tetrahydro[1,2,4]triazole [4,3-a]pyridin-3(2H)-one (racemate)

[01006] (5RS)-2-(4-Methylbenzyl)-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine -5-carboxylic acid (racemate) (36.0 mg, 124 μmol) was dissolved in 1.3 mL of THF. Triethylamine (57, 410 μmol), HATU (70.7 mg, 186 μmol), and 3,3-difluoropyrrolidine hydrochloride (21.4 mg, 149 μmol) were added, and the mixture was stirred at room temperature for 3 h. For preparation, the mixture was concentrated, and the resulting residue was dissolved in DMSO/acetonitrile/water and separated using preparatory HPLC (column: Kromasila C18, 250x30mm, 10μm, eluent: acetonitrile (B)/water + 0.1% TFA ( A), gradient: 0min 90%A, 6min90%A, 27min 5%A, 38min 5%A, 38min 5%A, 39min 90%A; flow rate: 50ml/min, detector: 210nm). The fractions containing the product were combined, concentrated and dried. This yielded 26.4 mg (57% chance) of the title compound. LC-MS (Method 3): Rt = 1.46 min; MS (ESIpos): m /z = 377 [M+H]+ 1H-NMR (400MHz, DMSO-d6): δ [ppm]= 1.59 - 1.78 (m, 2H), 1.90 - 2.12 (m, 2H), 2.27 (s, 3H), 2.35 - 2.66 (m, 4H, partially covered by solvent signal), 3.32 - 4.24 (m, 4H, partially overlapped by water signal), 4.69 - 4.85 (m, 3H), 7.09 - 715 (m, 4H). A rotamer mixture is present Example 43 (5RS)-2-[4-Chloro-3-(trifluoromethoxy)benzyl]-5-[(3,3-difluoropyrrolidin-1-yl)carbonyl]-5,6,7, 8-tetrahydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one (racemate)

[01007] (5RS)-2-[4-Chloro-3-(trifluoromethyl)benzyl]-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[ 4,3-a]pyridine-5-carboxylic acid (racemate) (138 mg, 367 μmol) was dissolved in 4.0 mL of THF. Triethylamine (160, 1.2 mmol), HATU (182 mg, 477 μmol) and 3,3-difluoropyrrolidine hydrochloride (63.3 mg, 441 μmol) were added, and the mixture was stirred at room temperature for 3 h. For elaboration, the mixture was concentrated, and the resulting residue was dissolved in acetonitrile/water and separated using preparatory HPLC (column: Kromasila C18, 125x30mm, 10μm, eluent: acetonitrile (B)/water + 0.1% TFA (A) , gradient: 0min 90%A, 6min 90%A, 18min 5%A, 20min 5%A, 21min 90%A, flow rate: 75ml/min, detector: 210nm). The fractions containing the product were combined, concentrated and dried. In this way, 135 mg (79% possibility) of the title compound were obtained. LC-MS (Method 3): Rt = 1.76 min; MS (ESIpos): m /z = 465 [M+H]+ 1H-NMR (400MHz, DMSO-d6): δ [ppm]= 1.58 - 1.80 (m, 2H), 1.93 - 2.14 (m, 2H), 2.34 - 2.69 (m, 4H, partially covered by the solvent signal), 3.41 - 4.26 (m, 4H, partially overlapped by the water signal), 4.78 (dd, 0.5H), 4.85 (dd, 0.5H), 4.93 ( s, 2H), 7.51 (dd, 1H), 7.72 (d, 1H), 7.76 (d, 1H). A rotamer mixture is present Example 44 (5RS)-2-(3-Chlorobenzyl)-5-[(3,3-difluoropyrrolidin-1-yl)carbonyl]-5,6,7,8-tetrahydro[1 ,2,4]triazolo[4,3-a]pyridin-3(2H)-one (racemate)

[01008] (5RS)-2-(3-Chlorobenzyl)-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine -5-carboxylic acid (racemate) (110 mg, 83% purity, 297 μmol) was dissolved in 3.5 mL of THF. Triethylamine (130 μl, 950 μmol), HATU (147 mg, 386 μmol), and 3,3-difluoropyrrolidine hydrochloride (51.1 mg, 356 μmol) were added and the mixture was stirred at room temperature overnight. For elaboration, the mixture was concentrated and the resulting residue was dissolved in acetonitrile/water and separated via preparatory HPLC (column: Kromasila C18, 125x30mm, 10μm, eluent: acetonitrile (B)/water + 0.1% TFA (A), gradient: 0min 90%A, 6min 90%A, 18min 5%A, 20min 5%A, 21min 90%A, flow rate: 75ml/min, detector: 210nm). The fractions containing the product were combined, concentrated and dried. This yielded 89.2 mg (76% chance) of the title compound. LC-MS (Method 3): Rt = 1.52 min; MS (ESIpos): m /z = 397 [M+H]+ 1H-NMR (400MHz, DMSO-d6): δ [ppm]= 1.59 - 1.81 (m, 2H), 1.92 - 2.14 (m, 2H), 2.35 - 2.69 (m, 4H, partially covered by solvent signal), ca. 3.43 - 4.25 (m, 4H, partially overlapped by water sign), 4.77 (dd, 0.5H), 4.80 - 4.89 (m, 2.5H), 7.19 (d, 1H), 7.29 (s, 1H), 7.32 - 7.42 (m, 2H). A rotamer mixture is present. Example 45 (5RS)-2-(3,4-Dichlorobenzyl)-5-[(3,3-difluoropyrrolidin-1-yl)carbonyl]-5,6,7,8-tetrahydro[1,2,4 ]triazolo[4,3-a]pyridin-3(2H)-one (racemate)

[01009] (5RS)-2-(3,4-Dichlorobenzyl)-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a ]pyridine-5-carboxylic acid (racemate) (120 mg, 80% purity, 281 μmol) was dissolved in 3.5 mL of THF. Triethylamine (125 μl, 900 μmol), HATU (147 mg, 386 μmol), and 3,3-difluoropyrrolidine hydrochloride (48.3 mg, 337 μmol) were added and the mixture was stirred at room temperature overnight. For elaboration, the mixture was concentrated and the resulting residue was dissolved in acetonitrile/water and separated via preparatory HPLC (column: Kromasila C18, 125x30mm, 10μm, eluent: acetonitrile (B)/water + 0.1% TFA (A), gradient: 0min 90%A, 6min 90%A, 18min 5%A, 20min 5%A, 21min 90%A, flow rate: 75ml/min, detector: 210nm). The fractions containing the product were combined, concentrated and dried. In this way, 112 mg (90% possibility) of the title compound were obtained. LC-MS (Method 3): Rt = 1.68 min; MS (ESIpos): m /z = 431 [M+H]+ 1H-NMR (400MHz, DMSO-d6): δ [ppm]= 1.59 - 1.80 (m, 2H), 1.92 - 2.14 (m, 2H), 2.34 - 2.69 (m, 4H, partially covered by solvent signal), 3.48 - 4.25 (m, 4H), 4.77 (dd, 0.5H) 4.81 - 4.89 (m, 2.5H), 7.22 (dd, 1H), 7.49 (d, 1H), 7.62 (d, 1H). A rotamer mixture is present. Example 46 (5RS)-2-(3-Chloro-4-methoxybenzyl)-5-(pyrrolidin-1-ylcarbonyl)-5,6,7,8-tetrahydro[1,2,4]triazolo[4, 3-a]pyridin-3(2H)-one (racemate)

[01010] (5RS)-2-(3-Chloro-4-methoxybenzyl)-3-oxo-2,3,5,6,7,8-hexahydro [1,2,4] triazole [4,3 -a]pyridine-5-carboxylic acid/trifluoroacetic acid (racemate) (70.0 mg, 155 μmol) was initially loaded into THF (3.0 mL), and 1-[bis(dimethylamino)methylene]-1H- [ 1,2,3]triazolo[4,5-b]pyridin-1-io 3-hexafluorophosphate oxide (76.6 mg, 201 μmol) and triethylamine (110 μl, 770 μmol) were subsequently added. After stirring at room temperature for 15 minutes, pyrrolidine (16 μl, 190 μmol) was added and the reaction mixture was stirred at room temperature overnight. The solvent was removed under reduced pressure, and the residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/water gradient). HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/gradient water). The fractions containing the product were concentrated under reduced pressure and 45.3 mg (75% possibility) of the title compound were obtained. LC-MS (Method 4): Rt = 0.76 min; MS (ESIpos): m /z = 391 [M+H]+ ¹H-NMR (400 MHz, DMSO-d6) δ [ppm]: 1.399 (1.48), 1.709 (3.03), 1.756 (1.37), 1.773 (4.59 ), 1,790 (8.04), 1,807 (6.19), 1,824 (1.87), 1,892 (1.96), 1,909 (5.76), 1,925 (7.26), 1,942 (5.02), 1,960 (1.89), 1,977 (2.42), 1,996 (1.92 ), 2.007 (1.53), 2.022 (1.92), 2.032 (1.45), 2.073 (0.76), 2.328 (0.59), 2.523 (4.16), 2.564 (2.07), 2.577 (1.91), 2.590 (3.62), 2.602 (2.05 ), 2.621 (0.90), 2.631 (1.41), 2.669 (0.57), 2.865 (0.84), 3.224 (1.07), 3.241 (2.33), 3.254 (2.24), 3.270 (4.01), 3.287 (1.82), 3.326 (1.86 ), 3.344 (4.00), 3.361 (2.11), 3.373 (2.39), 3.391 (1.09), 3.433 (1.24), 3.451 (2.64), 3.458 (2.04), 3.476 (3.38), 3.493 (1.52), 3.592 (1.52 ), 3609 (3.26), 3625 (1.85), 3633 (2.56), 3649 (1.34), 3729 (0.70), 3966 (1.62), 4696 (0.90), 4724 (3.54), 4735 (15.25), 4739 (16.00 ), 4,779 (0.92), 7,095 (6.08), 7,116 (10.56), 7,167 (5.32), 7,172 (5.46), 7,188 (2.99), 7,193 (3.23), 7,293 (9.06), 7,298 (8.15). Example 47 (5RS)-5-[(3,3-Difluoropyrrolidin-1-yl)carbonyl]-2-[3-(trifluoromethyl)benzyl]-5,6,7,8-tetrahydro[1,2, 4]triazolo[4,3-a]pyridin-3(2H)-one (racemate)

[01011] (5RS)-3-Oxo-2-[3-(trifluoromethyl)benzyl]-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3- a]pyridine-5-carboxylic acid/trifluoroacetic acid (racemate) (70.0 mg, 154 μmol) was loaded into THF (2.6 mL) and 1-[bis(dimethylamino)methylene]-1H-[1 ,2,3] triazolo[4, 5-b]pyridin-1-io 3-oxide hexafluorophosphate (76.0 mg, 200 μmol) and triethylamine (110 μl, 770 μmol) were subsequently added. After stirring at room temperature for 15 minutes, 3,3-difluoropyrrolidine hydrochloride (26.5 mg, 184 μmol) was added and the reaction mixture was stirred at room temperature overnight. The solvent was removed under reduced pressure, and the residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/water gradient). HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/gradient water). The fractions containing the product were concentrated under reduced pressure and 46.5 mg (70% possibility) of the title compound were obtained. LC-MS (Method 4): Rt = 0.86 min; MS (ESIpos): m /z = 431 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.150 (0.90), -0.008 (6.54), 0.008 (6.57), 0.146 (0.79) (1.50) (1.35) (2.37), 7,525 (3.94), 7,572 (2.37), 7,591 (4.39), 7,615 (5.78), 7,648 (3.79), 7,667 (2.22). Example 48 (5RS)-5-[(3,3-Difluoropyrrolidin-1-yl)carbonyl]-2-(3-methoxybenzyl)-5,6,7,8-tetrahydro[1,2,4]triazole [4,3-a]pyridin-3(2H)-one (racemate)

[01012] (5RS)-2-(3-methoxybenzyl)-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine -5-carboxylic acid/trifluoroacetic acid (racemate) (70.0 mg, 168 μmol) was initially loaded into THF (3.0 mL) and 1-[bis(dimethylamino)methylene]-1H-[1.2 ,3]triazolo[4,5-b]pyridin-1-io 3-oxide hexafluorophosphate (82.9 mg, 218 μmol) and triethylamine (120 μl, 840 μmol) were subsequently added. After stirring at room temperature for 15 minutes, 3,3-difluoropyrrolidine hydrochloride (28.9 mg, 201 μmol) was added and the reaction mixture was stirred at room temperature overnight. The solvent was removed under reduced pressure, and the residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/water gradient). HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/gradient water). The fractions containing the product were concentrated under reduced pressure and 47.1 mg (72% possibility) of the title compound were obtained. LC-MS (Method 4): Rt = 0.75 min; MS (ESIpos): m /z = 393 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: 1.176 (0.43), 1.664 (0.83), 1.676 (0.96), 1.688 (1.03 ), 1.702 (1.17), 1.715 (1.34), 1.724 (1.33), 1.969 (0.80), 1.978 (1.09), 1.992 (1.10), 2.002 (1.22), 2.009 (1.19), 2.026 (0.96), 2.037 (0.90 ), 2.045 (0.92), 2.052 (0.93), 2.062 (0.88), 2.072 (0.99), 2.080 (0.69), 2.088 (0.63), 2.365 (0.44), 2.380 (0.75), 2.392 (0.57), 2.401 (0.79 ), 2.409 (0.90), 2.430 (0.86), 2.451 (0.65), 2.472 (0.43), 2.517 (3.02), 2.559 (2.35), 2.569 (2.87), 2.585 (2.57), 2.601 (2.46), 2.612 (1.31 ), 2.631 (0.48), 2.644 (0.74), 2.669 (0.40), 3.534 (3.05), 3.548 (3.83), 3.554 (3.85), 3.566 (2.82), 3.573 (2.57), 3.635 (0.72), 3.669 (1.32 ), 3.702 (1.44), 3.769 (1.59), 3.783 (1.02), 3.792 (0.87), 3.802 (1.67), 3.809 (1.48), 3.828 (0.66), 3.894 (0.62), 3.913 (1.29), 3.932 (0.71 ), 3.939 (0.91), 3.958 (0.48), 3.993 (0.80), 4.021 (0.54), 4.035 (0.71), 4.063 (0.43), 4.147 (0.47), 4.178 (0.68), 4.205 (0.69), 4.750 (1.09 ), 4,776 (16.00), 4,824 (1.07), 4,834 (1.23), 4,840 (1.38), 4,849 (1.03), 6,773 (6.87), 6,777 (7.30), 6,793 (3.43), 6,823 (2.14), 6,827 (2.29 ), 6,832 (1.64), 6,845 (2.46), 6,851 (2.14), 7,220 (2.49), 7,241 (5.00), 7,261 (2.64). Example 49 (5RS)-2-(3-Chloro-4-methoxybenzyl)-5-[(3,3-difluoropyrrolidin-1-yl)carbonyl]-5,6,7,8-tetrahydro[1,2 ,4]triazolo[4,3-a]pyridin-3(2H)-one (racemate)

[01013] (5RS)-2-(3-Chloro-4-methoxybenzyl)-3-oxo-2,3,5,6,7,8-hexahydro [1,2,4] triazole [4,3 -a]pyridine-5-carboxylic acid/trifluoroacetic acid (racemate) (70.0 mg, 155 μmol) was initially loaded into THF (3.0 mL), and 1-[bis(dimethylamino)methylene]-1H- [ 1,2,3]triazolo[4,5-b]pyridin-1-io 3-hexafluorophosphate oxide (76.6 mg, 201 μmol) and triethylamine (110 μl, 770 μmol) were subsequently added. After stirring at room temperature for 15 minutes, 3,3-difluoropyrrolidine hydrochloride (26.7 mg, 186 μmol) was added and the reaction mixture was stirred at room temperature overnight. The solvent was removed under reduced pressure, and the residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/water gradient). HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/gradient water). The fractions containing the product were concentrated under reduced pressure and 36.0 mg (54% possibility) of the title compound were obtained. LC-MS (Method 4): Rt = 0.80 min; MS (ESIpos): m /z = 427 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: 1.176 (0.66), 1.669 (0.43), 1.682 (0.48), 1.695 (0.55 ), 1.707 (0.61), 1.717 (0.61), 1.969 (0.48), 1.981 (0.50), 1.993 (0.57), 2.038 (0.43), 2.045 (0.41), 2.411 (0.41), 2.423 (0.41), 2.565 (1.07 ), 2.580 (1.02), 2.595 (1.07), 2.607 (0.68), 3.529 (0.46), 3.537 (0.50), 3.546 (0.75), 3.558 (0.84), 3.577 (0.41), 3.666 (0.48), 3.700 (0.55 ), 3.775 (0.68), 3.806 (1.00), 3.833 (16.00), 3.910 (0.55), 4.745 (4.55), 4.765 (0.50), 4.815 (0.46), 4.825 (0.55), 4.831 (0.59), 4.840 (0.43 ), 7,097 (1.68), 7,118 (2.94), 7,167 (1.52), 7,172 (1.59), 7,188 (0.84), 7,193 (0.93), 7,292 (2.30), 7,297 (2.12). Example 50 (5S)-5-(Pyrrolidin-1-ylcarbonyl)-2-{[6-(trifluoromethyl)pyridin-3-yl]methyl}-2,5,6,7-tetrahydro-3H-pyrrole[ 2,1-c][1,2,4]triazol-3-one (enantiomer)

[01014] (5S)-3-Oxo-2-{[6-(trifluoromethyl)pyridin-3-yl]methyl}-2,5,6,7-tetrahydro-3H-pyrrol[2,1-c ][1,2,4]triazole-5-carboxylic acid (enantiomer) (100 mg, 305 μmol) was initially loaded into THF (2.0 mL) at room temperature. Subsequently, 1-[bis(dimethylamino)methylene]- 1H-[1,2,3]triazolo[4,5-b]pyridin-1-io 3-oxide hexafluorophosphate (151 mg, 396 μmol) and triethylamine (170 μl , 1.2 mmol) were added. After stirring for 15 minutes, pyrrolidine (31 μl, 370 μmol) was added and the reaction mixture was stirred at room temperature overnight. The reaction mixture was mixed with water and ethyl acetate. The organic phase was removed and the aqueous phase was extracted three times with ethyl acetate. The combined organic phases were washed with saturated aqueous sodium chloride solution, dried over sodium sulfate and filtered, and the filtrate was concentrated. The residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/gradient water). The fractions containing the product were concentrated under reduced pressure and 50.0 mg (43% possibility) of the title compound were obtained. LC-MS (Method 3): Rt = 1.13 min; MS (ESIpos): m /z = 382 [M+H]+ ¹H-NMR (400 MHz, DMSO-d6) δ [ppm]: 1.769 (0.78), 1.784 (3.02), 1.802 (5.93), 1.819 (5.24 ), 1,835 (1.78), 1,889 (1.56), 1,905 (4.92), 1,922 (6.24), 1,939 (3.71), 1,957 (0.94), 2,367 (1.77), 2,389 (1.77), 2,406 (1.84), 2,416 (1.09 ), 2.426 (0.84), 2.651 (0.49), 2.674 (1.03), 2.692 (2.10), 2.714 (4.83), 2.724 (2.25), 2.736 (4.61), 2.744 (3.26), 2.754 (1.23), 2.780 (1.92 ), 2.810 (2.02), 2.832 (1.50), 3.268 (0.55), 3.285 (1.24), 3.298 (2.66), 3.334 (5.63), 3.351 (2.20), 3.364 (1.29), 3.380 (1.63), 3.397 (2.45 ), 3.404 (1.65), 3.415 (1.42), 3.422 (2.86), 3.439 (1.27), 3.641 (1.30), 3.657 (2.74), 3.666 (1.47), 3.674 (1.51), 3.682 (2.39), 3.699 (1.08 ), 4,923 (3.04), 4,930 (2.28), 4,944 (3.23), 4,950 (2.23), 5,007 (16.00), 7,902 (2.10), 7,923 (8.79), 7,933 (5.24), 7,957 (1.23), 8,673 (5.78 ).

[01015] Subsequent analyzes of Example 175 showed that the 3H-pyrrolo[2,1-c][1,2,4]triazol-3-one systems undergo partial racemization using HATU and are no longer in the form of the pure enantiomer. Example 51 (5S)-2-(3-Chloro-4-fluorobenzyl)-5-(pyrrolidin-1-ylcarbonyl)-2,5,6,7-tetrahydro-3H-pyrrolo[2,1-c] [1,2,4]triazol-3-one (enantiomer)

[01016] (5S)-2-(3-Chloro-4-fluorobenzyl)-3-oxo-2,5,6,7-tetrahydro-3H-pyrrole [2,1-c][1,2, 4]triazole-5-carboxylic acid (enantiomer) (100 mg, 321 μmol) was initially loaded into THF (2.0 mL) at room temperature. Subsequently, 1-[bis(dimethylamino)methylene]-1H- [1,2,3]triazolo[4,5-b]pyridin-1-io 3-oxide hexafluorophosphate (159 mg, 417 μmol) and triethylamine (180 μl , 1.3 mmol) were added. After stirring for 15 minutes, pyrrolidine (32 μl, 380 μmol) was added and the reaction mixture was stirred at room temperature overnight. The reaction mixture was mixed with water and ethyl acetate. The organic phase was removed and the aqueous phase was extracted three times with ethyl acetate. The combined organic phases were washed with saturated aqueous sodium chloride solution, dried over sodium sulfate and filtered, and the filtrate was concentrated. The residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/gradient water). The fractions containing the product were concentrated under reduced pressure and 65.0 mg (56% possibility) of the title compound were obtained. LC-MS (Method 4): Rt = 0.73 min; MS (ESIpos): m /z = 365 [M+H]+ ¹H-NMR (400 MHz, DMSO-d6) δ [ppm]: 1.768 (1.33), 1.784 (5.17), 1.800 (10.32), 1.817 (9.23 ), 1,833 (3.24), 1,888 (2.78), 1,904 (8.68), 1,921 (10.97), 1,938 (6.38), 1,956 (1.55), 2,327 (1.35), 2,358 (2.20), 2,365 (2.34), 2,379 (3.19 ), 2,385 (2.61), 2,396 (3.26), 2,407 (1.96), 2,671 (2.13), 2,690 (3.70), 2,712 (7.35), 2,721 (3.63), 2,731 (8.75), 2,739 (5.90), 2,766 (2.80 ), 2.773 (3.72), 2.803 (3.55), 2.825 (2.63), 2.847 (0.68), 3.265 (1.09), 3.282 (2.37), 3.331 (9.81), 3.349 (3.94), 3.361 (2.22), 3.378 (2.90 ), 3.395 (4.21), 3.402 (2.85), 3.419 (5.00), 3.437 (2.32), 3.640 (2.37), 3.657 (4.95), 3.665 (2.54), 3.674 (2.66), 3.681 (4.23), 3.698 (1.79 ), 4,778 (1.21), 4,818 (16.00), 4,823 (15.78), 4,864 (1.11), 4,916 (5.34), 4,923 (3.79), 4,937 (5.68), 4,944 (3.79), 7,250 (2.44), 7,255 (2.66 ), 7,262 (2.71), 7,271 (4.01), 7,276 (3.79), 7,283 (3.70), 7,289 (3.48), 7,377 (7.40), 7,401 (9.52), 7,422 (5.37), 7,453 (5.78), 7,458 (5.41 ), 7,471 (5.78), 7,477 (5.32).

[01017] Subsequent analyzes of Example 175 showed that the 3H-pyrrolo[2,1-c][1,2,4]triazol-3-one systems undergo partial racemization using HATU and are no longer in the form of the pure enantiomer. Example 52 (5S)-2-[(6-Chloropyridin-3-yl)methyl]-5-(pyrrolidin-1-ylcarbonyl)-2,5,6,7-tetrahydro-3H-pyrrol[2,1 -c][1,2,4]triazol-3-one (enantiomer)

[01018] (5S)-2-[(6-Chloropyridin-3-yl)methyl]-3-oxo-2,5,6,7-tetrahydro-3H-pyrrole[2,1-c][1 ,2,4]triazole-5-carboxylic acid (enantiomer) (80.0 mg, 271 μmol) was initially loaded into THF (2.0 mL) at room temperature. Subsequently, 1-[bis(dimethylamino)methylene]-1H- [1,2,3]triazolo[4,5-b]pyridin-1-io 3-oxide hexafluorophosphate (134 mg, 353 μmol) and triethylamine (150 μl , 1.1 mmol) were added. After stirring for 15 minutes, pyrrolidine (27 μl, 330 μmol) was added and the reaction mixture was stirred at room temperature overnight. The reaction mixture was mixed with water and ethyl acetate. The organic phase was removed and the aqueous phase was extracted three times with ethyl acetate. The combined organic phases were washed with saturated aqueous sodium chloride solution, dried over sodium sulfate and filtered, and the filtrate was concentrated. The residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/gradient water). The fractions containing the product were concentrated under reduced pressure and 30.0 mg (32% possibility) of the title compound were obtained. LC-MS (Method 3): Rt = 0.97 min; MS (ESIpos): m /z = 348 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (0.44), 1.782 (2.91), 1.798 (5.45), 1.816 ( 4.87), 1.832 (1.60), 1.886 (1.48), 1.902 (4.67), 1.919 (5.91), 1.936 (3.46), 1.954 (0.86), 2.328 (0.66), 2.378 (1.73), 2.396 (1.70), 2.681 ( 1.98), 2.703 (4.30), 2.713 (2.17), 2.724 (4.48), 2.732 (3.11), 2.769 (1.81), 2.799 (1.89), 2.821 (1.40), 3.328 (6.29), 3.346 (2.24), 3.358 ( 1.33), 3.375 (1.71), 3.392 (2.30), 3.416 (2.65), 3.433 (1.15), 3.636 (1.17), 3.653 (2.62), 3.678 (2.16), 3.694 (0.97), 4.879 (16.00), 4.908 ( 2.88), 4.929 (3.09), 7.508 (5.17), 7.529 (6.17), 7.716 (3.34), 7.722 (3.44), 7.737 (2.73), 7.743 (2.78), 8.322 (5.32), 8.328 (5.20).

[01019] Subsequent analyzes of Example 175 showed that the 3H-pyrrolo[2,1-c][1,2,4]triazol-3-one systems undergo partial racemization using HATU and are no longer in the form of the pure enantiomer. Example 53 (5RS)-2-[(5-Chloro-2-thienyl)methyl]-5-(pyrrolidin-1-ylcarbonyl)-5,6,7,8-tetrahydro[1,2,4]triazole [4,3-a]pyridin-3(2H)-one (racemate)

[01020] (5RS)-2-[(5-Chloro-2-thienyl)methyl]-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4] triazolo[ 4,3-a]pyridine-5-carboxylic acid/trifluoroacetic acid (racemate) (80.0 mg, 187 μmol) was initially loaded into THF (2.0 mL) at room temperature. Subsequently, 1-[bis(dimethylamino)methylene]-1H-[1,2,3]triazolo[4,5-b]pyridin-1-io 3-oxide hexafluorophosphate (92.4 mg, 243 μmol) and triethylamine ( 130 μl, 940 μmol) were added. After stirring for 15 minutes, pyrrolidine (16.0 mg, 224 μmol) was added and the reaction mixture was stirred at room temperature overnight. The reaction mixture was mixed with water and ethyl acetate. The organic phase was removed and the aqueous phase was extracted three times with ethyl acetate. The combined organic phases were washed with saturated aqueous sodium chloride solution, dried over sodium sulfate and filtered, and the filtrate was concentrated. The residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/gradient water). The fractions containing the product were concentrated under reduced pressure and 37.9 mg (55% possibility) of the title compound were obtained. LC-MS (Method 4): Rt = 0.75 min; MS (ESIpos): m /z = 367 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: 0.008 (1.30), 1.667 (1.13), 1.679 (1.75), 1.702 (3.21 ), 1,711 (3.57), 1,723 (2.84), 1,753 (1.54), 1,769 (5.20), 1,787 (9.04), 1,804 (6.99), 1,821 (2.02), 1,889 (2.22), 1,906 (6.53), 1,923 (8.49 ), 1,939 (5.64), 1,958 (2.63), 1,970 (2.76), 1,982 (2.51), 1,991 (2.15), 2,001 (1.70), 2,017 (2.27), 2,027 (1.63), 2,033 (1.49), 2,042 (1.55 ), 2.052 (0.98), 2.068 (0.58), 2.078 (0.42), 2.327 (0.41), 2.564 (2.63), 2.579 (2.25), 2.592 (2.18), 2.604 (4.23), 2.617 (2.24), 2.634 (0.99 ), 2.646 (1.58), 2.659 (0.84), 2.669 (0.51), 2.865 (3.48), 3.219 (1.23), 3.236 (2.56), 3.248 (2.58), 3.265 (4.57), 3.282 (2.29), 3.333 (4.95 ), 3.345 (1.94), 3.350 (2.73), 3.362 (2.79), 3.380 (1.23), 3.428 (1.37), 3.445 (2.98), 3.453 (2.21), 3.462 (1.78), 3.470 (3.82), 3.487 (1.67 ), 3.586 (1.75), 3.602 (3.65), 3.611 (1.84), 3.619 (2.06), 3.627 (2.82), 3.644 (1.26), 4.707 (3.29), 4.717 (3.82), 4.722 (4.37), 4.732 (3.35 ), 4,872 (0.79), 4,914 (16.00), 4,957 (0.85), 6,898 (6.58), 6,908 (8.26), 6,973 (11.05), 6,982 (8.62). Example 54 (5RS)-2-[(5-Chloro-2-thienyl)methyl]-5-[(3,3-difluoropyrrolidin-1-yl)carbonyl]-5,6,7,8-tetrahydro[ 1,2,4]triazolo[4,3-a]pyridin-3(2H)-one (racemate)

[01021] (5RS)-2-[(5-Chloro-2-thienyl)methyl]-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4] triazolo[ 4,3-a]pyridine-5-carboxylic acid/trifluoroacetic acid (racemate) (80.0 mg, 187 μmol) was initially loaded into THF (2.0 mL) at room temperature. Subsequently, 1-[bis(dimethylamino)methylene]-1H-[1,2,3]triazolo[4,5-b]pyridin-1-io 3-oxide hexafluorophosphate (92.4 mg, 243 μmol) and triethylamine ( 130 μl, 940 μmol) were added. After stirring for 15 minutes, 3,3-difluoropyrrolidine hydrochloride (32.2 mg, 224 μmol) was added and the reaction mixture was stirred at room temperature overnight. The reaction mixture was mixed with water and ethyl acetate. The organic phase was removed and the aqueous phase was extracted three times with ethyl acetate. The combined organic phases were washed with saturated aqueous sodium chloride solution, dried over sodium sulfate and filtered, and the filtrate was concentrated. The residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/gradient water). The fractions containing the product were concentrated under reduced pressure and 42.9 mg (57% possibility) of the title compound were obtained. LC-MS (Method 4): Rt = 0.80 min; MS (ESIpos): m /z = 403 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.008 (1.94), 1.718 (1.95), 1.977 (1.59), 1.987 ( 1.79), 2.032 (1.31), 2.049 (1.24), 2.068 (1.06), 2.327 (0.63), 2.359 (0.64), 2.377 (1.04), 2.406 2.447 (1.16), 2.569 (3.54), 2.580 (3.06), 2. 594 (3.16) (0.45) (0.61), 3984 (1.06), 4012 (0.76), 4025 (0.96), 4054 (0.54), 4138 (0.59), 4170 (0.95), 4195 (0.98), 4226 (0.40), 4725 (1.42), 4740 (1.87) (10.97), 6,984 (8.41). Example 55 (5S)-5-(Pyrrolidin-1-ylcarbonyl)-2-[3-(trifluoromethyl)benzyl]-2,5,6,7-tetrahydro-3H-pyrrolo[2,1-c][ 1,2,4]triazol-3-one (enantiomer)

[01022] Methyl (5S)-3-oxo-2-[3-(trifluoromethyl)benzyl]-2,5,6,7-tetrahydro-3H-pyrrolo[2,1-c][1,2, 4] triazole-5-carboxylate (enantiomer) (129 mg, 378 μmol) was initially loaded into THF (2.0 mL) at room temperature. Subsequently, 1-[bis(dimethylamino)methylene]-1H- [1,2,3]triazolo[4,5-b]pyridin-1-io 3-oxide hexafluorophosphate (187 mg, 491 μmol) and triethylamine (160 μl , 1.1 mmol) were added. After stirring for 15 minutes, pyrrolidine (38 μl, 450 μmol) was added and the reaction mixture was stirred at room temperature overnight. The reaction mixture was mixed with water and ethyl acetate. The organic phase was removed and the aqueous phase was extracted three times with ethyl acetate. The combined organic phases were washed with saturated aqueous sodium chloride solution, dried over sodium sulfate and filtered, and the filtrate was concentrated. The residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/gradient water). The fractions containing the product were concentrated under reduced pressure and 92.4 mg (64% possibility) of the title compound were obtained. LC-MS (Method 3): Rt = 1.42 min; MS (ESIpos): m /z = 381 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: 1.766 (1.04), 1.782 (4.19), 1.799 (7.77), 1.816 (6.67 ), 1,832 (2.28), 1,887 (2.03), 1,903 (6.44), 1,920 (8.25), 1,937 (4.97), 1,954 (1.24), 2,349 (0.56), 2,360 (1.57), 2,365 (1.56), 2,380 (2.45 ), 2,387 (1.96), 2,397 (2.42), 2,408 (1.49), 2,417 (1.09), 2,650 (0.53), 2,672 (1.15), 2,691 (2.65), 2,712 (5.74), 2,722 (2.89), 2,733 (6.33 ), 2.740 (4.71), 2.749 (1.93), 2.767 (2.15), 2.774 (2.86), 2.781 (2.42), 2.797 (1.52), 2.804 (2.59), 2.818 (0.67), 2.826 (1.87), 2.848 (0.50 ), 3.265 (0.75), 3.282 (1.61), 3.295 (3.42), 3.330 (7.74), 3.348 (2.95), 3.360 (1.63), 3.377 (2.15), 3.394 (3.17), 3.401 (2.24), 3.412 (1.91 ), 3,419 (3.67), 3,436 (1.66), 3,642 (1.70), 3,659 (3.64), 3,667 (1.93), 3,676 (2.05), 3,684 (3.12), 3,701 (1.38), 4,883 (1.04), 4,923 (16.00 ), 4,929 (15.45), 4,946 (4.38), 4,953 (3.12), 4,969 (1.11), 7,540 (2.51), 7,559 (5.89), 7,578 (3.43), 7,597 (5.63), 7,616 (2.78), 7,637 (7.35 ), 7,650 (5.01), 7,669 (2.64).

[01023] Subsequent analyzes of Example 175 showed that the 3H-pyrrolo[2,1-c][1,2,4]triazol-3-one systems undergo partial racemization using HATU and are no longer in the form of the pure enantiomer. Example 56 (5RS)-5-[(3,3-Difluoropyrrolidin-1-yl)carbonyl]-2-(3-fluorobenzyl)-5,6,7,8-tetrahydro[1,2,4]triazole [4,3-a]pyridin-3(2H)-one (racemate)

[01024] (5RS)-2-(3-fluorobenzyl)-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine -5-carboxylic acid hydrochloride (race-mate) (140 mg, 427 μmol) was initially loaded into THF (4.4 mL) at room temperature. Subsequently, 1-[bis(dimethylamino)methylene]-1H-[1,2,3]triazolo[4,5-b]pyridin-1-io 3-oxide hexafluorophosphate (211 mg, 555 μmol) and triethylamine (300 μl, 2.1 mmol) were added. After stirring for 15 minutes, 3,3-difluoropyrrolidine hydrochloride (73.6 mg, 513 μmol) was added and the reaction mixture was stirred at room temperature overnight. The reaction mixture was mixed with water and ethyl acetate. The organic phase was removed and the aqueous phase was extracted three times with ethyl acetate. The combined organic phases were washed with saturated aqueous sodium chloride solution, dried over sodium sulfate and filtered, and the filtrate was concentrated. The residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/gradient water). The fractions containing the product were concentrated under reduced pressure and 103 mg (63% possibility) of the title compound were obtained. LC-MS (Method 3): Rt = 1.36 min; MS (ESIpos): m /z = 381 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.008 (2.16), 0.008 (2.37), 1.676 (0.97), 1.687 ( 0.91), 1.725 (1.22), 1.989 (1.10), 2.000 (1.15), 2.010 (1.23), 2.044 (0.92), 2.052 (0.94), 2.059 (0.96), 2.069 (0.86), 2.079 (0.71), 2.088 ( 0.73), 2.095 (0.65), 2.327 (0.76), 2.366 (0.86), 2.382 (0.86), 2.392 (0.62), 2.411 (0.99), 2.430 (0.96), 2.454 (0.79), 2.522 (2.93), 2.580 ( 2.11), 2.594 (2.22), 2.610 (2.37), 2.624 (1.23), 2.642 (0.57), 2.653 (0.79), 2.669 (1.02), 2.709 (0.62), 3.534 (1.02), 3.541 (1.18), 3.551 ( 1.70), 3.561 (1.83), 3.570 (1.12), 3.580 (1.01), 3.671 (1.12), 3.705 (1.23), 3.745 (0.68), 3.778 (1.44), 3.792 (0.76), 3.811 (2.30), 3.829 ( 0.58), 3.893 (0.57), 3.912 (1.20), 3.931 (0.68), 3.939 (0.83), 3.957 (0.42), 3.993 (0.75), 4.022 (0.50), 4.036 (0.68), 4.149 (0.44), 4.180 ( 0.66), 4.205 (0.68), 4.759 (1.01), 4.769 (1.15), 4.774 (1.33), 4.783 (0.99), 4.843 (16.00), 4.857 (1.28), 7.006 (1.90), 7.030 (1.98), 7.057 ( 2.87), 7.076 (3.29), 7.090 (1.01), 7.106 (1.95), 7.112 (1.82), 7.128 (1.09), 7.134 (1.04), 7.358 (1.62), 7.374 (1.96), 7.378 (2.58), 7.393 ( 2.53), 7.413 (1.28). Example 57 (5RS)-2-[2-(4-Methylphenyl)ethyl]-5-(pyrrolidin-1-ylcarbonyl)-5,6,7,8-tetrahydro[1,2,4]triazolo[4 ,3-a]pyridin-3(2H)-one (racemate)

[01025] (5RS)-2-[2-(4-methylphenyl)ethyl]-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4, 3-a]pyridine-5-carboxylic acid (racemate) (82.0 mg, 100% purity, 272 μmol) was initially loaded into THF (2.8 mL) and 1-[bis(dimethylamino)methylene]-1H -[1,2,3]triazolo[4,5-b]pyridin- 1-io 3-oxide hexafluorophosphate (135 mg, 354 μmol) and triethylamine (190 μl, 1.4 mmol) After stirring at room temperature for 15 minutes, pyrrolidine (27 μl, 330 μmol) was added and the reaction mixture was stirred at room temperature overnight. The solvent was removed under reduced pressure, and the residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/water gradient). HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/gradient water). The fractions containing the product were concentrated under reduced pressure and 77.0 mg (80% possibility) of the title compound were obtained. LC-MS (Method 3): Rt = 1.42 min; MS (ESIpos): m /z = 355 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.150 (0.41), -0.008 (3.12), 0.008 (3.21), 1.714 (0.99) (9.18) (0.94) (0.91), 3.798 (0.57), 4.660 (0.71), 4.675 (0.82), 4.685 (0.62), 7.085 (16.00). Example 58 (5RS)-2-(2-Methylbenzyl)-5-(pyrrolidin-1-ylcarbonyl)-5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a] pyridin-3(2H)-one (racemate)

[01026] (5RS)-2-(4-Methylbenzyl)-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine -5-carboxylic acid (racemate) (80.0 mg, 278 μmol) was initially loaded into THF (3.0 mL) at room temperature. Subsequently, 1-[bis(dimethylamino)methylene]-1H-[1,2,3]triazolo[4,5-b]pyridin-1-io 3-oxide hexafluorophosphate (138 mg, 362 μmol) and triethylamine ( 78 μl, 560 μmol) were added. After stirring for 15 minutes, pyrrolidine (28 μl, 330 μmol) was added and the reaction mixture was stirred at room temperature overnight. The reaction mixture was mixed with water and ethyl acetate. The organic phase was removed and the aqueous phase was extracted three times with ethyl acetate. The combined organic phases were washed with saturated aqueous sodium chloride solution, dried over sodium sulfate and filtered, and the filtrate was concentrated. The residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/gradient water). The fractions containing the product were concentrated under reduced pressure and 42.0 mg (44% possibility) of the title compound were obtained. LC-MS (Method 3): Rt = 1.27 min; MS (ESIpos): m /z = 341 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.008 (0.91), 0.008 (0.90), 1.110 (0.57), 1.680 ( 0.58), 1.703 (1.15), 1.712 (1.23), 1.723 (0.96), 1.756 (0.51), 1.772 (1.74), 1.790 (3.06), 1.807 (2.39), 1.823 (0.69), 1.892 (0.70), 1.909 ( 2.16), 1.925 (2.75), 1.942 (1.76), 1.959 (0.74), 1.973 (0.55), 1.984 (0.98), 1.996 (1.12), 2.008 (0.75), 2.023 (0.80), 2.034 (0.55), 2.040 ( 0.50), 2.049 (0.52), 2.293 (16.00), 2.475 (0.40), 2.574 (0.74), 2.585 (1.41), 2.598 (0.79), 2.627 (0.56), 3.226 (0.42), 3.243 (0.89), 3.255 ( 0.90), 3.272 (1.59), 3.290 (0.88), 3.321 (1.26), 3.340 (1.67), 3.352 (0.61), 3.357 (0.85), 3.369 (0.93), 3.387 (0.43), 3.436 (0.46), 3.454 ( 1.02), 3.461 (0.74), 3.471 (0.62), 3.479 (1.32), 3.496 (0.58), 3.594 (0.60), 3.610 (1.23), 3.619 (0.61), 3.627 (0.71), 3.635 (0.96), 3.652 ( 0.42), 4.727 (1.13), 4.736 (1.29), 4.742 (1.50), 4.751 (1.15), 4.778 (8.67), 7.070 (1.24), 7.088 (2.10), 7.117 (0.63), 7.125 (0.62), 7.131 ( 1.10), 7,139 (1.42), 7,157 (1.70), 7,166 (5.62), 7,180 (1.21), 7,184 (0.89). Example 59 (5RS)-2-[(2-Chloropyridin-4-yl)methyl]-5-(pyrrolidin-1-ylcarbonyl)-5,6,7,8-tetrahydro[1,2,4]triazole [4,3-a]pyridin-3(2H)-one (racemate)

[01027] (5RS)-2-[(2-Chloropyridin-4-yl)methyl]-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[ 4,3-a]pyridine-5-carboxylic acid/trifluoroacetic acid (racemate) (110 mg, 94% purity, 245 μmol) was loaded into THF (2.5 mL) at room temperature. Subsequently, 1-[bis(dimethylamino)methylene]-1H-[1,2,3]triazolo[4,5-b]pyridin-1-io 3-oxide hexafluorophosphate (121 mg, 318 μmol) and triethylamine (170 μl , 1.2 mmol) were added. After stirring for 15 minutes, pyrrolidine (25 μl, 290 μmol) was added and the reaction mixture was stirred at room temperature overnight. The reaction mixture was mixed with water and ethyl acetate. The organic phase was removed and the aqueous phase was extracted three times with ethyl acetate. The combined organic phases were washed with saturated aqueous sodium chloride solution, dried over sodium sulfate and filtered, and the filtrate was concentrated. The residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/gradient water). The fractions containing the product were concentrated under reduced pressure and 10.0 mg (11% possibility) of the title compound were obtained. LC-MS (Method 4): Rt = 0.60 min; MS (ESIpos): m /z = 362 [M+H]+ 1H-NMR (500 MHz, DMSO-d6) δ [ppm]: -0.120 (0.49), -0.007 (3.51), 0.006 (3.30), 0.117 (0.49) (1.95) (1.89) (2.81), 2592 (2.27), 2617 (2.11), 2627 (4.76), 2635 (5.08), 2650 (1.14), 2660 (1.84), 2865 (8.59), 3242 (1.73), 3256 (3.57), 3266 (3.41) (4.16) (4.59) (9.30), 8.378 (9.30). Example 60 (5RS)-2-[(4-Methyl-1,2,5-oxadiazol-3-yl)methyl]-5-(pyrrolidin-1-ylcarbonyl)-5,6,7,8-tetrahydro [1,2,4]triazolo[4,3-a]pyridin-3(2H)-one (racemate)

[01028] (5RS)-2-[(4-Methyl-1,2,5-oxadiazol-3-yl-yl)methyl]-3-oxo- 2,3,5,6,7,8-hexa- hydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylic acid (racemate) (91.0 mg, 326 μmol) was initially loaded into THF (3.0 mL) at room temperature. Subsequently, 1-[bis(dimethylamino)methylene]-1H-[1,2,3]triazolo[4,5-b]pyridin-1-io 3-oxide hexafluorophosphate (161 mg, 424 μmol) and triethylamine (91 μl , 650 μmol) were added. After stirring for 15 minutes, pyrrolidine (33 μl, 390 μmol) was added and the reaction mixture was stirred at room temperature overnight. The reaction mixture was mixed with water and ethyl acetate. The organic phase was removed and the aqueous phase was extracted three times with ethyl acetate. The combined organic phases were washed with saturated aqueous sodium chloride solution, dried over sodium sulfate and filtered, and the filtrate was concentrated. The residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/gradient water). The fractions containing the product were concentrated under reduced pressure and 14.0 mg (13% possibility) of the title compound were obtained. LC-MS (Method 3): Rt = 0.97 min; MS (ESIpos): m /z = 333 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.008 (1.20), 0.008 (1.14), 1.711 (0.58), 1.721 ( 0.49), 1.772 (1.12), 1.790 (2.07), 1.807 (1.67), 1.823 (0.52), 1.891 (0.52), 1.908 (1.52), 1.924 (1.83), 1.941 (1.16), 1.957 (0.46), 1.998 ( 0.83), 2.023 (0.48), 2.289 (16.00), 2.523 (1.52), 2.565 (0.60), 2.582 (0.53), 2.593 (0.89), 2.606 (0.52), 3.238 (0.56), 3.251 (0.62), 3.268 ( 1.07), 3.285 (0.55), 3.328 (1.23), 3.345 (0.59), 3.357 (0.61), 3.449 (0.70), 3.456 (0.52), 3.474 (0.90), 3.490 (0.41), 3.588 (0.43), 3.604 ( 0.83), 3.613 (0.44), 3.621 (0.47), 3.630 (0.66), 4.739 (0.79), 4.748 (0.87), 4.754 (1.02), 4.763 (0.76), 5.087 (4.25), 5.092 (4.25). Example 61 (5RS)-2-[(5-Methyl-1,2-oxazol-3-yl)methyl]-5-(pyrrolidin-1-ylcarbonyl)-5,6,7,8-tetrahydro[1 ,2,4]triazolo[4,3-a]pyridin-3(2H)-one (racemate)

[01029] (5RS)-2-[(5-Methyl-1,2-oxazol-3-yl)methyl]-3-oxo-2,3,5,6,7,8-hexahydro[1, 2,4]triazolo[4,3-a]pyridine-5-carboxylic acid (racemate) (133 mg, 94% purity, 449 μmol) was initially loaded into THF (4.7 mL), and 1-[bis (dimethylamino)methylene]-1H-[1,2,3]triazolo[4,5-b]pyridin-1-io 3-oxide hexafluorophosphate (222 mg, 584 μmol) and triethylamine (310 μl, 2.2 mmol) After stirring at room temperature for 15 minutes, pyrrolidine (45 μl, 540 μmol) was added and the reaction mixture was stirred at room temperature overnight. The solvent was removed under reduced pressure, and the residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/water gradient). HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/gradient water). The fractions containing the product were concentrated under reduced pressure and 18.0 mg (12% possibility) of the title compound were obtained. LC-MS (Method 4): Rt = 0.55 min; MS (ESIpos): m /z = 332 [M+H]+ 1H-NMR (500 MHz, DMSO-d6) δ [ppm]: -0.007 (0.94), 0.006 (0.97), 1.179 (0.41), 1.237 ( 0.58), 1.717 (1.18), 1.763 (0.56), 1.776 (2.23), 1.790 (3.84), 1.804 (2.83), 1.818 (0.75), 1.899 (0.86), 1.912 (2.55), 1.925 (3.24), 1.939 ( 2.02), 1.952 (0.90), 1.981 (0.90), 2.007 (0.47), 2.015 (0.60), 2.027 (0.77), 2.036 (0.64), 2.042 (0.66), 2.048 (0.64), 2.201 (1.16), 2.361 ( 1.31), 2,370 (15.57), 2,371 (16.00), 2,518 (3.75), 2,522 (3.17), 2,567 (0.92), 2,591 (0.79), 2,600 (1.50), 2,610 (0.86), 2,635 (1.63), 2.865 ( 1.80), 3.232 (0.54), 3.245 (1.12), 3.255 (1.05), 3.269 (1.84), 3.283 (1.07), 3.342 (2.62), 3.352 (1.14), 3.356 (1.29), 3.366 (1.44), 3.380 ( 0.69), 3.444 (0.60), 3.457 (1.24), 3.463 (0.90), 3.471 (0.75), 3.477 (1.59), 3.491 (0.71), 3.594 (0.69), 3.607 (1.46), 3.614 (0.77), 3.621 ( 0.86), 3.628 (1.16), 3.641 (0.51), 4.717 (1.24), 4.724 (1.48), 4.729 (1.63), 4.736 (1.35), 4.781 (0.66), 4.813 (5.96), 4.819 (6.01), 4.851 ( 0.64), 6.062 (4.18). Example 62 (5RS)-2-[(1-Methyl-1H-benzimidazol-2-yl)methyl]-5-(pyrrolidin-1-ylcarbonyl)-5,6,7,8-tetrahydro[1,2 ,4]triazolo[4,3-a]pyridin-3(2H)-one (racemate)

[01030] (5RS)-2-[(1-Methyl-1H-benzimidazol-2-yl)methyl]-3-oxo-2,3,5,6,7,8-hexahydro[1,2, 4]triazolo[4,3-a]pyridine-5-carboxylic acid (racemate) (120 mg, 367 μmol) was dissolved in DMF (2.8 mL) at room temperature. Subsequently, 1-[bis(dimethylamino)methylene]- 1H-[1,2,3]triazolo[4,5-b]pyridin-1-io 3-oxide hexafluorophosphate (181 mg, 477 μmol) and triethylamine (200 μl , 1.5 mmol) were added. After stirring for 15 minutes, pyrrolidine (37 μl, 440 μmol) was added and the reaction mixture was stirred at room temperature overnight. 1-[Bis(dimethylamino)methylene]-1H-[1,2,3]triazolo[4,5-b]pyridin-1-io 3-oxide hexafluorophosphate (139 mg, 367 μmol) and pyrrolidine (31 μl, 367 μmol) were added again, and the mixture was stirred at room temperature for 2 hours. The reaction mixture was mixed with water and ethyl acetate. The organic phase was removed and the aqueous phase was extracted three times with ethyl acetate. The combined organic phases were washed with saturated aqueous sodium chloride solution, dried over sodium sulfate and filtered, and the filtrate was concentrated. The residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/gradient water). The fractions containing the product were concentrated under reduced pressure and 46.0 mg (33% possibility) of the title compound were obtained. LC-MS (Method 3): Rt = 0.83 min; MS (ESIpos): m /z = 381 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.008 (0.51), 0.008 (0.44), 1.653 (0.44), 1.667 ( 0.48), 1.677 (0.52), 1.690 (0.67), 1.702 (0.81), 1.712 (0.59), 1.725 (0.41), 1.777 (1.23), 1.795 (2.26), 1.812 (1.88), 1.829 (0.60), 1.897 ( 0.57), 1.914 (1.73), 1.931 (2.23), 1.947 (1.48), 1.964 (0.58), 1.977 (0.48), 1.987 (0.82), 1.997 (1.01), 2.006 (0.73), 2.022 (0.56), 2.033 ( 0.46), 2.040 (0.44), 2.048 (0.42), 2.518 (1.12), 2.566 (1.13), 2.578 (0.64), 2.608 (0.40), 3.245 (0.71), 3.258 (0.74), 3.275 (1.21), 3.292 ( 0.62), 3.324 (0.72), 3.342 (1.30), 3.354 (0.50), 3.360 (0.67), 3.372 (0.73), 3.459 (0.82), 3.466 (0.60), 3.476 (0.51), 3.483 (1.02), 3.501 ( 0.45), 3.604 (0.47), 3.620 (1.00), 3.628 (0.51), 3.637 (0.58), 3.645 (0.78), 3.755 (16.00), 4.749 (0.91), 4.758 (1.02), 4.764 (1.18), 4.772 ( 0.87), 5.072 (1.17), 5.111 (3.74), 5.139 (3.71), 5.178 (1.17), 7.172 (0.65), 7.175 (0.66), 7.192 (1.54), 7.209 (1.33), 7.212 (1.19), 7.233 ( 1.09), 7.236 (1.14), 7.253 (1.60), 7.271 (0.78), 7.273 (0.68), 7.524 (1.79), 7.544 (1.56), 7.582 (1.63), 7.602 (1.52). Example 63 (5RS)-2-[4-Methoxy-3-(trifluoromethoxy)benzyl]-5-(pyrrolidin-1-ylcarbonyl)-5,6,7,8-tetrahydro[1,2,4]triazole [4,3-a]pyridin-3(2H)-one (racemate)

[01031] (5RS)-2-[4-Methoxy-3-(trifluoromethyl)benzyl]-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[ 4,3-a]pyridine-5-carboxylic acid (racemate) (75.0 mg, 202 μmol) was initially loaded into THF (2.3 mL) at room temperature. Subsequently, 1-[bis(dimethylamino)methylene]-1H-[1,2,3]triazolo[4,5-b]pyridin-1-io 3-oxide hexafluorophosphate (99.8 mg, 263 μmol) and triethylamine (140 μl, 1.0 mmol) were added. After stirring for 15 minutes, pyrrolidine (20 μl, 240 μmol) was added and the reaction mixture was stirred at room temperature overnight. The reaction mixture was mixed with water and ethyl acetate. The organic phase was removed and the aqueous phase was extracted three times with ethyl acetate. The combined organic phases were washed with saturated aqueous sodium chloride solution, dried over sodium sulfate and filtered, and the filtrate was concentrated. The residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/gradient water). The fractions containing the product were concentrated under reduced pressure and 40.0 mg (47% possibility) of the title compound were obtained. LC-MS (Method 4): Rt = 0.81 min; MS (ESIpos): m /z = 425 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.008 (1.02), 0.008 (0.93), 1.674 (0.45), 1.697 ( 0.88), 1.708 (0.99), 1.719 (0.77), 1.755 (0.43), 1.773 (1.40), 1.790 (2.47), 1.807 (1.91), 1.824 (0.55), 1.892 (0.61), 1.909 (1.78), 1.925 ( 2.25), 1.942 (1.58), 1.960 (0.51), 1.967 (0.47), 1.978 (0.78), 1.990 (0.76), 2.005 (0.53), 2.020 (0.62), 2.030 (0.44), 2.036 (0.41), 2.046 ( 0.43), 2.073 (0.94), 2.519 (1.40), 2.561 (0.63), 2.576 (0.59), 2.588 (1.12), 2.600 (0.62), 2.630 (0.44), 2.865 (0.45), 3.240 (0.73), 3.253 ( 0.72), 3.269 (1.28), 3.287 (0.68), 3.322 (1.06), 3.341 (1.35), 3.352 (0.53), 3.358 (0.70), 3.370 (0.77), 3.449 (0.83), 3.457 (0.61), 3.467 ( 0.49), 3.474 (1.05), 3.491 (0.46), 3.592 (0.48), 3.608 (1.00), 3.616 (0.50), 3.625 (0.57), 3.633 (0.77), 3.871 (16.00), 4.726 (0.91), 4.735 ( 1.03), 4.741 (1.21), 4.750 (0.90), 4.807 (4.91), 7.227 (1.60), 7.248 (1.89), 7.477 (1.19), 7.498 (1.06), 7.519 (2.24). Example 64 (5RS)-2-[(1-Methyl-1H-indazol-5-yl)methyl]-5-(pyrrolidin-1-ylcarbonyl)-5,6,7,8-tetrahydro[1,2 ,4]triazolo[4,3-a]pyridin-3(2H)-one (racemate)

[01032] (5RS)-2-[(1-Methyl-1H-indazol-5-yl)methyl]-3-oxo-2,3,5,6,7,8-hexahydro[1,2, 4]triazolo[4,3-a]pyridine-5-carboxylic acid (racemate) (65.0 mg, 199 μmol) was initially loaded into THF (2.3 mL) at room temperature. Subsequently, 1-[bis(dimethylamino)methylene]-1H-[1,2,3]triazolo[4,5-b]pyridin-1-io 3-oxide hexafluorophosphate (98.2 mg, 258 μmol) and triethylamine (140 μl, 990 μmol) were added. After stirring for 15 minutes, pyrrolidine (20 μl, 240 μmol) was added and the reaction mixture was stirred at room temperature overnight. The reaction mixture was mixed with water and ethyl acetate. The organic phase was removed and the aqueous phase was extracted three times with ethyl acetate. The combined organic phases were washed with saturated aqueous sodium chloride solution, dried over sodium sulfate and filtered, and the filtrate was concentrated. The residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/gradient water). The fractions containing the product were concentrated under reduced pressure and 26.0 mg (34% possibility) of the title compound were obtained. LC-MS (Method 3): Rt = 1.04 min; MS (ESIpos): m /z = 381 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.008 (1.76), 0.008 (1.67), 1.681 (0.57), 1.691 ( 0.92), 1.704 (1.22), 1.717 (0.94), 1.775 (1.31), 1.792 (2.33), 1.809 (1.80), 1.826 (0.53), 1.894 (0.59), 1.911 (1.69), 1.928 (2.24), 1.945 ( 1.49), 1.962 (0.71), 1.972 (0.74), 1.984 (0.67), 1.993 (0.54), 2.007 (0.47), 2.018 (0.55), 2.028 (0.45), 2.043 (0.42), 2.072 (0.79), 2.523 ( 1.39), 2.567 (0.67), 2.579 (1.17), 2.591 (0.61), 2.621 (0.45), 2.865 (0.91), 3.244 (0.73), 3.257 (0.73), 3.273 (1.25), 3.291 (0.83), 3.331 ( 0.80), 3.349 (1.31), 3.361 (0.51), 3.367 (0.68), 3.379 (0.74), 3.456 (0.79), 3.463 (0.57), 3.473 (0.48), 3.480 (1.00), 3.497 (0.44), 3.597 ( 0.45), 3.614 (0.97), 3.622 (0.48), 3.631 (0.54), 3.639 (0.75), 4.021 (16.00), 4.723 (0.86), 4.732 (0.98), 4.739 (1.17), 4.747 (0.84), 4.841 ( 0.57), 4.879 (2.97), 4.894 (2.98), 4.932 (0.56), 7.280 (1.34), 7.284 (1.16), 7.302 (1.36), 7.305 (1.54), 7.581 (1.86), 7.604 (4.27), 8.009 ( 2.76). Example 65 (5RS)-2-[2,5-Bis(trifluoromethyl)benzyl]-5-(pyrrolidin-1-ylcarbonyl)-5,6,7,8-tetrahydro[1,2,4]triazolo[ 4,3-a]pyridin-3(2H)-one (racemate)

[01033] (5RS)-2-[2,5-bis(trifluoromethyl)benzyl]-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4 ,3-a]pyridine-5-carboxylic acid (racemate) (50.0 mg, 122 μmol) was initially loaded into THF (2.0 mL), and 1-[bis(dimethylamino)methylene]-1H-[1 ,2,3]triazolo[4,5-b]pyridin-1-io 3-oxide hexafluorophosphate (60.4 mg, 159 μmol) and triethylamine (51 μl, 370 μmol) were subsequently added. After stirring at room temperature for 15 min, pyrrolidine (10.4 mg, 147 μmol) was added, and the reaction mixture was stirred at room temperature for 48 hours. The solvent was removed under reduced pressure, and the residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/water gradient). HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/gradient water). The fractions containing the product were concentrated under reduced pressure and 18.2 mg (32% possibility) of the title compound were obtained. LC-MS (Method 3): Rt = 1.72 min; MS (ESIpos): m /z = 463 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (0.98), -0.008 (11.17), 0.008 (8.68), 0.146 (1.03) (6.13) (3.04) (2.60) (3.74) (3.15), 4,794 (3.53), 4,800 (4.34), 4,808 (3.04), 5,077 (16.00), 7,654 (7.27), 7,917 (2.98), 7,938 (4.56), 8,013 (6.40), 8,034 (4.23). Example 66 (5RS)-2-[4-Fluoro-3-(trifluoromethoxy)benzyl]-5-(pyrrolidin-1-ylcarbonyl)-5,6,7,8-tetrahydro[1,2,4]triazole [4,3-a]pyridin-3(2H)-one (racemate)

[01034] (5RS)-2-[4-Fluoro-3-(trifluoromethyl)benzyl]-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[ 4,3-a]pyridine-5-carboxylic acid (racemate) (50.0 mg, 139 μmol) was initially loaded into THF (2.0 mL), and 1-[bis(dimethylamino)methylene]-1H-[ 1,2,3]triazolo[4,5-b]pyridin-1-io 3-oxide hexafluorophosphate (68.8 mg, 181 μmol) and triethylamine (58 μl, 420 μmol) were subsequently added. After stirring at room temperature for 15 minutes, pyrrolidine (11.9 mg, 167 μmol) was added and the reaction mixture was stirred at room temperature overnight. 1-[Bis(dimethylamino)methylene]-1H-[1,2,3]triazolo[4,5- b]pyridin-1-io 3-oxide hexafluorophosphate (68.8 mg, 181 μmol), pyrrolidine (11, 9 mg, 167 μmol) and triethylamine (58 μl, 420 μmol) were added again, and the mixture was stirred at room temperature for 48 hours. The solvent was removed under reduced pressure, and the residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/water gradient). HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/gradient water). The fractions containing the product were concentrated under reduced pressure and 25.6 mg (45% possibility) of the title compound were obtained. LC-MS (Method 3): Rt = 1.53 min; MS (ESIpos): m /z = 413 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (0.40), -0.008 (3.74), 0.008 (3.05), 0.146 (0.40) (6.75), 1807 (5.19), 1824 (1.46), 1892 (1.79), 1909 (4.77), 1925 (5.75), 1942 (3.51), 1958 (1.44), 1982 (1.14), 1992 (2.02), 2004 (2.51), 2014 (1.72), 2030 (1.46), 2041 (1.16), 2048 (1.16), 2056 (1.11), 2065 (0.58), 2323 (0.49), 2327 (0.67), 2332 (0.47), 2366 (0.58) (0.58), 2669 (0.72), 2674 (0.53), 2710 (0.63), 2865 (3.96), 3225 (0.96), 3242 (2.02), 3255 (1.96), 3272 (3.58), 3289 (2.11), 3340 (3.82), 3.351 (1.54), 3.357 (1.98), 3.369 (2.14), 3.387 (0.93), 3.435 (1.04), 3.452 (2.28), 3.460 (1.63), 3.470 (1.35), 3.477 (2.86), 3.494 (1.25) (2.39) (0.98), 7,600 (1.00), 7,669 (2.53), 7,674 (2.37), 7,687 (2.60). Example 67 (5RS)-2-[3-Fluoro-4-(trifluoromethoxy)benzyl]-5-(pyrrolidin-1-ylcarbonyl)-5,6,7,8-tetrahydro[1,2,4]triazole [4,3-a]pyridin-3(2H)-one (racemate)

[01035] (5RS)-2-[3-Fluoro-4-(trifluoromethoxy)benzyl]-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[ 4,3-a]pyridine-5-carboxylic acid (racemate) (80.0 mg, 213 μmol) was initially loaded into THF (2.0 mL) at room temperature. Subsequently, 1-[bis(dimethylamino)methylene]-1H-[1,2,3]triazolo[4,5-b]pyridin-1-io 3-oxide hexafluorophosphate (105 mg, 277 μmol) and triethylamine (89 μl , 640 μmol) were added. After stirring for 15 minutes, pyrrolidine (21 μl, 260 μmol) was added and the reaction mixture was stirred at room temperature overnight. The reaction mixture was mixed with water and ethyl acetate. The organic phase was removed and the aqueous phase was extracted three times with ethyl acetate. The combined organic phases were washed with saturated aqueous sodium chloride solution, dried over sodium sulfate and filtered, and the filtrate was concentrated. The residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/gradient water). The fractions containing the product were concentrated under reduced pressure and 45.0 mg (49% possibility) of the title compound were obtained. LC-MS (Method 4): Rt = 0.88 min; MS (ESIpos): m /z = 429 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.008 (1.37), 0.008 (1.36), 1.662 (0.74), 1.669 ( 0.77), 1.681 (1.08), 1.695 (1.22), 1.704 (1.35), 1.717 (1.75), 1.728 (2.05), 1.737 (1.56), 1.757 (1.39), 1.774 (4.00), 1.791 (6.45), 1.809 ( 4.96), 1.818 (1.10), 1.826 (1.95), 1.836 (1.76), 1.844 (0.70), 1.854 (0.69), 1.893 (1.41), 1.910 (4.09), 1.926 (5.10), 1.943 (3.12), 1.960 ( 1.11), 1.979 (0.73), 1.993 (1.14), 2.003 (2.00), 2.015 (2.49), 2.024 (1.73), 2.040 (1.41), 2.051 (1.14), 2.059 (1.12), 2.066 (1.07), 2.074 ( 0.68), 2.559 (1.84), 2.570 (1.70), 2.584 (1.52), 2.599 (1.51), 2.611 (2.77), 2.623 (1.59), 2.641 (0.71), 2.653 (1.09), 2.665 (0.70), 3.095 ( 0.74), 3.232 (0.86), 3.248 (1.81), 3.261 (1.80), 3.278 (3.18), 3.295 (1.57), 3.329 (1.65), 3.346 (3.24), 3.358 (1.22), 3.364 (1.70), 3.376 ( 1.90), 3.394 (0.86), 3.441 (0.95), 3.459 (2.08), 3.466 (1.55), 3.476 (1.27), 3.484 (2.68), 3.501 (1.19), 3.593 (1.23), 3.610 (2.48), 3.618 ( 1.30), 3.626 (1.47), 3.634 (1.92), 3.651 (0.90), 4.747 (2.31), 4.756 (2.57), 4.761 (3.04), 4.771 (2.27), 4.879 (16.00), 7.160 (2.64), 7.182 ( 2.97), 7.303 (2.85), 7.308 (2.71), 7.331 (2.93), 7.336 (2.75), 7.537 (1.68), 7.557 (3.12), 7.577 (1.50). Example 68 (5RS)-2-{[3-Chloro-5-(trifluoromethyl)pyridin-2-yl]methyl}-5-(pyrrolidin-1-ylcarbonyl)-5,6,7,8-tetrahydro[ 1,2,4]triazolo[4,3-a]pyridin-3(2H)-one (racemate)

[01036] (5RS)-2-{[3-Chloro-5-(trifluoromethyl)pyridin-2-yl]methyl}-3-oxo-2,3,5,6,7,8-hexahydro[1 ,2,4]triazolo[4,3-a]pyridine-5-carboxylic acid (racemate) (80.0 mg, 212 μmol) was initially loaded into THF (2.0 mL) at room temperature. Subsequently, 1-[bis(dimethylamino)methylene]-1H-[1,2,3]triazolo[4,5-b]pyridin-1-io 3-oxide hexafluorophosphate (105 mg, 276 μmol) and triethylamine (89 μl , 640 μmol) were added. After stirring for 15 minutes, pyrrolidine (21 μl, 250 μmol) was added and the reaction mixture was stirred at room temperature overnight. The reaction mixture was mixed with water and ethyl acetate. The organic phase was removed and the aqueous phase was extracted three times with ethyl acetate. The combined organic phases were washed with saturated aqueous sodium chloride solution, dried over sodium sulfate and filtered, and the filtrate was concentrated. The residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/gradient water). The fractions containing the product were concentrated under reduced pressure and 62.0 mg (68% possibility) of the title compound were obtained. LC-MS (Method 4): Rt = 0.75 min; MS (ESIpos): m /z = 430 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (0.57), -0.008 (5.51), 0.008 (4.76), 0.146 (0.58) (14.82) 5 (4.19) (1.94) (0.57) (4.42) (2.96) (15.54), 5,175 (4.67), 8,486 (11.75), 8,490 (11.76), 8,903 (11.49), 8,906 (11.69). Example 69 (5RS)-5-(Pyrrolidin-1-ylcarbonyl)-2-({5-[3-(trifluoromethyl)phenyl]-1,2,4-oxadiazol-3-yl}methyl)-5,6, 7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one (racemate)

[01037] (5RS)-3-Oxo-2-({-5-[3-(trifluoromethyl)phenyl]-1,2,4-oxadiazol-3-yl}methyl)-2,3,5,6, 7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylic acid (racemate) (70.0 mg, 88% purity, 151 μmol) was initially loaded into THF (2.0 mL) at room temperature. Subsequently, 1-[bis(dimethylamino)methylene]-1H-[1,2,3]triazolo[4,5-b]pyridin-1-io 3-oxide hexafluorophosphate (74.7 mg, 197 μmol) and triethylamine (63 μl, 450 μmol) were added. After stirring for 15 minutes, pyrrolidine (12.9 mg, 181 μmol) was added and the reaction mixture was stirred at room temperature overnight. The reaction mixture was mixed with water and ethyl acetate. The organic phase was removed and the aqueous phase was extracted three times with ethyl acetate. The combined organic phases were washed with saturated aqueous sodium chloride solution, dried over sodium sulfate and filtered, and the filtrate was concentrated. The residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/gradient water). The fractions containing the product were concentrated under reduced pressure and 27.6 mg (39% possibility) of the title compound were obtained. LC-MS (Method 3): Rt = 1.57 min; MS (ESIpos): m /z = 463 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (1.57), -0.008 (14.76), 0.008 (12.96), 0.146 (1.57) (9.52) (1.39) (1.84) (5.47) (2.02) (5.13) (4.53), 8,333 (8.39), 8,394 (5.43), 8,413 (5.17). Example 70 (5RS)-2-[(1-Ethyl-1H-imidazol-2-yl)methyl]-5-(pyrrolidin-1-ylcarbonyl)-5,6,7,8-tetrahydro[1,2 ,4]triazolo[4,3-a]pyridin-3(2H)-one (racemate)

[01038] (5RS)-2-[(1-Ethyl-1H-imidazol-2-yl)methyl]-3-oxo-2,3,5,6,7,8-hexahydro[1,2, 4]triazolo[4,3-a]pyridine-5-carboxylic acid (racemate) (80.0 mg, 60% purity, 165 μmol) was initially loaded into DMF (2.0 mL), and 1-[bis (dimethylamino)methylene]-1H-[1,2,3]triazolo[4,5- b]pyridin-1-io 3-oxide hexafluorophosphate (81.4 mg, 214 μmol) and triethylamine (92 μl, 660 μmol) were subsequently added. After stirring at room temperature for 15 minutes, pyrrolidine (17 μl, 200 μmol) was added and the reaction mixture was stirred at room temperature overnight. 1- [Bis(dimethylamino)methylene]-1H-[1,2,3]triazolo[4,5-b]pyridin-1-io 3-oxide hexafluorophosphate (63.8 mg, 165 μmol) and pyrrolidine (14 μl , 165 μmol) were added again, and the mixture was stirred at room temperature for 2 hours. The solvent was removed under reduced pressure, and the residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/water gradient). HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/gradient water). The fractions containing the product were concentrated under reduced pressure and 6.00 mg (11% possibility) of the title compound were obtained. LC-MS (Method 9): Rt = 3.74 min; MS (ESIpos): m /z = 345 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.008 (3.41), 0.008 (2.88), 1.300 (7.13), 1.319 ( 16.00), 1.337 (7.18), 1.655 (0.66), 1.666 (0.90), 1.679 (0.96), 1.691 (0.97), 1.705 (1.24), 1.717 (1.47), 1.729 (1.20), 1.757 (1.00), 1.774 ( 2.92), 1.791 (4.94), 1.808 (3.77), 1.825 (1.17), 1.894 (1.99), 1.910 (3.30), 1.927 (3.65), 1.943 (2.23), 1.961 (1.03), 1.975 (0.56), 1.988 ( 1.00), 1.999 (2.36), 2.009 (2.34), 2.023 (1.62), 2.034 (0.90), 2.040 (0.83), 2.049 (0.76), 2.072 (0.41), 2.322 (0.52), 2.327 (0.66), 2.332 ( 0.51), 2.366 (0.54), 2.518 (3.41), 2.523 (2.61), 2.561 (1.55), 2.576 (1.19), 2.592 (1.19), 2.605 (2.17), 2.617 (1.20), 2.634 (0.58), 2.646 ( 0.89), 2660 (0.62), 2665 (0.63), 2669 (0.75), 2674 (0.55), 2689 (0.58), 2710 (0.54), 2865 (13.73), 3219 (0.78), 3236 (1.55), 3249 ( 1.78), 3.266 (3.05), 3.283 (1.95), 3.298 (2.44), 3.315 (4.95), 3.334 (6.17), 3.345 (6.63), 3.445 (0.99), 3.462 (1.79), 3.469 (1.41), 3.479 ( 1.11), 3.487 (2.22), 3.504 (1.00), 3.581 (1.00), 3.597 (1.93), 3.606 (1.03), 3.614 (1.16), 3.622 (1.45), 3.639 (0.68), 4.145 (1.55), 4.162 ( 4.11), 4.180 (3.94), 4.183 (3.94), 4.200 (1.38), 4.728 (1.76), 4.738 (2.03), 4.743 (2.55), 4.753 (1.68), 5.163 (1.06), 5.204 (6.89), 5.216 ( 6.69), 5.257 (1.06), 6.939 (0.66), 7.066 (0.68), 7.194 (0.65), 7.642 (3.94), 7.646 (3.98), 7.776 (4.66), 7.780 (4.28). Example 71 (5RS)-2-[2-Fluoro-3-(trifluoromethoxy)benzyl]-5-(pyrrolidin-1-ylcarbonyl)-5,6,7,8-tetrahydro[1,2,4]triazole [4,3-a]pyridin-3(2H)-one (racemate)

[01039] (5RS)-2-[2-Fluoro-3-(trifluoromethyl)benzyl]-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[ 4,3-a]pyridine-5-carboxylic acid (racemate) (80.0 mg, 223 μmol) was initially loaded into THF (2.0 mL) at room temperature. Subsequently, 1-[bis(dimethylamino)methylene]- 1H-[1,2,3]triazolo[4,5-b]pyridin-1-io 3-oxide hexafluorophosphate (110 mg, 289 μmol) and triethylamine (93 μl , 670 μmol) were added. After stirring for 15 minutes, pyrrolidine (22 μl, 270 μmol) was added and the reaction mixture was stirred at room temperature overnight. The reaction mixture was mixed with water and ethyl acetate. The organic phase was removed and the aqueous phase was extracted three times with ethyl acetate. The combined organic phases were washed with saturated aqueous sodium chloride solution, dried over sodium sulfate and filtered, and the filtrate was concentrated. The residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/gradient water). The fractions containing the product were concentrated under reduced pressure and 55.0 mg (60% possibility) of the title compound were obtained. LC-MS (Method 3): Rt = 1.50 min; MS (ESIpos): m /z = 413 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.150 (0.92), 0.008 (8.29), 0.146 (1.03), 1.693 ( 3.76), 1.704 (5.42), 1.717 (6.38), 1.755 (3.06), 1.773 (9.29), 1.790 (16.00), 1.807 (12.53), 1.824 (3.65), 1.892 (3.91), 1.909 (11.28), ( 14.08), 1,942 (9.14), 1,960 (3.91), 1,988 (5.09), 2,030 (3.91), 2,073 (3.21), 2,328 (2.40), 2,367 (1.18), 2,559 (5.86), 2,573 (4.20), 2,588 ( 4.06), 2600 (7.48), 2613 (4.20), 2642 (2.91), 2669 (2.54), 2690 (1.25), 2710 (1.40), 3227 (2.43), 3243 (4.53), 3256 (4.57), 3273 ( 8.00), 3290 (4.39), 3325 (5.31), 3343 (8.41), 3361 (4.50), 3372 (4.94), 3391 (2.03), 3436 (2.43), 3454 (5.05), 3461 (4.02), 3479 ( 6.86), 3.496 (3.02), 3.590 (3.13), 3.607 (6.30), 3.623 (3.76), 3.632 (4.90), 3.649 (2.18), 4.737 (5.82), 4.747 (6.67), 4.752 (8.04), 4.761 ( 5.68) ( 7.63), 7,590 (3.65), 7,720 (4.13), 7,736 (7.82), 7,756 (3.91). Example 72 (5RS)-2-[3-Fluoro-5-(trifluoromethoxy)benzyl]-5-(pyrrolidin-1-ylcarbonyl)-5,6,7,8-tetrahydro[1,2,4]triazole [4,3-a]pyridin-3(2H)-one (racemate)

[01040] (5RS)-2-[3-Fluoro-5-(trifluoromethyl)benzyl]-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[ 4,3-a]pyridine-5-carboxylic acid (racemate) (80.0 mg, 223 μmol) was initially loaded into THF (2.0 mL) at room temperature. Subsequently, 1-[bis(dimethylamino)methylene]-1H-[1,2,3]triazolo[4,5-b]pyridin-1-io 3-oxide hexafluorophosphate (110 mg, 289 μmol) and triethylamine ( 93 μl, 670 μmol) were added. After stirring for 15 minutes, pyrrolidine (22 μl, 270 μmol) was added and the reaction mixture was stirred at room temperature overnight. The reaction mixture was mixed with water and ethyl acetate. The organic phase was removed and the aqueous phase was extracted three times with ethyl acetate. The combined organic phases were washed with saturated aqueous sodium chloride solution, dried over sodium sulfate and filtered, and the filtrate was concentrated. The residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/gradient water). The fractions containing the product were concentrated under reduced pressure and 48.0 mg (52% possibility) of the title compound were obtained. LC-MS (Method 3): Rt = 1.55 min; MS (ESIpos): m /z = 413 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.008 (3.15), 0.008 (2.63), 1.690 (1.16), 1.701 ( 1.12), 1.728 (1.86), 1.740 (1.51), 1.755 (1.38), 1.774 (4.07), 1.791 (6.54), 1.809 (5.03), 1.825 (1.42), 1.893 (1.52), 1.910 (4.33), 1.927 ( 5.32), 1943 (3.23), 1961 (1.03), 1972 (0.74), 2019 (2.53), 2028 (1.84), 2043 (1.33), 2054 (1.16), 2062 (1.14), 2073 (1.44), 2327 ( 0.72), 2.563 (2.11), 2.574 (1.91), 2.589 (1.64), 2.604 (1.57), 2.616 (2.72), 2.628 (1.55), 2.646 (0.75), 2.657 (1.15), 2.670 (1.25), 2.710 ( 0.45), 2.865 (0.60), 3.231 (0.84), 3.247 (1.83), 3.260 (1.90), 3.277 (3.31), 3.294 (1.92), 3.326 (1.93), 3.344 (3.35), 3.361 (1.78), 3.373 ( 1.90), 3.391 (0.87), 3.439 (0.94), 3.457 (2.17), 3.464 (1.54), 3.482 (2.73), 3.499 (1.19), 3.595 (1.24), 3.611 (2.50), 3.620 (1.31), 3.628 ( 1.51), 3.636 (1.92), 3.653 (0.88), 4.761 (2.42), 4.770 (2.59), 4.776 (3.10), 4.785 (2.31), 4.959 (16.00), 7.329 (2.37), 7.352 (2.34), 7.502 ( 5.85), 7.601 (2.38), 7.623 (2.42). Example 73 (5RS)-2-[3-Chloro-4-(trifluoromethoxy)benzyl]-5-(pyrrolidin-1-ylcarbonyl)-5,6,7,8-tetrahydro[1,2,4]triazole [4,3-a]pyridin-3(2H)-one (racemate)

[01041] (5RS)-2-[3-Chloro-4-(trifluoromethoxy)benzyl]-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[ 4,3-a]pyridine-5-carboxylic acid (racemate) (75.0 mg, 95% purity, 182 μmol) was initially loaded into THF (2.1 mL) at room temperature. Subsequently, 1-[bis(dimethylamino)methylene]-1H-[1,2,3]triazolo[4,5-b]pyridin-1-io 3-oxide hexafluorophosphate (89.9 mg, 236 μmol) and triethylamine ( 130 μl, 910 μmol) were added. After stirring for 15 minutes, pyrrolidine (18 μl, 220 μmol) was added and the reaction mixture was stirred at room temperature overnight. The reaction mixture was mixed with water and ethyl acetate. The organic phase was removed and the aqueous phase was extracted three times with ethyl acetate. The combined organic phases were washed with saturated aqueous sodium chloride solution, dried over sodium sulfate and filtered, and the filtrate was concentrated. The residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/gradient water). The fractions containing the product were concentrated under reduced pressure and 41.0 mg (51% possibility) of the title compound were obtained. LC-MS (Method 3): Rt = 1.69 min; MS (ESIpos): m /z = 445 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (0.80), -0.008 (6.96), 0.008 (5.94), 0.146 (0.78) (2.67) (1.21) (0.93), 2665 (1.28), 2669 (1.34), 2710 (0.59), 2865 (0.45), 3229 (0.69), 3246 (1.58), 3258 (1.52), 3275 (2.71), 3293 (1.56), 3329 (1.50), 3347 (2.73), 3365 (1.47), 3377 (1.61), 3394 (0.74), 3438 (0.78), 3456 (1.76), 3464 (1.28), 3473 (1.06), 3481 (2.25), 3498 (0.95) (2.10) (4.92), 7,547 (2.99), 7,551 (2.88), 7,569 (2.47), 7,572 (2.41). Example 74 (5RS)-5-(Pyrrolidin-1-ylcarbonyl)-2-{[2-(trifluoromethyl)pyridin-4-yl]methyl}-5,6,7,8-tetrahydro[1,2, 4]triazolo[4,3-a]pyridin-3(2H)-one (enantiomer 1)

[01042] (5RS)-3-Oxo-2-{[24-(trifluoromethyl)pyridin-4-yl]methyl}-2,3,5,6,7,8-hexahydro[1,2,4 ]triazolo[4,3-a]pyridine-5-carboxylic acid (enantiomer 1) (70.0 mg, 205 μmol) was initially loaded into THF (2 mL) at room temperature. Subsequently, 1-[bis(dimethylamino)methylene]-1H-[1,2,3]triazolo[4,5-b]pyridin-1-io 3-oxide hexafluorophosphate (97.1 mg, 255 μmol) and triethylamine ( 82 μl, 590 μmol) were added. After stirring for 15 minutes, pyrrolidine (20 μl, 240 μmol) was added and the reaction mixture was stirred at room temperature overnight. The reaction mixture was mixed with water and ethyl acetate. The organic phase was removed and the aqueous phase was extracted three times with ethyl acetate. The combined organic phases were washed with saturated aqueous sodium chloride solution, dried over sodium sulfate and filtered, and the filtrate was concentrated. The residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/gradient water). The fractions containing the product were concentrated under reduced pressure and 66.0 mg (85% possibility) of the title compound were obtained. LC-MS (Method 3): Rt = 1.18 min; MS (ESIpos): m /z = 396 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.008 (1.82), 0.008 (1.91), 1.663 (0.97), 1.683 ( 1.29) 1.68), 1.910 (4.88), 1.927 (6.01), 1.943 (3.66), 1.960 (1.07), 1.989 (0.74), 2.000 (0.78), 2.015 (1.44), 2.029 (3.22), 2.038 (3.51), 2.045 ( 2.41), 2.054 (1.95), 2.066 (1.46), 2.072 (1.43), 2.081 (1.30), 2.108 (0.49), 2.327 (0.55), 2.523 (1.95), 2.558 (2.98), 2.572 (2.50), 2.584 ( 2.37), 2.598 (1.98), 2.614 (1.90), 2.625 (3.38), 2.637 (2.01), 2.656 (0.92), 2.666 (1.65), 2.679 (0.87), 3.237 (1.07), 3.254 (2.30), 3.266 ( 2.34), 3.283 (4.24), 3.330 (2.25), 3.347 (4.22), 3.359 (1.53), 3.365 (2.21), 3.377 (2.39), 3.394 (1.07), 3.445 (1.23), 3.462 (2.68), 3.469 ( 2.01), 3.479 (1.58), 3.487 (3.47), 3.504 (1.50), 3.594 (1.62), 3.611 (3.15), 3.619 (1.64), 3.627 (1.83), 3.636 (2.39), 3.652 (1.14), 4.774 ( 2.95), 4.783 (3.30), 4.789 (4.07), 4.798 (2.91), 4.980 (0.51), 5.024 (16.00), 5.068 (0.51), 7.473 (4.22), 7.485 (4.38), 7.760 (8.48), 8.726 ( 6.15), 8.739 (6.08).

[01043] The (5S) configuration was assigned based on the elucidation of the crystal structure for Examples 26, 108, 113, 157, 237, 358 and 454. (5S)-5-(Pyrrolidin-1-ylcarbonyl)-2- {[2-(trifluoromethyl)pyridin-4-yl]methyl}-5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one Example 75 (5RS)-2-{[3-Fluoro-2-(trifluoromethyl)pyridin-4-yl]methyl}-5-(pyrrolidin-1-ylcarbonyl)-5,6,7,8-tetrahydro[ 1,2,4]triazolo[4,3-a]pyridin-3(2H)-one (enantiomer 1)

[01044] (5RS)-2-[[3-Fluoro-2-(trifluoromethyl)-4-pyridyl]methyl]-3-oxo-5,6,7,8-tetrahydro-[1,2,4 ]triazolo[4,3-a]pyridine-5-carboxylic acid (enantiomer 1) (80.0 mg, 214 μmol) was initially loaded into THF (2.0 mL) at room temperature. Subsequently, 1-[bis(dimethylamino)methylene]-1H-[1,2,3]triazolo[4,5-b]pyridin-1-io 3-oxide hexafluorophosphate (106 mg, 278 μmol) and triethylamine (89 μl , 640 μmol) were added. After stirring for 15 minutes, pyrrolidine (21 μl, 260 μmol) was added and the reaction mixture was stirred at room temperature overnight. The reaction mixture was mixed with water and ethyl acetate. The organic phase was removed and the aqueous phase was extracted three times with ethyl acetate. The combined organic phases were washed with saturated aqueous sodium chloride solution, dried over sodium sulfate and filtered, and the filtrate was concentrated. The residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/gradient water). The fractions containing the product were concentrated under reduced pressure and 67.0 mg (76% possibility) of the title compound were obtained. LC-MS (Method 3): Rt = 1.31 min; MS (ESIpos): m /z = 414 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.150 (0.52), 0.008 (3.36), 0.146 (0.57), 1.697 ( 2.60), 1.708 (2.42), 1.737 (3.98), 1.758 (3.80), 1.774 (8.57), 1.792 (13.17), 1.809 (9.76), 1.825 (2.72), 1.894 (3.04), 1.909 (7.95), 1.926 ( 9.58), 1.942 (5.78), 1.959 (1.76), 2.025 (5.07), 2.047 (3.06), 2.060 (2.40), 2.067 (2.35), 2.075 (2.15), 2.328 (1.01), 2.366 (0.69), 2.569 ( 4.00), 2.580 (3.80), 2.594 (3.25), 2.609 (3.31), 2.621 (5.56), 2.633 (3.16), 2.651 (1.53), 2.664 (2.51), 2.710 (0.69), 3.235 (1.85), 3.252 ( 3.80), 3.264 (4.16), 3.281 (7.27), 3.329 (3.57), 3.347 (6.42), 3.364 (3.45), 3.376 (3.57), 3.394 (1.65), 3.443 (2.03), 3.460 (4.21), 3.468 ( 3.22), 3.486 (5.21), 3.503 (2.33), 3.592 (2.63), 3.609 (4.96), 3.626 (3.00), 3.634 (3.73), 3.650 (1.62), 4.763 (4.87), 4.772 (5.33), 4.777 ( 6.22) ( 9.81).

[01045] The (5S) configuration was assigned based on the elucidation of the crystal structure for Examples 26, 108, 113, 157, 237, 358 and 454. (5S)-2-{[3-Fluoro-2-(trifluoromethyl )pyridin-4-yl]methyl}-5-(pyrrolidin-1-ylcarbonyl)-5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridin-3( 2H)-one Example 76 (5RS)-5-(Pyrrolidin-1-ylcarbonyl)-2-{[2-(trifluoromethyl)quinolin-4-yl]methyl}-5,6,7,8-tetrahydro[ 1,2,4]triazolo[4,3-a]pyridin-3(2H)-one (enantiomer 1)

[01046] (5RS)-3-Oxo-2-{[2-(trifluoromethyl)quinolin-4-yl]methyl}- 2,3,5,6,7,8-hexahydro[1,2,4 ]triazolo[4,3-a]pyridine-5-carboxylic acid (enantiomer 1) (94.0 mg, 240 μmol) was initially loaded into THF (2.1 mL) at room temperature. Subsequently, 1-[bis(dimethylamino)methylene]-1H-[1,2,3]triazolo[4,5-b]pyridin-1-io 3-oxide hexafluorophosphate (118 mg, 311 μmol) and triethylamine (100 μl , 720 μmol) were added. After stirring for 15 minutes, pyrrolidine (24 μl, 290 μmol) was added and the reaction mixture was stirred at room temperature overnight. The reaction mixture was mixed with water and ethyl acetate. The organic phase was removed and the aqueous phase was extracted three times with ethyl acetate. The combined organic phases were washed with saturated aqueous sodium chloride solution, dried over sodium sulfate and filtered, and the filtrate was concentrated. The residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/gradient water). The fractions containing the product were concentrated under reduced pressure and 57.0 mg (53% possibility) of the title compound were obtained. LC-MS (Method 3): Rt = 1.55 min; MS (ESIpos): m /z = 446 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.008 (2.70), 0.008 (2.54), 1.147 (0.45), 1.165 ( 0.90), 1.183 (0.45), 1.653 (1.17), 1.666 (1.66), 1.678 (1.86), 1.691 (1.77), 1.704 (2.52), 1.717 (3.00), 1.728 (2.29), 1.740 (1.51), 1.751 ( 1.17), 1.763 (1.72), 1.781 (5.12), 1.799 (9.24), 1.816 (7.40), 1.832 (2.22), 1.899 (2.19), 1.915 (6.75), 1.932 (8.65), 1.949 (5.19), 1.966 ( 1.61), 1983 (1.00), 1998 (1.85), 2010 (4.50), 2019 (4.62), 2034 (2.65), 2046 (1.72), 2052 (1.66), 2061 (1.55), 2071 (0.74), 2087 ( 0.51), 2.096 (0.42), 2.328 (0.56), 2.333 (0.49), 2.342 (1.75), 2.519 (3.00), 2.525 (4.32), 2.567 (2.15), 2.594 (2.16), 2.605 (3.87), 2.617 ( 2.31), 2.636 (1.19), 2.647 (1.75), 2.660 (1.01), 2.670 (0.71), 3.238 (1.31), 3.255 (2.81), 3.268 (2.72), 3.285 (4.87), 3.340 (2.36), 3.357 ( 4.92), 3.369 (1.89), 3.375 (2.60), 3.387 (2.96), 3.405 (1.31), 3.440 (1.47), 3.457 (3.21), 3.464 (2.37), 3.474 (1.97), 3.482 (4.04), 3.499 ( 1.75), 3.606 (1.82), 3.622 (3.91), 3.630 (2.00), 3.639 (2.22), 3.647 (3.07), 3.664 (1.36), 3.803 (0.57), 3.818 (0.56), 4.792 (3.51), 4.801 ( 3.91), 4,806 (4.95), 4,815 (3.45), 5,408 (3.17), 5,449 (10.04), 5,480 (10.14), 5,521 (3.20), 5,558 (0.51), 6,510 (2.74), 7,293 (0.56), 7,386 ( 0.63), 7.406 (0.59), 7.750 (16.00), 7.823 (2.56), 7.826 (2.72), 7.844 (5.54), 7.862 (3.75), 7.864 (3.71), 7.943 (3.44), 7.946 (3.64), 7.964 ( 5.87), 7.967 (4.51), 7.982 (3.21), 7.985 (3.11), 8.214 (6.39), 8.234 (5.46), 8.370 (6.19), 8.390 (5.70).

[01047] The (5S) configuration was assigned based on the elucidation of the crystal structure for Examples 26, 108, 113, 157, 237, 358 and 454. (5S)-5-(Pyrrolidin-1-ylcarbonyl)-2- {[2-(trifluoromethyl)quinolin-4-yl]methyl}-5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one Example 77 (5RS)-2-{[2-Methyl-4-(trifluoromethyl)-1,3-thiazol-5-yl]methyl}-5-(pyrrolidin-1-ylcarbonyl)-5,6,7,8 -tetrahydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one (racemate)

[01048] (5RS)-2-{[2-Methyl-4-(trifluoromethyl)-1,3-thiazol-5-yl]methyl}-3-oxo-2,3,5,6,7,8- Hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylic acid (racemate) (68.0 mg, 188 μmol) was initially loaded into THF (2.1 mL) at room temperature . Subsequently, 1-[bis(dimethylamino)methylene]-1H-[1,2,3]triazolo[4,5-b]pyridin-1-io 3-oxide hexafluorophosphate (92.8 mg, 244 μmol) and triethylamine ( 78 μl, 560 μmol) were added. After stirring for 15 minutes, pyrrolidine (19 μl, 230 μmol) was added and the reaction mixture was stirred at room temperature overnight. The reaction mixture was mixed with water and ethyl acetate. The organic phase was removed and the aqueous phase was extracted three times with ethyl acetate. The combined organic phases were washed with saturated aqueous sodium chloride solution, dried over sodium sulfate and filtered, and the filtrate was concentrated. The residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/gradient water). The fractions containing the product were concentrated under reduced pressure and 49.0 mg (63% possibility) of the title compound were obtained. LC-MS (Method 3): Rt = 1.21 min; MS (ESIpos): m /z = 416 [M+H]+ ¹H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.008 (2.56), 0.008 (2.06), 1.163 (2.87), 1.181 ( 6.08), 1.199 (2.98), 1.703 (0.97), 1.714 (1.06), 1.754 (0.51), 1.770 (1.54), 1.787 (2.65), 1.804 (2.06), 1.821 (0.60), 1.889 (0.63), 1.906 ( 1.90), 1.923 (2.45), 1.939 (1.73), 1.974 (0.84), 1.986 (0.78), 2.003 (0.52), 2.019 (0.67), 2.028 (0.50), 2.327 (0.46), 2.523 (1.51), 2.558 ( 0.99), 2.568 (0.83), 2.582 (0.68), 2.602 (0.66), 2.613 (1.27), 2.626 (0.75), 2.646 (16.00), 2.669 (0.74), 2.890 (0.45), 3.076 (1.10), 3.089 ( 1.24), 3.094 (1.13), 3.106 (1.07), 3.236 (0.78), 3.248 (0.79), 3.265 (1.40), 3.282 (0.69), 3.313 (0.78), 3.330 (1.69), 3.428 (0.64), 3.445 ( 0.98), 3.453 (0.73), 3.470 (1.21), 3.487 (0.56), 3.578 (0.51), 3.595 (1.09), 3.612 (0.63), 3.620 (0.80), 4.713 (0.95), 4.723 (1.09), 4.728 ( 1.30), 4.738 (0.95), 5.127 (2.30), 5.142 (2.33). Example 78 (5RS)-2-[(5-Chloropyridin-2-yl)methyl]-5-[(3,3-difluoropyrrolidin-1-yl)carbonyl]-5,6,7,8-tetrahydro[ 1,2,4]triazolo[4,3-a]pyridin-3(2H)-one (racemate)

[01049] hydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylic acid (racemate) (50.0 mg, 162 μmol) was initially loaded into THF (3.0 mL) at temperature environment. Subsequently, 1-[bis(dimethylamino)methylene]-1H-[1,2,3]triazolo[4,5-b]pyridin-1-io 3-oxide hexafluorophosphate (80.1 mg, 211 μmol) and triethylamine ( 68 μl, 490 μmol) were added. After stirring for 15 minutes, 3,3-difluoropyrrolidine hydrochloride (27.9 mg, 194 μmol) was added and the reaction mixture was stirred at room temperature overnight. The reaction mixture was mixed with water and ethyl acetate. The organic phase was removed and the aqueous phase was extracted three times with ethyl acetate. The combined organic phases were washed with saturated aqueous sodium chloride solution, dried over sodium sulfate and filtered, and the filtrate was concentrated. The residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/gradient water). The fractions containing the product were concentrated under reduced pressure and 25.2 mg (39% possibility) of the title compound were obtained. LC-MS (Method 4): Rt = 0.69 min; MS (ESIpos): m /z = 398 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.008 (2.72), 0.008 (2.55), 1.687 (1.41), 1.699 ( 1.48), 1.726 (1.92), 2.023 (1.76), 2.050 (1.24), 2.064 (1.31), 2.073 (2.50), 2.085 (1.00), 2.101 (0.87), 2.328 (0.75), 2.365 (0.71), 2.381 ( 1.04), 2.410 (1.31), 2.431 (1.22), 2.569 (4.02), 2.578 (3.03), 2.592 (3.63), 2.607 (3.88), 2.620 (1.88), 2.650 (1.12), 2.665 (1.04), 2.709 ( 0.48), 3.538 (1.74), 3.557 (2.71), 3.570 (1.44), 3.577 (1.41), 3.638 (0.51), 3.672 (1.50), 3.706 (1.75), 3.740 (1.36), 3.774 (2.31), 3.790 ( 1.31), 3.798 (1.21), 3.808 (2.23), 3.816 (1.89), 3.835 (0.93), 3.894 (0.74), 3.912 (1.70), 3.931 (0.99), 3.938 (1.22), 3.957 (0.58), 3.972 ( 0.49), 4.001 (1.06), 4.014 (0.56), 4.030 (0.71), 4.043 (0.99), 4.071 (0.60), 4.147 (0.64), 4.179 (1.00), 4.203 (1.01), 4.235 (0.43), 4.761 ( 1.40), 4.776 (1.83), 4.785 (1.34), 4.836 (1.45), 4.846 (1.72), 4.851 (1.89), 4.861 (1.45), 4.870 (0.73), 4.914 (16.00), 4.955 (0.69), 7.199 ( 6.18), 7.220 (6.60), 7.913 (4.28), 7.920 (4.38), 7.934 (4.15), 7.941 (4.23), 8.571 (5.89), 8.577 (5.93). Example 79 (5RS)-5-[(3,3-Difluoropyrrolidin-1-yl)carbonyl]-2-{[6-(trifluoromethyl)pyridin-3-yl]methyl}-5,6,7,8-tetra -hydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one (racemate)

[01050] (5RS)-3-Oxo-2-{[6-(trifluoromethyl)pyridin-3-yl]methyl}-2,3,5,6,7,8-hexahydro[1,2,4 ]triazolo[4,3-a]pyridine-5-carboxylic acid/trifluoroacetic acid (racemate) (70.0 mg, 153 μmol) was initially loaded into THF (3.0 mL) at room temperature. Subsequently, 1-[bis(dimethylamino)methylene]-1H-[1,2,3]triazolo[4,5-b]pyridin-1-io 3-oxide hexafluorophosphate (75.8 mg, 199 μmol) and triethylamine ( 110 μl, 770 μmol) were added. After stirring for 15 minutes, 3,3-difluoropyrrolidine hydrochloride (26.4 mg, 184 μmol) was added and the reaction mixture was stirred at room temperature overnight. The reaction mixture was mixed with water and ethyl acetate. The organic phase was removed and the aqueous phase was extracted three times with ethyl acetate. The combined organic phases were washed with saturated aqueous sodium chloride solution, dried over sodium sulfate and filtered, and the filtrate was concentrated. The residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/gradient water). The fractions containing the product were concentrated under reduced pressure and 37.7 mg (57% possibility) of the title compound were obtained. LC-MS (Method 4): Rt = 0.75 min; MS (ESIpos): m /z = 432 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.008 (3.24), 0.008 (3.00), 1.664 (1.10), 1.735 ( 1.37), 1908 (1.15), 1994 (1.34), 2008 (1.72), 2018 (1.67), 2033 (1.58), 2044 (1.35), 2052 (1.21), 2060 (1.13), 2073 (1.48), 2080 ( 0.80), 2.088 (0.84), 2.096 (0.75), 2.328 (0.80), 2.366 (0.81), 2.382 (0.98), 2.411 (1.16), 2.431 (1.11), 2.456 (0.84), 2.569 (3.33), 2.580 ( 2.48), 2.594 (2.56), 2.610 (2.91), 2.623 (1.48), 2.640 (0.60), 2.653 (0.91), 2.669 (1.06), 2.710 (0.48), 3.534 (1.23), 3.541 (1.45), 3.552 ( 2.00), 3.561 (2.15), 3.571 (1.27), 3.580 (1.08), 3.670 (1.29), 3.704 (1.47), 3.738 (0.63), 3.749 (0.72), 3.769 (0.56), 3.782 (1.84), 3.794 ( 0.96), 3.813 (2.64), 3.831 (0.71), 3.891 (0.68), 3.910 (1.45), 3.929 (0.81), 3.936 (1.06), 3.955 (0.49), 3.966 (0.43), 3.995 (0.88), 4.010 ( 0.45), 4.023 (0.60), 4.038 (0.82), 4.066 (0.49), 4.149 (0.51), 4.182 (0.79), 4.206 (0.79), 4.767 (1.21), 4.776 (1.43), 4.782 (1.63), 4.791 ( 1.15), 4,838 (1.28), 4,847 (1.44), 4,853 (1.63), 4,862 (1.17), 5,011 (14.35), 7,909 (15.74), 7,913 (16.00), 8,641 (5.64). Example 80 (5RS)-2-[(6-Chloropyridin-3-yl)methyl]-5-[(3,3-difluoropyrrolidin-1-yl)carbonyl]-5,6,7,8-tetrahydro[ 1,2,4]triazolo[4,3-a]pyridin-3(2H)-one (racemate)

[01051] (5RS)-2-[(6-Chloropyridin-3-yl)methyl]-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[ 4,3-a]pyridine-5-carboxylic acid (racemate) (350 mg, 15% purity, 170 μmol) was loaded into THF (3.0 mL) at room temperature. Subsequently, 1-[bis(dimethylamino)methylene]-1H-[1,2,3]triazolo[4,5-b]pyridin-1-io 3-oxide hexafluorophosphate (84.1 mg, 221 μmol) and triethylamine (71 μl, 510 μmol) were added. After stirring for 15 minutes, 3,3-difluoropyrrolidine hydrochloride (29.3 mg, 204 μmol) was added and the reaction mixture was stirred at room temperature overnight. The reaction mixture was mixed with water and ethyl acetate. The organic phase was removed and the aqueous phase was extracted three times with ethyl acetate. The combined organic phases were washed with saturated aqueous sodium chloride solution, dried over sodium sulfate and filtered, and the filtrate was concentrated. The residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/gradient water). The fractions containing the product were concentrated under reduced pressure and 46.4 mg (69% possibility) of the title compound were obtained. LC-MS (Method 4): Rt = 0.67 min; MS (ESIpos): m /z = 398 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: 1.661 (1.07), 1.726 (1.27), 1.996 (1.45), 2.007 (1.54 ), 2.043 (1.10), 2.060 (0.88), 2.071 (0.82), 2.327 (0.70), 2.366 (0.54), 2.379 (0.89), 2.408 (1.09), 2.427 (1.04), 2.452 (0.91), 2.560 (2.42 ), 2.569 (2.97), 2.585 (2.82), 2.602 (2.79), 2.644 (0.79), 2.669 (0.70), 3.537 (1.17), 3.546 (1.77), 3.556 (1.91), 3.565 (1.12), 3.575 (0.94 ), 3.665 (1.17), 3.700 (1.30), 3.743 (0.64), 3.776 (1.61), 3.807 (2.37), 3.825 (0.62), 3.887 (0.58), 3.906 (1.29), 3.931 (0.92), 3.962 (0.43 ), 3.991 (0.80), 4.018 (0.57), 4.032 (0.75), 4.063 (0.47), 4.143 (0.51), 4.175 (0.74), 4.200 (0.74), 4.749 (1.05), 4.764 (1.43), 4.773 (1.05 ), 4,821 (1.16), 4,836 (1.48), 4,846 (1.20), 4,884 (16.00), 7,505 (4.89), 7,525 (6.06), 7,686 (3.27), 7,692 (3.34), 7,707 (2.69), 7,713 (2.73 ), 8,296 (5.00), 8,301 (4.81). Example 81 (5RS)-2-(3,5-Dichlorobenzyl)-5-(pyrrolidin-1-ylcarbonyl)-5,6,7,8-tetrahydro[1,2,4]triazolo[4,3- a]pyridin-3(2H)-one (racemate)

[01052] (5RS)-2-(3,5-Dichlorobenzyl)-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a ]pyridine-5-carboxylic acid hydrochloride (racemate) (70.0 mg, 79% purity, 145 μmol) was initially loaded into THF (3.0 mL) at room temperature. Subsequently, 1-[bis(dimethylamino)methylene]-1H-[1,2,3]triazolo[4,5-b]pyridin-1-io 3-oxide hexafluorophosphate (71.7 mg, 189 μmol) and triethylamine (100 μl, 730 μmol) were added. After stirring for 15 minutes, pyrrolidine (12.4 mg, 174 μmol) was added and the reaction mixture was stirred at room temperature overnight. The reaction mixture was mixed with water and ethyl acetate. The organic phase was removed and the aqueous phase was extracted three times with ethyl acetate. The combined organic phases were washed with saturated aqueous sodium chloride solution, dried over sodium sulfate and filtered, and the filtrate was concentrated. The residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/gradient water). The fractions containing the product were concentrated under reduced pressure and 21.4 mg (37% possibility) of the title compound were obtained. LC-MS (Method 3): Rt = 1.61 min; MS (ESIpos): m /z = 395 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (0.96), -0.008 (8.42), 0.008 (7.50), 0.146 (1.00) (5.36) (1.40) (2.48) (1.88) (1.92), 3,651 (0.81), 4,753 (2.25), 4,762 (2.48), 4,768 (2.77), 4,777 (2,29), 4,851 (16.00), 7,273 (11.16), 7,278 (11,31), 7,533 (2.40), 7,538 (4.25), 7,543 (2.14). Example 82 (5RS)-2-(3,5-Dichlorobenzyl)-5-[(3,3-difluoropyrrolidin-1-yl)carbonyl]-5,6,7,8-tetrahydro[1,2,4 ]triazolo[4,3-a]pyridin-3(2H)-one (racemate)

[01053] (5RS)-2-(3,5-Dichlorobenzyl)-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a ]pyridine-5-carboxylic acid hydrochloride (racemate) (70.0 mg, 79% purity, 145 μmol) was initially loaded into THF (3.0 mL) at room temperature. Subsequently, 1-[bis(dimethylamino)methylene]-1H-[1,2,3]triazolo[4,5-b]pyridin-1-io 3-oxide hexafluorophosphate (71.7 mg, 189 μmol) and triethylamine (100 μl, 730 μmol) were added. After stirring for 15 minutes, 3,3-difluoropyrrolidine hydrochloride (25.0 mg, 174 μmol) was added and the reaction mixture was stirred at room temperature overnight. The reaction mixture was mixed with water and ethyl acetate. The organic phase was removed and the aqueous phase was extracted three times with ethyl acetate. The combined organic phases were washed with saturated aqueous sodium chloride solution, dried over sodium sulfate and filtered, and the filtrate was concentrated. The residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/gradient water). The fractions containing the product were concentrated under reduced pressure and 26.4 mg (94% purity, 40% possibility) of the title compound were obtained. LC-MS (Method 3): Rt = 1.73 min; MS (ESIpos): m /z = 431 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.008 (3.09), 0.008 (2.90), 1.670 (0.97), 1.734 ( 1.17), 1992 (1.13), 2004 (1.20), 2013 (1.32), 2048 (0.92), 2056 (1.04), 2063 (1.01), 2073 (6.09), 2084 (0.76), 2091 (0.75), 2100 ( 0.66), 2.327 (0.74), 2.366 (0.72), 2.382 (0.91), 2.412 (1.03), 2.424 (0.98), 2.453 (0.85), 2.523 (3.33), 2.565 (2.41), 2.580 (2.09), 2.590 ( 2.49), 2.605 (2.35), 2.622 (2.34), 2.633 (1.24), 2.665 (1.27), 2.674 (0.86), 2.709 (0.46), 3.533 (1.03), 3.541 (1.15), 3.551 (1.74), 3.562 ( 1.93), 3.569 (1.05), 3.581 (0.92), 3.672 (1.10), 3.705 (1.28), 3.742 (0.91), 3.764 (0.52), 3.776 (1.52), 3.790 (0.80), 3.808 (2.32), 3.827 ( 0.59), 3.894 (0.59), 3.912 (1.26), 3.931 (0.71), 3.939 (0.91), 3.958 (0.60), 3.989 (0.78), 4.017 (0.52), 4.032 (0.71), 4.060 (0.42), 4.149 ( 0.46), 4.183 (0.68), 4.206 (0.70), 4.775 (1.07), 4.784 (1.23), 4.790 (1.41), 4.799 (1.05) ( 2.16), 7,541 (3.82), 7,546 (2.01). Example 83 (5RS)-2-(3,4-Difluorobenzyl)-5-[(3,3-difluoropyrrolidin-1-yl)carbonyl]-5,6,7,8-tetrahydro[1,2,4 ]triazolo[4,3-a]pyridin-3(2H)-one (racemate)

[01054] (5RS)-2-(3,4-Difluorobenzyl)-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a ]pyridine-5-carboxylic acid hydrochloride (race-mate) (100 mg, 289 μmol) was initially loaded into THF (3.0 mL) at room temperature. Subsequently, 1-[bis(dimethylamino)methylene]-1H-[1,2,3]triazolo[4,5-b]pyridin-1-io 3-oxide hexafluorophosphate (143 mg, 376 μmol) and triethylamine (200 μl, 1.4 mmol) were added. After stirring for 15 minutes, 3,3-difluoropyrrolidine hydrochloride (49.8 mg, 347 μmol) was added and the reaction mixture was stirred at room temperature overnight. The reaction mixture was mixed with water and ethyl acetate. The organic phase was removed and the aqueous phase was extracted three times with ethyl acetate. The combined organic phases were washed with saturated aqueous sodium chloride solution, dried over sodium sulfate and filtered, and the filtrate was concentrated. The residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/gradient water). The fractions containing the product were concentrated under reduced pressure and 17.0 mg (15% possibility) of the title compound were obtained. LC-MS (Method 4): Rt = 0.78 min; MS (ESIpos): m /z = 399 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (0.64), -0.008 (5.78), 0.008 (4.12), 0.147 (0.54), 1734 (1.51), 2012 (1.51), 2327 (1.54), 2566 (2.86), 2591 (2.58), 2608 (2.98), 2669 (1.40), 2709 (0.76), 3559 (2.11), 3670 (1.33) (1.87), 7,230 (1.68), 7,259 (2.04), 7,278 (1.80), 7,375 (1.75), 7,396 (3.57), 7,402 (2.25), 7,423 (3.55), 7,445 (1.68). Example 84 (5RS)-5-(Pyrrolidin-1-ylcarbonyl)-2-{[6-(trifluoromethyl)pyridin-3-yl]methyl}-5,6,7,8-tetrahydro[1,2, 4]triazolo[4,3-a]pyridin-3(2H)-one (racemate)

[01055] (5RS)-3-Oxo-2-{[6-(trifluoromethyl)pyridin-3-yl]methyl}-2,3,5,6,7,8-hexahydro[1,2,4 ]triazolo[4,3-a]pyridine-5-carboxylic acid/trifluoroacetic acid (racemate) (70.0 mg, 153 μmol) was initially loaded into THF (3.0 mL) at room temperature. Subsequently, 1-[bis(dimethylamino)methylene]-1H-[1,2,3]triazolo[4,5-b]pyridin-1-io 3-oxide hexafluorophosphate (75.8 mg, 199 μmol) and triethylamine (110 μl, 770 μmol) were added. After stirring for 15 minutes, pyrrolidine (15 μl, 180 μmol) was added and the reaction mixture was stirred at room temperature overnight. The reaction mixture was mixed with water and ethyl acetate. The organic phase was removed and the aqueous phase was extracted three times with ethyl acetate. The combined organic phases were washed with saturated aqueous sodium chloride solution, dried over sodium sulfate and filtered, and the filtrate was concentrated. The residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/gradient water). The fractions containing the product were concentrated under reduced pressure and 32.2 mg (53% possibility) of the title compound were obtained. LC-MS (Method 3): Rt = 1.23 min; MS (ESIpos): m /z = 396 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.008 (3.63), 0.008 (3.14), 0.146 (0.40), 1.673 ( 1.10), 1.686 (1.21), 1.696 (1.21), 1.710 (1.60), 1.724 (1.93), 1.736 (1.54), 1.748 (1.13), 1.758 (1.55), 1.774 (4.10), 1.791 (6.82), 1.808 ( 5.25), 1825 (1.49), 1893 (1.46), 1909 (4.19), 1926 (5.20), 1942 (3.16), 1959 (1.12), 2013 (2.62), 2036 (1.46), 2048 (1.20), 2055 ( 1.18), 2.063 (1.13), 2.072 (0.66), 2.327 (0.97), 2.366 (0.58), 2.523 (3.85), 2.564 (2.19), 2.579 (1.70), 2.593 (1.65), 2.605 (2.93), 2.617 ( 1.70), 2.635 (0.78), 2.646 (1.13), 2.660 (0.89), 2.665 (0.89), 2.669 (1.07), 2.709 (0.62), 3.231 (0.96), 3.247 (1.93), 3.260 (1.93), 3.277 ( 3.53), 3.295 (2.62), 3.328 (2.30), 3.346 (3.58), 3.363 (1.83), 3.375 (2.02), 3.393 (0.92), 3.440 (0.99), 3.457 (2.20), 3.464 (1.62), 3.474 ( 1.34), 3.482 (2.82), 3.499 (1.26), 3.592 (1.28), 3.609 (2.61), 3.617 (1.34), 3.626 (1.57), 3.633 (2.02), 3.650 (0.94), 4.747 (2.45), 4.756 ( 2.74), 4.762 (3.26), 4.771 (2.36), 5.005 (13.36), 7.907 (15.77), 7.910 (16.00), 8.641 (5.00). Example 85 (5RS)-5-(Pyrrolidin-1-ylcarbonyl)-2-{[6-(trifluoromethyl)pyridin-3-yl]methyl}-5,6,7,8-tetrahydro[1,2, 4]triazolo[4,3-a]pyridin-3(2H)-one (enantiomer 2)

[01056] (5RS)-5-(Pyrrolidin-1-ylcarbonyl)-2-{[6-(trifluoromethyl)pyridin-3-yl]methyl}-5,6,7,8-tetrahydro[1,2 ,4]triazolo[4,3-a]pyridin-3(2H)-one (racemate) was separated by chiral preparatory HPLC. [Sample preparation: 75 mg dissolved in 1 mL of ethanol/acetonitrile; injection volume: 0.2 mL; column: Daicel Chiralpak® AD-H 5μm, 250 x 20 mm; eluent: n-heptane/ethanol 40:60, flow rate: 20 ml/min; temperature 40°C; UV detection: 220 nm]. After separation, 27 mg of enantiomer 1, which eluted first, and 27 mg of enantiomer 2, which eluted later, were isolated. Enantiomer 2:

[01057] Analytical chiral HPLC: Rt = 3.61 min, ee = 99.9% [column: Daicel Chiralcel® OJ-3 3μm 50 x 4.6 mm; eluent: n-heptane/isopropanol 1:1, 0.2% trifluoroacetic acid, 1% water; flow rate: 1 ml/min; UV detection: 220 nm]. LC-MS (Method 3): Rt = 1.22 min; MS (ESIpos): m /z = 396 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: 1.61-1.82 ( m , 4H). 1.87 - 1.95 ( m , 2H), 1.95 - 2.10 ( m , 2H), 2.56 - 2.72 ( m , 2H), 3.22 - 3.28 ( m , 1H), 3.33 - 3.39 ( m , 1H), 3.47 (dt, 1H) ), 3.62 (dt, 1H), 4.76 (dd, 1H), 5.00 (s, 2H), 7.91 (d, 2H), 8.64 (s, 1H). Example 86 (5RS)-2-(3-Chloro-4-fluorobenzyl)-5-[(3,3-difluoropyrrolidin-1-yl)carbonyl]-5,6,7,8-tetrahydro[1,2 ,4]triazolo[4,3-a]pyridin-3(2H)-one (racemate)

[01058] (5RS)-2-(3-Chloro-4-fluorobenzyl)-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3 -a]pyridine-5-carboxylic acid hydrochloride (racemate) (100 mg, 276 μmol) was initially loaded into THF (3.0 mL) at room temperature. Subsequently, 1-[bis(dimethylamino)methylene]-1H-[1,2,3]triazolo[4,5-b]pyridin-1-io 3-oxide hexafluorophosphate (136 mg, 359 μmol) and triethylamine (190 μl , 1.4 mmol) were added. After stirring for 15 minutes, 3,3-difluoropyrrolidine hydrochloride (47.6 mg, 331 μmol) was added and the reaction mixture was stirred at room temperature overnight. The reaction mixture was mixed with water and ethyl acetate. The organic phase was removed and the aqueous phase was extracted three times with ethyl acetate. The combined organic phases were washed with saturated aqueous sodium chloride solution, dried over sodium sulfate and filtered, and the filtrate was concentrated. The residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/gradient water). The fractions containing the product were concentrated under reduced pressure and 14.0 mg (12% possibility) of the title compound were obtained. LC-MS (Method 4): Rt = 0.83 min; MS (ESIpos): m /z = 415 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (0.46), -0.008 (3.79), 0.008 (3.46), 0.146 (0.44) (1.10), 2054 (1.05), 2063 (0.94), 2073 (0.88), (0.80), 2089 (0.70), 2323 (0.61), 2327 (0.83), 2332 (0.58), 2366 (0.83), 2381 ( 0.94), 2.391 (0.67), 2.411 (1.10), 2.425 (1.04), 2.452 (0.87), 2.523 (3.60), 2.566 (2.83), 2.576 (2.48), 2.591 (2.76), 2.608 (2.96), 2.619 ( 1.40), 2.639 (0.57), 2.650 (0.87), 2.665 (0.91), 2.669 (0.93), 2.710 (0.53), 3.531 (1.18), 3.538 (1.34), 3.549 (1.92), 3.559 (2.12), 3.567 ( 1.21), 3.578 (1.04), 3.668 (1.24), 3.703 (1.42), 3.742 (0.78), 3.764 (0.56), 3.775 (1.64), 3.790 (0.88), 3.808 (2.65), 3.826 (0.68), 3.891 ( 0.67), 3.909 (1.41), 3.928 (0.77), 3.935 (1.02), 3.954 (0.48), 3.962 (0.46), 3.991 (0.83), 4.005 (0.44), 4.019 (0.60), 4.033 (0.77), 4.061 ( 0.47), 4.145 (0.53), 4.176 (0.75), 4.201 (0.77), 4.755 (1.15), 4.765 (1.38), 4.771 (1.58), 4.780 (1.20), 4.824 (16.00), 4.838 (1.79), 4.844 ( 1.77), 4.853 (1.32), 7.220 (1.30), 7.225 (1.47), 7.232 (1.49), 7.241 (2.05), 7.246 (2.01), 7.253 (1.84), 7.258 (1.82), 7.373 (3.89), 7.396 ( 5.08), 7,418 (3.09), 7,429 (2.86), 7,434 (2.69), 7,447 (2.88), 7,452 (2.65). Example 87 (5RS)-5-[(3,3-Difluoropyrrolidin-1-yl)carbonyl]-2-(5,6,7,8-tetrahydronaphthalen-2-ylmethyl)-5,6,7,8-tetra -hydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one (racemate)

[01059] (5RS)-3-Oxo-2-(5,6,7,8-tetrahydronaphthalen-2-ylmethyl)- 2,3,5,6,7,8-hexahydro[1,2 ,4]triazolo[4,3-a]pyridine-5-carboxylic acid/trifluoroacetic acid (racemate) (100 mg, 227 μmol) was initially loaded into THF (2.0 mL) at room temperature. Subsequently, 1-[bis(dimethylamino)methylene]-1H-[1,2,3]triazolo[4,5- b]pyridin-1-io 3-oxide hexafluorophosphate (112 mg, 295 μmol) and triethylamine (160 μl , 1.1 mmol) were added. After stirring for 15 minutes, 3,3-difluoropyrrolidine hydrochloride (39.0 mg, 272 μmol) was added and the reaction mixture was stirred at room temperature overnight. The reaction mixture was mixed with water and ethyl acetate. The organic phase was removed and the aqueous phase was extracted three times with ethyl acetate. The combined organic phases were washed with saturated aqueous sodium chloride solution, dried over sodium sulfate and filtered, and the filtrate was concentrated. The residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/gradient water). The fractions containing the product were concentrated under reduced pressure and 44.0 mg (47% possibility) of the title compound were obtained. LC-MS (Method 1): Rt = 1.25 min; MS (ESIpos): m /z = 417 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (1.52), -0.008 (13.87), 0.008 (12.34), 0.146 (1.37), 1,708 (13.94), 1,996 (2.59), 2,327 (4.65), 2.366 (3.20), 2,523 (15.54), 2,565 (4,80), 2,584 (4,19), 2,598 (3.73), 2,69 (16.00), 2.702 (5.18) (1.68) (8.15), 6,933 (3.58), 6,979 (4.72), 6,988 (4.88), 7,009 (4.19), 7,028 (4.11), 7,047 (1.60), 7,069 (1.07). Example 88 (5RS)-5-(Pyrrolidin-1-ylcarbonyl)-2-(5,6,7,8-tetrahydronaphthalen-2-ylmethyl)-5,6,7,8-tetrahydro[1, 2,4]triazolo[4,3-a]pyridin-3(2H)-one (racemate)

[01060] (5RS)-3-Oxo-2-(5,6,7,8-tetrahydronaphthalen-2-ylmethyl)- 2,3,5,6,7,8-hexahydro[1,2 ,4]triazolo[4,3-a]pyridine-5-carboxylic acid/trifluoroacetic acid (racemate) (100 mg, 227 μmol) was initially loaded into THF (2.0 mL) at room temperature. Subsequently, 1-[bis(dimethylamino)methylene]-1H-[1,2,3]triazolo[4,5-b]pyridin-1-io 3-oxide hexafluorophosphate (112 mg, 295 μmol) and triethylamine (160 μl , 1.1 mmol) were added. After stirring for 15 minutes, pyrrolidine (19.3 mg, 272 μmol) was added and the reaction mixture was stirred at room temperature overnight. The reaction mixture was mixed with water and ethyl acetate. The organic phase was removed and the aqueous phase was extracted three times with ethyl acetate. The combined organic phases were washed with saturated aqueous sodium chloride solution, dried over sodium sulfate and filtered, and the filtrate was concentrated. The residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/gradient water). The fractions containing the product were concentrated under reduced pressure and 39.0 mg (45% possibility) of the title compound were obtained. LC-MS (Method 3): Rt = 1.60 min; MS (ESIpos): m /z = 381 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (0.77), -0.008 (6.64), 0.008 (5.97), 0.146 (0.77) 8 (8.28) (0.93) (2.11) (2.32) (2.62) (6.28) (3.91), 6,969 (2.11), 6,978 (5.09), 6,984 (5.30), 6,998 (2.73), 7,008 (4.32), 7,027 (4.78), 7,045 (1.59). Example 89 (5RS)-5-(Pyrrolidin-1-ylcarbonyl)-2-(2,4,5-trifluorobenzyl)-5,6,7,8-tetrahydro[1,2,4]triazolo[4, 3-a]pyridin-3(2H)-one (racemate)

[01061] (5RS)-3-oxo-2-(2,4,5-trifluorobenzyl)-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3 -a]pyridin-5-carboxylic acid/trifluoroacetic acid (racemate) (100 mg, 227 μmol) was initially loaded into THF (2.0 mL) at room temperature. Subsequently, 1-[bis(dimethylamino)methylene]-1H-[1,2,3]triazolo[4,5-b]pyridin-1-io 3-oxide hexafluorophosphate (112 mg, 295 μmol) and triethylamine (160 μl , 1.1 mmol) were added. After stirring for 15 minutes, pyrrolidine (19.3 mg, 272 μmol) was added and the reaction mixture was stirred at room temperature overnight. The reaction mixture was mixed with water and ethyl acetate. The organic phase was removed and the aqueous phase was extracted three times with ethyl acetate. The combined organic phases were washed with saturated aqueous sodium chloride solution, dried over sodium sulfate and filtered, and the filtrate was concentrated. The residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/gradient water). The fractions containing the product were concentrated under reduced pressure and 51.0 mg (59% possibility) of the title compound were obtained. LC-MS (Method 4): Rt = 0.75 min; MS (ESIpos): m /z = 381 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.150 (0.92), -0.008 (8.02), 0.008 (7.59), 1.716 (5.33) 1 (6.15) (2.19) (5.37) (2.65) (5.04), 7,580 (5.24), 7,589 (3.96), 7,606 (3.37). Example 90 (5RS)-5-[(3,3-Difluoropyrrolidin-1-yl)carbonyl]-2-[(1-methyl-1H-pyrazol-3-yl)methyl]-5,6,7,8- tetrahydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one (racemate)

[01062] (5RS)-2-[(1-Methyl-1H-pyrazol-3-yl)methyl]-3-oxo-2,3,5,6,7,8-hexahydro[1,2, 4]triazolo[4,3-a]pyridine-5-carboxylic acid/trifluoroacetic acid (racemate) (170 mg, 96% purity, 417 μmol) was loaded into THF (3.3 mL) at room temperature. Subsequently, 1-[bis(dimethylamino)methylene]-1H-[1,2,3]triazolo[4,5-b]pyridin-1-io 3-oxide hexafluorophosphate (206 mg, 542 μmol) and triethylamine (290 μl , 2.1 mmol) were added. After stirring for 15 minutes, 3,3-difluoropyrrolidine hydrochloride (71.9 mg, 500 μmol) was added and the reaction mixture was stirred at room temperature overnight. The reaction mixture was mixed with water and ethyl acetate. The organic phase was removed and the aqueous phase was extracted three times with ethyl acetate. The combined organic phases were washed with saturated aqueous sodium chloride solution, dried over sodium sulfate and filtered, and the filtrate was concentrated. The residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/gradient water). The fractions containing the product were concentrated under reduced pressure and 7.00 mg (4% possibility) of the title compound were obtained. LC-MS (Method 4): Rt = 0.54 min; MS (ESIpos): m /z = 367 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.008 (1.35), 0.008 (1.13), 1.700 (0.76), 1.982 ( 0.52), 2.044 (0.44), 2.429 (0.43), 2.566 (1.33), 2.580 (1.08), 3.529 (0.54), 3.549 (0.71), 3.663 (0.43), 3.696 (0.54), 3.730 (0.41), 3.774 ( 16.00), 3.797 (0.64), 3.908 (0.48), 4.693 (3.32), 4.702 (3.80), 4.741 (0.50), 4.783 (0.41), 4.798 (0.51), 4.807 (0.42), 6.032 (2.54), 6.038 ( 2.55), 7.571 (2.52), 7.577 (2.49). Example 91 (5RS)-5-[(3,3-Difluoropyrrolidin-1-yl)carbonyl]-2-(2,4,5-trifluorobenzyl)-5,6,7,8-tetrahydro[1,2 ,4]triazolo[4,3-a]pyridin-3(2H)-one (racemate)

[01063] (5RS)-3-oxo-2-(2,4,5-trifluorobenzyl)-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3 -a]pyridin-5-carboxylic acid/trifluoroacetic acid (racemate) (100 mg, 227 μmol) was initially loaded into THF (2.0 mL) at room temperature. Subsequently, 1-[bis(dimethylamino)methylene]-1H-[1,2,3]triazolo[4,5-b]pyridin-1-io 3-oxide hexafluorophosphate (112 mg, 295 μmol) and triethylamine (160 μl , 1.1 mmol) were added. After stirring for 15 minutes, 3,3-difluoropyrrolidine hydrochloride (39.0 mg, 272 μmol) was added and the reaction mixture was stirred at room temperature overnight. The reaction mixture was mixed with water and ethyl acetate. The organic phase was removed and the aqueous phase was extracted three times with ethyl acetate. The combined organic phases were washed with saturated aqueous sodium chloride solution, dried over sodium sulfate and filtered, and the filtrate was concentrated. The residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/gradient water). The fractions containing the product were concentrated under reduced pressure and 25.0 mg (94% purity, 25% possibility) of the title compound were obtained. LC-MS (Method 4): Rt = 0.78 min; MS (ESIpos): m /z = 417 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (0.95), 0.008 (5.95), 1.727 (3.05), 2.007 ( 3.36), 2.327 (3.00), 2.366 (1.95), 2.560 (5.45), 2.570 (6.68), 2.586 (6.00), 2.604 (6.32), 2.669 (2.68), 3.536 (3.14), 3.556 (4.45), 3.669 ( 2.59), 3.702 (3.18), 3.738 (2.64), 3.771 (3.36), 3.805 (4.82), 3.888 (1.50), 3.907 (3.09), 3.933 (2.23), 3.989 (1.86), 4.033 (1.91), 4.175 ( 1.64), 4.201 (1.68), 4,765 (3.45), 4,791 (2.09), 4,831 (15.50), 4,845 (16.00), 4,885 (2.36), 7,263 (2.77), 7,286 (3.82), 7,303 (3.73), 7,330 ( 3.05), 7,540 (2.95), 7,557 (3.59), 7,564 (4.77), 7,582 (4.55), 7,591 (3.41), 7,608 (3.18). Example 92 (5RS)-2-[(6-Methoxypyridin-3-yl)methyl]-5-(pyrrolidin-1-ylcarbonyl)-5,6,7,8-tetrahydro[1,2,4]triazole [4,3-a]pyridin-3(2H)-one (racemate)

[01064] (5RS)-2-[(6-Methoxypyridin-3-yl)methyl]-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[ 4,3-a]pyridine-5-carboxylic acid (racemate) (44.6 mg, 147 μmol) was initially loaded into THF (2.0 mL) at room temperature. Subsequently, 1-[bis(dimethylamino)methylene]-1H-[1,2,3]triazolo[4,5-b]pyridin-1-io 3-oxide hexafluorophosphate (72.4 mg, 191 μmol) and triethylamine ( 61 μl, 440 μmol) were added. After stirring for 15 minutes, pyrrolidine (12.5 mg, 176 μmol) was added and the reaction mixture was stirred at room temperature for 48 hours. 1-[Bis(dimethylamino)methylene]-1H-[1,2,3]triazolo[4,5-b]pyridin-1-io 3-oxide hexafluorophosphate (72.4 mg, 191 μmol), triethylamine (61 μl , 440 μmol) and pyrrolidine (12.5 mg, 176 μmol) were added again, and the mixture was stirred at room temperature overnight. The reaction mixture was mixed with water and ethyl acetate. The organic phase was removed and the aqueous phase was extracted three times with ethyl acetate. The combined organic phases were washed with saturated aqueous sodium chloride solution, dried over sodium sulfate and filtered, and the filtrate was concentrated. The residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/gradient water). The fractions containing the product were concentrated under reduced pressure and 12.7 mg (24% possibility) of the title compound were obtained. LC-MS (Method 3): Rt = 0.99 min; MS (ESIpos): m /z = 358 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.008 (2.07), 0.008 (1.18), 1.693 (0.72), 1.705 ( 0.80), 1.715 (0.62), 1.771 (1.14), 1.789 (2.00), 1.806 (1.55), 1.822 (0.43), 1.891 (0.57), 1.908 (1.48), 1.924 (1.84), 1.941 (1.24), 1.960 ( 0.57), 1.973 (0.63), 1.985 (0.59), 2.001 (0.43), 2.016 (0.51), 2.523 (1.70), 2.571 (0.63), 2.583 (1.01), 2.595 (0.58), 2.624 (0.41), 2.669 ( 0.40), 2.865 (1.35), 3.239 (0.63), 3.252 (0.63), 3.269 (1.20), 3.286 (1.14), 3.340 (1.20), 3.352 (0.55), 3.357 (0.67), 3.369 (0.68), 3.449 ( 0.71), 3.457 (0.53), 3.466 (0.43), 3.474 (0.86), 3.589 (0.42), 3.605 (0.82), 3.614 (0.43), 3.622 (0.47), 3.630 (0.64), 3.826 (16.00), 4.712 ( 0.78), 4.721 (0.89), 4.727 (1.04), 4.736 (0.82), 4.760 (5.47), 6.783 (1.59), 6.804 (1.70), 7.552 (1.12), 7.558 (1.13), 7.573 (1.08), 7.580 ( 1.07), 8.050 (1.33), 8.055 (1.26). Example 93 (5RS)-5-(Pyrrolidin-1-ylcarbonyl)-2-{[4-(trifluoromethyl)pyridin-2-yl]methyl}-5,6,7,8-tetrahydro[1,2, 4]triazolo[4,3-a]pyridin-3(2H)-one (enantiomer 1)

[01065] (5RS)-3-Oxo-2-{[4-(trifluoromethyl)pyridin-2-yl]methyl}-2,3,5,6,7,8-hexahydro[1,2,4 ]triazolo[4,3-a]pyridine-5-carboxylic acid (enantiomer 1) (55.0 mg, 161 μmol) was initially loaded into THF (2.0 mL) at room temperature. Subsequently, 1-[bis(dimethylamino)methylene]-1H-[1,2,3]triazolo[4,5-b]pyridin-1-io 3-oxide hexafluorophosphate (79.4 mg, 209 μmol) and triethylamine ( 67 μl, 480 μmol) were added. After stirring for 15 minutes, pyrrolidine (13.7 mg, 193 μmol) was added and the reaction mixture was stirred at room temperature overnight. The reaction mixture was mixed with water and ethyl acetate. The organic phase was removed and the aqueous phase was extracted three times with ethyl acetate. The combined organic phases were washed with saturated aqueous sodium chloride solution, dried over sodium sulfate and filtered, and the filtrate was concentrated. The residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/gradient water). The fractions containing the product were concentrated under reduced pressure and 51.0 mg (80% possibility) of the title compound were obtained. LC-MS (Method 4): Rt = 0.68 min; MS (ESIpos): m /z = 396 [M+H]+ ¹H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.008 (2.19), 0.008 (1.87), 1.681 (1.14), 1.693 ( 1.55), 1.707 (2.19), 1.718 (3.14), 1.731 (3.80), 1.741 (3.09), 1.755 (2.58), 1.773 (5.88), 1.790 (9.64), 1.807 (7.28), 1.824 (2.17), 1.894 ( 2.32), 1910 (6.68), 1927 (8.29), 1944 (4.94), 1962 (1.50), 1974 (1.07), 1986 (1.05), 2000 (1.63), 2010 (3.01), 2022 (3.35), 2034 ( 2.19), 2050 (2.32), 2060 (1.68), 2067 (1.61), 2075 (1.61), 2085 (0.90), 2096 (0.54), 2102 (0.54), 2111 (0.45), 2328 (0.54), 2366 ( 0.41), 2.524 (2.38), 2.559 (3.20), 2.569 (2.81), 2.583 (2.36), 2.597 (2.30), 2.609 (4.19), 2.621 (2.38), 2.639 (1.03), 2.650 (1.59), 2.664 ( 1.03), 2.670 (0.75), 2.710 (0.49), 2.731 (0.75), 2.865 (1.20), 2.890 (0.97), 3.232 (1.33), 3.249 (2.77), 3.261 (2.75), 3.278 (5.03), 3.296 ( 3.41), 3.341 (5.30), 3.353 (1.98), 3.358 (2.73), 3.370 (2.83), 3.388 (1.29), 3.445 (1.44), 3.462 (3.18), 3.470 (2.32), 3.479 (1.89), 3.487 ( 4.06), 3.504 (1.80), 3.597 (1.87), 3.614 (3.82), 3.622 (1.93), 3.630 (2.17), 3.638 (2.94), 3.655 (1.33), 4.764 (3.44), 4.773 (3.82), 4.779 ( 4.51), 4,788 (3.39), 4,992 (0.86), 5,034 (15,89), 5,037 (16.00), 5,079 (0.88), 7,555 (8.10), 7,701 (4,21), 7,713 (4,40), 8,813 (5,84), 8,826 ( 5.80).

[01066] The (5S) configuration was assigned based on the elucidation of the crystal structure for Examples 26, 108, 113, 157, 237, 358 and 454. (5S)-5-(Pyrrolidin-1-ylcarbonyl)-2- {[4-(trifluoromethyl)pyridin-2-yl]methyl}-5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one Example 94 (5RS)-5-(Pyrrolidin-1-ylcarbonyl)-2-{[2-(trifluoromethyl)pyrimidin-4-yl]methyl}-5,6,7,8-tetrahydro[1,2, 4]triazolo[4,3-a]pyridin-3(2H)-one (enantiomer 1)

[01067] (5RS)-3-Oxo-2-{[2-(trifluoromethyl)pyrimidin-4-yl]methyl}-2,3,5,6,7,8-hexahydro[1,2,4 ]triazolo[4,3-a]pyridine-5-carboxylic acid (enantiomer 1) (45.0 mg, 131 μmol) was initially loaded into THF (2.0 mL) at room temperature. Subsequently, 1-[bis(dimethylamino)methylene]-1H-[1,2,3]triazolo[4,5-b]pyridin-1-io 3-oxide hexafluorophosphate (64.8 mg, 170 μmol) and triethylamine ( 55 μl, 390 μmol) were added. After stirring for 15 minutes, pyrrolidine (11.2 mg, 157 μmol) was added and the reaction mixture was stirred at room temperature overnight. The reaction mixture was mixed with water and ethyl acetate. The organic phase was removed and the aqueous phase was extracted three times with ethyl acetate. The combined organic phases were washed with saturated aqueous sodium chloride solution, dried over sodium sulfate and filtered, and the filtrate was concentrated. The residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/gradient water). The fractions containing the product were concentrated under reduced pressure and 31.4 mg (100% purity, 60% chance) of the title compound were obtained. LC-MS (Method 4): Rt = 0.65 min; MS (ESIpos): m /z = 397 [M+H]+ ¹H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.008 (2.47), 0.008 (2.16), 1.699 (1.16), 1.712 ( 1.27), 1.722 (1.22), 1.757 (2.55), 1.776 (4.88), 1.793 (7.57), 1.810 (5.49), 1.827 (1.56), 1.894 (1.25), 1.911 (3.41), 1.927 (4.31), 1.943 ( 2.78), 1.960 (0.86), 2.005 (0.61), 2.017 (0.64), 2.030 (1.24), 2.043 (2.93), 2.053 (3.15), 2.068 (1.74), 2.079 (1.22), 2.086 (1.16), 2.094 ( 1.11), 2.327 (0.73), 2.367 (0.49), 2.523 (2.15), 2.571 (2.36), 2.586 (2.09), 2.597 (2.01), 2.611 (1.69), 2.625 (1.66), 2.636 (2.90), 2.649 ( 1.72), 2.666 (1.24), 2.679 (1.36), 2.690 (0.68), 2.710 (0.54), 3.242 (1.01), 3.259 (1.98), 3.272 (2.00), 3.288 (3.53), 3.335 (1.77), 3.353 ( 3.53), 3.364 (1.28), 3.370 (1.84), 3.382 (1.99), 3.400 (0.93), 3.453 (1.01), 3.471 (2.24), 3.478 (1.66), 3.488 (1.33), 3.496 (2.90), 3.513 ( 1.27), 3599 (1.36), 3615 (2.51), 3624 (1.36), 3633 (1.62), 3641 (1.96), 3657 (0.95), 4785 (2.52), 4794 (2.77), 4799 (3.42), 4808 ( 2.43), 5.035 (0.44), 5.080 (16.00), 5.125 (0.42), 7.480 (5.36), 7.493 (5.54), 9.047 (6.50), 9.060 (6.45).

[01068] The (5S) configuration was assigned based on the elucidation of the crystal structure for Examples 26, 108, 113, 157, 237, 358 and 454. (5S)-5-(Pyrrolidin-1-ylcarbonyl)-2- {[2-(trifluoromethyl)pyrimidin-4-yl]methyl}-5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one Example 95 (5RS)-2-(3-Chloro-4-fluorobenzyl)-5-[(3-hydroxyazetidin-1-yl)carbonyl]-5,6,7,8-tetrahydro[1,2,4 ]triazolo[4,3-a]pyridin-3(2H)-one (racemate)

[01069] (5RS)-2-(3-Chloro-4-fluorobenzyl)-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3 -a]pyridine-5-carboxylic acid hydrochloride (racem-ate) (193 mg, 532 μmol) was initially loaded into THF (5.0 mL) at room temperature. Subsequently, 1-[bis(dimethylamino)methylene]- 1H-[1,2,3]triazolo[4,5-b]pyridin-1-io 3-oxide hexafluorophosphate (263 mg, 692 μmol) and triethylamine (300 μl , 2.1 mmol) were added. After stirring for 15 minutes, azetidin-3-ol hydrochloride (70.0 mg, 639 μmol) was added and the reaction mixture was stirred at room temperature overnight. The reaction mixture was mixed with water and ethyl acetate. The organic phase was removed and the aqueous phase was extracted three times with ethyl acetate. The combined organic phases were washed with saturated aqueous sodium chloride solution, dried over sodium sulfate and filtered, and the filtrate was concentrated. The residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/gradient water). The fractions containing the product were concentrated under reduced pressure and 63.4 mg (31% possibility) of the title compound were obtained. LC-MS (Method 3): Rt = 1.17 min; MS (ESIpos): m /z = 381 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.008 (1.65), 0.008 (1.43), 1.677 (2.01), 1.695 ( 2.51), 1709 (2.94), 1718 (3.05), 1902 (1.44), 1927 (2.11), 1938 (3.11), 1994 (2.08), 2004 (2.25), 2016 (2.08), 2073 (3.94), 2327 ( 0.59), 2.366 (0.45), 2.572 (2.33), 2.580 (3.06), 2.592 (5.37), 2.605 (2.83), 2.622 (1.29), 2.634 (1.98), 2.646 (0.91), 2.669 (0.64), 2.690 ( 0.67), 2.710 (0.49), 3.596 (1.70), 3.603 (1.93), 3.621 (2.05), 3.629 (2.25), 3.638 (1.86), 3.649 (1.84), 3.664 (1.78), 3.674 (1.75), 3.921 ( 2.08), 3.932 (2.28), 3.952 (0.58), 4.021 (3.54), 4.045 (3.84), 4.055 (2.17), 4.062 (1.96), 4.105 (1.41), 4.120 (1.77), 4.131 (1.50), 4.146 ( 1.38), 4.339 (1.43), 4.357 (2.42), 4.378 (1.68), 4.473 (1.22), 4.485 (2.84), 4.502 (5.81), 4.520 (8.36), 4.531 (6.20), 4.546 (2.47), 4.818 ( 15.96), 4,823 (16.00), 5,789 (3.64), 5,802 (7.82), 5,817 (4,83), 7,223 (2.47), 7,244 (3.60), 7,250 (3.33), 7,256 (3.17), 7,367 (3,17) 3.18), 7,371 (3.21), 7,390 (5.20), 7,411 (2.59), 7,416 (2.59), 7,434 (4.30), 7,452 (4.27). Example 96 (5RS)-5-[(3-Fluoroazetidin-1-yl)carbonyl]-2-{[6-(trifluoromethyl)pyridin-3-yl]methyl}-5,6,7,8-tetrahydro [1,2,4]triazolo[4,3-a]pyridin-3(2H)-one (racemate)

[01070] (5RS)-3-Oxo-2-{[6-(trifluoromethyl)pyridin-3-yl]methyl}-2,3,5,6,7,8-hexahydro[1,2,4 ]triazolo[4,3-a]pyridine-5-carboxylic acid (racemate) (60.0 mg, 175 μmol) was initially loaded into THF (2.0 mL) at room temperature. Subsequently, 1-[bis(dimethylamino)methylene]-1H-[1,2,3]triazolo[4,5-b]pyridin-1-io 3-oxide hexafluorophosphate (86.6 mg, 228 μmol) and triethylamine ( 73 μl, 530 μmol) were added. After stirring for 15 minutes, 3-fluoroazetidine hydrochloride (23.5 mg, 210 μmol) was added and the reaction mixture was stirred at room temperature overnight. The reaction mixture was mixed with water and ethyl acetate. The organic phase was removed and the aqueous phase was extracted three times with ethyl acetate. The combined organic phases were washed with saturated aqueous sodium chloride solution, dried over sodium sulfate and filtered, and the filtrate was concentrated. The residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/gradient water). The fractions containing the product were concentrated under reduced pressure and 30.0 mg (43% possibility) of the title compound were obtained. LC-MS (Method 3): Rt = 1.18 min; MS (ESIpos): m /z = 400 [M+H]+ ¹H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.150 (0.47), -0.008 (4.45), 0.008 (3.73), 0.146 (0.42) (5.13), 2523 (4.20), 2560 (2.38), 2586 (3.13), 2599 (4.31), 2613 (2.17), 2628 (0.84), 2641 (1.42), 2655 (0.68), 2710 (0.84), 3.901 (0.56), 3930 (1.12), 3963 (1.21), 3991 (1.12), 4026 (0.68), 4160 (0.49), 4175 (0.54), 4228 (1.05), 4244 (0.98), 4256 (0.93), 4277 (1.24) (4.36) (0.72), 7,912 (16.00), 8,649 (6.27). Example 97 (5RS)-2-(3-Chloro-4-fluorobenzyl)-5-{[(3S)-3-hydroxypyrrolidin-1-yl]carbonyl}-5,6,7,8-tetrahydro[1 ,2,4]triazolo[4,3-a]pyridin-3(2H)-one (enantiomer 1)

[01071] (5RS)-2-(3-Chloro-4-fluorobenzyl)-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3 -a]pyridine-5-carboxylic acid (enantiomer 1) (55.0 mg, 169 μmol) was initially loaded into THF (2.0 mL) at room temperature. Subsequently, 1-[bis(dimethylamino)methylene]- 1H-[1,2,3]triazolo[4,5-b]pyridin-1-io 3-oxide hexafluorophosphate (83.5 mg, 220 μmol) and triethylamine ( 71 μl, 510 μmol) were added. After stirring for 15 minutes, (3S)-pyrrolidin-3-ol hydrochloride (25.0 mg, 203 μmol) was added and the reaction mixture was stirred at room temperature overnight. The reaction mixture was mixed with water and ethyl acetate. The organic phase was removed and the aqueous phase was extracted three times with ethyl acetate. The combined organic phases were washed with saturated aqueous sodium chloride solution, dried over sodium sulfate and filtered, and the filtrate was concentrated. The residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/gradient water). The fractions containing the product were concentrated under reduced pressure and 66.0 mg (97% possibility) of the title compound were obtained. LC-MS (Method 3): Rt = 1.19 min; MS (ESIpos): m /z = 395 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.008 (2.74), 0.008 (2.46), 1.668 (1.27), 1.681 ( 1.28), 1.731 (2.93), 1.741 (2.61), 1.754 (2.32), 1.763 (2.04), 1.827 (0.60), 1.839 (0.73), 1.849 (1.61), 1.860 (1.98), 1.872 (1.68), 1.882 ( 2.15), 1892 (1.71), 1904 (1.25), 1972 (2.44), 1983 (2.94), 1994 (2.98), 2005 (2.63), 2015 (2.47), 2023 (2.13), 2029 (2.09), 2038 ( 1.82), 2.050 (1.44), 2.058 (1.57), 2.066 (1.43), 2.073 (5.11), 2.086 (0.54), 2.327 (0.61), 2.366 (0.49), 2.523 (3.02), 2.571 (1.77), 2.580 ( 1.19), 2.593 (2.23), 2.604 (3.72), 2.616 (2.00), 2.634 (1.06), 2.646 (1.52), 2.660 (0.87), 2.669 (0.81), 2.710 (0.61), 2.731 (3.89), 2.877 ( 0.63), 2.890 (5.16), 3.199 (1.00), 3.231 (1.38), 3.298 (3.79), 3.339 (2.01), 3.375 (2.71), 3.397 (1.82), 3.415 (0.81), 3.432 (0.70), 3.442 ( 0.77), 3.454 (1.37), 3.461 (1.36), 3.470 (0.68), 3.483 (1.53), 3.520 (0.41), 3.545 (1.20), 3.562 (1.93), 3.569 (2.22), 3.585 (1.42), 3.640 ( 1.08), 3.651 (1.61), 3.667 (1.13), 3.678 (1.28), 3.734 (0.54), 3.754 (0.82), 3.774 (0.43), 4.268 (1.82), 4.362 (1.80), 4.687 (0.98), 4.695 ( 1.13), 4.702 (1.23), 4.710 (0.99), 4.738 (2.01), 4.745 (1.57), 4.794 (1.01), 4.817 (16.00), 4.955 (4.61), 4.964 (4.28), 5.073 (3.17), 5.075 ( 3.09), 5.082 (3.27), 7.222 (2.22), 7.227 (2.23), 7.238 (2.55), 7.243 (3.00), 7.249 (2.85), 7.255 (2.74), 7.362 (0.47), 7.371 (4.52), 7.394 ( 6.84), 7.406 (0.56), 7.416 (3.64), 7.430 (3.15), 7.448 (3.23), 7.953 (0.53).

[01072] The (5S) configuration was assigned based on the elucidation of the crystal structure for Examples 26, 108, 113, 157, 237, 358 and 454. (5S)-2-(3-Chloro-4-fluorobenzyl)- 5-{[(3S)-3-hydroxypyrrolidin-1-yl]carbonyl}- 5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridin-3(2H )-one Example 98 (5RS)-5-[(3-Hydroxyazetidin-1-yl)carbonyl]-2-[3-(trifluoromethyl)benzyl]-5,6,7,8-tetrahydro[1,2 ,4]triazolo[4,3-a]pyridin-3(2H)-one (enantiomer 1)

[01073] (5RS)-3-Oxo-2-[3-(trifluoromethyl)benzyl]-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3- a]pyridine-5-carboxylic acid (enantiomer 1) (55.0 mg, 161 μmol) was initially loaded into THF (2.0 mL) at room temperature. Subsequently, 1-[bis(dimethylamino)methylene]- 1H-[1,2,3]triazolo[4,5-b]pyridin-1-io 3-oxide hexafluorophosphate (79.7 mg, 209 μmol) and triethylamine ( 67 μl, 480 μmol) were added. After stirring for 15 minutes, azetidin-3-ol hydrochloride (21.2 mg, 193 μmol) was added and the reaction mixture was stirred at room temperature overnight. The reaction mixture was mixed with water and ethyl acetate. The organic phase was removed and the aqueous phase was extracted three times with ethyl acetate. The combined organic phases were washed with saturated aqueous sodium chloride solution, dried over sodium sulfate and filtered, and the filtrate was concentrated. The residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/gradient water). The fractions containing the product were concentrated under reduced pressure and 7.90 mg (12% possibility) of the title compound were obtained. LC-MS (Method 3): Rt = 1.24 min; MS (ESIpos): m /z = 397 [M+H]+ ¹H-NMR (500 MHz, DMSO-d6) δ [ppm]: 1.666 (2.27), 1.676 (2.26), 1.719 (3.03), 1.920 (1.91 ), 1,946 (3.45), 2,013 (2.68), 2,020 (2.73), 2,072 (11.94), 2,588 (2.90), 2,597 (5.00), 2,606 (2.91), 2,621 (1.59), 2,631 (2.38), 2,690 (0.66 ), 3.608 (2.01), 3.623 (2.15), 3.629 (2.19), 3.644 (1.80), 3.652 (1.89), 3.663 (1.89), 3.672 (1.75), 3.928 (2.17), 3.938 (2.46), 3.953 (0.71 ), 4,029 (3.39), 4,040 (3.81), 4,047 (4.10), 4,059 (2.67), 4,109 (1.41), 4,122 (1.81), 4,130 (1.69), 4,141 (1.49),4,343 (1.52), 4,358 (2.55 ), 4.374 (1.66), 4.404 (0.44), 4.495 (3.28), 4.510 (4.92), 4.521 (7.10), 4.533 (5.97), 4.541 (4.89), 4.925 (15.15), 4.931 (16.00), 5.817 (8.02 ), 7,510 (3.60), 7,524 (5.29), 7,574 (2.93), 7,589 (5.35), 7,604 (3.34), 7,623 (9.33), 7,649 (6.87), 7,664 (4.72).

[01074] The (5S) configuration was assigned based on the elucidation of the crystal structure for Examples 26, 108, 113, 157, 237, 358 and 454. (5S)-5-[(3-Hydroxiazetidin-1-yl) carbonyl]-2-[3-(trifluoromethyl)benzyl]-5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one Example 99 (5RS)-5-{[(3S)-3-Hydroxypyrrolidin-1-yl]carbonyl}-2-[3-(trifluoromethyl)benzyl]-5,6,7,8-tetrahydro[1,2, 4]triazolo[4,3-a]pyridin-3(2H)-one (enantiomer 1)

[01075] hydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylic acid (enantiomer 1) (55.0 mg, 161 μmol) was initially loaded into THF (2.0 mL) in room temperature. Subsequently, 1-[bis(dimethylamino)methylene]- 1H-[1,2,3]triazolo[4,5-b]pyridin-1-io 3-oxide hexafluorophosphate (79.7 mg, 209 μmol) and triethylamine ( 67 μl, 480 μmol) were added. After stirring for 15 minutes, (3S)-pyrrolidin-3-ol hydrochloride (23.9 mg, 193 μmol) was added and the reaction mixture was stirred at room temperature overnight. The reaction mixture was mixed with water and ethyl acetate. The organic phase was removed and the aqueous phase was extracted three times with ethyl acetate. The combined organic phases were washed with saturated aqueous sodium chloride solution, dried over sodium sulfate and filtered, and the filtrate was concentrated. The residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/gradient water). The fractions containing the product were concentrated under reduced pressure and 10.9 mg (16% possibility) of the title compound were obtained. LC-MS (Method 3): Rt = 1.26 min; MS (ESIpos): m /z = 411 [M+H]+ 1H-NMR (500 MHz, DMSO-d6) δ [ppm]: -0.007 (2.44), 0.006 (1.71), 1.677 (1.35), 1.733 ( 2.92), 1.753 (2.40), 1.835 (0.67), 1.845 (0.79), 1.853 (1.67), 1.862 (2.30), 1.871 (1.79), 1.879 (2.36), 1.888 (1.98), 1.958 (1.81), 1.967 ( 2.10), 1976 (2.36), 1985 (2.86), 1994 (2.94), 2003 (2.57), 2010 (2.04), 2024 (2.04), 2031 (2.30), 2044 (1.74), 2053 (1.72), 2060 ( 1.78), 2.066 (1.45), 2.072 (2.04), 2.087 (0.58), 2.362 (0.62), 2.519 (2.96), 2.563 (1.74), 2.574 (0.72), 2.608 (3.40), 2.640 (1.92), 2.689 ( 0.42), 2.877 (0.45), 3.205 (1.08), 3.230 (1.45), 3.353 (1.74), 3.369 (2.56), 3.375 (2.51), 3.393 (2.14), 3.400 (1.78), 3.412 (0.69), 3.436 ( 0.87), 3.444 (0.78), 3.454 (1.01), 3.461 (1.82), 3.484 (1.52), 3.530 (0.41), 3.550 (1.21), 3.563 (2.45), 3.571 (2.19), 3.583 (1.63), 3.647 ( 1.29), 3.655 (1.90), 3.668 (1.25), 3.677 (1.47), 3.741 (0.57), 3.755 (0.87), 3.772 (0.49), 4.266 (2.09), 4.366 (2.09), 4.392 (0.46), 4.403 ( 0.66), 4.699 (1.20), 4.705 (1.32), 4.711 (1.42), 4.717 (1.14), 4.742 (1.79), 4.748 (2.20), 4.754 (1.94), 4.806 (0.98), 4.813 (1.09), 4.818 ( 1.14), 4.825 (0.90), 4.896 (0.42), 4.923 (16.00), 4.968 (1.22), 5.089 (1.29), 7.218 (0.52), 7.507 (2.86), 7.523 (4.44), 7.540 (0.69), 7.574 ( 3.29), 7,590 (6.42), 7,605 (3.61), 7,621 (6.90), 7,647 (6.52), 7,663 (4.44).

[01076] The (5S) configuration was assigned based on the elucidation of the crystal structure for Examples 26, 108, 113, 157, 237, 358 and 454. (5S)-5-{[(3S)-3-Hydroxypyrrolidin- 1-yl]carbonyl}-2-[3-(trifluoromethyl)benzyl]-5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridin-3(2H) -one Example 100 (5RS)-5-{[(3R)-3-Fluoropyrrolidin-1-yl]carbonyl}-2-{[6-(trifluoromethyl)pyridin-3-yl]methyl}-5,6,7 ,8-tetrahydro[1,2,4]triazolo[4,3- a]pyridin-3(2H)-one (diastereomer mixture; 2 isomers)

[01077] (5RS)-3-Oxo-2-{[6-(trifluoromethyl)pyridin-3-yl]methyl}-2,3,5,6,7,8-hexahydro[1,2,4 ]triazolo[4,3-a]pyridine-5-carboxylic acid (racemate) (60.0 mg, 175 μmol) was initially loaded into THF (2.0 mL) at room temperature. Subsequently, 1-[bis(dimethylamino)methylene]-1H-[1,2,3]triazolo[4,5-b]pyridin-1-io 3-oxide hexafluorophosphate (86.6 mg, 228 μmol) and triethylamine ( 73 μl, 530 μmol) were added. After stirring for 15 minutes, (3R)-3-fluoropyrrolidine hydrochloride (26.4 mg, 210 μmol) was added and the reaction mixture was stirred at room temperature overnight. The reaction mixture was mixed with water and ethyl acetate. The organic phase was removed and the aqueous phase was extracted three times with ethyl acetate. The combined organic phases were washed with saturated aqueous sodium chloride solution, dried over sodium sulfate and filtered, and the filtrate was concentrated. The residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/gradient water). The fractions containing the product were concentrated under reduced pressure and 29.0 mg (40% possibility) of the title compound were obtained. LC-MS (Method 3): Rt = 1.21 min; MS (ESIpos): m /z = 414 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (0.59), -0.008 (5.76), 0.008 (4.91), 0.146 (0.59) (0.49) (0.81) (0.56) (0.68) (0.80) (5.57). Example 101 (5RS)-2-[4-Fluoro-3-(trifluoromethyl)benzyl]-5-{[(3S)-3-hydroxypyrrolidin-1-yl]carbonyl}-5,6,7,8-tetra- hydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one (diastereomer mixture; 2 isomers)

[01078] (5RS)-2-[4-Fluoro-3-(trifluoromethyl)benzyl]-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[ 4,3-a]pyridine-5-carboxylic acid (racemate) (90.0 mg, 250 μmol) was initially loaded into THF (2.0 mL) at room temperature. Subsequently, 1-[bis(dimethylamino)methylene]- 1H-[1,2,3]triazolo[4,5-b]pyridin-1-io 3-oxide hexafluorophosphate (124 mg, 326 μmol) and triethylamine (100 μl , 750 μmol) were added. After stirring for 15 minutes, (3S)-pyrrolidin-3-ol hydrochloride (37.1 mg, 301 μmol) was added and the reaction mixture was stirred at room temperature overnight. The reaction mixture was mixed with water and ethyl acetate. The organic phase was removed and the aqueous phase was extracted three times with ethyl acetate. The combined organic phases were washed with saturated aqueous sodium chloride solution, dried over sodium sulfate and filtered, and the filtrate was concentrated. The residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/gradient water). The fractions containing the product were concentrated under reduced pressure and 34.0 mg (32% possibility) of the title compound were obtained. LC-MS (Method 3): Rt = 1.30 min; MS (ESIpos): m /z = 429 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (1.32), -0.008 (12.62), 0.008 (10.09), 0.146 (1.26) (2.58), 1,984 (3.11), 1,995 (3.23), 2,005 (3.02), 2,017 (2.65), 2,037 (1.94), 2,056 (1.60), 2,065 (1.42), 2,328 (1.54), 2,366 (0.98), 2,524 (6.71) (2.34) (1.51) (0.92) (3.29), 7,671 (3.72), 7,690 (3.82). Example 102 (5RS)-5-(Pyrrolidin-1-ylcarbonyl)-2-(2,4,5-trimethylbenzyl)-5,6,7,8-tetrahydro[1,2,4]triazolo[4, 3-a]pyridin-3(2H)-one (enantiomer 1)

[01079] (5RS)-3-Oxo-2-(2,4,5-trimethylbenzyl)-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3 -a]pyridine-5-carboxylic acid (enantiomer 1) (93.0 mg, 295 μmol) was initially loaded into THF (2.0 mL) at room temperature. Subsequently, 1-[bis(dimethylamino)methylene]- 1H-[1,2,3]triazolo[4,5-b]pyridin-1-io 3-oxide hexafluorophosphate (146 mg, 383 μmol) and triethylamine (120 μl , 880 μmol) were added. After stirring for 15 minutes, pyrrolidine (30 μl, 350 μmol) was added and the reaction mixture was stirred at room temperature for 72 hours. The reaction mixture was mixed with water and ethyl acetate. The organic phase was removed and the aqueous phase was extracted three times with ethyl acetate. The combined organic phases were washed with saturated aqueous sodium chloride solution, dried over sodium sulfate and filtered, and the filtrate was concentrated. The residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/gradient water). The fractions containing the product were concentrated under reduced pressure and 55.0 mg (51% possibility) of the title compound were obtained. LC-MS (Method 3): Rt = 1.59 min; MS (ESIpos): m /z = 369 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.008 (0.95), 0.008 (0.80), 1.661 (0.42), 1.673 ( 0.74), 1.687 (1.21), 1.697 (1.43), 1.710 (1.15), 1.754 (0.47), 1.772 (1.91), 1.790 (3.37), 1.807 (2.63), 1.823 (0.77), 1.892 (0.79), 1.909 ( 2.45), 1926 (3.23), 1942 (2.13), 1961 (0.95), 1974 (1.22), 1985 (1.53), 1996 (1.03), 2010 (0.92), 2020 (0.64), 2026 (0.58), 2036 ( 0.58), 2.046 (0.40), 2.140 (15.41), 2.144 (16.00), 2.205 (14.00), 2.457 (0.40), 2.473 (0.58), 2.523 (1.61), 2.560 (0.86), 2.571 (1.56), ( 0.85), 2.613 (0.63), 3.224 (0.46), 3.240 (0.99), 3.253 (0.98), 3.270 (1.74), 3.287 (0.91), 3.321 (1.38), 3.340 (1.90), 3.352 (0.69), 3.357 ( 0.94), 3.369 (1.05), 3.387 (0.48), 3.433 (0.53), 3.450 (1.15), 3.458 (0.84), 3.468 (0.69), 3.475 (1.45), 3.492 (0.64), 3.591 (0.67), 3.608 ( 1.40), 3.616 (0.70), 3.625 (0.78), 3.633 (1.09), 3.649 (0.49), 4.684 (8.43), 4.716 (1.31), 4.725 (1.52), 4.731 (1.73), 4.740 (1.26), 6.890 ( 4.26), 6.914 (3.98).

[01080] The (5S) configuration was assigned based on the elucidation of the crystal structure for Examples 26, 108, 113, 157, 237, 358 and 454. (5S)-5-(Pyrrolidin-1-ylcarbonyl)-2- (2,4,5-trimethylbenzyl)-5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one Example 103 (5RS)- 5-(Pyrrolidin-1-ylcarbonyl)-2-[(3,5,6-trimethylpyrazin-2-yl)methyl]-5,6,7,8-tetrahydro[1,2,4]triazolo[4 ,3-a]pyridin-3(2H)-one (racemate)

[01081] (5RS)-3-Oxo-2-[(3,5,6-trimethylpyrazin-2-yl)methyl]-2,3,5,6,7,8-hexahydro[1,2, 4]triazolo[4,3-a]pyridine-5-carboxylic acid (racemate) (90.0 mg, 90% purity, 255 μmol) was initially loaded into DMF (1.9 mL) at room temperature. Subsequently, 1-[bis(dimethylamino)methylene]-1H-[1,2,3]triazolo[4,5-b]pyridin-1-io 3-oxide hexafluorophosphate (126 mg, 332 μmol) and triethylamine (110 μl , 770 μmol) were added. After stirring for 15 minutes, pyrrolidine (26 μl, 310 μmol) was added and the reaction mixture was stirred at room temperature overnight. 1-[Bis(dimethylamino)methylene]- 1H-[1,2,3]triazolo[4,5-b]pyridin-1-io 3-oxide hexafluorophosphate (97 mg, 255 μmol) and triethylamine (36 μl, 255 μmol) were added again, and the mixture was stirred at room temperature for 1 hour. The reaction mixture was mixed with water and ethyl acetate. The organic phase was removed and the aqueous phase was extracted three times with ethyl acetate. The combined organic phases were washed with saturated aqueous sodium chloride solution, dried over sodium sulfate and filtered, and the filtrate was concentrated. The residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/gradient water). The fractions containing the product were concentrated under reduced pressure and 57.0 mg (60% possibility) of the title compound were obtained. LC-MS (Method 3): Rt = 0.93 min; MS (ESIpos): m /z = 371 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: 1.649 (0.46), 1.662 (0.81), 1.675 (1.31), 1.685 (1.56 ), 1,699 (1.24), 1,756 (0.44), 1,773 (1.80), 1,790 (3.21), 1,807 (2.55), 1,824 (0.78), 1,893 (0.77), 1,909 (2.39), 1,926 (3.22), 1,943 (2.22 ), 1,959 (1.07), 1,969 (1.22), 1,981 (1.37), 1,993 (0.94), 2.007 (0.89), 2,018 (0.64), 2,032 (0.58), 2,384 (14,92), 2,409 (15.08), 2,417 (1600 ), 2.450 (0.52), 2.458 (0.45), 2.476 (1.25), 2.574 (0.48), 2.586 (0.61), 3.222 (0.45), 3.239 (0.92), 3.252 (0.96), 3.269 (1.63), 3.286 (0.80 ), 3.336 (1.71), 3.354 (0.89), 3.366 (0.96), 3.383 (0.44), 3.434 (0.50), 3.451 (1.10), 3.458 (0.82), 3.476 (1.38), 3.493 (0.63), 3.594 (0.64 ), 3.611 (1.35), 3.619 (0.70), 3.628 (0.78), 3.636 (1.06), 3.652 (0.47), 4.717 (1.21), 4.726 (1.43), 4.732 (1.62), 4.740 (1.19), 4.868 (9.21 ). Example 104 (5RS)-5-(Pyrrolidin-1-ylcarbonyl)-2-[(3,5,6-trimethylpyrazin-2-yl)methyl]-5,6,7,8-tetrahydro[1,2 ,4]triazolo[4,3-a]pyridin-3(2H)-one (enantiomer 2)

[01082] (5RS)-5-(Pyrrolidin-1-ylcarbonyl)-2-[(3,5,6-trimethylpyrazin-2-yl)methyl]-5,6,7,8-tetrahydro[1, 2,4]triazolo[4,3-a]pyridin-3(2H)-one (race-mate) was separated by chiral preparatory HPLC [sample preparation: 46 mg dissolved in 4 mL of ethanol; injection volume: 0.35 mL; column: Daicel Chiralpak® AD-H 5μm, 250 x 20 mm; eluent: n-heptane/ethanol: isocratic 60% ethanol, flow rate: 25 ml/min; temperature 25°C; UV detection: 210 nm]. After separation, 19 mg of enantiomer 1, which eluted first, and 19 mg (92% purity) of enantiomer 2, which eluted later, were isolated. Enantiomer 2:

[01083] Analytical chiral HPLC: Rt = 2.11 min, ee = 99% [column: Daicel Chiralcel® AD-3 3μm 50 x 4.6 mm; eluent: n-heptane/ethanol 1:1; flow rate: 1 ml/min; UV detection: 220 nm]. LC-MS (Method 4): Rt = 0.56 min; MS (ESIpos): m /z = 371 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: 1.63-1.68 (m, 2H), 1.79 (quin, 2H), 1.86 - 2.07 (m, 4H), 2.38 (s, 3H), 2.41 (d, 6H), 2.44 - 2.61 (m, 2H, partially covered by solvent signal), 3.14 - 3.29 (m, 1H), 3.33 - 3.39 ( m, 1H), 3.41 - 3.52 (m, 1H), 3.57 - 3.67 (m, 1H), 4.73 (dd, 1H), 4.87 (s, 2H). Example 105 5(RS)-5-Methyl-2-(4-methylbenzyl)-5-(pyrrolidin-1-ylcarbonyl)-5,6,7,8-tetrahydro[1,2,4]triazolo[4 ,3-a]pyridin-3(2H)-one (racemate)

[01084] (5RS)-5-Methyl-2-(4-methylbenzyl)-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3 -a]pyridine-5-carboxylic acid (racemate) (30.0 mg, 99.6 μmol) was initially loaded into THF (1.0 mL) at room temperature. Subsequently, 1-[bis(dimethylamino)methylene]-1H-[1,2,3]triazolo[4,5-b]pyridin-1-io 3-oxide hexafluorophosphate (49.2 mg, 129 μmol) and triethylamine ( 42 μl, 300 μmol) were added. After stirring for 15 minutes, pyrrolidine (10 μl, 120 μmol) was added and the reaction mixture was stirred at room temperature overnight. The reaction mixture was mixed with water and ethyl acetate. The organic phase was removed and the aqueous phase was extracted three times with ethyl acetate. The combined organic phases were washed with saturated aqueous sodium chloride solution, dried over sodium sulfate and filtered, and the filtrate was concentrated. The residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/gradient water). The fractions containing the product were concentrated under reduced pressure and 19.4 mg (55% possibility) of the title compound were obtained. LC-MS (Method 3): Rt = 1.46 min; MS (ESIpos): m /z = 355 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.008 (0.46), 0.008 (0.45), 1.155 (0.41), 1.173 ( 0.84), 1.192 (0.44), 1.202 (0.85), 1.218 (0.84), 1.563 (11.36), 1.715 (1.01), 1.754 (0.66), 1.767 (0.63), 1.781 (0.47), 1.817 (1.45), 1.845 ( 1.15), 1.958 (0.59), 1.986 (0.75), 2.269 (11.71), 2.599 (0.63), 2.611 (0.73), 2.624 (1.11), 2.635 (1.32), 3.237 (0.41), 4.664 (1.34), 4.702 ( 2.54), 4,780 (2.48), 4,818 (1.34), 7,127 (16.00). Example 106 (5RS)-2-{[3-Chloro-5-(trifluoromethyl)pyridin-2-yl]methyl}-5-(pyrrolidin-1-ylcarbonyl)-5,6,7,8-tetrahydro[ 1,2,4]triazolo[4,3-a]pyridin-3(2H)-one (enantiomer 1)

[01085] Methyl (5RS)-2-{[3-chloro-5-(trifluoromethyl)pyridin-2-yl]methyl}-3-oxo-2,3,5,6,7,8-hexahydro[ 1,2,4]triazolo[4,3-a]pyridine-5-carboxylate (enantiomer 1) (80.0 mg, 205 μmol) was initially loaded into THF (1.8 mL) at room temperature. Subsequently, 1-[bis(dimethylamino)methylene]-1H-[1,2,3]triazolo[4,5-b]pyridin-1-io 3-oxide hexafluorophosphate (101 mg, 266 μmol) and triethylamine (86 μl , 610 μmol) were added. After stirring for 15 minutes, pyrrolidine (21 μl, 250 μmol) was added and the reaction mixture was stirred at room temperature for 72 hours. The reaction mixture was mixed with water and ethyl acetate. The organic phase was removed and the aqueous phase was extracted three times with ethyl acetate. The combined organic phases were washed with saturated aqueous sodium chloride solution, dried over sodium sulfate and filtered, and the filtrate was concentrated. The residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/gradient water). The fractions containing the product were concentrated under reduced pressure and 4.20 mg (5% possibility) of the title compound were obtained. LC-MS (Method 3): Rt = 1.37 min; MS (ESIpos): m /z = 430 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (1.19), -0.008 (10.74), 0.008 (9.06), 0.146 (1.10) (3.31) (3.54) (1.81) (4.33) (3.05) (15.43), 5,175 (4.64), 8,486 (10.96), 8,489 (11.27), 8,905 (11.09).

[01086] The (5S) configuration was assigned based on the elucidation of the crystal structure for Examples 26, 108, 113, 157, 237, 358 and 454. (5S)-2-{[3-Chloro-5-(trifluoromethyl )pyridin-2-yl]methyl}-5-(pyrrolidin-1-ylcarbonyl)-5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridin-3( 2H)-one Example 107 (5RS)-2-{[5-Chloro-4-(trifluoromethyl)pyridin-2-yl]methyl}-5-(pyrrolidin-1-ylcarbonyl)-5,6,7,8- tetrahydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one (enantiomer 1)

[01087] (5RS)-2-{[5-Chloro-4-(trifluoromethyl)pyridin-2-yl]methyl}-3-oxo-2,3,5,6,7,8-hexahydro[1 ,2,4]triazolo[4,3-a]pyridine-5-carboxylic acid (enantiomer 1) (100 mg, 265 μmol) was initially loaded into THF (3.8 mL) at room temperature. Subsequently, 1-[bis(dimethylamino)methylene]-1H-[1,2,3]triazolo[4,5-b]pyridin-1-io 3-oxide hexafluorophosphate (131 mg, 345 μmol) and triethylamine (110 μl , 800 μmol) were added. After stirring for 15 minutes, pyrrolidine (27 μl, 320 μmol) was added and the reaction mixture was stirred at room temperature for 72 hours. The reaction mixture was mixed with water and ethyl acetate. The organic phase was removed and the aqueous phase was extracted three times with ethyl acetate. The combined organic phases were washed with saturated aqueous sodium chloride solution, dried over sodium sulfate and filtered, and the filtrate was concentrated. The residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/gradient water). The fractions containing the product were concentrated under reduced pressure and 65.0 mg (57% possibility) of the title compound were obtained. LC-MS (Method 4): Rt = 0.79 min; MS (ESIpos): m /z = 430 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.008 (2.42), 0.008 (2.12), 1.711 (2.02), 1.724 ( 2.54), 1.735 (2.04), 1.755 (1.54), 1.772 (4.25), 1.789 (6.89), 1.806 (5.25), 1.823 (1.54), 1.891 (1.57), 1.908 (4.70), 1.925 (5.85), 1.942 ( 3.54), 1.959 (1.16), 2.005 (2.17), 2.016 (2.70), 2.026 (1.79), 2.043 (1.62), 2.052 (1.21), 2.067 (1.15), 2.328 (0.72), 2.366 (0.47), 2.560 ( 2.01) 0.66), 2.890 (0.73), 3.229 (0.83), 3.246 (1.96), 3.258 (1.95), 3.275 (3.58), 3.293 (1.92), 3.335 (3.62), 3.353 (1.88), 3.365 (1.97), 3.383 ( 0.88), 3.441 (1.04), 3.458 (2.32), 3.465 (1.61), 3.482 (2.93), 3.500 (1.30), 3.593 (1.31), 3.609 (2.74), 3.626 (1.57), 3.634 (2.05), 3.650 ( 0.96), 4.755 (2.49), 4.764 (2.73), 4.770 (3.18), 4.779 (2.43), 4.992 (0.41), 5.034 (16.00), 5.076 (0.45), 7.719 (10.56), 8.902 (9.80).

[01088] The (5S) configuration was assigned based on the elucidation of the crystal structure for Examples 26, 108, 113, 157, 237, 358 and 454. (5S)-2-{[5-Chloro-4-(trifluoromethyl )pyridin-2-yl]methyl}-5-(pyrrolidin-1-ylcarbonyl)-5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridin-3( 2H)-one Example 108 (5RS)-2-(4-Methylbenzyl)-5-(1,3-thiazolidin-3-ylcarbonyl)-5,6,7,8-tetrahydro[1,2,4] triazolo[4,3-a]pyridin-3(2H)-one (enantiomer 1)

[01089] (5RS)-2-(4-Methylbenzyl)-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine -5-carboxylic acid (enantiomer 1) (75.0 mg, 261 μmol) was initially loaded into DMF (3.1 mL) and dichloromethane (1.5 mL) at room temperature. Subsequently, 1-[bis(dimethylamino)methylene]-1H-benzotriazol-1-ium 3-oxide hexafluorophosphate (129 mg, 339 μmol) and N,N-diisopropylethylamine (120 μl, 680 μmol) were added. After stirring for 15 minutes, 1,3-thiazolidine hydrochloride (39.3 mg, 313 μmol) was added and the reaction mixture was stirred at room temperature overnight. The solvent was removed under reduced pressure, and the residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/water gradient). HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/gradient water). The fractions containing the product were concentrated under reduced pressure and 44.7 mg (48% possibility) of the title compound were obtained. LC-MS (Method 4): Rt = 0.76 min; MS (ESIpos): m /z = 359 [M+H]+ ¹H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.008 (0.44), 1.647 (0.49), 1.721 (0.75), 1.731 ( 0.71), 1.952 (0.40), 1.978 (0.57), 1.987 (0.92), 2.039 (0.54), 2.049 (0.59), 2.059 (0.57), 2.272 (16.00), 2.567 (0.97), 2.576 (0.85), 2.588 ( 1.42), 2.600 (0.79), 2.630 (0.50), 2.999 (0.74), 3.015 (1.56), 3.031 (0.89), 3.128 (1.06), 3.144 (2.19), 3.159 (1.12), 3.624 (0.43), 3.639 ( 0.56), 3.688 (0.57), 3.768 (0.50), 3.779 (0.46), 3.794 (0.63), 3.941 (0.62), 3.955 (0.43), 3.968 (0.47), 4.367 (0.97), 4.392 (1.26), 4.551 ( 1.28), 4.577 (1.04), 4.609 (0.73), 4.632 (0.88), 4.749 (6.74), 4.801 (0.89), 4.824 (0.72), 4.845 (0.56), 4.854 (0.68), 4.860 (0.73), 4.868 ( 0.55), 4.928 (0.45), 4.942 (0.57), 7.101 (0.90), 7.108 (0.56), 7.123 (12.99), 7.125 (12.62), 7.147 (0.89).

[01090] The (5S) configuration was assigned based on the elucidation of the crystal structure for Example 108. (5S)-2-(4-Methylbenzyl)-5-(1,3-thiazolidin-3-ylcarbonyl)-5, 6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one Example 109 (2S)-1-{[(5RS)-2-(4-Methylbenzyl)-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[ 4,3-a]pyridin-5-yl]carbonyl}pyrrolidine-2-carbonitrile (enantiomer 1)

[01091] (5RS)-2-(4-Methylbenzyl)-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine -5-carboxylic acid (enantiomer 1) (75.0 mg, 261 μmol) was initially loaded into DMF (3.1 mL) and dichloromethane (1.5 mL) at room temperature. Subsequently, 1-[bis(dimethylamino)methylene]-1H-benzotriazol-1-ium 3-oxide hexafluorophosphate (129 mg, 339 μmol) and N,N-diisopropylethylamine (120 μl, 680 μmol) were added. After stirring for 15 minutes, (2S)-pyrrolidine-2-carbonitrile hydrochloride (41.5 mg, 313 μmol) was added and the reaction mixture was stirred at room temperature overnight. The solvent was removed under reduced pressure, and the residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/water gradient). HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/gradient water). The fractions containing the product were concentrated under reduced pressure and 35.4 mg (36% possibility) of the title compound were obtained. LC-MS (Method 1): Rt = 1.02 min; MS (ESIpos): m /z = 366 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.008 (1.03), 0.008 (0.89), 1.654 (0.52), 1.769 ( 0.69), 2.027 (1.21), 2.042 (1.71), 2.062 (2.62), 2.078 (2.62), 2.094 (1.23), 2.104 (1.05), 2.115 (0.95), 2.136 (0.93), 2.149 (1.11), 2.159 ( 0.93), 2.175 (0.45), 2.185 (0.59), 2.204 (1.26), 2.224 (1.18), 2.236 (0.75), 2.244 (0.47), 2.256 (0.74), 2.273 (16.00), 2.327 (0.30), 2.366 ( 0.18), 2.558 (0.99), 2.569 (0.98), 2.583 (0.79), 2.603 (0.74), 2.616 (1.37), 2.627 (0.79), 2.646 (0.35), 2.658 (0.59), 2.669 (0.49), 2.709 ( 0.17), 3.672 (2.09), 3.688 (4.23), 3.705 (2.02), 4.749 (8.60), 4.793 (2.28), 4.803 (3.16), 4.813 (2.75), 4.824 (1.44), 7.099 (1.37), 7.120 ( 9.43), 7.127 (9.47), 7.148 (1.26).

[01092] The (5S) configuration was assigned based on the elucidation of the crystal structure for Examples 26, 108, 113, 157, 237, 358 and 454. (2S)-1-{[(5S)-2-(4 -Methylbenzyl)-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridin-5-yl]carbonyl}pyrrolidine-2- carbonitrile Example 110 (5RS)-5-{[(3S)-3-Fluoropyrrolidin-1-yl]carbonyl}-2-(4-methylbenzyl)-5,6,7,8-tetrahydro[1,2, 4]triazolo[4,3-a]pyridin-3(2H)-one (enantiomer 1)

[01093] (5RS)-2-(4-Methylbenzyl)-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine -5-carboxylic acid (enantiomer 1) (75.0 mg, 261 μmol) was initially loaded into DMF (3.1 mL) and dichloromethane (1.5 mL) at room temperature. Subsequently, 1-[bis(dimethylamino)methylene]-1H-benzotriazol-1-ium 3-oxide hexafluorophosphate (129 mg, 339 μmol) and N,N-diisopropylethylamine (120 μl, 680 μmol) were added. After stirring for 15 minutes, (3S)-3-fluoropyrrolidine hydrochloride (39.3 mg, 313 μmol) was added and the reaction mixture was stirred at room temperature overnight. The solvent was removed under reduced pressure, and the residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/water gradient). HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/gradient water). The fractions containing the product were concentrated under reduced pressure and 56.2 mg (60% possibility) of the title compound were obtained. LC-MS (Method 3): Rt = 1.29 min; MS (ESIpos): m /z = 359 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.008 (0.69), 0.008 (0.65), 1.692 (0.66), 1.706 ( 1.32), 1.719 (1.54), 1.737 (0.99), 1.750 (0.44), 1.993 (0.51), 2.004 (0.68), 2.017 (0.58), 2.059 (0.73), 2.073 (0.83), 2.085 (0.81), 2.108 ( 0.79), 2.122 (0.48), 2.133 (0.55), 2.237 (0.43), 2.272 (16.00), 2.522 (1.18), 2.562 (0.69), 2.585 (1.09), 2.590 (1.13), 2.632 (0.42), 3.287 ( 0.45), 3.633 (1.34), 3.652 (0.99), 3.662 (0.87), 3.679 (0.60), 3.695 (0.51), 3.720 (0.55), 3.740 (0.92), 3.768 (0.67), 3.776 (0.60), 3.784 ( 0.65), 3.854 (1.17), 4.665 (0.61), 4.674 (0.73), 4.681 (0.78), 4.690 (0.65), 4.698 (0.71), 4.722 (0.84), 4.737 (5.72), 4.746 (3.53), 4.788 ( 0.47), 5.258 (0.57), 5.381 (0.72), 5.388 (0.75), 5.510 (0.42), 7.102 (0.76), 7.119 (6.24), 7.124 (13.58), 7.146 (0.84).

[01094] The (5S) configuration was assigned based on the elucidation of the crystal structure for Examples 26, 108, 113, 157, 237, 358 and 454. (5S)-5-{[(3S)-3-Fluoropyrrolidin- 1-yl]carbonyl}-2-(4-methylbenzyl)-5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one Example 111 (5RS)-5-{[(3R)-3-Fluoropyrrolidin-1-yl]carbonyl}-2-(4-methylbenzyl)-5,6,7,8-tetrahydro[1,2,4] triazolo[4,3-a]pyridin-3(2H)-one (enantiomer 1)

[01095] (5RS)-2-(4-Methylbenzyl)-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine -5-carboxylic acid (enantiomer 1) (75.0 mg, 261 μmol) was initially loaded into DMF (3.1 mL) and dichloromethane (1.5 mL) at room temperature. Subsequently, 1-[bis(dimethylamino)methylene]-1H-benzotriazol-1-ium 3-oxide hexafluorophosphate (129 mg, 339 μmol) and N,N-diisopropylethylamine (120 μl, 680 μmol) were added. After stirring for 15 minutes, (3R)-3-fluoropyrrolidine hydrochloride (39.3 mg, 313 μmol) was added and the reaction mixture was stirred at room temperature overnight. The solvent was removed under reduced pressure, and the residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/water gradient). HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/gradient water). The fractions containing the product were concentrated under reduced pressure and 59.0 mg (63% possibility) of the title compound were obtained. LC-MS (Method 1): Rt = 0.98 min; MS (ESIpos): m /z = 359 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: 0.008 (1.25), 1.715 (0.81), 1.979 (1.46), 2.021 (0.58 ), 2.103 (0.66), 2.135 (0.56), 2.272 (16.00), 2.573 (1.00), 2.585 (1.71), 2.598 (0.96), 2.627 (0.61), 3.359 (0.62), 3.378 (0.56), 3.388 (0.41 ), 3.503 (0.60), 3.522 (1.39), 3.548 (1.10), 3.569 (0.77), 3.593 (1.76), 3.920 (0.42), 3.942 (1.16), 3.965 (0.46), 4.004 (0.46), 4.746 (7.68 ), 4.787 (0.75), 4.801 (1.00), 4.811 (0.63), 4.825 (0.70), 4.841 (0.86), 4.850 (0.67), 5.270 (0.57), 5.347 (0.55), 5.398 (0.56), 5.478 (0.52 ), 7,103 (0.74), 7,125 (14.98), 7,145 (0.79).

[01096] The (5S) configuration was assigned based on the elucidation of the crystal structure for Examples 26, 108, 113, 157, 237, 358 and 454. (5S)-5-{[(3R)-3-Fluoropyrrolidin- 1-yl]carbonyl}-2-(4-methylbenzyl)-5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one Example 112 (5RS)-5-[(3-Fluoroazetidin-1-yl)carbonyl]-2-(4-methylbenzyl)-5,6,7,8-tetrahydro[1,2,4]triazolo[4, 3-a]pyridin-3(2H)-one (racemate)

[01097] (5RS)-2-(4-Methylbenzyl)-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine -5-carboxylic acid (racemate) (100 mg, 94% purity, 326 μmol) was initially loaded together with 3-fluoroazetidine hydrochloride (43.6 mg, 391 μmol) in pyridine/DMF (5/1) (2, 0 mL) at room temperature. Subsequently, O-(7-azabenzotriazol-1-yl)-N,N,N',N-tetramethyluronium hexafluorophosphate (161 mg, 423 μmol) was added, and the reaction mixture was stirred at room temperature overnight. . The solvent was removed under reduced pressure, and the residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/water gradient). HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/gradient water). The fractions containing the product were concentrated under reduced pressure and 90.8 mg (80% possibility) of the title compound were obtained. LC-MS (Method 4): Rt = 0.69 min; MS (ESIpos): m /z = 345 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: 1.706 (1.68), 1.917 (0.50), 1.930 (0.68), 1.940 (0.74 ), 2.004 (0.68), 2.017 (0.66), 2.039 (0.48), 2.270 (16.00), 2.522 (1.08), 2.561 (1.51), 2.575 (1.97), 2.588 (0.99), 2.616 (0.62), 3.924 (0.50 ), 3.953 (0.54), 3.984 (0.49), 4.220 (0.45), 4.235 (0.44), 4.251 (0.59), 4.263 (0.46), 4.277 (0.45), 4.286 (0.50), 4.319 (0.49), 4.515 (1.27 ), 4,528 (1.95), 4,541 (1.28), 4,745 (6.20), 5,753 (0.52), 7,104 (0.55), 7,125 (15.04), 7,145 (0.54). Example 113 (5RS)-5-[(3-Fluoroazetidin-1-yl)carbonyl]-2-(4-methylbenzyl)-5,6,7,8-tetrahydro[1,2,4]triazolo[4 ,3-a]pyridin-3(2H)-one (enantiomer 2)

[01098] (5RS)-5-[(3-Fluoroazetidin-1-yl)carbonyl]-2-(4-methylbenzyl)-5,6,7,8-tetrahydro[1,2,4]triazolo[ 4,3-a]pyridin-3(2H)-one (racemate) was separated by chiral preparatory HPLC [sample preparation: 69 mg dissolved in 4 mL of ethanol and 4 mL of acetonitrile; injection volume: 0.5 mL; column: Daicel Chiralcel® IA-H 5 μm, 250 x 20 mm; eluent: n-heptane/ethanol 50:50; flow rate: 15 ml/min; temperature 30°C; UV detection: 210 nm]. After separation, 32.3 mg of enantiomer 1, which eluted first, and 32.7 mg of enantiomer 2, which eluted later, were isolated.

[01099] Analytical chiral HPLC: Rt = 2.53 min, o.d. = 100% [column: Daicel Chiralcel® IA-3 50 x 4.6 mm; eluent: n-heptane/ethanol 50:50; flow rate: 1 ml/min; UV detection: 220 nm]. LC-MS (Method 3): Rt = 1.25 min; MS (ESIpos): m /z = 345 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: 1.702 (1.92), 1.940 (0.86), 2.005 (0.77), 2.017 (0.75 ), 2.270 (15.01), 2.561 (1.75), 2.575 (2.00), 2.588 (1.08), 2.616 (0.66), 3.921 (0.57), 3.952 (0.62), 3.985 (0.55), 4.219 (0.51), 4.233 (0.50 ), 4,250 (0.64), 4,286 (0.57), 4,319 (0.52), 4,516 (1.38), 4,528 (2.10), 4,541 (1.39), 4,709 (0.41), 4,745 (6.36), 7,125 (16.00).

[01100] The (5S) configuration was assigned based on the elucidation of the crystal structure for Example 113. (5S)-5-[(3-Fluoroazetidin-1-yl)carbonyl]-2-(4-methylbenzyl)-5 ,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one Example 114 (5RS)-5-[(3,3-Difluoroazetidin-1-yl)carbonyl]-2-(4-methylbenzyl)-5,6,7,8-tetrahydro[1,2,4]triazole [4,3-a]pyridin-3(2H)-one (racemate)

[01101] (5RS)-2-(4-Methylbenzyl)-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine -5-carboxylic acid (racemate) (150 mg, 522 μmol) was initially loaded together with 3,3-difluoroazetidine hydrochloride (71.0 mg, 548 μmol) in pyridine/DMF (5/1) (2.0 mL). at room temperature. Subsequently, O-(7-azabenzotriazol-1-yl)-N,N,N',N-tetramethyluronium hexafluorophosphate (218 mg, 574 μmol) was added, and the reaction mixture was stirred at room temperature overnight. The solvent was removed under reduced pressure, and the residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/water gradient). HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/gradient water). The fractions containing the product were concentrated under reduced pressure and 118 mg (62% possibility) of the title compound were obtained. LC-MS (Method 3): Rt = 1.42 min; MS (ESIpos): m /z = 363 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.008 (1.26), 0.008 (1.16), 1.697 (0.97), 1.712 ( 1.59), 1.726 (1.11), 1.959 (0.43), 1.970 (0.74), 1.983 (0.68), 2.029 (0.64), 2.045 (0.67), 2.063 (0.52), 2.271 (12.02), 2.574 (0.83), 2.583 ( 1.39), 2.598 (0.66), 2.625 (0.40), 4.355 (0.69), 4.384 (0.70), 4.416 (0.41), 4.568 (1.00), 4.583 (1.49), 4.595 (0.96), 4.712 (0.53), 4.752 ( 5.61), 4.843 (0.47), 7.105 (0.42), 7.127 (16.00), 7.149 (0.40). Example 115 (5RS)-5-[(3,3-Difluoroazetidin-1-yl)carbonyl]-2-(4-methylbenzyl)-5,6,7,8-tetrahydro[1,2,4]triazole [4,3-a]pyridin-3(2H)-one (enantiomer 2)

[01102] (5RS)-5-[(3,3-Difluoroazetidin-1-yl)carbonyl]-2-(4-methylbenzyl)-5,6,7,8-tetrahydro[1,2,4] triazolo[4,3-a]pyridin-3(2H)-one (racemate) was separated by chiral preparatory HPLC [sample preparation: 105 mg dissolved in 5 mL of ethanol and 5 mL of acetonitrile; injection volume: 0.5 mL; column: Daicel Chiralpak® IB 5 μm, 250 x 20 mm; eluent: n-heptane/ethanol 50:50; flow rate: 15 ml/min; temperature 40°C; UV detection: 210 nm]. After separation, 53.3 mg of enantiomer 1, which eluted first, and 53.2 mg of enantiomer 2, which eluted later, were isolated.

[01103] Analytical chiral HPLC: Rt = 3.04 min, de = 99% [column: Daicel Chiraltek® IB-3 50 x 4.6 mm; eluent: i-hexane/ethanol 50:50; flow rate: 1 ml/min; UV detection: 220 nm]. LC-MS (Method 3): Rt = 1.39 min; MS (ESIpos): m /z = 363 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.008 (0.65), 0.008 (0.71), 1.697 (1.02), 1.711 ( 1.66), 1.725 (1.18), 1.742 (0.44), 1.958 (0.42), 1.970 (0.78), 1.982 (0.72), 2.028 (0.68), 2.045 (0.73), 2.062 (0.54), 2.271 (11.98), 2.597 ( 0.69), 4.355 (0.74), 4.384 (0.75), 4.414 (0.42), 4.567 (0.98), 4.582 (1.51), 4.595 (0.97), 4.712 (0.53), 4.752 (5.92), 4.841 (0.48), 4.872 ( 0.41), 7.127 (16.00), 7.149 (0.43). Example 116 (5RS)-5-{[(3S)-3-Hydroxypyrrolidin-1-yl]carbonyl}-2-(4-methylbenzyl)-5,6,7,8-tetrahydro[1,2,4 ]triazolo[4,3-a]pyridin-3(2H)-one (enantiomer 1)

[01104] (5RS)-2-(4-Methylbenzyl)-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine -5-carboxylic acid (enantiomer 1) (75.0 mg, 261 μmol) was initially loaded into DMF (3.1 mL) and dichloromethane (1.5 mL) at room temperature. Subsequently, 1-[bis(dimethylamino)methylene]-1H-benzotriazol-1-ium 3-oxide hexafluorophosphate (129 mg, 339 μmol) and N,N-diisopropylethylamine (120 μl, 680 μmol) were added. After stirring for 15 minutes, (3S)-pyrrolidin-3-ol hydrochloride (38.7 mg, 313 μmol) was added and the reaction mixture was stirred at room temperature overnight. The solvent was removed under reduced pressure, and the residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/water gradient). HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/gradient water). The fractions containing the product were concentrated under reduced pressure and 54.0 mg (58% possibility) of the title compound were obtained. LC-MS (Method 1): Rt = 0.86 min; MS (ESIpos): m /z = 357 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.008 (0.41), 1.705 (1.37), 1.716 (1.38), 1.730 ( 1.13), 1.752 (0.63), 1.763 (0.58), 1.773 (0.48), 1.782 (0.43), 1.847 (0.72), 1.858 (0.82), 1.869 (0.69), 1.879 (0.90), 1.890 (0.66), 1.903 ( 0.57), 1.948 (0.77), 1.982 (0.83), 2.000 (1.05), 2.011 (0.90), 2.025 (0.93), 2.035 (0.75), 2.043 (0.63), 2.051 (0.61), 2.061 (0.41), 2.271 ( 16.00), 2,467 (0.41), 2,524 (1.22), 2.571 (0.77), 2,583 (1.42), 2,594 (0.75), 2,625 (0.59), 3.294 (2.42), 3.304 (3.08), 3.315 (14.88), 3.337 ( 1.33), 3.356 (0.54), 3.368 (0.86), 3.431 (0.43), 3.439 (0.46), 3.452 (0.54), 3.460 (0.69), 3.560 (0.52), 3.641 (0.79), 3.653 (1.21), 3.669 ( 0.82), 3.680 (0.94), 4.259 (0.66), 4.267 (0.63), 4.363 (0.76), 4.664 (0.74), 4.672 (0.85), 4.679 (0.94), 4.688 (0.77), 4.695 (0.44), 4.707 ( 0.69), 4.716 (0.77), 4.722 (0.98), 4.734 (3.46), 4.743 (4.98), 4.782 (0.43), 4.956 (1.20), 4.964 (1.17), 5.074 (1.13), 5.082 (1.11), 7.096 ( 0.75), 7.102 (0.81), 7.118 (7.66), 7.123 (13.54), 7.144 (0.90).

[01105] The (5S) configuration was assigned based on the elucidation of the crystal structure for Examples 26, 108, 113, 157, 237, 358 and 454. (5S)-5-{[(3S)-3-Hydroxypyrrolidin- 1-yl]carbonyl}-2-(4-methylbenzyl)-5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one Example 117 (5RS)-5-{[(cis)-6,6-Difluoro-3-azabicyclo[3.1.0]hex-3-yl]carbonyl}-2-(4-methylbenzyl)-5,6,7, 8-tetrahydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one (racemate)

[01106] (5RS)-2-(4-Methylbenzyl)-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine -5-carboxylic acid (racemate) (150 mg, 522 μmol) was initially loaded together with (cis)-6,6-difluoro-3-azabicyclo[3.1.0]hexane (65.3 mg, 548 μmol) into pyridi - na/DMF (5/1) (2.0 mL) at room temperature. Subsequently, O-(7-azabenzotriazoM-H)-N,N,N',N-tetramethylonium hexafluorophosphate (218 mg, 574 μmol) was added, and the reaction mixture was stirred at room temperature for 5 hours. The solvent was removed under reduced pressure, and the residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/water gradient). The fractions containing the product were concentrated under reduced pressure and 86.7 mg (43% possibility) of the title compound were obtained. LC-MS (Method 3): Rt = 1.48 min; MS (ESIpos): m /z = 389 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.008 (2.15), 0.008 (2.10), 1.697 (0.91), 1.707 ( 0.84), 1.743 (0.61), 1.980 (0.75), 2.048 (0.40), 2.270 (16.00), 2.327 (0.68), 2.518 (3.43), 2.523 (2.64), 2.563 (1.71), 2.573 (1.66), 2.585 ( 1.19) 0.93), 3.804 (0.68), 3.893 (0.70), 3.921 (1.33), 3.934 (0.58), 3.944 (0.65), 3.957 (0.54), 4.016 (0.82), 4.044 (0.58), 4.668 (0.70), 4.678 ( 0.89) 1.17). Example 118 (5RS)-2-(4-Methylbenzyl)-5-[(3-oxopyrrolidin-1-yl)carbonyl]-5,6,7,8-tetrahydro[1,2,4]triazolo[4 ,3-a]pyridin-3(2H)-one (racemate)

[01107] (5RS)-2-(4-Methylbenzyl)-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine -5-carboxylic acid (racemate) (150 mg, 94% purity, 489 μmol) was initially loaded together with pyrrolidin-3-one hydrochloride (71.3 mg, 586 μmol) in DMF (3.0 mL) at temperature environment. Subsequently, triethylamine (200 μl, 1.5 mmol) and O-(7-azabenzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate (242 mg, 635 μmol) were added, and the mixture of the reaction was stirred at room temperature overnight. The solvent was removed under reduced pressure, and the residue was mixed with pyridine (2.5 mL) and DMF (500 μl). After addition of (242 mg, 635 μmol) and pyrrolidin-3-one hydrochloride (71.3 mg, 586 μmol), the reaction mixture was stirred at room temperature for 2 hours. The reaction mixture was mixed with water and ethyl acetate, and acidified with 10% citric acid. The organic phase was removed and the aqueous phase was extracted three times with ethyl acetate. The combined organic phases were washed with saturated aqueous sodium chloride solution, dried over sodium sulfate and filtered, and the filtrate was concentrated. The residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/gradient water). The fractions containing the product were concentrated under reduced pressure and 80.7 mg (47% possibility) of the title compound were obtained. LC-MS (Method 4): Rt = 1.68 min; MS (ESIpos): m /z = 355 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: 1.689 (0.93), 1.705 (1.02), 2.006 (1.17), 2.020 (1.11 ), 2.050 (0.88), 2.062 (0.79), 2.072 (0.66), 2.272 (16.00), 2.559 (1.50), 2.579 (2.25), 2.599 (1.83), 2.634 (0.49), 2.675 (0.58), 2.694 (0.65 ), 2.709 (0.82), 2.726 (0.46), 3.659 (0.71), 3.677 (0.70), 3.710 (1.38), 3.744 (1.37), 3.774 (0.70), 3.794 (0.74), 3.942 (0.40), 3.961 (0.45 ), 4.009 (0.77), 4.054 (1.67), 4.072 (0.42), 4.127 (1.60), 4.171 (0.71), 4.687 (0.61), 4.699 (1.26), 4.711 (0.76), 4.750 (5.78), 4.927 (0.75 ), 4,938 (0.44), 7,101 (0.97), 7,123 (13.94), 7,148 (0.87). Example 119 (5RS)-2-(4-Methylbenzyl)-5-[(3-oxopyrrolidin-1-yl)carbonyl]-5,6,7,8-tetrahydro[1,2,4]triazolo[4 ,3-a]pyridin-3(2H)-one (enantiomer 2)

[01108] (5RS)-2-(4-Methylbenzyl)-5-[(3-oxopyrrolidin-1-yl)carbonyl]-5,6,7,8-tetrahydro[1,2,4]triazolo[ 4,3-a]pyridin-3(2H)-one (racemate) was separated by chiral preparatory HPLC [sample preparation: 71 mg dissolved in 6 mL of ethanol; injection volume: 0.5 mL; column: Daicel Chiralpak® IC 5 μm, 250 x 20 mm; eluent: 100% ethanol; flow rate: 15 ml/min; temperature 25°C; UV detection: 210 nm]. After separation, 21.8 mg of enantiomer 1, which eluted first, and 20.5 mg of enantiomer 2, which eluted later, were isolated.

[01109] Analytical chiral HPLC: Rt = 2.23 min, de = 99% [column: Daicel Chiralpak® IC 50 x 4.6 mm; eluent: 100% ethanol; flow rate: 1 ml/min; UV detection: 220 nm]. LC-MS (Method 3): Rt = 1.20 min; MS (ESIpos): m /z = 355 [M+H]+ ¹H-NMR (400 MHz, DMSO-d6) δ [ppm]: 1.234 (0.45), 1.652 (0.44), 1.666 (0.63), 1.690 (1.15 ), 1,704 (1.26), 1,719 (1.03), 1,994 (0.81), 2,007 (1.49), 2,022 (1.37), 2,038 (0.99), 2,051 (1.09), 2,063 (0.98), 2,272 (16.00), 2,579 (2.68 ), 2.599 (2.22), 2.634 (0.56), 2.677 (0.55), 2.696 (0.79), 2.709 (0.88), 2.726 (0.50), 3.649 (0.48), 3.660 (0.84), 3.678 (0.82), 3.699 (0.51 ), 3.710 (1.60), 3.744 (1.61), 3.755 (0.54), 3.775 (0.85), 3.785 (0.45), 3.794 (0.86), 3.805 (0.51), 3.942 (0.45), 3.960 (0.52), 4.010 (0.86 ), 4.055 (1.96), 4.072 (0.56), 4.090 (0.43), 4.127 (1.81), 4.172 (0.85), 4.687 (0.72), 4.699 (1.44), 4.711 (0.88), 4.750 (6.83), 4.914 (0.54 ), 4,927 (0.90), 4,938 (0.57), 7,102 (0.98), 7,109 (0.75), 7,124 (14.74), 7,147 (0.92). Example 120 (5RS)-5-[(3-Hydroxyazetidin-1-yl)carbonyl]-2-(4-methylbenzyl)-5,6,7,8-tetrahydro[1,2,4]triazolo[4,3 -a]pyridin-3(2H)-one (racemate)

[01110] (5RS)-2-(4-Methylbenzyl)-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine -5-carboxylic acid (racemate) (150 mg, 522 μmol) was initially loaded together with azetidin-3-ol hydrochloride (60.1 mg, 548 μmol) in DMF (1.7 mL) and pyridine (330 μl) at room temperature . Subsequently, O-(7-azabenzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate (218 mg, 574 μmol) was added, and the reaction mixture was stirred at room temperature overnight. The solvent was removed under reduced pressure, and the residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/water gradient). HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/gradient water). The fractions containing the product were concentrated under reduced pressure and 143 mg (80% possibility) of the title compound were obtained. LC-MS (Method 4): Rt = 0.62 min; MS (ESIpos): m /z = 343 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.008 (0.91), 0.008 (0.71), 1.696 (1.30), 1.706 ( 1.24), 1.889 (0.47), 1.902 (0.46), 1.913 (0.67), 1.925 (1.00), 1.967 (0.52), 1.980 (0.70), 1.992 (0.73), 2.001 (0.62), 2.270 (16.00), 2.522 ( 1.16), 2.570 (1.78), 2.582 (0.90), 2.612 (0.63), 3.598 (0.60), 3.617 (0.66), 3.624 (0.70), 3.636 (0.52), 3.648 (0.55), 3.661 (0.60), 3.673 ( 0.54), 3.917 (0.67), 3.928 (0.77), 4.018 (0.89), 4.032 (1.30), 4.042 (1.18), 4.056 (1.06), 4.103 (0.45), 4.118 (0.53), 4.129 (0.47), 4.144 ( 0.44), 4.328 (0.49), 4.348 (0.81), 4.368 (0.51), 4.481 (1.32), 4.495 (2.40), 4.504 (2.75), 4.518 (1.96), 4.740 (5.20), 4.745 (4.96), 5.800 ( 0.90), 7.103 (0.67), 7.123 (13.53), 7.143 (0.69). Example 121 (5RS)-5-[(3-Hydroxyazetidin-1-yl)carbonyl]-2-(4-methylbenzyl)-5,6,7,8-tetrahydro[1,2,4]triazolo[4 ,3-a]pyridin-3(2H)-one (enantiomer 2)

[01111] (5RS)-5-[(3-Hydroxyazetidin-1-yl)carbonyl]-2-(4-methylbenzyl)-5,6,7,8-tetrahydro[1,2,4]triazolo[ 4,3-a]pyridin-3(2H)-one (racemate) was separated by chiral preparative SFC [sample preparation: 115 mg dissolved in 15 mL of methanol. Injection volume: 0.5 mL; column: Daicel Chiralpak® AD 5 μm, 250 x 20 mm; eluent: CO2/methanol 80:20; flow rate: 80 ml/min; temperature 40°C; UV detection: 210 nm]. After separation, 57.4 mg of enantiomer 1, which eluted first, and 46.4 mg of enantiomer 2, which eluted later, were isolated.

[01112] Analytical chiral HPLC (SFC): Rt = 2.0 min, de = 99% [column: Daicel Chiralcel® AD 50 x 4.6 mm; eluent: CO2/methanol 80:20; flow rate: 3 ml/min; UV detection: 220 nm]. LC-MS (Method 3): Rt = 1.06 min; MS (ESIpos): m /z = 343 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: 1.696 (1.41), 1.706 (1.35), 1.889 (0.50), 1.901 (0.50 ), 1.913 (0.71), 1.925 (1.07), 1.980 (0.74), 1.992 (0.78), 2.002 (0.68), 2.270 (16.00), 2.522 (1.52), 2.570 (1.94), 2.583 (1.02), 2.599 (0.46 ), 2.612 (0.69), 3.598 (0.65), 3.616 (0.70), 3.624 (0.74), 3.634 (0.56), 3.647 (0.59), 3.660 (0.63), 3.673 (0.57), 3.917 (0.71), 3.928 (0.83 ), 4.018 (0.95), 4.032 (1.37), 4.042 (1.26), 4.056 (1.11), 4.103 (0.46), 4.118 (0.56), 4.129 (0.51), 4.144 (0.49), 4.328 (0.51), 4.348 (0.85 ), 4.368 (0.55), 4.496 (2.50), 4.504 (3.04), 4.518 (2.20), 4.740 (5.50), 4.745 (5.33), 5.801 (3.34), 7.103 (0.68), 7.123 (13.86). Example 122 (5RS)-5-{[(3R)-3-Hydroxypyrrolidin-1-yl]carbonyl}-2-(4-methylbenzyl)-5,6,7,8-tetrahydro[1,2,4 ]triazolo[4,3-a]pyridin-3(2H)-one (enantiomer 1)

[01113] (5RS)-2-(4-Methylbenzyl)-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine -5-carboxylic acid (enantiomer 1) (75.0 mg, 261 μmol) was initially loaded into DMF (3.1 mL) and dichloromethane (1.5 mL) at room temperature. Subsequently, 1-[bis(dimethylamino)methylene]-1H-benzotriazol-1-ium 3-oxide hexafluorophosphate (129 mg, 339 μmol) and N,N-diisopropylethylamine (91 μl, 520 μmol) were added. After stirring for 15 minutes, (3R)-pyrrolidin-3-ol hydrochloride (38.7 mg, 313 μmol) was added and the reaction mixture was stirred at room temperature overnight. The solvent was removed under reduced pressure, and the residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/water gradient). HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/gradient water). The fractions containing the product were concentrated under reduced pressure and 58.1 mg (62% possibility) of the title compound were obtained. LC-MS (Method 1): Rt = 0.86 min; MS (ESIpos): m /z = 357 [M+H]+ ¹H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.008 (0.58), 0.008 (0.62), 1.649 (0.52), 1.662 ( 0.50), 1.675 (0.55), 1.689 (0.69), 1.701 (0.85), 1.714 (1.02), 1.721 (1.03), 1.730 (0.92), 1.743 (0.71), 1.754 (0.61), 1.762 (0.56), 1.848 ( 0.52), 1.859 (0.74), 1.870 (0.56), 1.880 (0.78), 1.891 (0.73), 1.902 (0.55), 1.940 (0.57), 1.971 (1.66), 1.977 (1.57), 1.996 (0.91), 2.003 ( 0.74), 2.010 (0.72), 2.017 (0.69), 2.027 (0.62), 2.037 (0.43), 2.045 (0.47), 2.052 (0.40), 2.272 (16.00), 2.478 (0.56), 2.518 (1.68), 2.557 ( 0.61), 2.569 (0.78), 2.582 (1.40), 2.593 (0.73), 2.624 (0.54), 3.199 (0.79), 3.230 (1.12), 3.361 (1.13), 3.372 (1.78), 3.390 (1.59), 3.413 ( 0.60), 3.454 (0.53), 3.481 (0.81), 3.544 (0.72), 3.560 (1.02), 3.568 (1.26), 3.584 (0.76), 3.595 (0.51), 3.735 (0.41), 3.755 (0.62), 4.264 ( 0.76), 4.358 (0.65), 4.699 (0.78), 4.708 (0.78), 4.714 (0.96), 4.723 (0.76), 4.741 (4.48), 4.746 (5.17), 4.770 (0.77), 4.779 (0.99), 4.786 ( 1.01), 4.794 (0.71), 4.956 (0.76), 5.077 (0.89), 5.085 (0.87), 7.102 (0.70), 7.124 (15.25), 7.145 (0.84).

[01114] The (5S) configuration was assigned based on the elucidation of the crystal structure for Examples 26, 108, 113, 157, 237, 358 and 454. (5S)-5-{[(3R)-3-Hydroxypyrrolidin- 1-yl]carbonyl}-2-(4-methylbenzyl)-5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one Example 123 (5RS)-5-{[3-(Difluoromethoxy)azetidin-1-yl]carbonyl}-2-(4-methylbenzyl)-5,6,7,8-tetrahydro[1,2,4]triazole [4,3-a]pyridin-3(2H)-one (racemate)

[01115] (5RS)-2-(4-Methylbenzyl)-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine -5-carboxylic acid (racemate) (150 mg, 522 μmol) was initially loaded together with 3-(difluoromethoxy)azetidine (67.5 mg, 548 μmol) in pyridine/DMF (5/1) (3.0 mL). at room temperature. Subsequently, O-(7-azabenzotriazol-1-yl)-N,N,N',N-tetramethyluronium hexafluorophosphate (218 mg, 574 μmol) was added, and the reaction mixture was stirred at room temperature overnight. The solvent was removed under reduced pressure, and the residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/water gradient). HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/gradient water). The fractions containing the product were concentrated under reduced pressure and 27.3 mg (13% possibility) of the title compound were obtained. LC-MS (Method 1): Rt = 1.06 min; MS (ESIpos): m /z = 393 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: 0.008 (0.44), 1.701 (1.79), 1.714 (1.40), 1.941 (0.73 ), 2.003 (0.73), 2.017 (0.62), 2.271 (16.00), 2.327 (0.48), 2.366 (0.48), 2.518 (2.87), 2.559 (1.81), 2.573 (1.95), 2.587 (0.96), 2.602 (0.45 ), 2.615 (0.71), 2.670 (0.52), 2.710 (0.51), 3.701 (1.17), 3.840 (0.45), 3.858 (0.92), 3.867 (0.93), 3.885 (0.56), 3.895 (0.52), 4.175 (0.85 ), 4.189 (0.83), 4.201 (0.93), 4.253 (0.42), 4.271 (0.51), 4.281 (0.47), 4.300 (0.73), 4.327 (0.54), 4.336 (0.52), 4.530 (1.75), 4.553 (0.42 ), 4.651 (0.41), 4.669 (0.55), 4.691 (0.42), 4.746 (6.96), 4.774 (0.68), 5.004 (0.62), 5.050 (0.56), 6.587 (0.54), 6.600 (0.58), 6.773 (1.10 ), 6,786 (1.21), 6,960 (0.54), 6,972 (0.58), 7,105 (0.65), 7,126 (14.23). Example 124 (5RS)-2-(4-Methylbenzyl)-5-{[3-(trifluoromethyl)azetidin-1-yl]carbonyl}-5,6,7,8-tetrahydro[1,2,4] triazolo[4,3-a]pyridin-3(2H)-one (racemate)

[01116] (5RS)-2-(4-Methylbenzyl)-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine -5-carboxylic acid (racemate) (150 mg, 522 μmol) was initially loaded together with 3-(trifluoromethyl)azetidine hydrochloride (92.8 mg, 574 μmol) in pyridine/DMF (5/1) (3.0 mL ) at room temperature. Subsequently, O-(7-azabenzotriazol-1-yl)-N,N,N',N-tetramethyluronium hexafluorophosphate (208 mg, 548 μmol) was added, and the reaction mixture was stirred at room temperature overnight. . The solvent was removed under reduced pressure, and the residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/water gradient). HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/gradient water). The fractions containing the product were concentrated under reduced pressure and 139 mg (68% possibility) of the title compound were obtained. LC-MS (Method 1): Rt = 1.12 min; MS (ESIpos): m /z = 395 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: 1.694 (1.05), 1.707 (1.44), 1.720 (1.08), 2.003 (0.41 ), 2.014 (0.44), 2.027 (0.47), 2.271 (12.27), 2.501 (8.74), 2.567 (0.81), 2.575 (0.93), 3.845 (0.41), 3.871 (0.47), 3.934 (0.49), 3.948 (0.43 ), 4.081 (0.45), 4.105 (0.66), 4.160 (0.44), 4.184 (0.67), 4.207 (0.70), 4.219 (0.41), 4.230 (0.45), 4.386 (0.53), 4.401 (0.48), 4.430 (0.50 ), 4.453 (0.73), 4.522 (0.44), 4.536 (0.73), 4.548 (0.83), 4.560 (0.69), 4.572 (0.48), 4.584 (0.42), 4.607 (0.74), 4.750 (5.64), 7.104 (0.48 ), 7,125 (16.00), 7,147 (0.48). Example 125 (5RS)-5-[(3-Methoxyazetidin-1-yl)carbonyl]-2-(4-methylbenzyl)-5,6,7,8-tetrahydro[1,2,4]triazolo[4 ,3-a]pyridin-3(2H)-one (racemate)

[01117] (5RS)-2-(4-Methylbenzyl)-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine -5-carboxylic acid (racemate) (150 mg, 522 μmol) was initially loaded together with 3-methoxy azetidine (47.8 mg, 548 μmol) in pyridine/DMF (5/1) (3.0 mL) at temperature environment. Subsequently, O-(7-azabenzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate (218 mg, 574 μmol) was added, and the reaction mixture was stirred at room temperature overnight. The solvent was removed under reduced pressure, and the residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/water gradient). HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/gradient water). The fractions containing the product were concentrated under reduced pressure and 123 mg (66% possibility) of the title compound were obtained. LC-MS (Method 3): Rt = 1.25 min; MS (ESIpos): m /z = 357 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.008 (1.40), 0.008 (1.18), 1.674 (0.74), 1.686 ( 1.12), 1.697 (1.34), 1.928 (0.77), 1.989 (0.59), 1.999 (0.64), 2.024 (0.45), 2.270 (14.99), 2.522 (1.34), 2.571 (1.48), 2.584 (0.75), 2.613 ( 0.47) 0.89), 4.051 (0.44), 4.087 (0.43), 4.104 (0.57), 4.115 (0.77), 4.128 (0.73), 4.148 (0.57), 4.216 (0.43), 4.226 (0.61), 4.242 (0.49), 4.252 ( 0.47), 4.259 (0.44), 4.269 (0.62), 4.341 (0.53), 4.364 (0.53), 4.509 (1.78), 4.525 (0.92), 4.742 (6.60), 7.102 (0.59), 7.124 (16.00), 7.145 ( 0.52). Example 126 (5RS)-5-[(cis)-3-Azabicyclo[3.1.0]hex-3-ylcarbonyl]-2-(4-methylbenzyl)-5,6,7,8-tetrahydro[1, 2,4]triazolo[4,3-a]pyridin-3(2H)-one (racemate)

[01118] (5rs)-2-(4-methylbenzyl)-3-oxo-2,3,5,6,7,8-hexa-Hydro[1,2,4]Triazolo[4,3-a]Pyridine -5-Carboxylic Acid (Racemate) (150 Mg, 522 µmol) Was Initially Loaded Along With (Cys)-3-Azabicyclo[3.1.0]Hexane Hydrochloride (65.6 Mg, 548 µmol) In Pyridine/Dmf (5/ 1) (3.0 Ml) At Room Temperature. Subsequently, O-(7-azabenzotriazol-1-yl)-n,N,N',N-tetramethyluronium Hexafluoro-Phosphate (218 Mg, 574 µmol) was added, and the reaction mixture was stirred at room temperature overnight. . The solvent was removed under reduced pressure, and the residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/water gradient). HPLC (Chromatorex C18, 10μm, 125mm X 30mm; Eluent: Acetonitrile/Gradient Water). The Fractions Containing the Product Were Concentrated Under Reduced Pressure and 133 Mg (72% Possibility) of the Title Compound Were Obtained. Lc-ms (Method 4): Rt = 0.78 Min; Ms (Spipos): M /Z = 353 [M+h]+ 1h-nmr (400 Mhz, Dmso-d6) Δ [Ppm]: 0.049 (0.40), 0.060 (1.02), 0.071 (1.06), 0.081 (0.51 ), 0.096 (0.86), 0.107 (0.86), 0.689 (0.74), 0.701 (0.76), 0.707 (0.73), 0.713 (0.71), 0.725 (0.66), 1.515 (0.51), 1.524 (0.73), 1.534 (0.65 ), 1.543 (0.64), 1.550 (0.53), 1.559 (0.62), 1.568 (0.49), 1.612 (0.56), 1.621 (0.73), 1.630 (0.94), 1.639 (0.89), 1.649 (0.99), 1.659 (1.14 ), 1,674 (1.73), 1,684 (1.79), 1,695 (1.24), 1,922 (0.50), 1,935 (0.45), 1,976 (0.46), 1,994 (0.46), 2,002 (0.51), 2,019 (0.42), 2,270 (16.00 ), 2.518 (1.36), 2.559 (1.36), 2.571 (0.70), 2.601 (0.44), 3.203 (0.62), 3.214 (0.65), 3.232 (0.74), 3.243 (0.72), 3.335 (1.10), 3.346 (0.84 ), 3.497 (1.56), 3.526 (1.22), 3.533 (0.66), 3.544 (0.63), 3.560 (0.73), 3.570 (0.68), 3.659 (2.48), 3.667 (1.15), 3.692 (1.81), 3.722 (1.49 ), 3.840 (1.36), 3.867 (1.16), 4.618 (0.59), 4.627 (0.72), 4.633 (0.74), 4.643 (0.58), 4.679 (0.57), 4.718 (2.71), 4.729 (2.94), 4.738 (4.39 ), 4,778 (0.70), 7,094 (1.14), 7,116 (9.92), 7,121 (9.92), 7,142 (1.16). Example 127 2-(4-methylbenzyl)- (5rs)-{[(2s)-2-methylpyrrolidin-1-yl]Carbonyl}-5,6,7,8- Tetrahydro[1,2,4]Triazole [4,3-a]Pyridin-3(2h)-one (Enantiomer 1)

[01119] (5RS)-2-(4-Methylbenzyl)-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine -5-carboxylic acid (enantiomer 1) (75.0 mg, 261 μmol) was initially loaded into dichloromethane (1.5 mL) and DMF (3.0 mL) at room temperature. Subsequently, 1-[bis(dimethylamino)methylene]-1H-benzotriazol-1-ium 3-oxide hexafluorophosphate (129 mg, 339 μmol) and N,N-diisopropylethylamine (64 μl, 370 μmol) were added. After stirring for 15 minutes, (2S)-2-methylpyrrolidine (26.7 mg, 313 μmol) was added and the reaction mixture was stirred at room temperature overnight. The solvent was removed under reduced pressure, and the residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/water gradient). HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/gradient water). The fractions containing the product were concentrated under reduced pressure and 56.3 mg (61% possibility) of the title compound were obtained. LC-MS (Method 3): Rt = 1.45 min; MS (ESIpos): m /z = 355 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: 1.083 (4.23), 1.098 (4.29), 1.166 (1.19), 1.182 (1.20 ), 1.515 (0.43), 1.522 (0.45), 1.544 (0.43), 1.676 (0.49), 1.688 (0.88), 1.702 (1.05), 1.718 (0.90), 1.730 (0.42), 1.862 (0.51), 1.870 (0.56 ), 1.887 (0.78), 1.905 (1.14), 1.924 (0.88), 1.939 (1.13), 1.950 (1.08), 1.969 (0.74), 1.995 (0.83), 2.015 (0.71), 2.031 (0.56), 2.270 (12.19 ), 2.524 (0.87), 2.569 (1.14), 2.581 (0.54), 3.432 (0.49), 3.456 (0.49), 3.669 (0.44), 3.676 (0.51), 3.992 (0.54), 4.669 (0.86), 4.679 (1.59 ), 4,684 (0.95), 4,694 (0.68), 4,706 (0.71), 4,717 (1.84), 4,746 (0.81), 4,777 (1.77), 4,816 (0.82), 7,122 (16.00).

[01120] The (5S) configuration was assigned based on the elucidation of the crystal structure for Examples 26, 108, 113, 157, 237, 358 and 454. 2-(4-Methylbenzyl)-(5S)-{[(2S )-2-methylpyrrolidin-1-yl]carbonyl}-5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one Example 128 ( 5RS)-{[(3RS)-1,1-Difluoro-5-azaspiro[2.4]hept-5-yl]carbonyl}-2-(4-methylbenzyl)-5,6,7,8-tetrahydro[ 1,2,4]triazolo[4,3-a]pyridin-3(2H)-one (mixture of diastereomer; 2 isomers)

[01121] (5RS)-2-(4-Methylbenzyl)-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine -5-carboxylic acid (enantiomer 1) (200 mg, 696 μmol) was initially loaded into dichloromethane (4.0 mL) and DMF (8.0 mL) at room temperature. Subsequently, 1-[bis(dimethylamino)methylene]-1H-benzotriazol-1-ium 3-oxide hexafluorophosphate (343 mg, 905 μmol) and N,N-diisopropylethylamine (320 μl, 1.8 mmol) were added. After stirring for 15 minutes, (3RS)-1,1-difluoro-5-azaspiro[2.4]heptane hydrochloride (142 mg, 835 μmol) was added and the reaction mixture was stirred at room temperature overnight. The solvent was removed under reduced pressure, and the residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/water gradient). HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/gradient water). The fractions containing the product were concentrated under reduced pressure and 218 mg (78% possibility) of the title compound were obtained. LC-MS (Method 3): Rt = 1.56 min; MS (ESIpos): m /z = 403 [M+H]+ 7.101 (0.69), 7.125 (16.00), 7.146 (0.68). (Mixture of diastereomers)

[01122] The (5S) configuration was assigned based on the elucidation of the crystal structure for Examples 26, 108, 113, 157, 237, 358 and 454. (5S)-{[(3RS)-1,1-Difluoro- 5-azaspiro[2.4]hept-5-yl]carbonyl}-2-(4-methylbenzyl)-5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridin -3(2H)-one (diastereomer mixture; 2 isomers) Example 129 (5RS)-{[(3RS)-1,1-Difluoro-5-azaspiro[2.4]hept-5-yl]carbonyl}-2- (4-methylbenzyl)-5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one (isomer 2)

[01123] (5RS)-{[(3RS)-1,1-Difluoro-5-azaspiro[2.4]hept-5-yl]carbonyl}-2-(4-methylbenzyl)-5,6,7,8- tetrahydro[1,2,4]triazolo[4,3- a]pyridin-3(2H)-one (diastereomer mixture; 2 isomers) was separated by chiral preparatory HPLC [sample preparation: 210 mg dissolved in 4 mL of acetonitrile; injection volume: 0.2 mL; column: Daicel Chiralpak® ID 5 μm, 250 x 20 mm; eluent: methyl tert-butyl ether/acetonitrile 50:50; flow rate: 15 ml/min; temperature 40°C; UV detection: 210 nm]. After separation, 99.0 mg of enantiomer 1, which eluted first, and 101.0 mg of enantiomer 2, which eluted later, were isolated.

[01124] Analytical chiral HPLC: Rt = 10.49 min, de = 99% [column: Daicel Chiralcel® ID 250 x 4.6 mm; eluent: methyl tert-butyl ether/acetonitrile 50:50; flow rate: 1 ml/min; UV detection: 220 nm]. LC-MS (Method 4): Rt = 0.84 min; MS (ESIpos): m /z = 403 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.008 (1.53), 0.008 (1.55), 1.604 (0.44), 1.617 ( 0.64), 1.637 (0.89), 1.654 (1.26), 1.669 (1.51), 1.689 (1.60), 1.702 (1.64), 1.710 (1.61), 1.721 (1.32), 2.008 (1.66), 2.025 (1.55), 2.051 ( 0.73), 2.070 (0.51), 2.084 (0.52), 2.102 (0.51), 2.115 (0.48), 2.165 (0.55), 2.181 (0.52), 2.272 (15.03), 2.561 (0.81), 2.572 (0.83), 2.584 ( 1.54), 2.596 (0.83), 2.626 (0.57), 3.455 (2.27), 3.478 (0.59), 3.486 (0.60), 3.497 (1.15), 3.515 (0.61), 3.640 (0.76), 3.647 (0.80), 3.665 ( 0.96), 3.804 (0.82), 3.831 (0.61), 3.881 (0.48), 3.895 (0.42), 4.710 (0.54), 4.725 (0.81), 4.743 (5.21), 4.750 (2.79), 4.783 (0.76), 4.798 ( 0.93), 4.808 (0.62), 7.101 (0.75), 7.123 (16.00), 7.147 (0.72). Example 130 (5RS)-{[(3S)-3-Methoxypyrrolidin-1-yl]carbonyl}-2-(4-methylbenzyl)-5,6,7,8-tetrahydro[1,2,4]triazole [4,3-a]pyridin-3(2H)-one (enantiomer 1)

[01125] (5RS)-2-(4-Methylbenzyl)-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine -5-carboxylic acid (enantiomer 1) (75.0 mg, 261 μmol) was initially loaded into DMF (3.1 mL) and dichloromethane (1.5 mL) at room temperature. Subsequently, 1-[bis(dimethylamino)methylene]-1H-benzotriazol-1-ium 3-oxide hexafluorophosphate (129 mg, 339 μmol) and N,N-diisopropylethylamine (120 μl, 680 μmol) were added. After stirring for 15 minutes, (3S)-3-methoxypyrrolidine hydrochloride (43.1 mg, 313 μmol) was added and the reaction mixture was stirred at room temperature overnight. The solvent was removed under reduced pressure, and the residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/water gradient). HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/gradient water). The fractions containing the product were concentrated under reduced pressure and 40.8 mg (42% possibility) of the title compound were obtained. LC-MS (Method 1): Rt = 0.96 min; MS (ESIpos): m /z = 371 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.008 (2.98), 0.008 (2.66), 1.644 (0.58), 1.656 ( 0.64), 1.668 (0.67), 1.702 (0.97), 1.712 (0.97), 1.723 (0.75), 1.860 (0.43), 1.884 (0.68), 1.894 (0.70), 1.906 (0.55), 1.918 (0.89), 1.931 ( 0.91), 1.940 (0.92), 1.981 (1.60), 1.993 (1.41), 2.003 (1.20), 2.017 (0.89), 2.038 (0.66), 2.065 (0.57), 2.272 (16.00), 2.567 (0.89), 2.578 ( 1.51), 2,590 (0.88), 2,621 (0.54), 3,235 (12.99), 3,269 (13.24), 3,362 (1.64), 3.384 (0.55), 3,392 (0.75), 3.405 (1.07), 3.416 (1.20), 3.438 ( 0.53), 3.449 (0.86), 3.455 (0.70), 3.473 (0.65), 3.556 (0.51), 3.567 (0.57), 3.585 (0.78), 3.596 (0.75), 3.709 (0.94), 3.737 (0.69), 3.768 ( 0.42), 3.787 (0.61), 3.956 (0.89), 4.044 (0.83), 4.742 (6.80), 4.765 (0.83), 4.779 (1.64), 4.788 (1.54), 4.797 (0.73), 7.100 (0.86), 7.123 ( 14.91), 7.145 (0.90).

[01126] The (5S) configuration was assigned based on the elucidation of the crystal structure for Examples 26, 108, 113, 157, 237, 358 and 454. (5S)-{[(3S)-3-Methoxypyrrolidin-1- yl]carbonyl}-2-(4-methylbenzyl)-5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one Example 131 ( 5RS)-{[3-Hydroxy-3-(trifluoromethyl)azetidin-1-yl]carbonyl}-2-(4-methylbenzyl)-5,6,7,8-tetrahydro[1,2,4]triazole [4,3-a]pyridin-3(2H)-one (racemate)

[01127] (5RS)-2-(4-Methylbenzyl)-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine -5-carboxylic acid (racemate) (150 mg, 522 μmol) was initially loaded together with 3-(trifluoromethyl)azetidine-3-ol hydrochloride (97.3 mg, 548 μmol) in pyridine/DMF (5/1) ( 3.0 mL) at room temperature. Subsequently, O-(7-azabenzotriazol-1-yl)-N,N,N',N'-tetramethylluronium hexafluorophosphate (218 mg, 574 μmol) was added, and the reaction mixture was stirred at room temperature during night. The solvent was removed under reduced pressure, and the residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/water gradient). HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/gradient water). The fractions containing the product were concentrated under reduced pressure and 147 mg (68% possibility) of the title compound were obtained. LC-MS (Method 4): Rt = 0.76 min; MS (ESIpos): m /z = 411 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.008 (0.49), 0.008 (0.45), 1.704 (1.35), 1.715 ( 1.20), 2.019 (0.55), 2.027 (0.58), 2.036 (0.57), 2.271 (16.00), 2.518 (0.75), 2.567 (1.09), 2.575 (1.21), 2.587 (1.01), 2.598 (0.45), 3.857 ( 0.57), 3.885 (0.67), 3.933 (0.61), 3.961 (0.86), 4.081 (1.14), 4.108 (0.81), 4.164 (0.94), 4.192 (1.19), 4.222 (0.65), 4.351 (0.56), 4.376 ( 0.89), 4.454 (1.17), 4.479 (0.74), 4.558 (0.60), 4.573 (0.90), 4.585 (0.67), 4.593 (0.61), 4.609 (0.77), 4.621 (1.19), 4.647 (0.77), 4.741 ( 2.29), 4.747 (2.82), 4.754 (4.40), 7.103 (0.62), 7.125 (13.60), 7.145 (0.56), 7.545 (1.60). Example 132 (5RS)-2-(4-Methylbenzyl)-{[(2R)-2-methylpyrrolidin-1-yl]carbonyl}-5,6,7,8-tetrahydro[1,2,4]triazole [4,3-a]pyridin-3(2H)-one (enantiomer 1)

[01128] (5RS)-2-(4-Methylbenzyl)-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine -5-carboxylic acid (enantiomer 1) (75.0 mg, 261 μmol) was initially loaded into dichloromethane (1.3 mL) and DMF (2.9 mL) at room temperature. Subsequently, 1-[bis(dimethylamino)methylene]-1H-benzotriazol-1-ium 3-oxide hexafluorophosphate (129 mg, 339 μmol) and N,N-diisopropylethylamine (64 μl, 370 μmol) were added. After stirring for 15 minutes, (2R)-2-methylpyrrolidine (26.7 mg, 313 μmol) was added and the reaction mixture was stirred at room temperature overnight. The solvent was removed under reduced pressure, and the residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/water gradient). HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/gradient water). The fractions containing the product were concentrated under reduced pressure and 46.4 mg (50% possibility) of the title compound were obtained. LC-MS (Method 3): Rt = 1.47 min; MS (ESIpos): m /z = 355 [M+H]+

[01129] 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.008 (1.50), 0.008 (1.44), 1.057 (6.00), 1.073 (6.07), 1.265 (2.61), 1.281 (2.63), 1.497 (0.42), 1.508 (0.57), 1.517 (0.66), 1.526 (0.56), 1.650 (0.63), 1.659 (0.58), 1.679 (0.60), 1.694 (0.82), 1.714 (1.10), 1.724 (0.98), 1,859 (0.74), 1,870 (0.72), 1,876 (0.73), 1,886 (0.73), 1,897 (1.06), 1,915 (1.11), 1,924 (0.87), 1,933 (1.01), 1,945 (1.27), 1,963 (1.63), 1,977 (1.11), 1,997 (0.92), 2,005 (0.85), 2,015 (0.70), 2,025 (0.74), 2,033 (0.69), 2,042 (0.64), 2,062 (0.48), 2,272 (16.00), 2,583 (1.13), 2.595 (0.65), 2.625 (0.44), 3.247 (0.43), 3.379 (0.41), 3.516 (0.46), 3.523 (0.68), 3.541 (0.68), 3.552 (0.42), 3.566 (0.43), 3.584 (0.85), 3.602 (0.48), 3.609 (0.46), 4.022 (0.62), 4.030 (0.60), 4.038 (0.47), 4.107 (0.46), 4.691 (0.89), 4.700 (1.13), 4.707 (1.26), 4.715 (1.20), 4,739 (6.57), 7,099 (1.02), 7,120 (11.38), 7,124 (11.23), 7,145 (0.99).

[01130] The (5S) configuration was assigned based on the elucidation of the crystal structure for Examples 26, 108, 113, 157, 237, 358 and 454. (5S)-2-(4-Methylbenzyl)-{[(2R )-2-methylpyrrolidin-1-yl]carbonyl}-5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one Example 133 ( 5RS)-2-(4-Methylbenzyl)-5-[(3-oxoazetidin-1-yl)carbonyl]-5,6,7,8-tetrahydro[1,2,4]triazolo[4,3- a]pyridin-3(2H)-one (racemate)

[01131] (5RS)-2-(4-Methylbenzyl)-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine -5-carboxylic acid (racemate) (150 mg, 522 μmol) was initially loaded together with azetidin-3-one (39.0 mg, 548 μmol) in pyridine/DMF (5/1) (3.0 mL) in room temperature. Subsequently, O-(7-azabenzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate (218 mg, 574 μmol) was added, and the reaction mixture was stirred at room temperature overnight. The solvent was removed under reduced pressure, and the residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/water gradient). HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/gradient water). The fractions containing the product were concentrated under reduced pressure and 72.2 mg (41% possibility) of the title compound were obtained. LC-MS (Method 1): Rt = 0.89 min; MS (ESIpos): m /z = 341 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: 1.710 (0.41), 1.721 (0.65), 1.731 (0.63), 1.743 (0.59 ), 2.059 (0.86), 2.072 (1.04), 2.085 (0.67), 2.271 (10.99), 2.517 (0.67), 2.559 (0.57), 2.590 (0.46), 2.603 (0.95), 2.616 (0.48), 4.662 (0.54 ), 4,675 (1.04), 4,688 (0.55), 4,743 (0.87), 4,758 (4.04), 4,766 (1.64), 7,128 (16.00). Example 134 (5RS,7RS)-5-[(3-Hydroxyazetidin-1-yl)carbonyl]-7-methyl-2-{[6-(trifluoromethyl)pyridin-3-yl]methyl}-5,6,7 ,8-tetrahydro[1,2,4]triazolo[4,3- a]pyridin-3(2H)-one (diastereomer mixture; 4 isomers)

[01132] (5RS,7RS)-7-Methyl-3-oxo-2-{[6-(trifluoromethyl)pyridin-3-yl]methyl}-2,3,5,6,7,8-hexahydro [1,2,4]triazolo[4,3-a]pyridine-5-carboxylic acid (diastereomer mixture; 4 isomers) (100 mg, 281 μmol) was initially loaded into dichloromethane (1.0 mL) and DMF (2 .0 mL) at room temperature. Subsequently, 1-[bis(dimethylamino)methylene]-1H-benzotriazol-1-ium 3-oxide hexafluorophosphate (138 mg, 365 μmol) and N,N-diisopropylethylamine (130 μl, 730 μmol) were added. After stirring for 15 minutes, azetidin-3-ol hydrochloride (36.9 mg, 337 μmol) was added and the reaction mixture was stirred at room temperature overnight. The solvent was removed under reduced pressure, and the residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/water gradient). HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/gradient water). The fractions containing the product were concentrated under reduced pressure and 85.4 mg (74% possibility) of the title compound were obtained. LC-MS (Method 1): Rt = 0.87 min; MS (ESIpos): m /z = 412 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.008 (2.42), 0.008 (2.61), 1.010 (8.92), 1.020 ( 11.30), 1,026 (11.21), 1,036 (9.74), 1.308 (0.59), 1,339 (1.81), 1,370 (2.83), 1,400 (2.12), 1,433 (0.76), 1,876 (1.61), 2,142 (3.55), 2.174 ( 4.35), 2.206 (1.62), 2.213 (1.69), 2.327 (0.64), 2.366 (0.41), 2.622 (2.64), 2.669 (2.68), 2.690 (0.68), 2.710 (0.45), 2.731 (6.01), 2.890 ( 7.03), 3.578 (1.58), 3.585 (1.51), 3.604 (1.66), 3.643 (1.32), 3.655 (1.35), 3.668 (1.47), 3.680 (1.39), 3.903 (1.92), 3.914 (1.76), 4.002 ( 1.25), 4.021 (1.65), 4.045 (2.41), 4.058 (1.45), 4.067 (1.50), 4.079 (1.42), 4.112 (1.16), 4.126 (1.43), 4.137 (1.26), 4.153 (1.15), 4.325 ( 1.22), 4.344 (2.16), 4.355 (1.88), 4.370 (3.12), 4.387 (2.44), 4.398 (2.75), 4.414 (1.49), 4.507 (4.97), 4.521 (3.48), 4.986 (16.00), 5.754 ( 1.00), 5,779 (4.75), 5,793 (4.89), 7,899 (1.61), 7,919 (11.72), 7,951 (1.52), 8,669 (7.52). Example 135 (5RS,7RS)-5-[(3-Hydroxyazetidin-1-yl)carbonyl]-7-methyl-2-{[6-(trifluoromethyl)pyridin-3-yl]methyl}-5,6,7 ,8-tetrahydro[1,2,4]triazolo[4,3- a]pyridin-3(2H)-one (isomer 1)

[01133] (5RS,7RS)-5-[(3-Hydroxiazetidin-1-yl)carbonyl]-7-methyl-2-{[6-(trifluoromethyl)pyridin-3-yl]methyl}-5,6, 7,8-tetrahydro[1,2,4]triazolo[4,3- a]pyridin-3(2H)-one (diastereomer mixture; 4 isomers) was separated by chiral preparatory HPLC [sample preparation: 80 mg dissolved in 4 mL of ethanol; injection volume: 0.3 mL; column: Daicel Chiralpak® IC 5 μm, 250 x 20 mm; eluent: n-heptane/ethanol 50:50; flow rate: 15 ml/min; temperature 40°C; UV detection: 220 nm]. After separation, 32.0 mg of isomer 1, which eluted first, and 35.0 mg of isomer 2, which eluted later, were isolated. Isomer 1:

[01134] Analytical chiral HPLC: Rt = 5.13 min, de = 95% [column: Daicel Chiralcel® IAC 250 x 4.6 mm; eluent: i-hexane/ethanol 50:50; flow rate: 1 ml/min; UV detection: 220 nm]. LC-MS (Method 4): Rt = 0.63 min; MS (ESIpos): m /z = 412 [M+H]+ 1H-NMR (600 MHz, DMSO-d6) δ [ppm]: 0.005 (0.61), 1.011 (8.14), 1.022 (16.00), 1.033 (8.42 ), 1.320 (0.60), 1.340 (1.30), 1.354 (0.89), 1.361 (1.38), 1.374 (1.45), 1.381 (0.86), 1.394 (1.38), 1.414 (0.70), 1.872 (1.32), 1.876 (1.34 ), 2.136 (1.59), 2.142 (1.78), 2.148 (2.62), 2.156 (2.85), 2.168 (2.59), 2.176 (2.80), 2.183 (1.75), 2.195 (1.42), 2.203 (1.39), 2.517 (0.80 ), 2.521 (0.80), 2.524 (0.64), 2.615 (0.44), 2.630 (2.25), 2.633 (2.12), 2.654 (2.01), 2.657 (2.01), 2.660 (1.79), 3.584 (1.49), 3.589 (1.37 ), 3.601 (1.52), 3.607 (1.32), 3.649 (1.18), 3.657 (1.22), 3.666 (1.31), 3.674 (1.27), 3.907 (1.65), 3.915 (1.54), 4.011 (1.14), 4.023 (1.42 ), 4.027 (1.24), 4.040 (1.18), 4.051 (1.14), 4.059 (1.27), 4.066 (1.30), 4.074 (1.23), 4.119 (1.10), 4.129 (1.22), 4.135 (1.21), 4.147 (1.04 ), 4,335 (1.09), 4,347 (1.87), 4,363 (2.11), 4,373 (1.76), 4,381 (3.04), 4,391 (3.07), 4,399 (1.69), 4,410 (1.48), 4,496 (2.30), 4,507 (4.00 ), 4.518 (2.41), 4.531 (0.73), 4.986 (10.70), 4.991 (10.02), 5.802 (6.92), 5.812 (6.99), 7.905 (1.16), 7.911 (1.30), 7.919 (6.21), 7.924 (8.62 ), 8,671 (4.90). Example 136 (5RS,7RS)-5-{[(3S)-3-Fluoropyrrolidin-1-yl]carbonyl}-7-methyl-2-{[6-(trifluoromethyl)pyridin-3-yl]methyl}-5 ,6,7,8-tetrahydro[1,2,4]triazolo[4,3- a]pyridin-3(2H)-one (diastereomer mixture; 4 isomers)

[01135] (5RS,7RS)-7-Methyl-3-oxo-2-{[6-(trifluoromethyl)pyridin-3-yl]methyl}-2,3,5,6,7,8-hexahydro [1,2,4]triazolo[4,3-a]pyridine-5-carboxylic acid (diastereomer mixture; 4 isomers) (100 mg, 281 μmol) was initially loaded into dichloromethane (1.0 mL) and DMF (2 .0 mL) at room temperature. Subsequently, 1-[bis(dimethylamino)methylene]-1H-benzotriazol-1-ium 3-oxide hexafluorophosphate (138 mg, 365 μmol) and N,N-diisopropylethylamine (130 μl, 730 μmol) were added. After stirring for 15 min, (3S)-3-fluoropyrrolidine hydrochloride (42.3 mg, 337 μmol) was added, and the reaction mixture was stirred at room temperature for 2 hours. The solvent was removed under reduced pressure, and the residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/water gradient). HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/gradient water). The fractions containing the product were concentrated under reduced pressure and 93.0 mg (78% possibility) of the title compound were obtained. LC-MS (Method 3): Rt = 1.31 min; MS (ESIpos): m /z = 428 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (0.54), -0.008 (4.36), 0.008 (4.13), 0.146 (0.54) (1.42) (2.55), 2680 (2.36), 2710 (0.54), 3340 (0.76), 3353 (0.71), 3370 (0.92), 3381 (0.80), 3408 (0.50), 3496 (0.64), 3505 (0.60), 3550 (1.42) (1.07) (1.09) (0.62), 5,391 (1.04), 5,474 (0.61), 5,513 (0.60), 7,899 (1.19), 7,918 (15.34), 7,942 (0.74), 8,134 (0.60), 8,664 (7.69). (Mixture of diastereomers) Example 137 (5RS,7RS)-5-{[(3S)-3-Fluoropyrrolidin-1-yl]carbonyl}-7-methyl-2-{[6-(trifluoromethyl)pyridin-3-yl ]methyl}-5,6,7,8-tetrahydro[1,2,4]triazolo[4,3- a]pyridin-3(2H)-one (isomer 1)

[01136] (5RS,7RS)-5-{[(3S)-3-Fluoropyrrolidin-1-yl]carbonyl}-7-methyl- 2-{[6-(trifluoromethyl)pyridin-3-yl]methyl}- 5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one (diastereomer mixture; 4 isomers) was separated by chiral preparatory HPLC [preparation sample: 87 mg dissolved in 3 mL of ethanol; injection volume: 0.1 mL; column: Daicel Chiralcel® OX-H 5 μm, 250 x 20 mm; eluent: n-heptane/ethanol 50:50; flow rate: 20 ml/min; temperature 25°C; UV detection: 215 nm]. After separation, 30.1 mg of isomer 1, which eluted first, and 37.4 mg of isomer 2, which eluted later, were isolated. Isomer 1:

[01137] Analytical chiral HPLC: Rt = 2.07 min, de = 100% [column: Daicel Chiralcel® OX-3 50 x 4.6 mm; eluent: n-heptane/ethanol 50:50; flow rate: 1 ml/min; UV detection: 220 nm]. LC-MS (Method 4): Rt = 0.75 min; MS (ESIpos): m /z = 428 [M+H]+ 1H-NMR (500 MHz, DMSO-d6) δ [ppm]: 0.862 (0.42), 1.021 (8.42), 1.030 (11.85), 1.033 (10.67 ), 1.043 (9.64), 1.236 (0.53), 1.312 (0.68), 1.336 (1.44), 1.363 (2.05), 1.390 (1.65), 1.414 (0.83), 1.896 (1.37), 1.968 (0.43), 1.990 (0.47 ), 2.055 (0.44), 2.080 (0.57), 2.103 (1.00), 2.116 (0.94), 2.138 (1.19), 2.159 (2.57), 2.184 (2.56), 2.192 (2.90), 2.214 (3.67), 2.240 (2.57 ), 2,252 (2.56), 2,278 (1.16), 2,648 (2.43), 2,681 (2.11), 3,333 (1.13), 3,347 (1.49), 3,356 (2.24), 3,370 (2.60), 3,379 (2.36), 3,392 (2.36 ), 3.467 (0.90), 3.474 (0.87), 3.496 (1.25), 3.503 (1.23), 3.558 (2.68), 3.574 (3.46), 3.580 (3.36), 3.607 (2.29), 3.635 (0.61), 3.701 (0.58 ), 3.708 (0.66), 3.726 (0.80), 3.733 (0.69), 3.778 (0.56), 3.785 (0.59), 3.803 (0.74), 3.810 (0.68), 3.932 (1.39), 3.949 (2.22), 3.967 (1.42 ), 3.987 (0.98), 4.012 (0.73), 4.665 (1.30), 4.677 (1.47), 4.686 (1.41), 4.698 (1.25), 4.727 (1.56), 4.739 (1.77), 4.748 (1.71), 4.761 (1.51 ), 4,986 (16.00), 5,289 (1.44), 5,354 (1.14), 5,394 (1.40), 5,460 (1.13), 7,902 (1.50), 7,918 (12.17), 7,940 (0.91), 8,665 (6.94). Example 138 (5RS,7RS)-5-{[(3S)-3-Fluoropyrrolidin-1-yl]carbonyl}-7-methyl-2-{[6-(trifluoromethyl)pyridin-3-yl]methyl}-5 ,6,7,8-tetrahydro[1,2,4]triazolo[4,3- a]pyridin-3(2H)-one (isomer 2)

[01138] (5RS,7RS)-5-{[(3S)-3-Fluoropyrrolidin-1-yl]carbonyl}-7-methyl-2- {[6-(trifluoromethyl)pyridin-3-yl]methyl}- 5,6,7,8-tetrahydro[1,2,4]triazolo[4,3- a]pyridin-3(2H)-one (diastereomer mixture; 4 isomers) was separated by chiral preparatory HPLC [preparation sample: 87 mg dissolved in 3 mL of ethanol; injection volume: 0.1 mL; column: Daicel Chiralcel® OX-H 5 μm, 250 x 20 mm; eluent: n-heptane/ethanol 50:50; flow rate: 20 ml/min; temperature 25°C; UV detection: 215 nm]. After separation, 30.1 mg of isomer 1, which eluted first, and 37.4 mg of isomer 2, which eluted later, were isolated. Isomer 2:

[01139] Analytical chiral HPLC: Rt = 2.43 min, de = 100% [column: Daicel Chiralcel® OX-3 50 x 4.6 mm; eluent: n-heptane/ethanol 50:50; flow rate: 1 ml/min; UV detection: 220 nm]. LC-MS (Method 4): Rt = 0.74 min; MS (ESIpos): m /z = 428 [M+H]+ 1H-NMR (500 MHz, DMSO-d6) δ [ppm]: 0.847 (0.50), 0.861 (0.56), 1.028 (15.91), 1.041 (16.00 ), 1.056 (0.79), 1.088 (0.43), 1.101 (0.58), 1.235 (0.87), 1.314 (0.86), 1.336 (1.78), 1.360 (2.56), 1.384 (1.62), 1.406 (0.75), 1.896 (1.43 ), 1,908 (1.51), 1,963 (0.52), 1,984 (0.55), 2,048 (0.49), 2,070 (0.63), 2,109 (0.83), 2,122 (1.06), 2,158 (3.53), 2,182 (3.07), 2,190 (3.79 ), 2,214 (3.63), 2,233 (1.72), 2,259 (1.72), 2,273 (1.57), 2,286 (1.33), 2,300 (1.19), 2,313 (0.87), 2,645 (2.47), 2,649 (2.45), 2,677 (2.20 ), 2,681 (2.08), 3,273 (1.17), 3,288 (1.58), 3,296 (2.22), 3,311 (2.69), 3,319 (2.69), 3,333 (3.51), 3,347 (3.48), 3,387 (2.00), 3,394 (1.81 ), 3.415 (1.45), 3.423 (1.35), 3.434 (0.69), 3.448 (0.59), 3.465 (0.88), 3.472 (0.89), 3.493 (1.06), 3.501 (0.98), 3.639 (0.74), 3.653 (1.90 ), 3.658 (1.96), 3.673 (2.34), 3.682 (1.99), 3.694 (2.41), 3.703 (1.33), 3.714 (1.05), 3.733 (0.91), 3.765 (1.34), 3.782 (2.43), 3.801 (1.78 ), 3.831 (1.27), 3.855 (0.63), 3.880 (2.40), 4.581 (1.40), 4.594 (1.59), 4.603 (1.53), 4.615 (1.36), 4.646 (1.58), 4.658 (1.80), 4.668 (1.73 ), 4,680 (1.53), 4,982 (14.44), 5,273 (1.35), 5,379 (1.41), 5,387 (1.38), 5,394 (1.28), 5,500 (1.11), 7,901 (1.80), 7,916 (12.89), 7,940 (0.85 ), 8,664 (6.94). Example 139 (5RS,6RS)-6-Methyl-2-(4-methylbenzyl)-5-(pyrrolidin-1-ylcarbonyl)-5,6,7,8-tetrahydro[1,2,4]triazolo[ 4,3-a]pyridin-3(2H)-one (isomer 2)

[01140] (5RS,6RS)-6-Methyl-2-(4-methylbenzyl)-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4 ,3-a]pyridine-5-carboxylic acid (diastereomer mixture) (95.0 mg, 315 μmol) was initially loaded together with pyrrolidine (28 μl, 330 μmol) in pyridine/DMF (5/1) ( 3.0 mL) at room temperature. Subsequently, O-(7-azabenzotriazol-1-yl)-N,N,N‘,N‘-tetramethyluronium hexafluorophosphate (132 mg, 347 μmol) was added, and the reaction mixture was stirred at room temperature overnight. The solvent was removed under reduced pressure, and the residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/water gradient). HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/gradient water). The fractions containing the product were concentrated under reduced pressure and subjected directly to a chiral preparatory HPLC^separation (sample preparation: 35 mg dissolved in 3 mL of ethanol; injection volume: 0.5 mL; column: Daicel Chiralcel® IC 5 μm, 250 x 20 mm; eluent: n-heptane/ethanol 40:60; flow rate: 15 ml/min; UV detection: 220 nm]. , which eluted first, and 11 mg of isomer 2, which eluted later, were isolated: Isomer 2:

[01141] Analytical chiral HPLC: Rt = 12.49 min, de = 99% [column: Daicel Chiralcel® IC 250 x 4.6 mm; eluent: i-hexane/ethanol 40:60; flow rate: 1 ml/min; UV detection: 220 nm]. LC-MS (Method 3): Rt = 1.48 min; MS (ESIpos): m /z = 355 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]= 0.99 (d, 3H), 1.49 - 1.62 (m, 1H), 1.70 - 1.84 (m, 2H), 1.84 - 2.10 (m, 3H), 2.20 (dtd, 1H), 2.27 (s, 3H), 2.55 - 2.60 (m, 1H), 2.62 - 2.71 (m, 1H), 3.21 - 3.29 (m, 1H), 3.32 - 3.39 (m, 1H), 3.41 - 3.41 (m, 1H), 3.57 (dt, 1H), 3.77 (dt, 1H), 4.62 - 4.83 (m, 3H), 7.07 - 7.19 (m, 4H). Example 140 (5RS)-5-{[(3S,4S)-3,4-Difluoropyrrolidin-1-yl]carbonyl}-2-(4-methylbenzyl)-5,6,7,8-tetrahydro[1 ,2,4]triazolo[4,3-a]pyridin-3(2H)-one (enantiomer 1)

[01142] (5RS)-2-(4-Methylbenzyl)-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine -5-carboxylic acid (enantiomer 1) (75.0 mg, 261 μmol) was initially loaded into DMF (2.0 mL) and dichloromethane (1.0 mL) at room temperature. Subsequently, 1-[bis(dimethylamino)methylene]-1H-benzotriazol-1-ium 3-oxide hexafluorophosphate (129 mg, 339 μmol) and N,N-diisopropylethylamine (120 μl, 680 μmol) were added. After stirring for 15 min, (3S,4S)-3,4-difluoropyrrolidine hydrochloride (45.0 mg, 313 μmol) was added, and the reaction mixture was stirred at room temperature for 2 hours. The solvent was removed under reduced pressure, and the residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/water gradient). HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/gradient water). The fractions containing the product were concentrated under reduced pressure and 53.7 mg (55% possibility) of the title compound were obtained. LC-MS (Method 4): Rt = 0.74 min; MS (ESIpos): m /z = 377 [M+H]+ 1H-NMR (600 MHz, DMSO-d6) δ [ppm]: 1.624 (0.44), 1.629 (0.48), 1.632 (0.47), 1.637 (0.44 ), 1.642 (0.54), 1.646 (0.55), 1.651 (0.53), 1.722 (0.68), 1.729 (0.74), 1.738 (0.57), 1.744 (0.43), 1.952 (0.45), 1.957 (0.48), 1.962 (0.44 ), 1.969 (0.54), 1.976 (0.78), 1.980 (0.81), 1.985 (0.70), 2.022 (0.42), 2.027 (0.51), 2.032 (0.49), 2.037 (0.60), 2.040 (0.52), 2.045 (0.67 ), 2.051 (0.69), 2.056 (0.65), 2.273 (16.00), 2.518 (0.67), 2.563 (0.77), 2.584 (0.76), 2.592 (1.47), 2.600 (0.80), 2.612 (0.47), 2.620 (0.70 ), 3.647 (2.34), 3.697 (1.29), 3.706 (0.58), 3.711 (0.90), 3.716 (0.50), 3.830 (0.50), 3.853 (0.57), 3.899 (0.49), 3.922 (0.57), 4.152 (0.84 ), 4.175 (0.78), 4.195 (0.88), 4.217 (0.74), 4.749 (5.23), 4.752 (5.07), 4.873 (1.32), 4.879 (1.49), 4.883 (1.59), 4.890 (1.27), 5.336 (0.63 ), 5,346 (0.57), 5,429 (0.99), 5,516 (0.64), 7,109 (1.69), 7,123 (9.34), 7,129 (8.38), 7,143 (1.51).

[01143] The (5S) configuration was assigned based on the elucidation of the crystal structure for Examples 26, 108, 113, 157, 237, 358 and 454. (5S)-5-{[(3S,4S)-3, 4-Difluoropyrrolidin-1-yl]carbonyl}-2-(4-methylbenzyl)- 5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridin-3(2H )-one Example 141 (5RS)-2-(4-Methylbenzyl)-5-{[(1RS)-1-oxide-1,3-thiazolidin-3-yl]carbonyl}- 5,6,7,8- tetrahydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one (mixture of diastereomer; 2 isomers)

[01144] (5RS)-2-(4-Methylbenzyl)-5-(1,3-thiazolidin-3-ylcarbonyl)-5,6,7,8-tetrahydro[1,2,4]triazolo[4 ,3-a]pyridin-3(2H)-one (enantiomer 1) (80.0 mg, 223 μmol) was initially loaded into dichloromethane (3.0 mL) and 3-chlorobenzenecarboperoxoic acid (55.0 mg) was added. , 70% purity, 223 μmol). After 4 hours at room temperature, saturated aqueous sodium hydrogencarbonate solution was added, and the reaction mixture was extracted with dichloromethane. The combined organic phases were dried over magnesium sulfate and filtered, and the filtrate was concentrated. The residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/gradient water). The fractions containing the product were concentrated under reduced pressure and 40.0 mg (48% possibility) of the title compound were obtained. LC-MS (Method 1): Rt = 0.85 min; MS (ESIpos): m /z = 375 [M+H]+ 1H-NMR (500 MHz, DMSO-d6) δ [ppm]: 1.627 (0.41), 1.740 (0.62), 1.762 (0.45), 1.987 (0.63 ), 1.995 (0.76), 2.004 (0.69), 2.022 (0.56), 2.084 (0.42), 2.274 (16.00), 2.514 (0.79), 2.518 (0.79), 2.521 (0.60), 2.568 (0.47), 2.591 (0.73 ), 2.599 (1.07), 2.634 (0.57), 3.058 (0.50), 3.077 (0.45), 3.097 (0.45), 3.125 (0.46), 3.175 (0.50), 3.262 (0.59), 3.274 (0.75), 3.966 (0.48 ), 3.974 (0.70), 3.987 (0.64), 3.994 (0.60), 4.088 (0.42), 4.109 (0.64), 4.121 (0.44), 4.287 (0.64), 4.308 (0.49), 4.313 (0.64), 4.342 (0.74 ), 4.368 (0.88), 4.421 (0.66), 4.446 (0.72), 4.489 (0.59), 4.513 (0.64), 4.610 (0.76), 4.614 (0.82), 4.636 (0.60), 4.640 (0.66), 4.755 (5.93 ), 4.859 (0.41), 4.864 (0.49), 4.983 (0.64), 4.995 (0.55), 5.002 (0.52), 5.008 (0.55), 5.016 (0.87), 5.020 (0.92), 5.045 (0.78), 5.753 (0.47 ), 7,105 (0.99), 7,122 (5.96), 7,130 (11.47), 7,145 (0.98). (Mixture of diastereomers)

[01145] The (5S) configuration was assigned based on the elucidation of the crystal structure for Examples 26, 108, 113, 157, 237, 358 and 454. (5S)-2-(4-Methylbenzyl)-5-{[ (1RS)-1-oxide-1,3-thiazolidin-3-yl]carbonyl}-5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridin-3 (2H)-one (diastereomer mixture; 2 isomers) Example 142 (5RS)-5-[(1,1-Dioxide-1,3-thiazolidin-3-yl)carbonyl]-2-(4-methylbenzyl)- 5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one (enantiomer 1)

[01146] (5RS)-2-(4-Methylbenzyl)-5-(1,3-thiazolidin-3-ylcarbonyl)-5,6,7,8-tetrahydro[1,2,4]triazolo[4 ,3-a]pyridin-3(2H)-one (enantiomer 1) (32.0 mg, 89.3 μmol) was initially loaded into dichloromethane (2.4 mL) and 3-chlorobenzenecarboperoxoic acid (77.0 mL) was added. 0 mg, 70% purity, 312 μmol). After 4 hours at room temperature, saturated aqueous sodium hydrogencarbonate solution was added, and the reaction mixture was extracted with dichloromethane. The combined organic phases were dried over magnesium sulfate and filtered, and the filtrate was concentrated. The residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/gradient water). The fractions containing the product were concentrated under reduced pressure and 25.5 mg (73% possibility) of the title compound were obtained. LC-MS (Method 4): Rt = 0.69 min; MS (ESIpos): m /z = 391 [M+H]+ ¹H-NMR (500 MHz, DMSO-d6) δ [ppm]: 1.583 (0.40), 1.730 (0.58), 1.741 (0.60), 1.962 (0.42 ), 1.990 (0.89), 1.996 (0.83), 2.015 (0.42), 2.272 (16.00), 2.514 (0.74), 2.518 (0.59), 2.521 (0.48), 2.558 (0.75), 2.569 (0.62), 2.595 (1.12 ), 2.628 (0.49), 3.423 (0.53), 3.439 (0.95), 3.449 (0.62), 3.455 (0.75), 3.461 (0.76), 3.476 (0.70), 3.580 (0.60), 3.593 (1.14), 3.607 (0.63 ), 3.850 (0.41), 3.859 (0.62), 3.874 (1.06), 3.884 (0.72), 3.889 (0.69), 3.896 (0.71), 3.901 (0.67), 3.912 (0.60), 4.158 (0.41), 4.247 (0.41 ), 4.470 (0.46), 4.495 (0.88), 4.544 (0.89), 4.569 (0.47), 4.755 (8.51), 4.844 (1.10), 4.868 (2.16), 4.874 (0.98), 4.880 (0.97), 4.886 (0.71 ), 4.982 (1.43), 5.006 (1.07), 5.020 (0.41), 5.027 (0.47), 5.032 (0.47), 5.752 (4.50), 7.105 (1.46), 7.122 (9.73), 7.127 (9.02), 7.144 (1.29 ).

[01147] The (5S) configuration was assigned based on the elucidation of the crystal structure for Examples 26, 108, 113, 157, 237, 358 and 454. (5S)-5-[(1,1-Dioxide-1, 3-thiazolidin-3-yl)carbonyl]-2-(4-methylbenzyl)-5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridin-3(2H )-one Example 143 (5RS)-5-{[(3S)-3-(Difluoromethyl)pyrrolidin-1-yl]carbonyl}-2-(4-methylbenzyl)-5,6,7,8-tetrahydro [1,2,4]triazolo[4,3-a]pyridin-3(2H)-one (enantiomer 1)

[01148] (5RS)-2-(4-Methylbenzyl)-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine -5-carboxylic acid (enantiomer 1) (100 mg, 348 μmol) was initially loaded into DMF (4.0 mL) and dichloromethane (2.0 mL) at room temperature. Subsequently, 1-[bis(dimethylamino)methylene]-1H-benzotriazol-1-ium 3-oxide hexafluorophosphate (172 mg, 452 μmol) and N,N-diisopropylethylamine (160 μl, 900 μmol) were added. After stirring for 15 min, (3S)-3-(difluoromethyl)pyrrolidine hydrochloride (65.8 mg, 418 μmol) was added, and the reaction mixture was stirred at room temperature for 2 hours. The solvent was removed under reduced pressure, and the residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/water gradient). The fractions containing the product were concentrated under reduced pressure and 78.6 mg (58% possibility) of the title compound were obtained. LC-MS (Method 3): Rt = 1.47 min; MS (ESIpos): m /z = 391 [M+H]+ 1H-NMR (500 MHz, DMSO-d6) δ [ppm]: 1.665 (0.43), 1.676 (0.55), 1.709 (1.13), 1.829 (0.41 ), 1.934 (0.46), 1.943 (0.53), 1.950 (0.75), 1.959 (0.76), 1.984 (0.90), 1.994 (0.95), 2.005 (0.70), 2.013 (0.90), 2.026 (0.70), 2.034 (0.69 ), 2.041 (0.55), 2.046 (0.49), 2.053 (0.41), 2.115 (0.44), 2.271 (16.00), 2.517 (1.18), 2.574 (0.72), 2.583 (1.40), 2.593 (0.75), 2.617 (0.64 ), 3.270 (0.49), 3.286 (0.47), 3.295 (0.60), 3.341 (0.43), 3.437 (0.44), 3.454 (0.41), 3.479 (0.49), 3.516 (0.79), 3.533 (0.62), 3.542 (0.59 ), 3.610 (0.48), 3.647 (0.44), 4.707 (0.48), 4.715 (0.44), 4.722 (0.57), 4.728 (0.96), 4.738 (3.89), 4.745 (3.45), 4.760 (0.44), 4.775 (0.87 ), 4,780 (0.80), 4,787 (0.40), 6,130 (0.51), 6,139 (0.54), 6,162 (0.52), 7,104 (1.25), 7,120 (10.70), 7,125 (10.23), 7,141 (1.15).

[01149] The (5S) configuration was assigned based on the elucidation of the crystal structure for Examples 26, 108, 113, 157, 237, 358 and 454. (5S)-5-{[(3S)-3-(Difluoromethyl )pyrrolidin-1-yl]carbonyl}-2-(4-methylbenzyl)-5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridin-3(2H) -one Example 144 (5RS)-5-[(cis)-2-Azabicyclo[3.1.0]hex-2-ylcarbonyl]-2-(4-methylbenzyl)-5,6,7,8-tetrahydro[ 1,2,4]triazolo[4,3-a]pyridin-3(2H)-one (mixture of diastereomer; 2 isomers)

[01150] (5RS)-2-(4-Methylbenzyl)-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine -5-carboxylic acid (enantiomer 1) (100 mg, 348 μmol) was initially loaded into DMF (4.0 mL) and dichloromethane (2.0 mL) at room temperature. Subsequently, 1-[bis(dimethylamino)methylene]-1H-benzotriazol-1-ium 3-oxide hexafluorophosphate (172 mg, 452 μmol) and N,N-diisopropylethylamine (160 μl, 900 μmol) were added. After stirring for 15 min, cis-2-azabicyclo[3.1.0]hexane hydrochloride (racemate) (49.9 mg, 418 μmol) was added, and the reaction mixture was stirred at room temperature for 2 hours. The solvent was removed under reduced pressure, and the residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/water gradient). The fractions containing the product were concentrated under reduced pressure and 92.9 mg (76% possibility) of the title compound were obtained. LC-MS (Method 3): Rt = 1.41 min; MS (ESIpos): m /z = 353 [M+H]+ 1H-NMR (500 MHz, DMSO-d6) δ [ppm]: 0.618 (0.56), 0.623 (0.56), 0.628 (0.79), 0.633 (0.69 ), 0.639 (0.64), 0.644 (0.61), 0.650 (0.49), 0.654 (0.45), 0.811 (0.53), 0.828 (0.52), 1.567 (0.43), 1.744 (0.75), 1.755 (0.95), 1.767 (1.00 ), 1.772 (0.92), 1.784 (0.62), 1.860 (0.57), 1.866 (0.43), 1.877 (0.51), 1.884 (0.64), 1.890 (0.41), 1.902 (0.42), 1.908 (0.42), 2.001 (0.55 ), 2.012 (0.48), 2.019 (0.70), 2.032 (0.79), 2.039 (0.78), 2.047 (0.76), 2.065 (0.53), 2.078 (0.41), 2.145 (0.74), 2.150 (0.68), 2.272 (15.30 ), 2.518 (0.58), 2.522 (0.77), 2.586 (1.07), 2.596 (0.62), 2.620 (0.47), 2.959 (0.55), 2.984 (0.56), 3.154 (0.42), 3.495 (0.42), 3.499 (0.40 ), 3.699 (0.42), 3.704 (0.67), 3.711 (0.88), 3.716 (0.65), 3.724 (0.71), 3.729 (0.78), 4.738 (1.92), 4.743 (2.32), 4.753 (3.33), 4.934 (0.45 ), 4,940 (0.46), 5,070 (0.56), 5,076 (0.65), 5,083 (0.61), 5,089 (0.52), 7,109 (0.79), 7,127 (16.00), 7,144 (0.66).

[01151] The (5S) configuration was assigned based on the elucidation of the crystal structure for Examples 26, 108, 113, 157, 237, 358 and 454. (5S)-5-[(cis)-2-Azabiciclo[3.1 .0]hex-2-ylcarbonyl]-2-(4-methylbenzyl)-5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridin-3(2H) -one (diastereomer mixture; 2 isomers) Example 145 (5RS)-2-(4-Methylbenzyl)-5-[(3,3,4,4-tetrafluoropyrrolidin-1-yl)carbonyl]- 5,6,7 ,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one (enantiomer 1)

[01152] (5RS)-2-(4-Methylbenzyl)-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine -5-carboxylic acid (enantiomer 1) (50.0 mg, 174 μmol) was initially loaded into DMF (4.0 mL) and dichloromethane (2.0 mL) at room temperature. Subsequently, 1-[bis(dimethylamino)methylene]-1H-benzotriazol-1-ium 3-oxide hexafluorophosphate (85.8 mg, 226 μmol) and N,N-diisopropylethylamine (79 μl, 450 μmol) were added. After stirring for 15 min, 3,3,4,4-tetrafluoropyrrolidine hydrochloride (37.5 mg, 209 μmol) was added, and the reaction mixture was stirred at room temperature for 2 hours. The solvent was removed under reduced pressure, and the residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/water gradient). The fractions containing the product were concentrated under reduced pressure and 11.0 mg (15% possibility) of the title compound were obtained. LC-MS (Method 3): Rt = 1.68 min; MS (ESIpos): m /z = 413 [M+H]+ ¹H-NMR (500 MHz, DMSO-d6) δ [ppm]: -0.007 (0.56), 1.141 (2.17), 1.236 (0.42), 1.658 ( 0.47), 1.665 (0.57), 1.678 (0.56), 1.686 (0.71), 1.697 (0.83), 1.704 (0.92), 1.716 (0.72), 1.726 (0.43), 1.952 (0.43), 1.958 (0.45), 1.964 ( 0.44), 1.972 (0.62), 1.980 (0.69), 1.986 (0.74), 1.993 (0.62), 2.048 (0.50), 2.054 (0.48), 2.061 (0.69), 2.069 (0.65), 2.076 (0.65), 2.082 ( 0.64), 2.090 (0.45), 2.116 (0.98), 2.271 (16.00), 2.481 (0.93), 2.514 (0.53), 2.518 (0.54), 2.562 (1.05), 2.568 (1.04), 2.580 (1.52), 2.591 ( 1.69), 2.601 (0.83), 2.624 (0.53), 4.007 (0.64), 4.037 (0.76), 4.105 (0.74), 4.132 (0.59), 4.411 (0.54), 4.440 (0.52), 4.620 (0.73), 4.646 ( 0.65), 4.716 (0.43), 4.747 (4.79), 4.752 (4.59), 4.783 (0.41), 4.830 (1.29), 4.838 (1.55), 4.842 (1.66), 4.851 (1.23), 7.104 (1.48), 7.109 ( 0.84), 7,116 (1.66), 7,121 (10.49), 7,126 (9.73), 7,143 (1.20).

[01153] The (5S) configuration was assigned based on the elucidation of the crystal structure for Examples 26, 108, 113, 157, 237, 358 and 454. (5S)-2-(4-Methylbenzyl)-5-[( 3,3,4,4-tetrafluoropyrrolidin-1-yl)carbonyl]- 5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)- one Example 146 (5RS)-5-{[3-(Fluoromethyl)azetidin-1-yl]carbonyl}-2-(4-methylbenzyl)-5,6,7,8-tetrahydro[1,2,4 ]triazolo[4,3-a]pyridin-3(2H)-one (enantiomer 1)

[01154] (5RS)-2-(4-Methylbenzyl)-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine -5-carboxylic acid (enantiomer 1) (50.0 mg, 174 μmol) was initially loaded into DMF (2.0 mL) and dichloromethane (1.0 mL) at room temperature. Subsequently, 1-[bis(dimethylamino)methylene]-1H-benzotriazol-1-ium 3-oxide hexafluorophosphate (85.8 mg, 226 μmol) and N,N-diisopropylethylamine (79 μl, 450 μmol) were added. After stirring for 15 min, 3-(fluoromethyl)azetidine trifluoroacetate (42.4 mg, 209 μmol) was added, and the reaction mixture was stirred at room temperature for 2 hours. The solvent was removed under reduced pressure, and the residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/water gradient). The fractions containing the product were concentrated under reduced pressure and 23.2 mg (37% possibility) of the title compound were obtained. LC-MS (Method 3): Rt = 1.31 min; MS (ESIpos): m /z = 359 [M+H]+ 1H-NMR (500 MHz, DMSO-d6) δ [ppm]: -0.007 (0.41), 1.683 (0.67), 1.694 (1.11), 1.705 ( 1.36), 1.715 (1.05), 1.725 (0.44), 1.911 (0.49), 1.917 (0.52), 1.923 (0.43), 1.986 (0.51), 1.993 (0.63), 2.001 (0.62), 2.005 (0.47), 2.014 ( 0.63) 0.50), 3.650 (0.50), 3.659 (0.56), 3.670 (0.52), 3.704 (0.47), 3.716 (0.48), 3.724 (0.56), 3.735 (0.52), 3.921 (0.43), 3.939 (0.70), 3.963 ( 0.59), 3.974 (0.57), 3.980 (0.62), 3.991 (0.87), 4.007 (0.80), 4.110 (0.43), 4.122 (0.48), 4.128 (0.56), 4.139 (0.50), 4.252 (0.44), 4.269 ( 0.79), 4.399 (0.45), 4.416 (0.86), 4.488 (0.61), 4.497 (1.30), 4.500 (1.08), 4.505 (1.00), 4.509 (1.33), 4.518 (1.67), 4.530 (1.10), 4.545 ( 1.22), 4.556 (1.11), 4.613 (1.09), 4.624 (1.10), 4.639 (1.18), 4.651 (1.12), 4.744 (6.33), 7.107 (0.78), 7.125 (13.27), 7.137 (0.43), 7.142 ( 0.70).

[01155] The (5S) configuration was assigned based on the elucidation of the crystal structure for Examples 26, 108, 113, 157, 237, 358 and 454. (5S)-5-{[3-(Fluoromethyl)azetidin-1 -yl]carbonyl}-2-(4-methylbenzyl)-5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one Example 147 (5RS)-5-{[(3RS)-3-Fluoro-3-(hydroxymethyl)pyrrolidin-1-yl]carbonyl}-2-(4-methylbenzyl)-5,6,7,8-tetrahydro[ 1,2,4]triazolo[4,3-a]pyridin-3(2H)-one (mixture of diastereomer; 2 isomers)

[01156] (5RS)-2-(4-Methylbenzyl)-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine -5-carboxylic acid (enantiomer 1) (100 mg, 348 μmol) was initially loaded into DMF (4.0 mL) and dichloromethane (2.0 mL) at room temperature. Subsequently, 1-[bis(dimethylamino)methylene]-1H-benzotriazol-1-ium 3-oxide hexafluorophosphate (172 mg, 452 μmol) and N,N-diisopropylethylamine (160 μl, 900 μmol) were added. After stirring for 15 min, [(3RS)-3-fluoropyrrolidin-3-yl]methanol hydrochloride (racemate)(65.0 mg, 418 μmol) was added, and the reaction mixture was stirred at room temperature for 2 hours. . The solvent was removed under reduced pressure, and the residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/water gradient). The fractions containing the product were concentrated under reduced pressure and 62.8 mg (46% possibility) of the title compound were obtained. LC-MS (Method 3): Rt = 1.17 min; MS (ESIpos): m /z = 389 [M+H]+ 1H-NMR (500 MHz, DMSO-d6) δ [ppm]: -0.007 (0.53), 1.670 (0.41), 7.108 (1.04), 7.120 ( 7.69), 7.125 (11.68), 7.142 (0.91).

[01157] The (5S) configuration was assigned based on the elucidation of the crystal structure for Examples 26, 108, 113, 157, 237, 358 and 454. (5S)-5-{[(3RS)-3-Fluoro- 3-(hydroxymethyl)pyrrolidin-1-yl]carbonyl}-2-(4-methylbenzyl)-5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridin- 3(2H)-one (diastereomer mixture; 2 isomers) Example 148 (5RS)-5-{[(2S)-2-Methylazetidin-1-yl]carbonyl}-2-(4-methylbenzyl)-5,6 ,7,8- tetrahydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one (enantiomer 1)

[01158] (5RS)-2-(4-Methylbenzyl)-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine -5-carboxylic acid (enantiomer 1) (100 mg, 348 μmol) was initially loaded into DMF (4.0 mL) and dichloromethane (2.0 mL) at room temperature. Subsequently, 1-[bis(dimethylamino)methylene]-1H-benzotriazol-1-ium 3-oxide hexafluorophosphate (172 mg, 452 μmol) and N,N-diisopropylethylamine (160 μl, 900 μmol) were added. After stirring for 15 min, (2S)-2-methylazetidine hydrochloride (44.9 mg, 418 μmol) was added, and the reaction mixture was stirred at room temperature for 2 hours. The solvent was removed under reduced pressure, and the residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/water gradient). The fractions containing the product were concentrated under reduced pressure and 70.3 mg (59% possibility) of the title compound were obtained. LC-MS (Method 3): Rt = 1.36 min; MS (ESIpos): m /z = 341 [M+H]+ 1H-NMR (500 MHz, DMSO-d6) δ [ppm]: 1.314 (3.24), 1.326 (3.25), 1.349 (1.64), 1.361 (1.62 ), 1.450 (1.44), 1.462 (1.41), 1.520 (1.03), 1.533 (1.02), 1.706 (1.29), 1.797 (0.63), 1.803 (0.73), 1.815 (0.86), 1.819 (0.85), 1.826 (0.82 ), 1.838 (0.72), 1.849 (0.51), 1.917 (0.49), 1.924 (0.51), 1.933 (0.42), 1.987 (0.52), 2.001 (0.52), 2.008 (0.53), 2.017 (0.46), 2.270 (16.00 ), 2.395 (0.54), 2.401 (0.60), 2.413 (0.61), 2.418 (0.61), 2.434 (0.49), 2.517 (0.78), 2.522 (0.97), 2.557 (0.73), 2.567 (1.38), 2.576 (0.76 ), 2.601 (0.57), 4.120 (0.46), 4.132 (0.46), 4.207 (0.60), 4.220 (0.64), 4.238 (0.42), 4.329 (0.43), 4.340 (0.59), 4.357 (0.58), 4.370 (0.61 ), 4.423 (0.90), 4.431 (1.03), 4.435 (1.11), 4.443 (0.76), 4.681 (0.41), 4.697 (0.42), 4.712 (0.94), 4.728 (1.99), 4.743 (3.47), 4.756 (0.78 ), 4,776 (0.69), 7,107 (0.87), 7,126 (13.90), 7,142 (0.72).

[01159] The (5S) configuration was assigned based on the elucidation of the crystal structure for Examples 26, 108, 113, 157, 237, 358 and 454. (5S)-5-{[(2S)-2-Methylazetidin- 1-yl]carbonyl}-2-(4-methylbenzyl)-5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one Example 149 (5RS)-5-{[3-(Difluoromethyl)azetidin-1-yl]carbonyl}-2-(4-methylbenzyl)-5,6,7,8-tetrahydro[1,2,4]triazole [4,3-a]pyridin-3(2H)-one (enantiomer 1)

[01160] (5RS)-2-(4-Methylbenzyl)-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine -5-carboxylic acid (enantiomer 1) (50.0 mg, 174 μmol) was initially loaded into DMF (4.0 mL) and dichloromethane (2.0 mL) at room temperature. Subsequently, 1-[bis(dimethylamino)methylene]-1H-benzotriazol-1-ium 3-oxide hexafluorophosphate (85.8 mg, 226 μmol) and N,N-diisopropylethylamine (79 μl, 450 μmol) were added. After stirring for 15 min, 3-(difluoromethyl)azetidine hydrochloride (30.0 mg, 209 μmol) was added, and the reaction mixture was stirred at room temperature for 2 hours. The solvent was removed under reduced pressure, and the residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/water gradient). The fractions containing the product were concentrated under reduced pressure and 32.3 mg (48% possibility) of the title compound were obtained. LC-MS (Method 4): Rt = 0.76 min; MS (ESIpos): m /z = 377 [M+H]+ 1H-NMR (500 MHz, DMSO-d6) δ [ppm]: 1.676 (0.59), 1.696 (1.28), 1.705 (1.35), 1.714 (1.08 ), 1,912 (0.46), 1,949 (0.44), 1,984 (0.48), 1,996 (0.65), 2,004 (0.71), 2,012 (0.62), 2,016 (0.60), 2,024 (0.53), 2,270 (16.00), 2,519 (1.23 ), 2.568 (0.69), 2.577 (1.28), 2.586 (0.71), 2.610 (0.51), 2.689 (1.41), 2.889 (0.42), 3.178 (0.43), 3.186 (0.44), 3.196 (0.46), 3.204 (0.40 ), 3.775 (0.53), 3.786 (0.55), 3.796 (0.64), 3.806 (0.59), 3.846 (0.43), 3.858 (0.47), 3.866 (0.64), 3.878 (0.59), 3.941 (0.56), 3.959 (0.84 ), 4.017 (0.59), 4.036 (0.95), 4.055 (0.48), 4.111 (0.55), 4.122 (0.60), 4.129 (0.64), 4.139 (0.56), 4.272 (1.16), 4.275 (1.15), 4.284 (0.93 ), 4.293 (0.92), 4.434 (0.55), 4.452 (1.03), 4.470 (0.47), 4.518 (1.08), 4.528 (1.66), 4.538 (1.06), 4.746 (7.75), 6.314 (0.51), 6.322 (0.52 ), 6,352 (0.57), 6,361 (0.56), 7,106 (1.00), 7,124 (14.14), 7,141 (0.85).

[01161] The (5S) configuration was assigned based on the elucidation of the crystal structure for Examples 26, 108, 113, 157, 237, 358 and 454. (5S)-5-{[3-(Difluoromethyl)azetidin-1 -yl]carbonyl}-2-(4-methylbenzyl)-5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one Example 150 5RS)-5-{[cis-3,4-Difluoropyrrolidin-1-yl]carbonyl}-2-(4-methylbenzyl)-5,6,7,8-tetrahydro[1,2,4]triazolo[ 4,3-a]pyridin-3(2H)-one (enantiomer 1)

[01162] (5RS)-2-(4-Methylbenzyl)-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine -5-carboxylic acid (enantiomer 1) (100 mg, 348 μmol) was initially loaded into DMF (8.0 mL) and dichloromethane (4.0 mL) at room temperature. Subsequently, 1-[bis(dimethylamino)methylene]-1H-benzotriazol-1-ium 3-oxide hexafluorophosphate (172 mg, 452 μmol) and N,N-diisopropylethylamine (160 μl, 900 μmol) were added. After stirring for 15 min, cis-3,4-difluoropyrrolidine hydrochloride (60.0 mg, 418 μmol) was added, and the reaction mixture was stirred at room temperature for 2 hours. The solvent was removed under reduced pressure, and the residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/water gradient). The fractions containing the product were concentrated under reduced pressure and 97.6 mg (75% possibility) of the title compound were obtained. LC-MS (Method 1): Rt = 1.03 min; MS (ESIpos): m /z = 377 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: 0.008 (0.52), 1.636 (0.49), 1.643 (0.54), 1.668 (0.75 ), 1.678 (0.74), 1.695 (0.84), 1.707 (1.04), 1.717 (0.98), 1.730 (0.79), 1.949 (0.69), 1.957 (0.59), 1.974 (0.44), 1.996 (0.88), 2.005 (0.65 ), 2.022 (0.54), 2.031 (0.62), 2.039 (0.67), 2.047 (0.64), 2.056 (0.56), 2.066 (0.49), 2.074 (0.53), 2.082 (0.46), 2.272 (16.00), 2.522 (1.21 ), 2.558 (0.95), 2.571 (1.24), 2.585 (1.60), 2.597 (0.90), 2.628 (0.53), 3.485 (0.56), 3.493 (0.47), 3.506 (0.41), 3.514 (0.43), 3.523 (0.49 ), 3.533 (0.69), 3.541 (0.64), 3.575 (0.43), 3.612 (0.45), 3.626 (0.52), 3.668 (0.51), 3.681 (0.72), 3.688 (0.61), 3.701 (0.94), 3.714 (0.56 ), 3.724 (0.66), 3.733 (0.53), 3.753 (0.60), 3.766 (0.54), 3.865 (0.45), 3.924 (0.44), 3.938 (0.50), 3.973 (0.48), 3.987 (0.48), 4.172 (0.59 ), 4.703 (0.41), 4.743 (7.59), 4.750 (3.74), 4.768 (1.29), 4.779 (1.99), 4.789 (1.52), 5.254 (0.49), 5.265 (0.49), 5.275 (0.55), 5.284 (0.44 ), 5.338 (0.40), 5.349 (0.42), 5.375 (0.53), 5.387 (0.60), 5.398 (0.49), 5.407 (0.49), 5.415 (0.44), 5.457 (0.42), 5.470 (0.40), 5.479 (0.42 ), 7,096 (0.75), 7,102 (0.98), 7,117 (6.91), 7,123 (13.48), 7,144 (1.02).

[01163] The (5S) configuration was assigned based on the elucidation of the crystal structure for Examples 26, 108, 113, 157, 237, 358 and 454. 5S)-5-{[cis-3,4-Difluoropyrrolidin-1 -yl]carbonyl}-2-(4-methylbenzyl)-5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one Example 151 (5RS)-5-{[(3RS)-3-Fluoro-3-methylpyrrolidin-1-yl]carbonyl}-2-(4-methylbenzyl)-5,6,7,8-tetrahydro[1,2 ,4]triazolo[4,3-a]pyridin-3(2H)-one (mixture of diastereomer; 2 isomers)

[01164] (5RS)-2-(4-Methylbenzyl)-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine -5-carboxylic acid (enantiomer 1) (100 mg, 348 μmol) was initially loaded into DMF (8.0 mL) and dichloromethane (4.0 mL) at room temperature. Subsequently, 1-[bis(dimethylamino)methylene]-1H-benzotriazol-1-ium 3-oxide hexafluorophosphate (172 mg, 452 μmol) and N,N-diisopropylethylamine (160 μl, 900 μmol) were added. After stirring for 15 min, (3RS)-3-fluoro-3-methylpyrrolidine hydrochloride (racemate) (58.3 mg, 418 μmol) was added, and the reaction mixture was stirred at room temperature for 2 hours. The solvent was removed under reduced pressure, and the residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/water gradient). The fractions containing the product were concentrated under reduced pressure and 97.9 mg (75% possibility) of the title compound were obtained. LC-MS (Method 1): Rt = 1.06 min; MS (ESIpos): m /z = 373 [M+H]+ ¹H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.008 (0.81), 0.008 (0.67), 1.487 (2.19), 1.496 ( 2.37), 1.505 (2.23), 1.521 (2.02), 1.539 (2.25), 1.548 (2.39), 1.557 (2.22), 1.573 (1.99), 1.717 (1.18), 1.971 (0.64), 1.983 (0.87), 1.994 ( 0.92), 2.041 (0.65), 2.065 (0.84), 2.102 (0.67), 2.199 (0.44), 2.222 (0.52), 2.272 (16.00), 2.558 (0.72), 2.583 (1.28), 2.625 (0.46), 3.335 ( 0.59), 3.354 (0.54), 3.370 (0.45), 3.525 (0.49), 3.552 (0.51), 3.572 (0.69), 3.613 (0.67), 3.631 (0.55), 3.643 (0.63), 3.660 (0.57), 3.679 ( 0.57), 3.729 (0.64), 3.750 (0.40), 3.951 (0.55), 3.973 (0.40), 4.718 (0.47), 4.724 (0.59), 4.745 (6.15), 4.765 (0.40), 4.824 (0.41), 4.831 ( 0.44), 7.101 (0.69), 7.124 (13.52), 7.145 (0.82).

[01165] The (5S) configuration was assigned based on the elucidation of the crystal structure for Examples 26, 108, 113, 157, 237, 358 and 454. (5S)-5-{[(3RS)-3-Fluoro- 3-methylpyrrolidin-1-yl]carbonyl}-2-(4-methylbenzyl)- 5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridin-3(2H )-one (diastereomer mixture; 2 isomers) Example 152 (5RS)-5-{[(3RS)-3-Hydroxy-3-(trifluoromethyl)pyrrolidin-1-yl]carbonyl}-2-(4-methylbenzyl) -5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one (diastereomer mixture; 2 isomers)

[01166] (5RS)-2-(4-Methylbenzyl)-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine -5-carboxylic acid (enantiomer 1) (100 mg, 348 μmol) was initially loaded into DMF (8.0 mL) and dichloromethane (4.0 mL) at room temperature. Subsequently, 1-[bis(dimethylamino)methylene]-1H-benzotriazol-1-ium 3-oxide hexafluorophosphate (172 mg, 452 μmol) and N,N-diisopropylethylamine (160 μl, 900 μmol) were added. After stirring for 15 min, (3RS)-3-(trifluoromethyl)pyrrolidine-3-ol (racemate) 64.8 mg, 418 μmol) was added, and the reaction mixture was stirred at room temperature for 2 hours. The solvent was removed under reduced pressure, and the residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/water gradient). The fractions containing the product were concentrated under reduced pressure and 110 mg (73% possibility) of the title compound were obtained. LC-MS (Method 1): Rt = 1.06 min; MS (ESIpos): m /z = 425 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.008 (0.70), 0.008 (0.56), 1.664 (0.42), 1.674 ( 0.50), 1.687 (0.58), 1.719 (1.06), 1.979 (0.80), 1.997 (0.55), 2.015 (0.85), 2.031 (1.20), 2.060 (0.60), 2.077 (0.73), 2.101 (0.91), 2.111 ( 0.73), 2.124 (0.84), 2.243 (0.48), 2.272 (16.00), 2.299 (0.41), 2.523 (0.93), 2.577 (0.98), 2.588 (1.35), 2.600 (0.67), 2.630 (0.49), 3.444 ( 0.70), 3.476 (1.14), 3.492 (0.90), 3.539 (1.03), 3.572 (0.71), 3.585 (0.70), 3.617 (0.50), 3.678 (0.77), 3.707 (0.78), 3.733 (0.51), 3.753 ( 0.43), 3.761 (0.78), 3.778 (0.56), 3.802 (0.94), 3.840 (0.65), 3.868 (0.45), 4.743 (5.23), 4.748 (5.82), 4.769 (0.84), 4.779 (0.40), 4.836 ( 0.45), 4.842 (0.49), 6.549 (1.70), 6.564 (1.56), 6.615 (1.15), 6.631 (1.25), 7.099 (0.87), 7.124 (12.86), 7.146 (0.94).

[01167] The (5S) configuration was assigned based on the elucidation of the crystal structure for Examples 26, 108, 113, 157, 237, 358 and 454. (5S)-5-{[(3RS)-3-Hydroxy- 3-(trifluoromethyl)pyrrolidin-1-yl]carbonyl}-2-(4-methylbenzyl)-5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridin- 3(2H)-one (diastereomer mixture; 2 isomers) Example 153 (5RS)-5-(Pyrrolidin-1-ylcarbonyl)-2-{[6-(2,2,2-trifluoroethoxy)pyridin-3-yl ]methyl}-5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one (racemate)

[01168] Under argon, 2,2,2-trifluoroethanol (180 μl, 2.5 mmol) was dissolved in 3 mL of DMF (dried on a molecular sieve). At 0°C, sodium hydroxide (101 mg, 60% purity, 2.52 mmol) was added, and the mixture was stirred at 0°C for an additional 30 min. After addition of (5RS)-2-[(6-chloropyridin-3-yl)methyl]-5-(pyrrolidin-1-ylcarbonyl)-5,6,7,8-tetrahydro[1,2,4 ]triazolo[4,3-a]pyridin-3(2H)-one (racemate) (210 mg, 87% purity, 505 μmol), dissolved in 1 mL of DMF, the mixture was stirred at 60°C for 3 days.

[01169] For further conversion, first 2,2,2-trifluoroethanol (180 μl, 2.5 mmol) was dissolved in 1 mL of DMF, then sodium hydroxide (101 mg, 60% purity, 2.52 mmol) was added at 0°C, and the mixture was stirred at 0°C for an additional 30 min. The reagent solution was formed and then added to the master batch solution and stirred at 60°C for a further 48 h.

[01170] For preparation, the cooled mixture was mixed with water, saturated with sodium chloride and repeatedly extracted with ethyl acetate. The combined organic phases were dried over magnesium sulfate, filtered and concentrated. The remaining residue was purified via preparatory HPLC (column: Chromatorex, 125x30mm 10μm. Flow rate: 50 ml/min. Gradient (A = water + 0.1% formic acid, B = acetonitrile). Run time per separation 38 min Detection: 210 nm => 0min 0% B, 6min 10%B, 27min 95% B, 38min 95% B, 40min 0%B =>). By lyophilization of the product-containing fractions, 24.4 mg (11% possibility) of the title compound were obtained. LC-MS (Method 3): Rt = 1.47 min; MS (ESIpos): m /z = 426 [M+H]+ 1H-NMR (400MHz, DMSO-d6): δ [ppm]= 1.59 - 1.84 (m, 4H), 1.86 - 2.10 (m, 4H), 2.45 - 2.65 (m, 2H, partially covered by solvent signal), 3.20 - 3.41 (m, 2H, partially overlapped by water signal), 3.46 (dt, 1H), 3.62 (dt, 1H), 4.73 (dd, 1H), 4.81 (s, 2H), 4.98 (q, 2H), 6.97 (d, 1H), 7.67 (dd, 1H), 8.08 (d, 1H). Example 154 4-{[(5RS)-3-Oxo-5-(pyrrolidin-1-ylcarbonyl)-5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a] pyridin-2(3H)-yl]methyl}benzoic acid (racemate)

[01171] tert-Butyl 4-{[(5RS)-3-oxo-5-(pyrrolidin-1-ylcarbonyl)-5,6,7,8-tetrahydro[1,2,4]triazolo[4, 3-a]pyridin-2(3H)-yl]methyl}benzoate (racemate) (245 mg, 574 μmol) was dissolved in 5 mL of dichloromethane. After adding 750 μl (9.7 mmol) of trifluoroacetic acid, the reaction mixture was stirred at room temperature overnight. For elaboration, the mixture was mixed with 3 N aqueous sodium hydroxide solution while cooling with an ice bath and vigorous stirring and was thus adjusted to pH 3. After dilution with dichloromethane/water and extraction, the phase organic was removed, then the aqueous phase was extracted twice with dichloromethane. The combined organic phases were washed with saturated sodium chloride solution, dried over sodium sulfate, and concentrated and freed from residual solvent under reduced pressure. In this way, 195 mg (92% possibility) of the title compound were obtained. LC-MS (Method 4): Rt = 0.58 min; MS (ESIpos): m /z = 371 [M+H]+ 1H-NMR (400MHz, DMSO-d6): δ [ppm]= 1.62 - 1.84 (m, 4H), 1.89 - 2.10 (m, 4H), 2.52 - 2.67 (m, 2H, partially covered by the solvent signal), 3.22 - 3.41 (m, 2H, partially overlapped by the water signal), 3.47 (dt, 1H), 3.62 (dt, 1H), 4.75 (dd, 1H), 4.84 - 4.94 (m, 2H), 7.31 - 7.36 (m, 2H), 7.88 - 7.93 (m, 2H), 12.92 (br s, 1H). Example 155 N-Methyl-4-{[(5RS)-3-oxo-5-(pyrrolidin-1-ylcarbonyl)-5,6,7,8-tetrahydro[1,2,4]triazolo[4, 3-a]pyridin-2(3H)-yl]methyl}benzamide (racemate)

[01172] 4-{[(5RS)-3-Oxo-5-(pyrrolidin-1-ylcarbonyl)-5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a ]pyridin-2(3H)-yl]methyl}benzoic acid (racemate) (78.0 mg, 211 μmol) was initially loaded into 2.5 mL of dichloromethane, then HATU (160 mg, 421 μmol), N ,N-diisopropylethylamine (73 μl, 420 μmol) and methylamine, 33% in ethanol (31 μl, 250 μmol) were added. The mixture was stirred at room temperature overnight. Methylamine, 33% in ethanol (13 μl, 110 μmol), was added, and the mixture was allowed to stir at room temperature for an additional 5 hours. For elaboration, the mixture was diluted with dichloromethane/water, acidified with 1 N aqueous hydrochloric acid, and the organic phase was removed. The aqueous phase was extracted twice more with dichloromethane, and then the combined organic phases were washed with saturated sodium chloride solution, dried over sodium sulfate and concentrated, and residual solvents were removed under reduced pressure. The crude product was separated by preparatory HPLC (instrument: Waters Prep LC/MS System, column: Phenomenex Kinetex C18 5μm 100x30 mm; eluent A: water, eluent B: acetonitrile, flow rate: 65 ml/min plus 5 ml acid 2% formic in water, room temperature, wavelength 200-400 nm, in column injection (full injection); gradient profiles: 0 to 2 min 10% eluent B, 2 to 2.2 min in eluent B a 20%, 2.2 to 7 min in 60% eluent B, 7 to 7.5 min in 92% eluent B, 7.5 to 9 min in 92% B. By combining the lyophilized fractions containing product, 2.00 mg (2.5% possibility) of the title compound were obtained. LC-MS (Method 12): Rt = 1.00 min; MS (ESIpos): m /z = 384 [M+H]+ 1H-NMR (500MHz, DMSO-d6): δ [ppm]= 1.62 - 1.83 (m, 4H), 1.87 - 2.11 (m, 4H), 2.47 - 2.67 (m, 2H, partially covered by solvent signal), 2.62 (dt, 1H), 2.77 (d, 3H), 3.23 - 3.40 (m, 2H, partially overlapped by water signal), 3.47 (dt, 1H), 3.62 (dt, 1H), 4.75 (dd, 1H), 4.85 (s, 2H), 7.28 (d, 2H), 7.78 (d, 2H), 8.39 (br q, 1H). Example 156 N,N-Dimethyl-4-{[(5RS)-3-oxo-5-(pyrrolidin-1-ylcarbonyl)-5,6,7,8-tetrahydro[1,2,4]triazolo[ 4,3-a]pyridin-2(3H)-yl]methyl}benzamide (racemate)

[01173] 4-{[(5RS)-3-Oxo-5-(pyrrolidin-1-ylcarbonyl)-5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a ]pyridin-2(3H)-yl]methyl}benzoic acid (racemate) (78.0 mg, 211 μmol) was initially loaded into 2.5 mL of dichloromethane, then HATU (160 mg, 421 μmol) were added , N,N-diisopropylethylamine (73 μl, 420 μmol) and dimethylamine, 2 M in THF (126 μl, 252 μmol). The mixture was stirred at room temperature for 4 hours and then for a weekend. Dimethylamine, 2 M in THF (105 μl, 210 μmol), was added, and the mixture was allowed to stir at room temperature for an additional 54 hours. For elaboration, the mixture was diluted with dichloromethane/water, acidified with 1 N aqueous hydrochloric acid, and the organic phase was removed. The aqueous phase was extracted twice more with dichloromethane, and then the combined organic phases were washed with saturated sodium chloride solution, dried over sodium sulfate and concentrated, and residual solvents were removed under reduced pressure. The crude product was dissolved in acetonitrile/water and separated by preparatory HPLC (column: Kromasila C18, 125x30mm, 10μm, eluent: acetonitrile (B)/water + 0.1% TFA (A), gradient: 0min 90% A, 6min 90 %A, 18min 5%A, 20min 5%A, 21min 90%A, flow rate: 75ml/min, detector: 210nm). Combining the fractions containing the product and removing the solvent under reduced pressure, 36.7 mg (42% possibility) of the title compound were obtained. LC-MS (Method 3): Rt = 0.95 min; MS (ESIpos): m /z = 398 [M+H]+ 1H-NMR (400MHz, DMSO-d6): δ [ppm]= 1.62 - 1.84 (m, 4H), 1.87 - 2.11 (m, 4H), 2.46 - 2.69 (m, 2H, partially covered by solvent signal), 2.90 (br s, 3H), 2.97 (br s, 3H), 3.26 (dt, 1H), 3.36 (dt, 1H), 3.47 (dt, 1H), 3.62 (dt, 1H, partially overlapped by the water signal), 4.75 (dd, 1H), 4.85 (s, 2H), 7.24 - 7.29 (m, 2H), 7.34 - 7.39 (m, 2H). Example 157 (5S)-2-(4-Methylbenzyl)-5-(pyrrolidin-1-ylcarbonyl)-2,5,6,7-tetrahydro-3H-pyrrolo[2,1-c][1,2 ,4]triazol-3-one (enantiomer)

[01174] (5S)-2-(4-Methylbenzyl)-3-oxo-2,5,6,7-tetrahydro-3H-pyrrolo[2,1-c][1,2,4]triazol- 5-Carboxylic acid (enantiomer) (50.0 mg, 183 μmol) was initially loaded into DMF (2.2 mL) and dichloromethane (1.1 mL) at room temperature. Subsequently, 1-[bis(dimethylamino)methylene]-1H-benzotriazol-1-ium 3-oxide hexafluorophosphate (90.2 mg, 238 μmol) and N,N-diisopropylethylamine (64 μl, 370 μmol) were added. After stirring for 15 minutes, pyrrolidine (15.6 mg, 220 μmol) was added and the reaction mixture was stirred at room temperature overnight. The reaction mixture was mixed with water and ethyl acetate. The organic phase was removed and the aqueous phase was extracted three times with ethyl acetate. The combined organic phases were washed with saturated aqueous sodium chloride solution, dried over sodium sulfate and filtered, and the filtrate was concentrated. The residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/gradient water). The fractions containing the product were concentrated under reduced pressure. The residue was purified by chiral preparatory HPLC [sample preparation: 37 mg dissolved in 1 mL of acetonitrile; injection volume: 0.20 mL; column: Daicel Chiralpak® AD-H 5μm, 250 x 20 mm; eluent: n-heptane/ethanol: 30:70; flow rate: 20 ml/min; temperature 23°C; UV detection: 220 nm]. 19 mg (31% chance) of the title compound was obtained. Analytical chiral HPLC: Rt = 3.49 min, e.e. = 99.9% [column: Daicel Chiralcel® AD-3 3μm 50 x 4.6 mm; eluent: n-heptane/i-propanol 1:1, 0.2% trifluoroacetic acid, 1% water; flow rate: 1 ml/min; UV detection: 220 nm LC-MS (Method 4): Rt = 0.70 min; MS (ESIpos): m /z = 327 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.008 (2.92), 0.008 (2.77), 1.781 (0.76), 1.798 ( 1.57), 1.816 (1.43), 1.832 (0.52), 1.887 (0.43), 1.903 (1.35), 1.919 (1.69), 1.936 (1.00), 2.274 (9.31), 2.327 (0.50), 2.366 (0.66), 2.377 ( 0.48), 2.388 (0.45), 2.524 (1.50), 2.670 (1.06), 2.685 (0.85), 2.693 (1.02), 2.706 (1.21), 2.715 (1.32), 2.748 (0.45), 2.755 (0.48), 2.786 ( 0.55), 2.808 (0.43), 3.291 (0.62), 3.309 (1.49), 3.328 (1.53), 3.345 (0.62), 3.396 (0.72), 3.403 (0.49), 3.414 (0.42), 3.421 (0.84), 3.438 ( 0.42), 3.527 (1.79), 3.646 (2.87), 3.663 (3.01), 3.688 (2.02), 3.705 (1.07), 4.698 (0.41), 4.736 (2.51), 4.748 (2.52), 4.897 (0.83), 4.905 ( 0.63), 4.919 (0.97), 4.925 (0.62), 7.137 (16.00).

[01175] The (5S) configuration was assigned based on the elucidation of the crystal structure for Example 157. Example 158 (5RS)-5-(3,6-Dihydropyridin-1(2H)-ylcarbonyl)-2-( 4-methylbenzyl)-5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one (racemate)

[01176] 1,2,3,6-Tetrahydropyridine (8.3 mg, 0.10 mmol) was initially loaded into one well of a 96-well microtiter plate, and (5RS)-2-(4- methylbenzyl)-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylic acid (racemate) (28.7 mg, 0.10 mmol) and HATU (49.4 mg, 0.13 mmol), dissolved in 0.8 mL of DMF, were added. 50 μl of 4-methylmorpholine was added, and the microtiter plate was closed and stirred at room temperature overnight. Subsequently, the mixture was filtered, and the filtrate was separated by preparatory LC-MS. (MS instrument: Waters, HPLC instrument: Waters (Waters X-Bridge C18 column, 19 mm x 50 mm, 5 μm, eluent A: water, eluent B: acetonitrile (ULC) with gradient; flow rate: 38.5 ml /min; modifier: 5% aq. ammonia, flow rate: 1.5 ml/min; UV detection: DAD; (2) 100A, AXIA Tech. 50 x 21.2 mm, eluent A: water, eluent B: acetonitrile (ULC), with flow rate: 38.5 ml/min; flow rate: 1.5 ml/min; UV detection: DAD;

[01177] The product-containing fractions were concentrated using a centrifugal dryer. The residue of all product fractions were dissolved in a total of 1.8 mL of DMSO, combined and concentrated again. In this way, 19.8 mg (56% possibility) of the title compound were obtained. LC/MS (Method 13): Rt = 0.95 min, MS (ESIpos): m/z = 353[M+H]+.

[01178] In analogy to Example 158, the example compounds shown in Table 1 were prepared. Table 1 Example 163 (5RS)-2-[(6-Chloropyridin-3-yl)methyl]-5-{[(3S)-3-fluoropyrrolidin-1-yl]carbonyl}-2,5,6,7-tetra- hydro-3H-pyrrole[2,1-c][1,2,4]triazol-3-one (mixture of diastereomer; 2 isomers)

[01179] (5S)-2-[(6-Chloropyridin-3-yl)methyl]-3-oxo-2,5,6,7-tetrahydro-3H-pyrrole[2,1-c][1 ,2,4]triazole-5-carboxylic acid (75.0 mg, 78% purity, 199 μmol) was initially loaded into THF (2.1 mL) at room temperature. Subsequently, (3S)-3-fluoropyrrolidine hydrochloride (29.9 mg, 238 μmol), HATU (98.1 mg, 258 μmol), and triethylamine (170 μl, 1.2 mmol) were added. The reaction mixture was stirred at room temperature overnight. Triethylamine (55 μl, 400 μmol), (3S)-3-fluoropyrrolidinTa hydrochloride (12.5 mg, 99.3 μmol), and HATU (37.7 mg, 99.3 μmol) were added again, and the mixture was stirred. for another 90 minutes. The reaction mixture was mixed with water and concentrated under reduced pressure. The residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: gradient (acetonitrile/water with 0.1% formic acid). The fractions containing the product were concentrated under reduced pressure and were obtained 5.91 mg (8% possibility) of the title compound. LC-MS (Method 3): Rt = 0.94 min (ESIpos): m / z = 366 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.008 (1.89), 0.008 (1.61), 2.100 (1.11), 2.115 (1.07), 2.137 (1.07), 2.147 (1.03), 2.161 (0.86), 2.217 (0.84 ), 2.234 (0.96), 2.264 (1.15), 2.288 (0.52), 2.301 (0.58), 2.307 (0.66), 2.319 (0.78), 2.326 (0.84), 2.334 (0.82), 2.342 (0.82), 2.349 (0.56 ), 2.357 (0.66), 2.367 (0.62), 2.375 (0.60), 2.383 (0.74), 2.390 (1.01), 2.396 (1.11), 2.403 (0.98), 2.411 (1.03), 2.420 (1.15), 2.430 (0.78 ), 2.441 (0.66), 2.450 (0.48), 2.671 (1.15), 2.690 (1.41), 2.711 (3.40), 2.719 (3.04), 2.731 (4.98), 2.743 (2.57), 2.752 (4.06), 2.771 (0.86 ), 2.785 (0.78), 2.792 (1.25), 2.806 (0.64), 2.817 (1.35), 2.825 (1.37), 2.838 (1.27), 2.848 (1.59), 2.859 (1.03), 2.870 (1.01), 2.881 (0.68 ), 3.342 (1.25), 3.369 (0.74), 3.384 (0.56), 3.393 (0.78), 3.419 (0.66), 3.428 (0.70), 3.468 (0.40), 3.482 (0.72), 3.491 (0.86), 3.516 (1.11 ), 3.525 (0.74), 3.563 (0.56), 3.573 (0.52), 3.600 (1.29), 3.624 (2.33), 3.646 (1.45), 3.664 (1.89), 3.669 (1.89), 3.685 (2.33), 3.700 (1.55 ), 3.710 (1.21), 3.726 (1.75), 3.758 (0.58), 3.790 (0.72), 3.832 (0.54), 3.840 (0.62), 3.927 (0.54), 3.935 (0.56), 3.966 (0.74), 3.988 (0.68 ), 4.013 (0.58), 4.885 (16.00), 4.901 (1.47), 4.939 (1.43), 4.946 (1.55), 4.961 (1.61), 4.967 (1.35), 5.001 (0.46), 5.008 (0.60), 5.018 (0.88 ), 5.024 (1.17), 5.039 (0.76), 5.045 (0.56), 5.277 (1.37), 5.363 (0.78), 5.372 (0.92), 5.410 (1.37), 5.504 (0.90), 7.511 (6.01), 7.531 (7.46 ), 7,722 (3.92), 7,743 (3.34), 8,325 (4.96), 8,330 (5.23). Example 164 (5RS)-5-{[(3S)-3-Fluoropyrrolidin-1-yl]carbonyl}-2-{[6-(trifluoromethyl)pyridin-3-yl]methyl}-2,5,6,7 -tetrahydro-3H-pyrrole[2,1- c][1,2,4]triazol-3-one (mixture of diastereomer; 2 isomers)

[01180] (5S)-3-Oxo-2-{[6-(trifluoromethyl)pyridin-3-yl]methyl}-2,5,6,7-tetrahydro-3H-pyrrolo[2,1-c ][1,2,4]triazole-5-carboxylic acid (75.0 mg, 228 μmol) was initially loaded into THF (2.4 mL) at room temperature. Subsequently, (3S)-3-fluoropyrrolidine hydrochloride (34.4 mg, 274 μmol), HATU (113 mg, 297 μmol), and triethylamine (190 μl, 1.4 mmol) were added. The reaction mixture was stirred at room temperature for 20 hours. HATU (113 mg, 297 μmol), (3S)-3-fluoropyrrolidine hydrochloride (17.2 mg, 137 μmol), and triethylamine (190 μl, 1.4 mmol) were added again and the mixture was stirred overnight. The reaction mixture was mixed with water and concentrated under reduced pressure. HATU (113 mg, 297 μmol), (3S)-3-fluoropyrrolidine hydrochloride (17.2 mg, 137 μmol), and triethylamine (190 μl, 1.4 mmol) were added again and the mixture was stirred at 40°C overnight. . The reaction mixture was mixed with water and concentrated under reduced pressure. The residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: gradient (acetonitrile/water with 0.1% formic acid). The fractions containing the product were concentrated under reduced pressure and 39. 4 mg (43% possibility) of the title compound. LC-MS (Method 4): Rt = 0.63 min; MS (ESIpos): m / z = 400 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.008 (2.09), 0.008 (1.78), 1.994 (0.41), 2.073 (0.50), 2.101 (1.23), 2.119 (1.08), 2.140 (1.10), 2.150 (1.06), 2,165 (0.94), 2,220 (0.88), 2,238 (1.01), 2,266 (1.21), 2,327 (0.97), 2,333 (0.76), 2,343 (0.61), 2,351 (0.76), 2,358 (0.67), 2,366 (1.12), 2,385 (0.86), 2,393 (0.90), 2,407 (1.42), 2,413 (1.23), 2,422 (0.97), 2,431 (1.21), 2,440 (0.76), 2,451 (0.58), 2,665 (0.68), 2,680 (1.14), 2,700 (1.42), 2,721 (3.08), 2,729 (3.64), 2,741 (5.50), 2,762 (3.84), 2,772 (1.50), 2,782 (1.32), 2,795 (0.92), 2,803 (1.51), 2,827 (1.32), 2,835 (1.30), 2,848 (1.23), 2,858 (1.50), 2,870 (0.94), 2,881 (0.88), 2,893 (0.59), 3,372 (1.39), 3,398 (1.01), 3,424 (0.68), 3,432 (0.72), 3.472 (0.70), 3.488 (0.86), 3.496 (1.10), 3.518 (1.44), 3.541 (0.49), 3.567 (0.92), 3.578 (0.83), 3.605 (2.02), 3.630 (2.74), 3.651 (1.28), 3,669 (1.78), 3,674 (1.66), 3,688 (2.11), 3,704 (1.37), 3,714 (1.06), 3,729 (1.77), 3,761 (0.50), 3,794 (0.61), 3,834 (0.47), 3,843 (0.50), 3,930 (0.45), 3,938 (0.49), 3,969 (0.88), 3,991 (1.12), 4,017 (0.81), 4,053 (0.47), 4,079 (0.56), 4,110 (0.45), 4,886 (0.94), 4,893 (1.03), 4,908 (1.06), 4,915 (0.92), 4,953 (1.19), 4,960 (1.32), 4,975 (1.41), 4,982 (1.23), 5,012 (16.00), 5,032 (1.64), 5,039 (2.07), 5,054 (1.35), 5,060 (0.95), 5,279 (1.44), 5,365 (0.95), 5,374 (0.94), 5,412 (1.44), 5,497 (0.92), 5,506 (0.90), 7,904 (2.50), 7,925 (10.38), 7,937 (6.31), 7,958 (1.66), 8,675 (6.00). Example 165 (5RS)-2-(3-Chloro-4-fluorobenzyl)-5-{[(3S)-3-fluoropyrrolidin-1-yl]carbonyl}-2,5,6,7-tetrahydro-3H -pyrrole[2,1-c][1,2,4]triazol-3-one (mixture of diastereomer; 2 isomers)

[01181] (5S)-2-(3-Chloro-4-fluorobenzyl)-3-oxo-2,5,6,7-tetrahydro-3H-pyrrole[2,1-c][1,2, 4]triazole-5-carboxylic acid (75.0 mg, 87% purity, 209 μmol) was initially loaded into THF (2.2 mL) at room temperature. Subsequently, (3S)-3-fluoropyrrolidine hydrochloride (31.5 mg, 251 μmol), HATU (103 mg, 272 μmol), and triethylamine (180 μl, 1.3 mmol) were added. The reaction mixture was stirred at room temperature overnight. (3S)-3-Fluoropyrrolidine hydrochloride (15.8 mg, 126 μmol), HATU (103 mg, 272 μmol) and triethylamine (180 μl, 1.3 mmol) were added again and the mixture was stirred at 70°C for 4 hours. The reaction mixture was mixed with water and concentrated under reduced pressure. The residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/water with 0.1% formic acid gradient). The fractions containing the product were concentrated under reduced pressure and 16.4 mg (20% possibility) of the title compound were obtained. LC-MS (Method 3): Rt = 1.37 min; MS (ESIpos): m /z = 383 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (1.85), -0.008 (16.00), 0.008 (13.87), 0.146 (1.80) (1.91) (0.62) (7.92) (0.90), 5.503 (0.56), 6.922 (0.45), 7.276 (1.96), 7.288 (1.74), 7.379 (2.86), 7.402 (4.38), 7.424 (2.13), 7.458 (2.19), 7.473 (2.19). Example 166 (5RS)-2-[(6-Chloropyridin-3-yl)methyl]-5-[(3,3-difluoropyrrolidin-1-yl)carbonyl]-2,5,6,7-tetrahydro- 3H-pyrrole[2,1-c][1,2,4]triazol-3-one (racemate)

[01182] (5S)-2-[(6-Chloropyridin-3-yl)methyl]-3-oxo-2,5,6,7-tetrahydro-3H-pyrrole[2,1-c][1 ,2,4]triazole-5-carboxylic acid (75.0 mg, 78% purity, 199 μmol) was initially loaded into THF (2.1 mL) at room temperature. Subsequently, 3,3-difluoropyrrolidine hydrochloride (34.2 mg, 238 μmol), HATU (98.1 mg, 258 μmol), and triethylamine (170 μl, 1.2 mmol) were added. The reaction mixture was stirred at room temperature for 20 hours. 3,3-Difluoropyrrolidine hydrochloride (17.1 mg, 119 μmol), HATU (98.1 mg, 258 μmol) and triethylamine (55 μl, 400 μmol) were added again and the mixture was stirred overnight. The reaction mixture was mixed with water and concentrated under reduced pressure. The residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: gradient (acetonitrile/water with 0.1% formic acid). The fractions containing the product were concentrated under reduced pressure and 21. 2 mg (28% possibility) of the title compound. LC-MS (Method 3): Rt = 1.11 min; MS (ESIpos): m / z = 384 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (1.41), -0.008 (11.99), 0.008 (10.88), 0.146 (1.35), 2.327 (0.96), 2.366 (0.96), 2.391 (1.02), 2.412 (2.04) , 2,424 (2.13), 2,440 (2.52), 2,450 (1.77), 2,459 (1.59), 2,523 (3.45), 2,561 (1.41), 2,578 (0.78), 2,596 (0.42), 2,669 (1.20), 2,675 (1.14) , 2.686 (1.05), 2.694 (1.20), 2.716 (2.52), 2.736 (2.79), 2.743 (3.48), 2.751 (1.65), 2.777 (1.92), 2.791 (1.44), 2.820 (1.29), 2.842 (0.75) , 3,550 (2.13), 3,569 (3.63), 3,588 (1.86), 3,682 (0.54), 3,699 (1.80), 3,729 (2.31), 3,744 (1.20), 3,763 (0.75), 3,774 (1.65), 3,808 (1.20) , 3.895 (0.48), 3.925 (0.96), 3.962 (1.08), 3.976 (1.29), 3.995 (1.08), 4.002 (1.05), 4.021 (0.51), 4.230 (0.48), 4.259 (1.05), 4.291 (1.05) , 4,886 (16.00), 4,927 (1.44), 4,934 (1.17), 4,948 (1.53), 5,011 (1.47), 5,018 (1.14), 5,032 (1.59), 5,039 (1.02), 7,510 (4,82), 7,531 (5,96) , 7,718 (2.61), 7,723 (2.67), 7,739 (2.25), 7,744 (2.22), 8,324 (4.01), 8,329 (3.93). Example 167 (5RS)-5-[(3,3-Difluoropyrrolidin-1-yl)carbonyl]-2-{[6-(trifluoromethyl)pyridin-3-yl]methyl}-2,5,6,7-tetra -hydro-3H-pyrrole[2,1-c][1,2,4]triazol-3-one (racemate)

[01183] (5S)-3-Oxo-2-{[6-(trifluoromethyl)pyridin-3-yl]methyl}-2,5,6,7-tetrahydro-3H-pyrrolo[2,1-c ][1,2,4]triazole-5-carboxylic acid (75.0 mg, 228 μmol) was initially loaded into THF (2.4 mL) at room temperature. Subsequently, 3,3-difluoropyrrolidine hydrochloride (39.4 mg, 274 μmol), HATU (113 mg, 297 μmol), and triethylamine (190 μl, 1.4 mmol) were added. The reaction mixture was stirred at room temperature for 20 hours. 3,3-Difluoropyrrolidine hydrochloride (19.7 mg, 137 μmol), HATU (113 mg, 297 μmol), and triethylamine (64 μl, 460 μmol) were added again and the mixture was stirred overnight. The reaction mixture was mixed with water and concentrated under reduced pressure. The residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: gradient (acetonitrile/water with 0.1% formic acid). The fractions containing the product were concentrated under reduced pressure and 15. 4 mg (16% chance) of the title compound. LC-MS (Method 3): Rt = 1.30 min; MS (ESIpos): m / z = 418 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.150 (1.95), -0.034 (0.54), - 0.009 (16.00), 0.007 (14.34), 0.146 (1.95), 2.327 (1.41), 2.331 (1.16), 2.365 (1.04 ), 2.408 (0.83), 2.421 (1.16), 2.442 (1.16), 2.460 (1.33), 2.523 (3.69), 2.581 (0.46), 2.669 (1.53), 2.710 (1.08), 2.725 (1.08), 2.747 (1.20 ), 2.753 (1.37), 2.762 (0.79), 2.787 (0.83), 2.801 (0.58), 2.830 (0.50), 3.556 (0.75), 3.573 (1.41), 3.592 (0.66), 3.702 (0.75), 3.732 (0.87 ), 3.748 (0.46), 3.770 (0.33), 3.779 (0.62), 3.812 (0.50), 3.929 (0.37), 3.964 (0.46), 3.979 (0.46), 3.998 (0.41), 4.006 (0.41), 4.263 (0.46 ), 4.293 (0.46), 4.948 (0.46), 4.963 (0.66), 5.012 (5.68), 5.025 (0.79), 5.046 (0.62), 5.053 (0.50), 7.904 (0.75), 7.924 (3.07), 7.935 (1.82 ), 7,958 (0.54), 8,673 (2.03). Example 168 (5RS)-2-(3-Chloro-4-fluorobenzyl)-5-[(3,3-difluoropyrrolidin-1-yl)carbonyl]-2,5,6,7-tetrahydro-3H-pyrrole [2,1-c][1,2,4]triazol-3-one (racemate)

[01184] (5S)-2-(3-Chloro-4-fluorobenzyl)-3-oxo-2,5,6,7-tetrahydro-3H-pyrrole[2,1-c][1,2, 4]triazole-5-carboxylic acid (75.0 mg, 87% purity, 209 μmol) was initially loaded into THF (2.2 mL) at room temperature. Subsequently, 3,3-difluoropyrrolidine hydrochloride (36.1 mg, 251 μmol), HATU (103 mg, 272 μmol), and triethylamine (180 μl, 1.3 mmol) were added. The reaction mixture was stirred at room temperature overnight. The reaction mixture was mixed with water and concentrated under reduced pressure. The residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: gradient (acetonitrile/water with 0.1% formic acid). The fractions containing the product were concentrated under reduced pressure and 64. 0 mg (71% chance) of the title compound. LC-MS (Method 4): Rt = 0.79 min; MS (ESIpos): m / z = 401 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.150 (1.35), 0.008 (10.27), 0.146 (1.18), 2.327 (2.69), 2.366 (2.86), 2.387 (1.85), 2.410 (3.37), 2.430 (3.54), 2,440 (3.87), 2,460 (2.86), 2,523 (9.60), 2,578 (1.85), 2,669 (3.03), 2,710 (3.54), 2,724 (3.87), 2,744 (5.56), 2,750 (5.73), 2,781 (3.71), 2,797 (2.53), 2,825 (2.02), 2,847 (1.35), 3,552 (3.37), 3,571 (5.73), 3,590 (3.03), 3,701 (3.20), 3,727 (7.58), 3,745 (1.85), 3,776 (2.69), 3,809 (2.02), 3,896 (0.67), 3,926 (1.52), 3,962 (2.02), 3,979 (2.02), 3,996 (1.68), 4,024 (0.84), 4,231 (0.84), 4,260 (1.68), 4,290 (1.68), 4.322 (0.51), 4.785 (1.01), 4.825 (16.00), 4.868 (0.84), 4.934 (1.85), 4.941 (1.85), 4.954 (2.36), 5.018 (2.36), 5.026 (1.68), 5.040 (2.36), 7,270 (3.20), 7,379 (5.22), 7,402 (7.24), 7,424 (3.87), 7,455 (3.87), 7,472 (3.87). Example 169 (5RS)-2-[(6-Chloropyridin-3-yl)methyl]-5-[(3-fluoroazetidin-1-yl)carbonyl]-2,5,6,7-tetrahydro-3H- pyrrole[2,1-c][1,2,4]triazol-3-one (racemate)

[01185] (5S)-2-[(6-Chloropyridin-3-yl)methyl]-3-oxo-2,5,6,7-tetrahydro-3H-pyrrole[2,1-c][1 ,2,4]triazole-5-carboxylic acid (75.0 mg, 78% purity, 199 μmol) was initially loaded into THF (2.1 mL) at room temperature. Subsequently, 3-fluoroazetidine hydrochloride (26.6 mg, 238 μmol), HATU (98.1 mg, 258 μmol) and triethylamine (170 μl, 1.2 mmol) were added. The reaction mixture was stirred at room temperature overnight. 3-Fluoroazetidine hydrochloride (13.3 mg, 119 μmol), HATU (98.1 mg, 258 μmol), and triethylamine (55 μl, 400 μmol) were added again and the mixture was stirred for another 5 hours. The reaction mixture was mixed with water and concentrated under reduced pressure. The residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: gradient (acetonitrile/water with 0.1% formic acid). The fractions containing the product were concentrated under reduced pressure and 15. 4 mg (21% possibility) of the title compound. LC-MS (Method 4): Rt = 0.52 min; MS (ESIpos): m / z = 352 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (0.73), -0.008 (6.62), 0.008 (5.33), 0.146 (0.69), 2.328 (0.95), 2.367 (0.90), 2.390 (0.90), 2.422 (4.13) , 2,453 (1.25), 2,524 (2.58), 2,670 (1.38), 2,675 (1.55), 2,690 (1.68), 2,723 (12.26), 3,724 (0.60), 3,929 (1.25), 3,962 (1.55), 3.95 (1.25) , 4.024 (1.42), 4.193 (0.69), 4.207 (0.77), 4.225 (1.20), 4.253 (1.72), 4.277 (2.02), 4.293 (1.33), 4.310 (1.46), 4.321 (1.25), 4.343 (0.86) , 4.429 (0.60), 4.455 (1.12), 4.489 (1.29), 4.514 (1.55), 4.544 (1.03), 4.557 (1.12), 4.582 (0.39), 4.664 (0.65), 4.679 (0.77), 4.695 (0.77) , 4,719 (3.23), 4,731 (4,39), 4,757 (0.69), 4,834 (0.65), 4,877 (16.00), 4,917 (0.77), 5,093 (0.60), 5,343 (0.82), 5,350 (0.99), 5,358 (0.77) , 5.374 (0.56), 5.390 (0.77), 5.398 (0.95), 5.486 (0.82), 5.493 (0.99), 5.500 (0.82), 5.532 (0.77), 5.540 (0.90), 7.495 (1.08), 7.506 (6.37) , 7,516 (1.55), 7,526 (7.87), 7,720 (4.22), 7,741 (3.61), 8,326 (6.06). Example 170 (5RS)-5-[(3-Fluoroazetidin-1-yl)carbonyl]-2-{[6-(trifluoromethyl)pyridin-3-yl]methyl}-2,5,6,7-tetrahydro -3H-pyrrole[2,1-c][1,2,4]triazol-3-one (racemate)

[01186] (5S)-3-Oxo-2-{[6-(trifluoromethyl)pyridin-3-yl]methyl}-2,5,6,7-tetrahydro-3H-pyrrol[2,1-c ][1,2,4]triazole-5-carboxylic acid (75.0 mg, 228 μmol) was initially loaded into THF (2.4 mL) at room temperature. Subsequently, 3-fluoroazetidine hydrochloride (30.6 mg, 274 μmol), HATU (113 mg, 297 μmol), and triethylamine (190 μl, 1.4 mmol) were added. The reaction mixture was stirred at room temperature for 20 hours. The reaction mixture was mixed with water and concentrated under reduced pressure. The residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: gradient (acetonitrile/water with 0.1% formic acid). The fractions containing the product were concentrated under reduced pressure and 5. 30 mg (6% chance) of the title compound. LC-MS (Method 3): Rt = 1.12 min; MS (ESIpos): m / z = 386 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.008 (3.13), 0.008 (3.01), 2.328 (0.70), 2.366 (0.52), 2.405 (0.67), 2.432 (3.56), 2.464 (1.22), 2.523 (2.04), 2,670 (0.85), 2,734 (10.77), 3,729 (1.73), 3,938 (1.10), 3,966 (1.37), 3,999 (1.13), 4,028 (1.28), 4,200 (0.64), 4,215 (0.67), 4,230 (1.03), 4,257 (1.52), 4,284 (1.83), 4,296 (1.28), 4,314 (1.16), 4,326 (1.19), 4,348 (0.73), 4,434 (0.46), 4,459 (0.94), 4,494 (1.13), 4,518 (1.37), 4,547 (0.82), 4,561 (0.79), 4,669 (0.55), 4,684 (0.64), 4,746 (3.95), 4,960 (0.43), 5,003 (13.17), 5,043 (0.46), 5,352 (0.88), 5,392 (0.70), 5,400 (0.85), 5,495 (0.88), 5,503 (0.70), 5,543 (0.82), 5,754 (16.00), 7,899 (2.74), 7,919 (9.79), 7,934 (6.11), 7,955 (1.83), 8,674 (6.48). Example 171 (5RS)-2-(3-Chloro-4-fluorobenzyl)-5-[(3-fluoroazetidin-1-yl)carbonyl]-2,5,6,7-tetrahydro-3H-pyrrole[2 ,1-c][1,2,4]triazol-3-one (racemate)

[01187] (5S)-2-(3-Chloro-4-fluorobenzyl)-3-oxo-2,5,6,7-tetrahydro-3H-pyrrole[2,1-c][1,2, 4]triazole-5-carboxylic acid (75.0 mg, 87% purity, 209 μmol) was initially loaded into THF (2.2 mL) at room temperature. Subsequently, 3-fluoroazetidine hydrochloride (28.0 mg, 251 μmol), HATU (103 mg, 272 μmol) and triethylamine (180 μl, 1.3 mmol) were added. The reaction mixture was stirred at room temperature over the weekend. 3-Fluoroazetidine hydrochloride (14.0 mg, 126 μmol), HATU (103 mg, 272 μmol), and triethylamine (180 μl, 1.3 mmol) were added again, and the mixture was stirred at 70°C for 4 hours. The reaction mixture was mixed with water and concentrated under reduced pressure. The residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: gradient (acetonitrile/water with 0.1% formic acid). The fractions containing the product were concentrated under reduced pressure and 31. 2 mg (40% possibility) of the title compound. LC-MS (Method 3): Rt = 1.34 min; MS (ESIpos): m / z = 369 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (1.75), -0.008 (16.00), 0.146 (1.81), 2.328 (1.81), 2.366 (1.17), 2.423 (4.50), 2.454 (1.58), 2.670 (1.99) , 2,731 (14.31), 3,935 (1.46), 3,965 (1.87), 3,996 (1.46), 4,023 (1.87), 4,227 (1.46), 4,254 (2.10), 4,281 (2.57), 4,297 (1.69), 4,309 (1.75) , 4,430 (0.70), 4,455 (1.34), 4,487 (1.58), 4,516 (1.81), 4,543 (1.11), 4,557 (1.05), 4,737 (4,96), 4,75 (1.40), 4,816 (12,67), 4,862 (0.93) , 5,351 (1.23), 5,398 (1.11), 5,494 (1.11), 5,540 (1.05), 5,753 (1.69), 7,273 (3.62), 7,374 (5.26), 7,397 (7.82), 7,419 (3.68), 7,453 (4.67) , 7,470 (4.67). 2,5,6,7-tetrahydro-3H-pyrrolo[2,1-c][1,2,4]triazol-3-one (racemate)

[01188] (5S)-2-[(6-Chloropyridin-3-yl)methyl]-3-oxo-2,5,6,7-tetrahydro-3H-pyrrole[2,1-c][1 ,2,4]triazole-5-carboxylic acid (75.0 mg, 78% purity, 199 μmol) was initially loaded into THF (2.0 mL) at room temperature. Subsequently, (3R,4S)-3,4-difluoropyrrolidine hydrochloride (34.2 mg, 238 μmol), HATU (98.1 mg, 258 μmol) and triethylamine (170 μl, 1.2 mmol) were added. The reaction mixture was stirred at room temperature for 20 hours. HATU (98.1 mg, 258 μmol), triethylamine (55 μl, 400 μmol) and (3R,4S)-3,4-difluoropyrrolidine hydrochloride (17.1 mg, 119 μmol) were added again and the mixture was stirred at room temperature overnight. The reaction mixture was mixed with water and concentrated under reduced pressure. The residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: gradient (acetonitrile/water with 0.1% formic acid). The fractions containing the product were concentrated under reduced pressure and 45. 7 mg (59% possibility) of the title compound. LC-MS (Method 3): Rt = 1.01 min; MS (ESIpos): m / z = 384 [M+H] ¹H-NMR (400 MHz, DMSO -d6) δ [ppm]: 2.327 (0.78), 2.350 (0.62), 2.358 (0.83), 2.366 (1.14), 2.384 (1.04), 2.401 (1.27), 2.409 (1.25), 2.418 (1.33), 2.447 ( 1.17), 2.633 (0.44), 2.674 (1.90), 2.694 (2.26), 2.706 (1.74), 2.722 (2.89), 2.728 (4.29), 2.748 (5.23), 2.783 (2.50), 2.806 (2.06), 2.818 ( 1.01), 2.828 (1.61), 2.839 (1.27), 2.852 (0.60), 2.862 (0.96), 3.478 (1.04), 3.487 (0.99), 3.512 (1.46), 3.521 (1.59), 3.532 (1.30), 3.567 ( 1.27), 3.652 (1.35), 3.666 (1.72), 3.687 (1.67), 3.700 (1.87), 3.722 (1.51), 3.734 (0.83), 3.752 (1.27), 3.763 (0.88), 3.784 (0.62), 3.797 ( 0.62), 3.849 (0.47), 3.862 (0.52), 3.877 (0.94), 3.892 (1.17), 3.926 (1.67), 3.940 (1.40), 3.966 (0.88), 4.181 (0.68), 4.196 (0.78), 4.209 ( 0.70), 4.223 (1.27), 4.237 (0.81), 4.249 (0.73), 4.265 (0.68), 4.885 (16.00), 4.961 (1.80), 4.968 (1.93), 4.983 (3.69), 4.990 (3.17), 5.004 ( 2.24), 5.094 (0.60), 5.262 (1.04), 5.274 (1.07), 5.284 (1.04), 5.322 (0.96), 5.344 (0.81), 5.356 (0.86), 5.367 (0.86), 5.383 (0.91), 5.394 ( 0.96), 5.407 (1.09), 5.420 (1.01), 5.430 (0.99), 5.450 (0.94), 5.458 (0.78), 5.473 (0.86), 5.486 (0.88), 7.511 (5.36), 7.531 (6.56), 7.715 ( 2.39), 7.720 (4.14), 7.726 (2.60), 7.741 (3.54), 7.746 (2.13), 8.324 (5.18). Example 173 (5RS)-5-{[(3R,4S)-3,4-Difluoropyrrolidin-1-yl]carbonyl}-2-{[6-(trifluoromethyl)pyridin-3-yl]methyl}-2,5 ,6,7-tetrahydro-3H-pyrrolo[2,1-c][1,2,4]triazol-3-one (racemate)

[01189] (5S)-3-Oxo-2-{[6-(trifluoromethyl)pyridin-3-yl]methyl}-2,5,6,7-tetrahydro-3H-pyrrol[2,1-c ][1,2,4]triazole-5-carboxylic acid (75.0 mg, 228 μmol) was initially loaded into THF (2.4 mL) at room temperature. Subsequently, (3R,4S)-3,4-difluoropyrrolidine hydrochloride (39.4 mg, 274 μmol), HATU (113 mg, 297 μmol) and triethylamine (190 μl, 1.4 mmol) were added. The reaction mixture was stirred at room temperature overnight. The reaction mixture was mixed with water and concentrated under reduced pressure. The residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: gradient (acetonitrile/water with 0.1% formic acid). The fractions containing the product were concentrated under reduced pressure and 80. 3 mg (84% possibility) of the title compound. LC-MS (Method 3): Rt = 1.24 min; MS (ESIpos): m / z = 418 [M+H]+ ¹H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (0.65), -0.008 (6.58), 0.008 (5.20), 0.146 (0.66), 2.327 (0.78), 2.366 (0.98), 2.428 (0.72), 2.457 (0.73) , 2.670 (0.88), 2.682 (0.76), 2.703 (1.20), 2.710 (0.90), 2.715 (0.88), 2.731 (1.59), 2.738 (2.23), 2.758 (2.66), 2.794 (1.35), 2.816 (1.01) , 2,838 (0.82), 2,850 (0.69), 2,872 (0.50), 3,364 (16.00), 3,482 (0.98), 3,517 (0.94), 3.525 (0.95), 3.572 (0.75), 3,656 (0.69), 3.670 (0.91) , 3.692 (0.87), 3.705 (1.00), 3.726 (0.82), 3.745 (0.44), 3.756 (0.65), 3.768 (0.51), 3.882 (0.50), 3.896 (0.60), 3.930 (0.79), 3.944 (0.72) , 3.971 (0.44), 4.199 (0.44), 4.227 (0.66), 4.240 (0.41), 4.975 (0.98), 4.982 (1.03), 4.997 (2.25), 5.012 (8.25), 5.264 (0.53), 5.286 (0.56) , 5.324 (0.51), 5.369 (0.44), 5.387 (0.44), 5.409 (0.54), 5.489 (0.48), 7.904 (1.09), 7.924 (4.96), 7.935 (3.27), 7.956 (0.75), 8.672 (3.24) . Example 174 (5RS)-2-(3-Chloro-4-fluorobenzyl)-5-{[(3R,4S)-3,4-difluoropyrrolidin-1-yl)carbonyl]-2,5,6,7-tetra -hydro-3H-pyrrole[2,1-c][1,2,4]triazol-3-one (racemate)

[01190] (5S)-2-(3-Chloro-4-fluorobenzyl)-3-oxo-2,5,6,7-tetrahydro-3H-pyrrole[2,1-c][1,2, 4]triazole-5-carboxylic acid (75.0 mg, 87% purity, 209 μmol) was initially loaded into THF (2.2 mL) at room temperature. Subsequently, (3R,4S)-3,4-difluoropyrrolidine hydrochloride (36.1 mg, 251 μmol), HATU (103 mg, 272 μmol) and triethylamine (180 μl, 1.3 mmol) were added. The reaction mixture was stirred at room temperature overnight. The reaction mixture was mixed with water and concentrated under reduced pressure. The residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: gradient (acetonitrile/water with 0.1% formic acid). The fractions containing the product were concentrated under reduced pressure and 62. 9 mg (74% possibility) of the title compound. LC-MS (Method 3): Rt = 1.40 min; MS (ESIpos): m / z = 401 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.150 (0.49), -0.008 (4.42), 0.008 (3.97), 0.146 (0.49), 2.073 (1.28), 2.328 (0.88), 2.351 (0.74), 2.359 (1.01) , 2.366 (1.55), 2.378 (1.10), 2.384 (1.24), 2.396 (1.31), 2.402 (1.46), 2.410 (1.42), 2.418 (1.49), 2.435 (0.81), 2.446 (1.28), 2.455 (0.79) , 2.524 (2.73), 2.642 (0.58), 2.664 (1.38), 2.670 (1.24), 2.683 (1.76), 2.703 (2.73), 2.713 (2.19), 2.730 (3.31), 2.736 (5.21), 2.745 (3.81) , 2.755 (6.60), 2.766 (1.38), 2.773 (1.40), 2.789 (3.58), 2.803 (1.13), 2.810 (2.52), 2.822 (1.20), 2.832 (1.94), 2.844 (1.62), 2.856 (0.74) , 2,866 (1.24), 3,480 (1.28), 3,490 (1.29), 3,514 (1.73), 3,523 (1.89), 3,532 (1.56), 3,570 (1.60), 3,655 (1.51), 3,668 (2.03), 3,689 (2.10) , 3.703 (2.28), 3.711 (1.82), 3.727 (4.12), 3.738 (1.04), 3.744 (1.01), 3.755 (1.49), 3.766 (1.10), 3.787 (0.79), 3.801 (0.76), 3.851 (0.59) , 3.866 (0.68), 3.880 (1.19), 3.894 (1.42), 3.929 (2.01), 3.943 (1.51), 3.968 (1.08), 4.184 (0.83), 4.198 (1.01), 4.212 (0.84), 4.225 (1.55) , 4,239 (0.95), 4,252 (0.84), 4,267 (0.77), 4,785 (0.79), 4,826 (16.00), 4,868 (0.67), 4,969 (2.05), 4,977 (2.23), 4,991 (4,24), 4,998 (3.85) , 5.011 (2.70), 5.018 (1.64), 5.252 (0.76), 5.261 (1.19), 5.274 (1.24), 5.284 (1.20), 5.323 (1.24), 5.332 (0.97), 5.346 (0.99), 5.355 (1.01) , 5,368 (1.06), 5,384 (1.11), 5,395 (1.13), 5,408 (1.28), 5,422 (1.17), 5,445 (0.99), 5,451 (1.11), 5,461 (0.92), 5,475 (1.06), 5,489 (0.99) , 5,498 (0.68), 7,247 (1.13), 7,252 (2.10), 7,258 (2.23), 7,264 (2.55), 7,269 (2.79), 7,274 (3.33), 7,280 (3.02), 7,286 (2.98), 7,291 (1.74) , 7,380 (4.01), 7,402 (6.63), 7,425 (2.97), 7,455 (3.85), 7,473 (3.87), 8,385 (0.41). Example 175 (5RS)-5-{[(3R,4S)-3,4-Difluoropyrrolidin-1-yl]carbonyl}-2-{[3-fluoro-2-(trifluoromethyl)pyridin-4-yl]methyl} -2,5,6,7-tetrahydro-3H-pyrrolo[2,1- c][1,2,4]triazol-3-one (racemate)

[01191] (5S)-2-{[3-Fluoro-2-(trifluoromethyl)pyridin-4-yl]methyl}-3-oxo-2,5,6,7-tetrahydro-3H-pyrrole[2 ,1-c][1,2,4]triazol-5-carboxylic acid (66.0 mg, 183 μmol) was initially loaded into THF (1.9 mL) at room temperature. Subsequently, (3R,4S)-3,4-difluoropyrrolidine hydrochloride (31.5 mg, 220 μmol), HATU (90.5 mg, 238 μmol) and triethylamine (150 μl, 1.1 mmol) were added. The reaction mixture was stirred at room temperature overnight. HATU (90.5 mg, 238 μmol), triethylamine (150 μl, 1.1 mmol) and (3R,4S)-3,4-difluoropyrrolidine hydrochloride (52.5 mg, 366 μmol) were added again and the mixture was stirred at room temperature overnight. The reaction mixture was mixed with water and concentrated under reduced pressure. The residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: gradient (acetonitrile/water with 0.1% formic acid). The fractions containing the product were concentrated under reduced pressure and 53. 0 mg (63% chance) of the title compound. LC-MS (Method 4): Rt = 0.71 min; MS (ESIpos): m / z = 436 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (1.77), -0.008 (15.84), 0.008 (16.00), 0.146 (1.77), 0.854 (1.39), 1.236 (6.21), 1.410 (2.19), 2.327 (2.41) , 2,366 (2.62), 2,438 (1.87), 2,670 (2.94), 2,700 (2.09), 2,710 (2.78), 2,719 (3.10), 2,732 (2.62), 2,755 (5.83), 2,775 (6.85), 2,808 (4.76) , 2,827 (2.57), 2,850 (2.03), 2,862 (1.93), 2,884 (1.50), 3,487 (1.50), 3,530 (1.98), 3,578 (2.30), 3,675 (2.35), 3,695 (2.52), 3,707 (2.68) , 3,730 (2.09), 3,772 (1.55), 3,793 (0.96), 3,805 (0.96), 3,886 (1.44), 3,900 (1.61), 3,936 (2.30), 3,973 (1.34), 4,198 (1.28), 4,225 (1.93) , 4,239 (1.28), 4,991 (2.41), 4,999 (2.78), 5,014 (5.24), 5,020 (5.83), 5,035 (3.05), 5,062 (11.99), 5,073 (10.70), 5,113 (1.28), 5,288 (1.50 ) , 5,388 (1.55), 7,607 (3.80), 7,620 (7.44), 7,632 (4.12), 8,573 (8.51), 8,585 (8.56), 10,193 (1.07). Example 176 (5RS)-5-{[(3R,4S)-3,4-Difluoropyrrolidin-1-yl]carbonyl}-2-{[3-fluoro-2-(trifluoromethyl)pyridin-4-yl]methyl} -2,5,6,7-tetrahydro-3H-pyrrole[2,1- c][1,2,4]triazol-3-one (enantiomer 1)

[01192] (5RS)-5-{[(3R,4S)-3,4-Difluoropyrrolidin-1-yl]carbonyl}-2-{[3-fluoro-2-(trifluoromethyl)pyridin-4-yl]methyl }-2,5,6,7-tetrahydro-3H-pyrrolo[2,1- c][1,2,4]triazol-3-one (racemate) was separated by chiral preparatory HPLC [sample preparation: 53 mg dissolved in 3 mL of acetonitrile and 1 mL of ethanol (heated); injection volume: 0.25 mL; column: Daicel Chiralpak® AS-H 5 μm, 250 x 20 mm; eluent: n-heptane/ethanol 50:50; flow rate: 15 ml/min; temperature 25°C; UV detection: 210 nm]. After separation, 9.2 mg of enantiomer 1, which elutes first, and 12.4 mg of enantiomer 2, which elutes later, were isolated. Enantiomer 1:

[01193] Analytical chiral HPLC: Rt = 2.22 min, ee = 99% [column: Daicel Chiraltek® AS, 50 x 4.6 mm; eluent: i-hexane/ethanol 50:50; flow rate: 1 ml/min; UV detection: 220 nm]. LC-MS (Method 4): Rt = 0.70 min; MS (ESIpos): m /z = 436 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (7.43), -0.059 (1.78), - 0.045 (2.59), -0.029 (4.69), 0.019 (5.82), 0.146 (7.43), 1.238 (2.26), 2.328 (8.08), 2.365 (8.40), 2.425 (4.04), 2.433 (4.36), 2.559 (4.53), 2.670 (7.92) , 2,709 (7.11), 2,731 (2.75), 2,753 (7.11), 2,775 (8.08), 2,805 (5.01), 2,825 (2.91), 2,848 (2.26), 3,524 (2.59), 3,580 (2.75), 3,673 (3.39) , 3,694 (3.07), 3,708 (3.23), 3,716 (3.07), 3,726 (2.26), 3,760 (2.10), 3,896 (1.94), 3,934 (2.75), 3,980 (1.78), 4,224 (2.10), 4,998 (3.72) , 5,017 (7.11), 5,035 (3.88), 5,063 (16.00), 5,114 (2.10), 5,277 (2.26), 5,326 (1.94), 5,373 (2.10), 5,397 (2.26), 5,411 (2.26), 5,454 (1.94) , 7,606 (4.69), 7,619 (9.05), 7,631 (4.85), 8,572 (9.70), 8,583 (9.05). Example 177 (5RS)-5-{[(3R,4S)-3,4-Difluoropyrrolidin-1-yl]carbonyl}-2-{[3-fluoro-2-(trifluoromethyl)pyridin-4-yl]methyl} -2,5,6,7-tetrahydro-3H-pyrrole[2,1- c][1,2,4]triazol-3-one (enantiomer 2)

[01194] (5RS)-5-{[(3R,4S)-3,4-Difluoropyrrolidin-1-yl]carbonyl}-2-{[3-fluoro-2-(trifluoromethyl)pyridin-4-yl]methyl }-2,5,6,7-tetrahydro-3H-pyrrolo[2,1- c][1,2,4]triazol-3-one (racemate) was separated by chiral preparatory HPLC [sample preparation: 53 mg dissolved in 3 mL of acetonitrile and 1 mL of ethanol (heated); injection volume: 0.25 mL; column: Daicel Chiralpak® AS-H 5 μm, 250 x 20 mm; eluent: n-heptane/ethanol 50:50; flow rate: 15 ml/min; temperature 25°C; UV detection: 210 nm]. After separation, 9.2 mg of enantiomer 1, which elutes first, and 12.4 mg of enantiomer 2, which elutes later, were isolated. Enantiomer 2:

[01195] Analytical chiral HPLC: Rt = 3.86 min, ee = 98% [column: Daicel Chiraltek® AS, 50 x 4.6 mm; eluent: i-hexane/ethanol 40:60; flow rate: 1 ml/min; UV detection: 220 nm]. LC-MS (Method 4): Rt = 0.71 min; MS (ESIpos): m /z = 436 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (1.89), -0.027 (0.41), - 0.025 (0.54), -0.022 (0.63), -0.019 (0.99), -0.016 (1.17), -0.015 (1.44), - 0.008 (16.00), 0.008 (15.19), 0.014 (1.98), 0.016 (1.26), 0.019 (0.90), 0.021 (0.72), 0.024 (0.50), 0.030 (0.45), 0.146 (1.89), 2.327 (0.90), 2.332 (0.68), 2.366 (0.95), 2.523 (2.52), 2.560 (0.72), 2.669 (1.04), 2,710 (0.99), 2,718 (0.41), 2,755 (0.72), 2,775 (0.90), 2,808 (0.63), 5,021 (0.77), 5,036 (0.41), 5,063 (1.58), 5,072 (1.35), 7,607 (0.50), 7,620 (0.95), 7,632 (0.50), 8,572 (1.08), 8,585 (1.04). Example 178 (5RS)-5-{[(3S)-3-Fluoropyrrolidin-1-yl]carbonyl}-2-{[3-fluoro-2-(trifluoromethyl)pyridin-4-yl]methyl}-2.5 ,6,7-tetrahydro-3H-pyrrole[2,1- c][1,2,4]triazol-3-one (diastereomer mixture; 2 isomers)

[01196] (5S)-2-{[3-Fluoro-2-(trifluoromethyl)pyridin-4-yl]methyl}-3-oxo-2,5,6,7-tetrahydro-3H-pyrrole[2 ,1-c][1,2,4]triazol-5-carboxylic acid (66.0 mg, 182 μmol) was initially loaded into THF (1.9 mL) at room temperature. Subsequently, (3S)-3-fluoropyrrolidine hydrochloride (27.5 mg, 219 μmol), HATU (90.2 mg, 237 μmol), and triethylamine (150 μl, 1.1 mmol) were added. The reaction mixture was stirred at room temperature overnight. (3S)-3- Fluoropyrrolidine hydrochloride (13.7 mg, 109 μmol), HATU (90.2 mg, 237 μmol) and triethylamine (150 μl, 1.1 mmol) were added again and the mixture was stirred at room temperature during the night. The reaction mixture was mixed with water and concentrated under reduced pressure. The residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: gradient (acetonitrile/water with 0.1% formic acid). The fractions containing the product were concentrated under reduced pressure and 60. 9 mg (78% possibility) of the title compound. LC-MS (Method 4): Rt = 0.69 min; MS (ESIpos): m / z = 418 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (0.93), 0.008 (7.50), 0.146 (0.99), 2.121 (2.67), 2.267 (2.36), 2.327 (3.16), 2.367 (3.29), 2.670 (2.60), 2,698 (2.11), 2,716 (2.91), 2,738 (6.08), 2,745 (5.95), 2,758 (9.67), 2,779 (6.82), 2,815 (2.48), 2,837 (2.36), 2,859 (2.17), 2,868 (2.85), 2,882 (2.29), 3,352 (2.29), 3,376 (1.43), 3,437 (1.18), 3,500 (1.80), 3,519 (2.17), 3,609 (3.04), 3,634 (4.16), 3,654 (2.60), 3,679 (3.47), 3,691 (3.53), 3,732 (3.04), 3,798 (1.18), 3,843 (0.99), 3,938 (1.05), 3,970 (1.49), 3,991 (1.61), 4,014 (0.93), 4,080 (0.81), 4,701 (1.12), 4,715 (0.99), 4,902 (2.05), 4,909 (2.11), 4,924 (2.29), 4,931 (1.80), 4,970 (2.42), 4,977 (2.60), 4,992 (2.79), 5,020 (2.11), 5,061 (15.01), 5,070 (16.00), 5,113 (1.55), 5,281 (2.42), 5,378 (1.74), 5,414 (2.42), 5,500 (1.55), 5,730 (0.68), 7,610 (5.40), 7,622 (9.67), 7,635 (5.21), 8,573 (11.22), 8,585 (10.60). Example 179 (5RS)-5-{[(3S)-3-Fluoropyrrolidin-1-yl]carbonyl}-2-{[3-fluoro-2-(trifluoromethyl)pyridin-4-yl]methyl}-2.5 ,6,7-tetrahydro-3H-pyrrole[2,1- c][1,2,4]triazol-3-one (isomer 1)

[01197] (5RS)-5-{[(3S)-3-Fluoropyrrolidin-1-yl]carbonyl}-2-{[3-fluoro-2-(trifluoromethyl)pyridin-4-yl]methyl}-2, 5,6,7-tetrahydro-3H-pyrrole[2,1- c][1,2,4]triazol-3-one (diastereomer mixture; 2 isomers) was separated by chiral preparatory HPLC [sample preparation : 60 mg dissolved in 3 mL of acetonitrile and 1 mL of ethanol; injection volume: 0.25 mL; column: Daicel Chiralpak® AS-H 5 μm, 250 x 20 mm; eluent: n-heptane/ethanol 50:50; flow rate: 15 ml/min; temperature 25°C; UV detection: 210 nm]. After separation, 10.7 mg of isomer 1, which elutes first, and 15.6 mg of isomer 2, which elutes later, were isolated. Isomer 1:

[01198] Analytical chiral HPLC: Rt = 2.20 min, de = 99% [column: Daicel Chiraltek® AS, 50 x 4.6 mm; eluent: i-hexane/ethanol 50:50; flow rate: 1 ml/min; UV detection: 220 nm]. LC-MS (Method 4): Rt = 0.68 min; MS (ESIpos): m /z = 418 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (1.73), -0.008 (15.96), 0.008 (16.00), 0.146 (1.78) (0.43) 8,586 (2.99). Example 180 (5RS)-5-{[(3S)-3-Fluoropyrrolidin-1-yl]carbonyl}-2-{[3-fluoro-2-(trifluoromethyl)pyridin-4-yl]methyl}-2.5 ,6,7-tetrahydro-3H-pyrrole[2,1-c][1,2,4]triazol-3-one (isomer 2)

[01199] (5RS)-5-{[(3S)-3-Fluoropyrrolidin-1-yl]carbonyl}-2-{[3-fluoro-2-(trifluoromethyl)pyridin-4-yl]methyl}-2, 5,6,7-tetrahydro-3H-pyrrole[2,1- c][1,2,4]triazol-3-one (diastereomer mixture; 2 isomers) was separated by chiral preparatory HPLC [sample preparation : 60 mg dissolved in 3 mL of acetonitrile and 1 mL of ethanol; injection volume: Daicel Chiralpak® AS-H 5 μm, 250 x 20 mm; eluent: n-heptane/ethanol 50:50; flow rate: 15 ml/min; temperature 25°C; UV detection: 210 nm]. After separation, 10.7 mg of isomer 1, which elutes first, and 15.6 mg of isomer 2, which elutes later, were isolated. Isomer 2:

[01200] Analytical chiral HPLC: Rt = 3.51 min, d = 97.4% [column: Daicel Chiraltek® AS, 50 x 4.6 mm; eluent: i-hexane/ethanol 50:50; flow rate: 1 ml/min; UV detection: 220 nm]. LC-MS (Method 4): Rt = 0.67 min; MS (ESIpos): m /z = 418 [M+H]+ ¹H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (1.64), -0.008 (16.00), 0.008 (14.04), 0.146 (1.71) (0.98) (0.87) (4.51) (1.31) (0.76) (1.78) (1.75) (0.98), 5.282 (1.38), 5.377 (1.09), 5.415 (1.35), 5.510 (1.02), 7.609 (2.69), 7.622 (5.16), 7.635 (2.95), 8.573 (5.60), 8.585 (5.67). Example 181(5RS)-5-[(3,3-Difluoropyrrolidin-1-yl)carbonyl]-2-{[3-fluoro-2-(trifluoromethyl)pyridin-4-yl]methyl}-2,5,6 ,7-tetrahydro-3H-pyrrole[2,1-c][1,2,4]triazol-3-one (racemate)

[01201] (5S)-2-{[3-Fluoro-2-(trifluoromethyl)pyridin-4-yl]methyl}-3-oxo-2,5,6,7-tetrahydro-3H-pyrrole[2 ,1-c][1,2,4]triazol-5-carboxylic acid (66.0 mg, 182 μmol) was initially loaded into THF (1.9 mL) at room temperature. Subsequently, 3,3-difluoropyrrolidine hydrochloride (31.4 mg, 219 μmol), HATU (90.2 mg, 237 μmol), and triethylamine (150 μl, 1.1 mmol) were added. The reaction mixture was stirred at room temperature overnight. 3,3-Difluoropyrrolidine hydrochloride (15.7 mg, 109 μmol), HATU (90.2 mg, 237 μmol) and triethylamine (150 μl, 1.1 mmol) were added again and the mixture was stirred at room temperature during the night. The reaction mixture was mixed with water and concentrated under reduced pressure. The residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: gradient (acetonitrile/water with 0.1% formic acid). The fractions containing the product were concentrated under reduced pressure and 38. 9 mg (49% possibility) of the title compound. LC-MS (Method 4): Rt = 0.75 min; MS (ESIpos): m / z = 436 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (0.93), -0.008 (7.61), 0.008 (6.67), 0.146 (0.86), 1.410 (1.15), 2.328 (1.87), 2.366 (2.22), 2.392 (1.51) , 2,411 (2.51), 2,432 (4.52), 2,440 (3.30), 2,451 (3.66), 2,461 (3.95), 2,469 (3.09), 2,524 (5.96), 2,565 (3.01), 2,583 (1.94), 2,600 (1.08) , 2,670 (2.30), 2,694 (1.00), 2,701 (1.08), 2,711 (3.52), 2,720 (2.22), 2,733 (2.44), 2,742 (4.52), 2,749 (3.01), 2,760 (4.66), 2,765 (5.24) , 2,771 (5.67), 2,779 (3.52), 2,804 (3.37), 2,813 (3.23), 2,818 (2.94), 2,842 (2.51), 2,864 (1.58), 3,559 (4.09), 3,578 (6.82), 5,042 (2.73) , 5,049 (2.37), 5,063 (16.00), 5,073 (14.28), 5,115 (1.72), 7,610 (2.58), 7,621 (5.09), 7,632 (2.80), 8,572 (8.18), 8,584 (8.18). Example 182 (5RS)-5-[(3-Fluoroazetidin-1-yl)carbonyl]-2-{[3-fluoro-2-(trifluoromethyl)pyridin-4-yl]methyl}-2,5,6,7 -tetrahydro-3H-pyrrole[2,1- c][1,2,4]triazol-3-one (racemate)

[01202] (5S)-2-{[3-Fluoro-2-(trifluoromethyl)pyridin-4-yl]methyl}-3-oxo-2,5,6,7-tetrahydro-3H-pyrrole[2 ,1-c][1,2,4]triazol-5-carboxylic acid (66.0 mg, 182 μmol) was initially loaded into THF (1.9 mL) at room temperature. Subsequently, 3-fluoroazetidine hydrochloride (24.4 mg, 219 μmol), HATU (90.2 mg, 237 μmol), and triethylamine (150 μl, 1.1 mmol) were added. The reaction mixture was stirred at room temperature overnight. 3-Fluoroazetidine hydrochloride (12.2 mg, 109 μmol), HATU (90.2 mg, 237 μmol), and triethylamine (150 μl, 1.1 mmol) were added again and the mixture was stirred at room temperature overnight. The reaction mixture was mixed with water and concentrated under reduced pressure. The residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: gradient (acetonitrile/water with 0.1% formic acid). The fractions containing the product were concentrated under reduced pressure and 39. 0 mg (52% chance) of the title compound. LC-MS (Method 4): Rt = 0.67 min; MS (ESIpos): m / z = 404 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: 0.146 (0.43), 2.328 (1.09), 2.366 (0.75), 2.412 (1.14), 2.444 (4.98), 2.670 (1.11), 2.710 (1.84), 2.749 (16.00), 3.942 (1.73), 3970 (2.16), 4003 (1.75), 4033 (2.11), 4204 (0.91), 4221 (1.02), 4235 (1.70), 4250 (1.86), 4263 (2.36), 4274 (2.30), 4287 (2.57) (0.77) (1.27), 5.544 (1.23), 5.733 (0.75), 7.612 (4.61), 7.625 (8.73), 7.638 (4.84), 7.870 (0.66), 8.567 (9.82), 8.579 (9.68). Example 183 (5S)-5-{[(3R,4R)-3-Fluoro-4-hydroxypyrrolidin-1-yl]carbonyl}-2-(4-methylbenzyl)-5,6,7,8-tetrahydro [1,2,4]triazolo[4,3-a]pyridin-3(2H)-one

[01203] (5S)-2-(4-Methylbenzyl)-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine -5-carboxylic acid (100 mg, 327 μmol) was initially loaded into THF (5.0 mL) at room temperature. Subsequently, HBTU (161 mg, 425 μmol) and N,N-diisopropylethylamine (280 μl, 1.6 mmol) were added. After stirring for 15 minutes, (3R, 4R)-4-fluoropyrrolidin-3-ol hydrochloride (55.6 mg, 393 μmol) was added and the reaction mixture was stirred at room temperature overnight. The reaction mixture was concentrated under reduced pressure. The residue was purified via preparatory HPLC (Method 10). The fractions containing the product were concentrated under reduced pressure and 27.0 mg (22% possibility) of the title compound were obtained. LC-MS (Method 3): Rt = 1.19 min; MS (ESIpos): m /z = 375 [M+H]+ ¹H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.008 (1.05), 0.008 (0.98), 1.721 (0.88), 1.913 ( 0.46), 1.950 (0.66), 2.040 (0.52), 2.047 (0.53), 2.056 (0.46), 2.273 (16.00), 2.518 (1.63), 2.522 (1.63), 2.562 (0.77), 2.585 (1.21), 2.628 ( 0.44), 3.350 (0.47), 3.381 (0.72), 3.457 (0.51), 3.474 (0.47), 3.531 (0.80), 3.557 (0.57), 3.601 (0.59), 3.651 (0.61), 3.690 (1.43), 3.757 ( 0.46), 4.230 (0.42), 4.338 (0.47), 4.748 (5.25), 4.794 (0.41), 4.809 (0.78), 4.818 (0.72), 4.825 (0.49), 4.903 (0.56), 5.032 (0.53), 5.571 ( 0.87) 0.89). Example 184 (5S)-2-(Cyclopropylmethyl)-5-{[(3R,4S)-3,4-difluoropyrrolidin-1-yl]carbonyl}-5,6,7,8-tetrahydro[1,2 ,4]triazolo[4,3-a]pyridin-3(2H)-one

[01204] Under argon: (5S)-2-(Cyclopropylmethyl)-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a] Pyridine-5-carboxylic acid (115 mg, 460 μmol) was initially loaded into THF (8.5 mL) at room temperature. Subsequently, HATU (228 mg, 599 μmol) and N,N-diisopropylethylamine (240 μl, 1.4 mmol) were added. After stirring for 15 minutes, (3R,4S)-3,4-difluoropyrrolidine hydrochloride (79.3 mg, 553 μmol) was added and the reaction mixture was stirred at room temperature overnight. The reaction mixture was concentrated under reduced pressure, and the residue was dissolved with water and acetonitrile and purified by preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: gradient (acetonitrile/water with 0.1% formic acid ).The fractions containing the product were concentrated under reduced pressure and 53.3 mg (35% possibility) of the title compound were obtained LC-MS (Method 4): Rt = 0.56 min (ESIpos): m /z = 327 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: 0.261 (12.07), 0.267 (12.21), 0.273 (12.25), 0.437 (10.80), 0.455 (10.86 ), 1,058 (3.69), 1,715 (5.00), 1,724 (4.78), 1,901 (1.20), 1,936 (2.51), 1,975 (2.53), 1,996 (2.05), 2,005 (1.59), 2,023 (2.13), 2,031 (2.37 ), 2.040 (2.55), 2.047 (2.47), 2.057 (2.29), 2.067 (1.95), 2.074 (1.97), 2.082 (1.71), 2.328 (0.60), 2.351 (0.50), 2.366 (0.78), 2.567 (3.73 ), 2.578 (4.58), 2.602 (5.04), 2.612 (6.20), 2.625 (3.47), 2.655 (1.93), 2.669 (1.41), 2.709 (0.42), 3.418 (0.94), 3.454 (14.61), 3.471 (16.00 ), 3.497 (2.67), 3.510 (2.61), 3.521 (2.53), 3.531 (2.55), 3.540 (1.59), 3.554 (1.24), 3.563 (1.65), 3.604 (1.57), 3.617 (1.89), 3.637 (1.35 ), 3,651 (1.65), 3,660 (2.07), 3,674 (3.47), 3,690 (3.05), 3,708 (2.67), 3,723 (2.69), 3,740 (2.27), 3,752 (2.17), 3,772 (1.39), 3,786 (1.06 ), 3.854 (1.63), 3.895 (1.18), 3.921 (1.51), 3.935 (1.67), 3.949 (1.12), 3.969 (1.67), 3.984 (1.63), 3.998 (1.04), 4.013 (0.94), 4.119 (1.06 ), 4,133 (1.22), 4,147 (1.18), 4,161 (2.13), 4,175 (1.37), 4,189 (1.16), 4,204 (1.02), 4,729 (4.68), 4,741 (6.85), 4,752 (4.56), 5,248 (1.77 ), 5,259 (1.83), 5,269 (2.07), 5,279 (1.73), 5,290 (1.26), 5,323 (1.55), 5,331 (1.57), 5,344 (1.71), 5,358 (1.65), 5,368 (1.99), 5,381 (2.29 ), 5,392 (1.87), 5,401 (1.93), 5,434 (1.30), 5,466 (1.55), 5,474 (1.55), 5,487 (1.22), 5,753 (11.24). Example 185 (5S)-5-(Pyrrolidin-1-ylcarbonyl)-2-{[trans/cis-4-(trifluoromethyl)cyclohexyl]methyl}-5,6,7,8-tetrahydro[1,2, 4]triazol[4,3- a]pyridin-3(2H)-one (isomer 1)

[01205] (5S)-3-Oxo-2-{[cis/trans-4-(trifluoromethyl)cyclohexyl]methyl}-2,3,5,6,7,8-hexahydro[1,2,4 ]triazolo[4,3-a]pyridine-5-carboxylic acid (mixture of diastereomer, 2 isomers) (445 mg, 1.26 mmol) was initially loaded into THF (13 mL) at room temperature. Subsequently, pyrrolidine (120 μl, 1.5 mmol), HATU (621 mg, 1.63 mmol), and triethylamine (880 μl, 6.3 mmol) were added, and the mixture was stirred at room temperature over the weekend. . The reaction mixture was mixed with water and concentrated under reduced pressure. The residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 40mm; eluent: gradient (acetonitrile/water with 0.1% formic acid). The fractions containing the product were concentrated under reduced pressure and 158 mg were obtained (31% possibility) of the diastereomer mixture (2 isomers).

[01206] (5S)-5-(Pyrrolidin-1-ylcarbonyl)-2-{[trans/cis-4-(trifluoromethyl)cyclohexyl]methyl}-5,6,7,8-tetrahydro[1,2 ,4]triazolo[4,3- a]pyridin-3(2H)-one (diastereomer mixture; 2 isomers) was separated by chiral HPLC preparatory HPLC [sample preparation: 158 mg dissolved in 15 mL of methanol; injection volume: 1 mL; column: Daicel Chiralpak® IB 5 μm, 250 x 30 mm; eluent: carbon dioxide/ethanol 70:30; flow rate: 80 ml/min; temperature 40°C; UV detection: 210 nm]. After separation, 56 mg of isomer 1, which elutes first, and 54 mg of isomer 2, which elutes later, were isolated. Isomer 1:

[01207] Analytical chiral HPLC: Rt = 0.85 min, de = 99% [column: Daicel Chiralpak® IB, 50 x 4.6 mm; eluent: n-heptane/ethanol 70:30; flow rate: 3 ml/min; UV detection: 210 nm]. LC-MS (Method 3): Rt = 1.53 min; MS (ESIpos): m /z = 401 [M+H]+ 1H-NMR (600 MHz, DMSO-d6) δ [ppm]: 1.465 (2.98), 1.473 (3.40), 1.480 (3.84), 1.487 (4.67 ), 1.490 (4.53), 1.502 (2.02), 1.507 (1.91), 1.513 (1.33), 1.517 (1.11), 1.524 (1.67), 1.532 (1.52), 1.539 (1.17), 1.549 (1.06), 1.554 (0.73 ), 1.586 (1.97), 1.591 (2.58), 1.598 (2.08), 1.605 (1.53), 1.612 (1.40), 1.619 (0.96), 1.666 (0.68), 1.679 (0.82), 1.684 (0.90), 1.688 (0.91 ), 1.693 (0.73), 1.702 (0.78), 1.707 (1.03), 1.711 (1.20), 1.717 (1.36), 1.723 (1.20), 1.733 (0.80), 1.763 (0.70), 1.775 (3.05), 1.786 (5.27 ), 1.798 (4.12), 1.809 (1.20), 1.899 (1.02), 1.910 (3.13), 1.921 (4.16), 1.932 (2.69), 1.944 (0.83), 1.945 (0.83), 1.954 (0.68), 1.971 (0.80 ), 1,977 (1.36), 1,986 (1.26), 1,999 (0.71), 2,005 (0.80), 2,009 (0.82), 2,015 (1.00), 2,017 (0.86), 2,023 (0.93), 2,028 (1.06), 2,033 (0.95 ), 2.047 (0.72), 2.051 (1.08), 2.057 (1.44), 2.064 (1.42), 2.071 (1.20), 2.077 (0.81), 2.265 (0.75), 2.273 (0.73), 2.281 (0.74), 2.512 (0.95 ), 2.520 (0.72), 2.558 (1.03), 2.603 (1.01), 2.610 (1.93), 2.618 (1.12), 2.630 (0.67), 2.638 (1.12), 3.226 (0.77), 3.237 (1.55), 3.246 (1.41 ), 3.249 (1.09), 3.257 (2.33), 3.269 (1.10), 3.312 (1.21), 3.324 (2.53), 3.331 (1.48), 3.337 (16.00), 3.343 (1.86), 3.355 (0.76), 3.439 (0.82 ), 3,450 (1.78), 3,455 (1.23), 3,462 (1.08), 3,467 (2.08), 3,478 (0.95), 3,567 (0.52), 3,580 (0.64), 3,590 (4.31), 3,596 (3.89), 3,604 (4.32 ), 3,610 (3.99), 3,618 (1.89), 3,629 (0.84), 3,633 (0.57), 4,706 (1.96), 4,711 (2.09), 4,716 (2.32), 4,721 (1.86), 5,759 (13.81). Example 186 (5S)-5-(Pyrrolidin-1-ylcarbonyl)-2-{[trans/cis-4-(trifluoromethyl)cyclohexyl]methyl}-5,6,7,8-tetrahydro[1,2, 4]triazol[4,3- a]pyridin-3(2H)-one (isomer 2)

[01208] (5S)-5-(Pyrrolidin-1-ylcarbonyl)-2-{[trans/cis-4-(trifluoromethyl)cyclohexyl]methyl}-5,6,7,8-tetrahydro[1,2 ,4]triazolo[4,3- a]pyridin-3(2H)-one (diastereomer mixture; 2 isomers) was separated by chiral HPLC preparatory HPLC [sample preparation: 158 mg dissolved in 15 mL of methanol; injection volume: 1 mL; column: Daicel Chiralpak® IB 5 μm, 250 x 30 mm; eluent: carbon dioxide/ethanol 70:30; flow rate: 80 ml/min; temperature 40°C; UV detection: After separation, 56 mg of isomer 1, which elutes first, and 54 mg of isomer 2, which elutes later, were isolated. Isomer 2:

[01209] Analytical chiral HPLC: Rt = 1.84 min, d = 99% [column: Daicel Chiralpak® IB, 50 x 4.6 mm; eluent: n-heptane/ethanol 70:30; flow rate: 3 ml/min; UV detection: 210 nm]. LC-MS (Method 3): Rt = 1.55 min; MS (ESIpos): m /z = 401 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: 0.957 (1.26), 0.991 (4.36), 1.023 (5.17), 1.043 (2.00 ), 1.053 (2.17), 1.147 (2.40), 1.155 (2.66), 1.179 (6.23), 1.186 (6.72), 1.211 (5.99), 1.218 (6.21), 1.243 (2.34), 1.621 (0.98), 1.637 (2.09 ), 1647 (2.92), 1681 (10.46), 1693 (11.63), 1706 (11.51), 1747 (2.77), 1765 (7.80), 1782 (12.99), 1799 (10.09), 1817 (4.65), 1832 (7. 41 ), 1,863 (6.74), 1,885 (3.67), 1,902 (9.17), 1,918 (11.87), 1,935 (8.62), 1,952 (3.10), 1,960 (2.94), 1,971 (5.00), 1,983 (5.77), 1,995 (4.03 ), 2,010 (3.59), 2,020 (2.67), 2,035 (2.39), 2,045 (1.37), 2,057 (0.91), 2,070 (0.68), 2,152 (1.28), 2,160 (1.36), 2,182 (2.42), 2,192 (1.94 ), 2.204 (2.33), 2.235 (1.10), 2.568 (2.93), 2.588 (3.12), 2.600 (6.14), 2.612 (3.25), 2.629 (1.51), 2.642 (2.49), 2.653 (1.16), 3.212 (1.80 ), 3.229 (3.63), 3.242 (4.02), 3.258 (6.37), 3.275 (3.12), 3.325 (7.13), 3.343 (3.58), 3.355 (3.72), 3.373 (1.75), 3.390 (0.75), 3.407 (1.01 ), 3.427 (13.83), 3.443 (16.00), 3.468 (5.79), 3.485 (2.63), 3.578 (2.60), 3.595 (5.41), 3.603 (2.82), 3.611 (3.18), 3.619 (4.08), 3.636 (1.81 ), 4,682 (4.94), 4,692 (5.90), 4,697 (6.35), 4,706 (4.55), 5,754 (5.05). Example 187 (5S)-5-(2-Azabicyclo[2.1.1]hex-2-ylcarbonyl)-2-{[3-fluoro-2-(trifluoromethyl)pyridin-4-yl]methyl}-5.6, 7,8-tetrahydro[1,2,4]triazolo[4,3- a]pyridin-3(2H)-one

[01210] (5S)-2-{[3-Fluoro-2-(trifluoromethyl)pyridin-4-yl]methyl}-3-oxo-2,3,5,6,7,8-hexahydro[1 ,2,4]triazolo[4,3-a]pyridine-5-carboxylic acid (126 mg, 319 μmol) was initially loaded into THF (10 mL) at room temperature. Subsequently, HBTU (157 mg, 414 μmol) and N,N-diisopropylethylamine (560 μl, 3.2 mmol) were added. After stirring for 10 min, 2-(3-azabicyclo[2.1.1]hexane)trifluoroacetic acid (75.4 mg, 382 μmol) was added, and the reaction mixture was stirred at room temperature for 30 min. The reaction mixture was mixed with water and ethyl acetate, and the organic phase was removed. The organic phase was washed with saturated aqueous sodium chloride solution, dried over sodium sulfate and filtered, and the filtrate was concentrated. The residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile with 0.1% formic acid gradient). The fractions containing the product were concentrated under reduced pressure and 23.6 mg (17% possibility) of the title compound were obtained. LC-MS (Method 3): Rt = 1.31 min; MS (ESIpos): m /z = 426 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (1.09), -0.008 (10.21), 0.008 (7.21), 0.146 (0.87) (5.57) (6.44) (3.66) (3.06) (3.11) (0.44), 8,564 (9.67), 8,576 (9.72). Example 188 (5S)-5-[(1SR,5RS)-2-Azabicyclo[3.1.0]hex-2-ylcarbonyl]-2-(4-methylbenzyl)-5,6,7,8-tetrahydro[ 1,2,4]triazolo[4,3-a]pyridin-3(2H)-one (Isomer 1)

[01211] (5S)-5-[(cis)-2-Azabicyclo[3.1.0]hex-2-ylcarbonyl]-2-(4-methylbenzyl)-5,6,7,8-tetrahydro[1 ,2,4]triazolo[4,3-a]pyridin-3(2H)-one (diastereomer mixture; 2 isomers) was separated by chiral preparatory HPLC [sample preparation: 85 mg dissolved in 5 mL ethanol; injection volume: 0.4 mL; column: Daicel Chiralpak® AY-H 5 μm, 250 x 20 mm; eluent: n-heptane/ethanol 20:80; flow rate: 20 ml/min; temperature 25°C; UV detection: 220 nm]. After separation, 32.5 mg of isomer 1, which elutes first, and 38.2 mg of isomer 2, which elutes later, were isolated. Isomer 1:

[01212] Analytical chiral HPLC: Rt = 4.02 min, de = 100% [column: Daicel Chiraltrek® AY-3-3 μm 50 x 6 mm; eluent: n-heptane/ethanol 20:80; flow rate: 1 ml/min; UV detection: 220 nm]. LC-MS (Method 3): Rt = 1.40 min; MS (ESIpos): m /z = 353 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: 0.615 (0.46), 0.622 (0.54), 0.629 (0.93), 0.635 (0.92 ), 0.641 (0.61), 0.648 (0.51), 0.809 (0.76), 0.817 (0.50), 0.823 (0.47), 0.831 (0.78), 1.567 (0.43), 1.572 (0.41), 1.588 (0.43), 1.714 (0.42 ), 1.738 (0.72), 1.752 (0.82), 1.767 (0.82), 1.772 (0.81), 1.788 (0.56), 1.876 (0.40), 1.884 (0.65), 1.892 (0.58), 1.907 (0.57), 1.914 (0.54 ), 2.006 (0.50), 2.019 (0.71), 2.027 (0.71), 2.039 (0.88), 2.047 (0.75), 2.055 (0.78), 2.062 (0.61), 2.072 (0.55), 2.085 (0.41), 2.147 (0.65 ), 2.273 (12.38), 2.521 (1.08), 2.563 (0.61), 2.575 (0.60), 2.585 (0.88), 2.597 (0.58), 2.956 (0.78), 2.965 (0.46), 2.978 (0.41), 2.987 (0.84 ), 3.697 (0.82), 3.703 (0.88), 3.712 (0.99), 3.718 (0.98), 3.729 (1.15), 3.755 (0.41), 4.754 (5.01), 5.069 (0.77), 5.077 (0.94), 5.085 (0.87 ), 5,092 (0.76), 7,105 (0.41), 7,127 (16.00), 7,149 (0.41). Example 189 (5S)-5-[(1SR,5RS)-2-Azabicyclo[3.1.0]hex-2-ylcarbonyl]-2-(4-methylbenzyl)-5,6,7,8-tetrahydro[ 1,2,4]triazolo[4,3-a]pyridin-3(2H)-one (Isomer 2)

[01213] (5S)-5-[(cis)-2-Azabicyclo[3.1.0]hex-2-ylcarbonyl]-2-(4-methylbenzyl)-5,6,7,8-tetrahydro[1 ,2,4]triazolo[4,3-a]pyridin-3(2H)-one (diastereomer mixture; 2 isomers) was separated by chiral preparatory HPLC [sample preparation: 85 mg dissolved in 5 mL ethanol; injection volume: 0.4 mL; column: Daicel Chiralpak® AY-H 5 μm, 250 x 20 mm; eluent: n-heptane/ethanol 20:80; flow rate: 20 ml/min; temperature 25°C; UV detection: 220 nm]. After separation, 32.5 mg of isomer 1, which elutes first, and 38.2 mg of isomer 2, which elutes later, were isolated. Isomer 2:

[01214] Analytical chiral HPLC: Rt = 5.66 min, de = 100% [column: Daicel Chiraltrek® AY-3-3 μm 50 x 6 mm; eluent: n-heptane/ethanol 20:80; flow rate: 1 ml/min; UV detection: 220 nm]. LC-MS (Method 3): Rt = 1.40 min; MS (ESIpos): m /z = 353 [M+H]+ ¹H-NMR (400 MHz, DMSO-d6) δ [ppm]: 0.614 (0.50), 0.620 (0.50), 0.626 (0.41), 0.635 (0.65 ), 0.641 (0.60), 0.649 (1.02), 0.655 (1.00), 0.662 (0.63), 0.668 (0.58), 0.882 (0.78), 0.890 (0.52), 0.896 (0.49), 0.904 (0.80), 1.650 (0.44 ), 1.663 (0.49), 1.675 (0.55), 1.686 (0.65), 1.699 (0.66), 1.711 (0.49), 1.717 (0.46), 1.738 (0.71), 1.752 (1.01), 1.766 (0.91), 1.773 (0.80 ), 1.787 (0.63), 1.849 (0.41), 1.859 (0.77), 1.869 (0.51), 1.881 (0.53), 1.891 (0.53), 1.931 (0.50), 1.940 (0.52), 1.957 (0.47), 1.974 (0.44 ), 1.984 (0.56), 1.990 (0.56), 2.008 (0.63), 2.029 (0.60), 2.043 (0.80), 2.057 (0.46), 2.070 (0.43), 2.083 (0.41), 2.117 (0.70), 2.125 (0.46 ), 2.133 (0.56), 2.145 (0.56), 2.153 (0.61), 2.161 (0.55), 2.272 (15.63), 2.523 (0.89), 2.569 (0.89), 2.584 (1.31), 2.596 (0.68), 2.625 (0.46 ), 3.130 (0.70), 3.151 (1.03), 3.161 (0.58), 3.171 (0.50), 3.181 (0.88), 3.202 (0.43), 3.480 (0.51), 3.486 (0.56), 3.495 (0.90), 3.501 (0.87 ), 3.510 (0.57), 3.516 (0.48), 3.578 (0.46), 3.588 (0.49), 3.603 (0.58), 3.612 (0.61), 3.619 (0.51), 3.634 (0.43), 3.677 (0.56), 3.683 (0.53 ), 3.944 (0.41), 4.710 (0.44), 4.719 (0.51), 4.725 (0.68), 4.742 (5.01), 4.750 (1.90), 4.925 (0.82), 4.934 (0.96), 4.941 (1.03), 4.949 (0.79 ), 7,104 (0.56), 7,126 (16.00), 7,147 (0.61). Example 190 (5S)-5-{[(2S)-2-Glycoloylpyrrolidin-1-yl]carbonyl}-2-(4-methylbenzyl)-5,6,7,8-tetrahydro[1,2,4 ]triazolo[4,3-a]pyridin-3(2H)-one

[01215] 2-[(2S)-1-{[(5S)-2-(4-Methylbenzyl)-3-oxo-2,3,5,6,7,8-hexahydro[1,2, 4]triazolo[4,3-a]pyridin-5-yl]carbonyl}pyrrolidin-2-yl]-2-oxoethyl acetate (124 mg, 282 μmol) was initially loaded into THF (1.5 mL) and water ( 1.5 mL) and lithium hydroxide (16.9 mg, 706 μmol) dissolved in water was added. After stirring for 30 minutes, the reaction mixture was mixed at room temperature with water, 1N aqueous hydrochloric acid and saturated aqueous sodium chloride solution. The organic phase was removed and the aqueous phase was extracted three times with ethyl acetate. The combined organic phases were dried over sodium sulfate and filtered, and the filtrate was concentrated. The residue was purified via preparatory HPLC (Method 11). The fractions containing the product were concentrated under reduced pressure and 21.7 mg (19% possibility) of the title compound were obtained. LC-MS (Method 3): Rt = 1.16 min; MS (ESIpos): m /z = 399 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.008 (2.58), 0.008 (2.09), 1.569 (0.46), 1.595 ( 0.59), 1.606 (0.60), 1.632 (0.43), 1.697 (0.48), 1.715 (1.13), 1.730 (1.83), 1.746 (1.66), 1.753 (1.01), 1.762 (1.38), 1.778 (0.83), 1.892 ( 0.57), 1.910 (1.44), 1.922 (1.77), 1.927 (1.91), 1.939 (1.34), 1.945 (1.40), 2.036 (1.22), 2.047 (2.10), 2.058 (2.01), 2.123 (0.47), 2.140 ( 0.76), 2.161 (0.86), 2.172 (0.80), 2.193 (0.71), 2.269 (16.00), 2.467 (0.53), 2.523 (1.88), 2.559 (1.48), 2.573 (1.07), 2.601 (0.45), 3.540 ( 0.50), 3.558 (1.07), 3.565 (0.78), 3.575 (0.71), 3.582 (1.28), 3.600 (0.60), 3.740 (0.62), 3.756 (1.21), 3.765 (0.70), 3.773 (0.74), 3.781 ( 0.96), 3.797 (0.45), 4.153 (3.51), 4.170 (3.94), 4.559 (1.33), 4.573 (1.48), 4.580 (1.52), 4.595 (1.23), 4.731 (5.31), 4.735 (5.29), 4.808 ( 1.25) 1.22). Example 191 (5S)-5-[(1,1-Difluoro-5-azaspiro[2.3]hex-5-yl)carbonyl]-2-(4-methylbenzyl)-5,6,7,8-tetrahydro [1,2,4]triazolo[4,3-a]pyridin-3(2H)-one

[01216] (5S)-2-(4-Methylbenzyl)-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine -5-carboxylic acid (50.0 mg, 174 μmol) was initially loaded into dichloromethane (4.0 mL) and DMF (7.0 mL) at room temperature. Subsequently, 1-[bis(dimethylamino)methylene]-1H-benzotriazol-1-ium 3-oxide hexafluorophosphate (85.8 mg, 226 μmol) and N,N-diisopropylethylamine (42 μl, 240 μmol) were added. After stirring for 15 min, 1,1-difluoro-5-azaspiro[2,3]hexane hydrochloride (32.5 mg, 209 μmol) was added, and the reaction mixture was stirred at room temperature for 2 hours. The solvent was removed under reduced pressure, and the residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/water gradient). The fractions containing the product were concentrated under reduced pressure and 22.0 mg (30% possibility) of the title compound were obtained. LC-MS (Method 1): Rt = 1.10 min; MS (ESIpos): m /z = 389 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: 1.702 (1.18), 1.715 (1.79), 1.728 (1.34), 1.745 (0.60 ), 1,766 (1.06), 1,787 (1.43), 1,812 (1.15), 1,970 (0.63), 1,982 (0.82), 1,995 (0.85), 2,012 (0.82), 2,029 (0.80), 2,045 (0.53), 2,271 (12.65 ), 2.567 (1.06), 2.580 (1.02), 3.983 (0.66), 4.007 (1.20), 4.056 (1.17), 4.079 (0.63), 4.363 (0.81), 4.385 (0.86), 4.481 (0.52), 4.510 (0.93 ), 4.531 (1.39), 4.544 (0.53), 4.574 (0.46), 4.588 (0.69), 4.600 (0.40), 4.753 (5.83), 5.753 (0.46), 7.107 (0.42), 7.128 (16.00), 7.149 (0.45 ). Example 192 (5S)-5-[(3-Methylazetidin-1-yl)carbonyl]-2-(4-methylbenzyl)-5,6,7,8-tetrahydro[1,2,4]triazolo[4 ,3-a]pyridin-3(2H)-one

[01217] (5S)-2-(4-Methylbenzyl)-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine -5-carboxylic acid (50.0 mg, 174 μmol) was initially loaded into DMF (4.0 mL) and dichloromethane (2.0 mL) at room temperature. Subsequently, 1-[bis(dimethylamino)methylene]-1H-benzotriazol-1-ium 3-oxide hexafluorophosphate (85.8 mg, 226 μmol) and N,N-diisopropylethylamine (79 μl, 450 μmol) were added. After stirring for 15 min, 3-methylazetidine hydrochloride (22.5 mg, 209 μmol) was added, and the reaction mixture was stirred at room temperature for 2 hours. The solvent was removed under reduced pressure, and the residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/water gradient). The fractions containing the product were concentrated under reduced pressure and 39.3 mg (63% possibility) of the title compound were obtained. LC-MS (Method 1): Rt = 1.02 min; MS (ESIpos): m /z = 341 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.008 (0.45), 0.008 (0.43), 1.183 (4.30), 1.191 ( 4.27), 1.201 (4.62), 1.208 (4.13), 1.688 (1.31), 1.700 (1.87), 1.715 (1.47), 1.728 (0.65), 1.890 (0.48), 1.902 (0.53), 1.913 (0.79), 1.925 ( 0.90), 1.935 (0.57), 1.974 (0.74), 1.988 (0.69), 1.994 (0.69), 2.009 (0.68), 2.270 (14.75), 2.568 (1.78), 2.581 (0.90), 2.610 (0.61), 2.688 ( 0.48), 2.709 (0.62), 2.719 (0.54), 2.733 (0.45), 3.399 (0.56), 3.413 (0.56), 3.423 (0.61), 3.437 (0.57), 3.454 (0.58), 3.469 (0.59), 3.478 ( 0.65), 3.493 (0.60), 3.696 (0.54), 3.710 (0.60), 3.716 (0.64), 3.730 (0.55), 3.844 (0.53), 3.859 (0.61), 3.865 (0.65), 3.879 (0.56), 3.937 ( 0.60), 3.959 (0.95), 3.981 (0.54), 4.002 (0.61), 4.024 (0.99), 4.047 (0.54), 4.258 (0.58), 4.278 (1.15), 4.299 (0.52), 4.387 (0.55), 4.408 ( 1.09), 4.429 (0.52), 4.451 (0.63), 4.464 (1.38), 4.478 (1.38), 4.489 (0.61), 4.741 (6.73), 7.103 (0.54), 7.124 (16.00), 7.145 (0.55). Example 193 (5S)-2-(4-Methylbenzyl)-5-{[(1RS)-1-oxide-1,3-thiazolidin-3-yl]carbonyl}-5,6,7,8-tetrahydro [1,2,4]triazolo[4,3-a]pyridin-3(2H)-one (isomer 1)

[01218] (5S)-2-(4-Methylbenzyl)-5-{[(1RS)-1-oxide-1,3-thiazolidin-3-yl]carbonyl}-5,6,7,8-tetra- hydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one (diastereomer mixture; 2 isomers) was separated by chiral preparatory HPLC [sample preparation: 24.8 mg dissolved in 1 .5 mL of ethanol; injection volume: 1.5 mL; column: Daicel Chiralpak® IA 5 μm, 250 x 20 mm; eluent: ethanol; flow rate: 15 ml/min; temperature 60°C; UV detection: 220 nm]. After separation, 8.0 mg of isomer 1, which elutes first, and 10 mg of isomer 2, which elutes later, were isolated. Isomer 1:

[01219] Analytical chiral HPLC: Rt = 9.22 min, de = 100% [column: Daicel Chiralpak® IA 5 μm, 250 x 20 mm; eluent: ethanol; flow rate: 15 ml/min; UV detection: 220 nm]. LC-MS (Method 3): Rt = 1.05 min; MS (ESIpos): m /z = 375 [M+H]+ ¹H-NMR (400 MHz, DMSO-d6) δ [ppm]: 1.617 (0.54), 1.629 (0.55), 1.641 (0.49), 1.703 (0.50 ), 1.712 (0.48), 1.727 (0.47), 1.736 (0.52), 2.022 (1.00), 2.033 (1.04), 2.044 (0.82), 2.078 (0.73), 2.088 (0.68), 2.274 (16.00), 2.557 (0.73 ), 2.576 (0.73), 2.589 (1.02), 2.601 (0.86), 2.617 (0.53), 2.630 (0.43), 3.037 (0.51), 3.060 (1.07), 3.082 (1.14), 3.093 (0.85), 3.100 (0.84 ), 3.117 (0.44), 3.125 (0.49), 3.755 (0.42), 3.770 (0.42), 3.778 (0.77), 3.785 (0.54), 3.800 (0.46), 3.807 (0.42), 4.063 (0.41), 4.082 (0.56 ), 4.086 (0.53), 4.093 (0.44), 4.105 (0.47), 4.112 (0.48), 4.117 (0.44), 4.162 (0.48), 4.174 (0.85), 4.191 (0.74), 4.198 (0.79), 4.284 (0.75 ), 4.317 (0.90), 4.418 (1.33), 4.449 (1.48), 4.608 (0.60), 4.613 (0.60), 4.641 (0.49), 4.646 (0.50), 4.753 (7.88), 4.850 (0.71), 4.864 (1.03 ), 4.874 (0.71), 4.898 (0.46), 4.912 (0.61), 4.921 (0.44), 5.018 (0.94), 5.046 (0.85), 7.103 (0.85), 7.128 (12.94), 7.150 (1.01). Example 194 (5S)-2-(4-Methylbenzyl)-5-{[(1RS)-1-oxide-1,3-thiazolidin-3-yl]carbonyl}-5,6,7,8-tetrahydro [1,2,4]triazolo[4,3-a]pyridin-3(2H)-one (isomer 2)

[01220] (5S)-2-(4-Methylbenzyl)-5-{[(1RS)-1-oxide-1,3-thiazolidin-3-yl]carbonyl}-5,6,7,8-tetra- hydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one (diastereomer mixture; 2 isomers) was separated by chiral preparatory HPLC [sample preparation: 24.8 mg dissolved in 1 .5 mL of ethanol; injection volume: 1.5 mL; column: Daicel Chiralpak® IA 5 μm, 250 x 20 mm; eluent: ethanol; flow rate: 15 ml/min; temperature 60°C; UV detection: 220 nm]. After separation, 8.0 mg of isomer 1, which elutes first, and 10 mg of isomer 2, which elutes later, were isolated. Isomer 2:

[01221] Analytical chiral HPLC: Rt = 11.44 min, de = 100% [column: Daicel Chiralpak® IA 5 μm, 250 x 20 mm; eluent: ethanol; flow rate: 15 ml/min; UV detection: 220 nm]. LC-MS (Method 3): Rt = 1.05 min; MS (ESIpos): m /z = 375 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: 1.739 (0.77), 1.994 (1.34), 2.114 (0.42), 2.274 (16.00 ), 2.560 (1.09), 2.574 (0.86), 2.598 (1.53), 2.610 (0.98), 2.640 (0.61), 2.938 (0.54), 2.972 (0.59), 3.132 (0.43), 3.160 (0.56), 3.181 (0.77 ), 3.209 (0.40), 3.273 (0.59), 3.972 (1.19), 3.989 (1.18), 3.997 (1.06), 4.108 (0.72), 4.122 (0.72), 4.135 (0.43), 4.286 (0.52), 4.308 (0.71 ), 4,338 (1.47), 4,371 (1.58), 4,486 (1.01), 4,516 (1.12), 4,606 (1.00), 4,611 (0.98), 4,644 (0.79), 4,756 (6.31), 4,985 (1.16), 4,994 (1.28 ), 5.010 (0.98), 5.019 (1.39), 5.050 (0.71), 7.130 (14.05). Example 195 (5S)-5-[(3-Fluoro-3-methylazetidin-1-yl)carbonyl]-2-(4-methylbenzyl)-5,6,7,8-tetrahydro[1,2,4 ]triazolo[4,3-a]pyridin-3(2H)-one

[01222] (5S)-2-(4-Methylbenzyl)-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine -5-carboxylic acid (50.0 mg, 174 μmol) was initially loaded into DMF (2.0 mL) and N,N-diisopropylethylamine (79 μl, 450 μmol) at room temperature. Subsequently, 1-[bis(dimethylamino)methylene]-1H-benzotriazol-1-io 3-oxide hexafluorophosphate (85.8 mg, 226 μmol) and dichloromethane (1.0 mL) were added. After stirring for 15 min, 3-fluoro 3-methylazetidine hydrochloride (24.0 mg, 191 μmol) was added, and the reaction mixture was stirred at room temperature for 2.5 hours. The solvent was removed under reduced pressure, and the residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/water gradient). The fractions containing the product were concentrated under reduced pressure and 23.9 mg (38% possibility) of the title compound were obtained. LC-MS (Method 3): Rt = 1.42 min; MS (ESIpos): m /z = 359 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: 1.569 (3.12), 1.577 (3.06), 1.624 (3.10), 1.632 (3.04 ), 1.712 (1.77), 1.941 (0.71), 2.011 (0.74), 2.024 (0.68), 2.271 (13.50), 2.577 (1.67), 2.620 (0.50), 3.933 (0.54), 3.951 (0.47), 3.980 (1.33 ), 3.998 (0.90), 4.028 (0.93), 4.043 (0.99), 4.068 (0.41), 4.253 (0.47), 4.301 (0.51), 4.337 (0.49), 4.389 (0.52), 4.403 (0.55), 4.424 (0.65 ), 4,448 (0.83), 4,474 (0.70), 4,503 (0.81), 4,519 (1.19), 4,533 (1.19), 4,748 (7.16), 7,126 (16.00). Example 196 (2S)-1-{[(5S)-2-(4-Methylbenzyl)-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[ 4,3-a]pyridin-5-yl]carbonyl}pyrrolidine-2-carbaldehyde

[01223] Oxalyl chloride (20 μl, 230 μmol) was initially loaded into dichloromethane (2 mL) and cooled to -78°C. Subsequently, a solution of dimethyl sulfoxide (36 μl, 500 μmol) and dichloromethane (1 mL) was added dropwise, and the mixture was stirred at −78°C for 15 min. (5S)-5-{[(2S)-2-(Hydroxymethyl)pyrrolidin-1-yl]carbonyl}-2-(4-methylbenzyl)- 5,6,7,8-tetrahydro[1,2, 4]triazolo[4,3-a]pyridin-3(2H)-one (77.8 mg, 210 μmol), dissolved in dichloromethane (2 mL), was added dropwise, and the reaction mixture was stirred at - 78°C for another 60 min. Triethylamine (150 μl, 1.1 mmol) and pyridine were added dropwise, and the mixture was stirred at −78°C for an additional 20 min. The reaction mixture reached room temperature. The reaction mixture was mixed with water. The organic phase was removed and the aqueous phase was extracted three times with dichloromethane. The combined organic phases were washed with saturated aqueous sodium chloride solution, dried over sodium sulfate and filtered, and the filtrate was concentrated. The residue was purified via column chromatography (SiO2; eluent: methanol/dichloromethane 10/90). The fractions containing the product were concentrated under reduced pressure and 48.9 mg (57% possibility) of the title compound were obtained. LC-MS (Method 3): Rt = 1.35 min; MS (ESIpos): m /z = 369 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.008 (3.81), 0.008 (2.35), 1.013 (0.57), 1.091 ( 0.63), 1.235 (0.83), 1.645 (0.74), 1.657 (0.74), 1.670 (0.86), 1.691 (0.85), 1.705 (0.93), 1.724 (0.92), 1.735 (1.12), 1.748 (1.29), 1.760 ( 1.25), 1.771 (1.10), 1.782 (0.89), 1.826 (0.52), 1.842 (0.89), 1.858 (1.06), 1.875 (1.07), 1.883 (1.06), 1.892 (1.32), 1.906 (1.40), 1.922 ( 1.29), 1.937 (1.22), 1.949 (1.42), 1.966 (1.33), 1.985 (1.17), 1.996 (1.25), 2.011 (1.16), 2.020 (1.35), 2.037 (1.48), 2.049 (1.29), 2.064 ( 1.15), 2.078 (1.20), 2.086 (1.68), 2.099 (1.92), 2.110 (1.86), 2.122 (0.92), 2.233 (0.40), 2.268 (16.00), 2.327 (0.42), 2.518 (2.56), 2.567 ( 1.27), 2.575 (1.43), 2.587 (1.83), 2.602 (1.80), 2.616 (0.59), 2.628 (0.66), 2.669 (0.42), 3.184 (1.05), 3.211 (1.19), 3.239 (0.57), 3.248 ( 0.79), 3.266 (1.32), 3.401 (0.42), 3.425 (0.46), 3.576 (0.44), 3.593 (0.86), 3.600 (0.69), 3.618 (1.06), 3.634 (0.49), 3.745 (0.60), 3.763 ( 0.86), 3.771 (0.74), 3.785 (0.64), 4.323 (0.62), 4.332 (0.73), 4.338 (1.13), 4.344 (0.76), 4.354 (0.60), 4.359 (0.59), 4.709 (0.52), 4.740 ( 9.55), 4.780 (0.79), 4.792 (0.69), 4.801 (0.52), 4.838 (1.16), 4.849 (1.96), 4.862 (0.99), 5.000 (0.52), 5.007 (0.50), 5.686 (0.85), 5.701 ( 0.80), 5.753 (1.65), 5.816 (0.77), 5.832 (0.74), 7.090 (1.40), 7.097 (1.38), 7.112 (9.05), 7.118 (13.08), 7.139 (1.38), 9.344 (3.27), 9.349 ( 3.19). Example 197 (5S)-5-[(1RS,5SR)-2-Azabicyclo[3.1.0]hex-2-ylcarbonyl]-2-[(6-chloropyridin-3-yl)methyl]-5,6,7 ,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one (isomer 1)

[01224] (5S)-2-[(6-Chloropyridin-3-yl)methyl]-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[ 4,3-a]pyridine-5-carboxylic acid (68.0 mg, 220 μmol) was initially loaded into THF (3.7 mL) at room temperature. Subsequently, HATU (109 mg, 286 μmol), (1RS,5SR)-2-azabicyclo[3.1.0]hexane hydrochloride (31.6 mg, 264 μmol) and N,N-diisopropylethylamine (120 μl, 660 μmol) were added. The reaction mixture was stirred at room temperature overnight. The reaction mixture was concentrated under reduced pressure. The residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: gradient (acetonitrile/water with 0.1% formic acid). The fractions containing the product were concentrated under reduced pressure and 63. 0 mg (77% possibility) of a diastereomer mixture (2 isomers).

[01225] The diastereomer mixture (2 isomers) was separated by chiral preparatory HPLC [sample preparation: 63 mg dissolved in 2 mL of acetonitrile; injection volume: 0.25 mL; column: Daicel Chiralpak® IF 5 μm, 250 x 20 mm; eluent: n-heptane/ethanol 20:80; flow rate: 20 ml/min; temperature 30°C; UV detection: 220 nm]. After separation, 15.3 mg of isomer 1, which elutes first, and 17.2 mg of isomer 2, which elutes later, were isolated. Isomer 1:

[01226] Analytical chiral HPLC: Rt = 2.91 min, > 99% [column: Daicel Chiralpak® IB, 50 x 4.6 mm; eluent: n-heptane/ethanol 50:50; flow rate: 1 ml/min; UV detection: 220 nm]. LC-MS (Method 3): Rt = 1.14 min; MS (ESIpos): m /z = 374 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (1.50), -0.008 (13.97), 0.008 (12.20), 0.146 (1.59) (3.54) (1.33) (5.04), 7,708 (2.74), 7,714 (3.89), 8,296 (5.04), 8,302 (6.72). Example 198 (5S)-5-[(1SR,5RS)-2-Azabicyclo[3.1.0]hex-2-ylcarbonyl]-2-[(6-chloropyridin-3-yl)methyl]-5,6,7 ,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one (isomer 2)

[01227] (5S)-5-[(1RS,5SR)-2-Azabicyclo[3.1.0]hex-2-ylcarbonyl]-2-[(6-chloropyridin-3-yl)methyl]-5,6, 7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one (diastereomer mixture; 2 isomers) was separated by chiral preparatory HPLC [sample preparation: 63 mg dissolved in 2 mL of acetonitrile; injection volume: 0.25 mL; column: Daicel Chiralpak® IF 5 μm, 250 x 20 mm; eluent: n-heptane/ethanol 20:80; flow rate: 20 ml/min; temperature 30°C; UV detection: 220 nm]. After separation, 15.3 mg of isomer 1, which elutes first, and 17.2 mg of isomer 2, which elutes later, were isolated. Isomer 2:

[01228] Analytical chiral HPLC: Rt = 4.28 min, de = 98% [column: Daicel Chiralpak® IB, 50 x 4.6 mm; eluent: n-heptane/ethanol 50:50; flow rate: 1 ml/min; UV detection: 220 nm]. LC-MS (Method 3): Rt = 1.15 min; MS (ESIpos): m /z = 374 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (1.33), -0.008 (16.00), 0.008 (9.33), 0.146 (1.24) (3.38), 0.818 (2.22), 0.834 (3.38), 0.847 (1.60), 1.578 (2.04), 1.756 (3.91), 1.791 (2.93), 1.854 (1.42) (2.76), 1.894 (2.31), 1.908 (2.22), 1.915 (2.13), 2.028 (3.11), 2.038 (3.02), 2.048 (3.38), 2.086 (1.69), 2.163 (2.58), 2.322 (1.69), 2.327 (2.22) (1.87) (1.24) (1.33) (8.98), 7,690 (5.96), 7,697 (5.87), 7,711 (4.98), 7,717 (4.80), 8,300 (6.76), 8,306 (6.49). Example 199 (5S)-5-(2-Azabicyclo[2.1.1]hex-2-ylcarbonyl)-2-{[6-(trifluoromethyl)pyridin-3-yl]methyl}-5,6,7,8- tetrahydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one

[01229] (5S)-3-Oxo-2-{[6-(trifluoromethyl)pyridin-3-yl]methyl}-2,3,5,6,7,8-hexahydro[1,2,4 ]triazolo[4,3-a]pyridine-5-carboxylic acid (112 mg, 327 μmol) was initially loaded into THF (5.0 mL) at room temperature. Subsequently, HATU (161 mg, 425 μmol) and N,N-diisopropylethylamine (570 μl, 3.3 mmol) were added. After stirring for 10 min, 2-(3-azabicyclo[2.1.1]hexane)trifluoroacetic acid (77.4 mg, 393 μmol) was added, and the reaction mixture was stirred at room temperature for 60 min. The reaction mixture was mixed with water and ethyl acetate, and the organic phase was removed. The organic phase was washed with saturated aqueous sodium chloride solution, dried over sodium sulfate and filtered, and the filtrate was concentrated. The residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: gradient (acetonitrile/water with 0.1% formic acid). The fractions containing the product were concentrated under reduced pressure and 24. 2 mg (18% chance) of the title compound. LC-MS (Method 4): Rt = 0.69 min; MS (ESIpos): m / z = 408 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.008 (3.67), 0.008 (3.09), 1.223 (0.73), 1.241 (0.84), 1.249 (1.36), 1.267 (1.47), 1.304 (1.61), 1.321 (1.54), 1,330 (1.47), 1,355 (3.02), 1,369 (4.75), 1,383 (2.69), 1,410 (1.26), 1,647 (0.82), 1,744 (1.96), 1,758 (1.82), 1,815 (0.96), 1,856 (1.05), 1,931 (1.87), 2,036 (3.56), 2,072 (0.98), 2,327 (0.98), 2,366 (0.98), 2,558 (3.13), 2,571 (2.48), 2,593 (2.60), 2,605 (3.58), 2,618 (2.08), 2,635 (0.84), 2,647 (1.24), 2,669 (1.26), 2,710 (1.15), 2,861 (1.59), 2,869 (1.57), 2,877 (1.64), 2,932 (1.01), 2,949 (1.05), 3,228 (1.66), 3,252 (2.90), 3,514 (1.43), 3,534 (1.87), 3,634 (1.78), 3,654 (1.26), 4,555 (1.47), 4,573 (1.50), 4,636 (1.03), 4,651 (1.47), 4,663 (1.10), 4,676 (2.08), 4,693 (2.01), 4,896 (1.50), 4,904 (1.78), 4,911 (1.80), 4,919 (1.47), 4,966 (0.73), 5,001 (7.72), 5,018 (5.08), 5,059 (0.70), 7,913 (16.00), 8,645 (5.01). Example 200 (5S)-5-[(1RS,5SR)-2-Azabicyclo[3.1.0]hex-2-ylcarbonyl]-2-{[6-(trifluoromethyl)pyridin-3-yl]methyl}-5, 6,7,8-tetrahydro[1,2,4]triazolo[4,3- a]pyridin-3(2H)-one (isomer 1)

[01230] (5S)-3-Oxo-2-{[6-(trifluoromethyl)pyridin-3-yl]methyl}-2,3,5,6,7,8-hexahydro[1,2,4 ]triazolo[4,3-a]pyridine-5-carboxylic acid (251 mg, 733 μmol) was initially loaded into THF (12 mL) at room temperature. Subsequently, HATU (362 mg, 953 μmol), (1R,5S)-2-azabicyclo[3.1.0]hexane hydrochloride (105 mg, 880 μmol) and N,N-diisopropylethylamine (380 μl, 2.2 mmol) were added. The reaction mixture was stirred at room temperature overnight. HATU (279 mg, 733 μmol), (1RS,5SR)-2-azabicyclo[3.1.0]hexane hydrochloride (88 mg, 733 μmol) and N,N-diisopropylethylamine (127 μl, 1.7 mmol) were added again , and the mixture was stirred for another 20 hours. The reaction mixture was concentrated under reduced pressure. The residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: gradient (acetonitrile/water with 0.1% formic acid). The fractions containing the product were concentrated under reduced pressure and 54. 0 mg (18% possibility) of a diastereomer mixture (2 isomers).

[01231] The diastereomer mixture (2 isomers) was separated by chiral preparatory HPLC [sample preparation: 54 mg dissolved in 20 mL of methanol; injection volume: 1 mL; column: Daicel Chiralpak® IE 5 μm, 250 x 20 mm; eluent: carbon dioxide/methanol 80:20; flow rate: 80 ml/min; temperature 40°C; UV detection: 210 nm]. After separation, 20.2 mg of isomer 1, which elutes first, and 21.3 mg of isomer 2, which elutes later, were isolated. Isomer 1:

[01232] Analytical chiral HPLC: Rt = 5.41 min, > 99.5% [column: Daicel Chiralpak® IE, 50 x 4.6 mm; eluent: n-heptane/methanol 80:20; flow rate: 3 ml/min; UV detection: 210 nm]. LC-MS (Method 3): Rt = 1.32 min; MS (ESIpos): m /z = 408 [ M +H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (0.66), -0.008 (5.58), 0.008 (5.50), 0.146 (0.59) (1.61) (0.81) (5.43) (1.32) (1.03) (0.73), 3920 (0.51), 3943 (0.88), 3970 (0.51), 4761 (1.17), 4769 (0.81), 4951 (1.69), 4959 (2.06), 4965 (2.20), 4974 (1.76), 5004 (9.69), 7,908 (10.94), 7,912 (16.00), 8,642 (3.82). Example 201 (5S)-5-[(1SR,5RS)-2-Azabicyclo[3.1.0]hex-2-ylcarbonyl]-2-{[6-(trifluoromethyl)pyridin-3-yl]methyl}-5, 6,7,8-tetrahydro[1,2,4]triazolo[4,3- a]pyridin-3(2H)-one (isomer 2)

[01233] 5S)-5-[(1RS,5SR)-2-Azabicyclo[3.1.0]hex-2-ylcarbonyl]-2-{[6-(trifluoromethyl)pyridin-3-yl]methyl}-5, 6,7,8-tetrahydro[1,2,4]triazolo[4,3- a]pyridin-3(2H)-one (diastereomer mixture; 2 isomers) was separated by chiral preparatory HPLC [sample preparation : 54 mg dissolved in 20 mL of methanol; injection volume: 1 mL; column: Daicel Chiralpak® IE 5 μm, 250 x 20 mm; eluent: carbon dioxide/methanol 80:20; flow rate: 80 ml/min; temperature 40°C; UV detection: 210 nm]. After separation, 20.2 mg of isomer 1, which elutes first, and 21.3 mg of isomer 2, which elutes later, were isolated. Isomer 2:

[01234] Analytical chiral HPLC: Rt = 6.82 min, > 99.5% [column: Daicel Chiralpak® IE, 50 x 4.6 mm; eluent: n-heptane/methanol 80:20; flow rate: 3 ml/min; UV detection: 210 nm]. LC-MS (Method 3): Rt = 1.33 min; MS (ESIpos): m /z = 408 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (0.51), -0.008 (4.45), 0.008 (4.11), 0.146 (0.51) (0.96), 0.816 (2.03) (1.01), 1889 (1.69), 1896 (1.35), 1911 (1.30), 1918 (1.18), 1992 (0.90), 2031 (1.80), 2039 (1.58), 2047 (1.58), 2059 (1.75), 2185 (1.52) (1.63) (2.14) (1.13) (1.97), 7,912 (15.94), 7,915 (16.00), 8,646 (5.41). Example 202 (5S)-5-[(1RS,5SR)-2-Azabicyclo[3.1.0]hex-2-ylcarbonyl]-2-(3-chloro-4-fluorobenzyl)-5,6,7,8- tetrahydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one (isomer 1)

[01235] (5S)-2-(3-Chloro-4-fluorobenzyl)-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3 -a]pyridine-5-carboxylic acid (533 mg, 1.64 mmol) was initially loaded into THF (1.5 mL) at room temperature. Subsequently, HATU (809 mg, 2.13 mmol), (1RS,5SR)-2-azabicyclo[3.1.0]hexane hydrochloride (235 mg, 1.96 mmol) and N,N-diisopropylethylamine (860 μl, 4. 9 mmol) were added. HATU (622 mg, 1.64 mmol), (1RS,5SR)-2-azabicyclo[3.1.0]hexane hydrochloride (196 mg, 1.63 mmol) and N,N-diisopropylethylamine (287 μl, 1. 6 mmol) were added again, and the mixture was stirred for another 20 hours. The reaction mixture was concentrated under reduced pressure. The residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: gradient (acetonitrile/water with 0.1% formic acid). The fractions containing the product were concentrated under reduced pressure and 112 mg were obtained (18% possibility) of a mixture of diastereomers (2 isomers).

[01236] The diastereomer mixture (2 isomers) was separated by chiral preparatory HPLC [sample preparation: 112 mg dissolved in 2 mL of ethanol; injection volume: 0.35 mL; column: Daicel Chiralpak® AY-H 5 μm, 250 x 20 mm; eluent: n-heptane/ethanol 40:60; flow rate: 15 ml/min; temperature 40°C; UV detection: 220 nm]. After separation, 42.1 mg of isomer 1, which elutes first, and 63.6 mg of isomer 2, which elutes later, were isolated. Isomer 1:

[01237] Analytical chiral HPLC: Rt = 7.43 min, de = 99% [column: Daicel Chiralpak® AY-H 5 μm, 250 x 4.6 mm; eluent: n-heptane/ethanol 50:50; flow rate: 1 ml/min; UV detection: 220 nm]. LC-MS (Method 3): Rt = 1.49 min; MS (ESIpos): m /z = 391 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (0.75), -0.008 (6.67), 0.008 (5.91), 0.146 (0.75) (1.22), 0.727 (0.52), 0.870 (1.16), 0.885 (2.26), 0.892 (1.51), 0.906 (2.38), 0.920 (0.99), 1.548 (0.81), 1.569 (0.99), 1.583 (0.87), 1.657 (1.45) (1.51) (1.22) (2.38) (2.09) (1.74) (0.93) (16.00), 4825 (9.39), 4942 (2.43), 4950 (2.84), 4957 (3.01), 4966 (2.32), 7228 (2.03), 7234 (2.20), 7243 (2.67), 7248 (3.01), 7255 (2.84), 7,260 (2.61), 7,372 (5.62), 7,395 (7.59), 7,417 (4.35), 7,435 (3.71), 7,453 (3.71). Example 203 (5S)-5-[(1SR,5RS)-2-Azabicyclo[3.1.0]hex-2-ylcarbonyl]-2-(3-chloro-4-fluorobenzyl)-5,6,7,8- tetrahydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one (isomer 2)

[01238] (5S)-5-[(1SR,5RS)-2-Azabicyclo[3.1.0]hex-2-ylcarbonyl]-2-(3-chloro-4-fluorobenzyl)-5,6,7,8 -tetrahydro[1,2,4]triazolo[4,3-a]pyridin- 3(2H)-one (diastereomer mixture; 2 isomers) was separated by chiral preparatory HPLC [sample preparation: 112 mg dissolved in 2 mL of ethanol; injection volume: 0.35 mL; column: Daicel Chiralpak® AY-H 5 μm, 250 x 20 mm; eluent: n-heptane/ethanol 40:60; flow rate: 15 ml/min; temperature 40°C; UV detection: 220 nm]. After separation, 42.1 mg of isomer 1, which elutes first, and 63.6 mg of isomer 2, which elutes later, were isolated. Isomer 2:

[01239] Analytical chiral HPLC: Rt = 10.06 min, d = 99% [column: Daicel Chiralpak® AY-H 5 μm, 250 x 4.6 mm; eluent: n-heptane/ethanol 50:50; flow rate: 1 ml/min; UV detection: 220 nm]. LC-MS (Method 3): Rt = 1.50 min; MS (ESIpos): m /z = 391 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.008 (4.82), 0.008 (3.02), 0.564 (0.72), 0.577 ( 0.47), 0.619 (1.70), 0.625 (1.95), 0.632 (3.12), 0.638 (3.02), 0.645 (2.02), 0.651 (1.67), 0.729 (0.60), 0.750 (0.60), 0.798 (1.29), 0.813 ( 2.58), 0.820 (1.70), 0.826 (1.61), 0.834 (2.55), 0.848 (1.13), 1.554 (1.32), 1.567 (1.48), 1.575 (1.42), 1.590 (1.51), 1.726 (1.32), 1.741 ( 2.27), 1.755 (3.06), 1.770 (2.93), 1.776 (2.83), 1.791 (2.30), 1.806 (0.94), 1.855 (1.07), 1.862 (1.20), 1.877 (1.45), 1.886 (2.14), 1.894 ( 1.83), 1909 (1.83), 1915 (1.73), 1973 (0.57), 1994 (1.10), 2007 (1.39), 2018 (2.30), 2026 (2.30), 2032 (2.30), 2041 (2.39), 2053 ( 2.61), 2.061 (2.39), 2.084 (1.39), 2.099 (1.01), 2.161 (2.08), 2.195 (1.20), 2.328 (0.60), 2.366 (0.54), 2.524 (3.59), 2.559 (2.80), 2.572 ( 2.46), 2.586 (2.14), 2.597 (2.14), 2.606 (2.93), 2.619 (1.98), 2.638 (0.88), 2.647 (1.07), 2.661 (0.82), 2.670 (0.69), 2.710 (0.50), 2.935 ( 1.23), 2.957 (2.65), 2.966 (1.57), 2.979 (1.45), 2.989 (2.77), 3.010 (1.13), 3.243 (0.76), 3.528 (0.47), 3.534 (0.50), 3.544 (0.88), 3.549 ( 0.85), 3.559 (0.47), 3.705 (2.93), 3.714 (3.46), 3.721 (3.31), 3.733 (3.69), 3.758 (1.42), 3.765 (1.23), 3.778 (0.44), 3.805 (0.66), 4.649 ( 0.69), 4.658 (0.79), 4.664 (0.82), 4.674 (0.60), 4.821 (4.98), 4.833 (16.00), 5.093 (2.68), 5.100 (3.18), 5.108 (2.87), 5.115 (2.46), 7.226 ( 2.02), 7.232 (2.11), 7.238 (2.20), 7.244 (2.52), 7.248 (2.83), 7.253 (2.68), 7.260 (2.52), 7.265 (2.14), 7.372 (4.63), 7.396 (6.17), 7.417 ( 3.62), 7,437 (3.94), 7,442 (3.75), 7,455 (3.87), 7,460 (3.53). Example 204 (5S)-2-[(E)-2-(4-Fluorophenyl)vinyl]-5-(pyrrolidin-1-ylcarbonyl)-5,6,7,8-tetrahydro[1,2,4 ]triazolo[4,3-a]pyridin-3(2H)-one

[01240] (5S)-2-[(E)-2-(4-Fluorophenyl)vinyl]-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4] triazolo[4,3-a]pyridine-5-carboxylic acid (195 mg, 643 μmol) was initially loaded into THF (6.0 mL) at room temperature. Subsequently, HBTU (317 mg, 836 μmol) and N,N-diisopropylethylamine (560 μl, 3.2 mmol) were added. After stirring for 15 minutes, pyrrolidine (64 μl, 770 μmol) was added and the reaction mixture was stirred at room temperature overnight. The reaction mixture was mixed with water and ethyl acetate, and the organic phase was removed. The organic phase was washed with saturated aqueous sodium chloride solution, dried over sodium sulfate and filtered, and the filtrate was concentrated. The residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 40mm; eluent: acetonitrile with 0.1% formic acid gradient). The fractions containing the product were concentrated under reduced pressure and 68.5 mg (30% possibility) of the title compound were obtained. LC-MS (Method 3): Rt = 1.58 min; MS (ESIpos): m /z = 357 [M+H]+ ¹H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (0.95), -0.008 (8.77), 0.008 (8.91), 0.146 (1.02) (2.63) (1.97), 2.072 (2.41), 2.085 (3.43), 2.091 (2.19), 2.099 (1.97), 2.327 (1.39), 2.366 (1.39), 2.523 (5.11) (1.17) (0.88) (1.83) (3.65) (16.00), 7,166 (8.62), 7,330 (11.69), 7,367 (10.37), 7,519 (8.18), 7,533 (9.28), 7,541 (8.99), 7,555 (7.67). Example 205 (5S)-5-[(1RS,5SR)-2-Azabicyclo[3.1.0]hex-2-ylcarbonyl]-2-{[3-fluoro-2-(trifluoromethyl)pyridin-4-yl]methyl }-5,6,7,8-tetrahydro[1,2,4]triazolo[4,3- a]pyridin-3(2H)-one (diastereomer mixture; 2 isomers)

[01241] (5S)-2-{[3-Fluoro-2-(trifluoromethyl)pyridin-4-yl]methyl}-3-oxo-2,3,5,6,7,8-hexahydro[1 ,2,4]triazolo[4,3-a]pyridine-5-carboxylic acid (52.0 mg, 144 μmol) was initially loaded into THF (130 μl) at room temperature. Subsequently, HATU (71.3 mg, 188 μmol), N,N-diisopropylethylamine (76 μl, 430 μmol) and (1RS,5SR)-2-azabicyclo[3.1.0]hexane hydrochloride (20.7 mg, 173 μmol ) were added. The reaction mixture was stirred at room temperature overnight. The reaction mixture was concentrated under reduced pressure. The residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: gradient (acetonitrile/water with 0.1% formic acid). The fractions containing the product were concentrated under reduced pressure and 35. 0 mg (57% possibility) of the title compound. LC-MS (Method 3): Rt = 1.40 min; MS (ESIpos): m / z = 426 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (1.74), -0.008 (16.00), 0.008 (14.61), 0.146 (1.74), 0.562 (0.63), 0.640 (2.99), 0.728 (0.49), 0.805 (0.90) , 0.820 (1.88), 0.842 (1.88), 0.856 (0.83), 0.907 (0.56), 1.595 (1.25), 1.773 (3.20), 1.795 (2.43), 1.861 (1.11), 1.889 (1.67), 1.912 (1.25) , 1,991 (1.32), 2,071 (2.02), 2,192 (1.67), 2,327 (2.23), 2,366 (2.16), 2,523 (7.51), 2,563 (2.92), 2,578 (2.37), 2,592 (2.09), 2,625 (2.92) , 2.670 (3.27), 2.710 (2.16), 2.942 (0.90), 2.965 (1.81), 2.974 (1.04), 2.996 (2.09), 3.016 (0.83), 3.151 (0.56), 3.512 (0.63), 3.556 (0.63) , 3.715 (2.23), 3.740 (2.99), 3.765 (1.04), 3.814 (0.49), 4.682 (0.63), 4.777 (0.42), 4.977 (0.63), 5.076 (9.25), 5.122 (2.23), 5.129 (2.30) , 5,138 (2.16), 7,549 (2.50), 7,562 (4.52), 7,575 (2.71), 8,562 (4.94), 8,574 (5.08). Example 206 (5S)-2-{[6-(Difluoromethyl)pyridin-3-yl]methyl}-5-{[(3S)-3-fluoropyrrolidin-1-yl]carbonyl}-5,6,7,8 -tetrahydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one

[01242] (5S)-2-{[6-(Difluoromethyl)pyridin-3-yl]methyl}-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4 ]triazolo[4,3-a]pyridine-5-carboxylic acid (100 mg, 25% purity, 77.1 μmol) was initially loaded into THF (800 μl) at room temperature. Subsequently, (3S)-3-fluoropyrrolidine (8.24 mg, 92.5 μmol), HATU (38.1 mg, 100 μmol), and triethylamine (54 μl, 390 μmol) were added. The reaction mixture was stirred at room temperature overnight. The reaction mixture was mixed with water and concentrated under reduced pressure. The residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: gradient (acetonitrile/water with 0.1% formic acid). The fractions containing the product were concentrated under reduced pressure and 15. 8 mg (52% possibility) of the title compound. LC-MS (Method 3): Rt = 1.05 min; MS (ESIpos): m / z = 396 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (0.69), 0.146 (0.74), 0.950 (0.66), 1.007 (0.42), 1.732 (3.05), 1.874 (0.54), 1.914 (0.71), 1.998 (2.72), 2,026 (1.96), 2,090 (2.37), 2,106 (2.49), 2,137 (1.90), 2,268 (1.44), 2,327 (1.00), 2,366 (0.80), 2,565 (3.31), 2,605 (4.05), 2,648 (1.58), 2,665 (1.37), 2,710 (0.88), 3,273 (1.54), 3,302 (2.23), 3,320 (2.42), 3,368 (3.38), 3,396 (3.86), 3,406 (3.83), 3,468 (4.74), 3,494 (5.02), 3,523 (5.54), 3,546 (4.81), 3,572 (4.14), 3,599 (4.61), 3,636 (4.12), 3,654 (3.67), 3,679 (3.24), 3,705 (2.27), 3,725 (2.15), 3,745 (3.12), 3,775 (2.34), 3,786 (2.18), 3,857 (2.61), 3,918 (0.97), 3,943 (1.47), 4,008 (0.83), 4,039 (0.69), 4,688 (0.97), 4,698 (1.25), 4,704 (1.28), 4,713 (1.00), 4,746 (1.23), 4,761 (1.63), 4,769 (1.26), 4,818 (0.85), 4,831 (1.23), 4,870 (1.11), 4,955 (16.00), 5,261 (1.33), 5,350 (0.68), 5,392 (1.59), 5,481 (0.69), 5,515 (0.81), 6,807 (4.02), 6,944 (7.57), 7,081 (3.72), 7,682 (5.61), 7,702 (7.55), 7,819 (4.74), 7,839 (3.67), 8,563 (6.89). Example 207 (5S)-2-{[6-(Difluoromethyl)pyridin-3-yl]methyl}-5-{[(3R,4S)-3,4-difluoropyrrolidin-1-yl]carbonyl}-5.6 ,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one

[01243] (5S)-2-{[6-(Difluoromethyl)pyridin-3-yl]methyl}-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4 ]triazolo[4,3-a]pyridine-5-carboxylic acid (100 mg, 25% purity, 77.1 μmol) was initially loaded into THF (800 μl) at room temperature. Subsequently, (3R,4S)-3,4-difluoropyrrolidine (9.91 mg, 92.5 μmol), HATU (38.1 mg, 100 μmol), and triethylamine (54 μl, 390 μmol) were added. The reaction mixture was stirred at room temperature overnight. The reaction mixture was mixed with water and concentrated under reduced pressure. The residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: gradient (acetonitrile/water with 0.1% formic acid). The fractions containing the product were concentrated under reduced pressure and 16. 4 mg (49% possibility) of the title compound. LC-MS (Method 3): Rt = 1.13 min; MS (ESIpos): m / z = 414 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.154 (1.88), -0.013 (16.00), 0.141 (1.83), 0.941 (0.39), 1.657 (0.55), 1.729 (0.61), 1.769 (0.33), 1.952 (0.39) , 1,966 (0.55), 2,013 (0.66), 2,032 (0.50), 2,055 (0.55), 2,067 (0.50), 2,076 (0.50), 2,089 (0.44), 2,125 (0.33), 2,322 (2.33), 2,327 (1.77) , 2,361 (2.05), 2,518 (5.92), 2,561 (1.38), 2,572 (0.94), 2,585 (0.89), 2,598 (1.33), 2,660 (1.83), 2,664 (2.44), 2,705 (1.94), 3,347 (0.39) , 3.448 (0.33), 3.486 (0.39), 3.530 (0.50), 3.612 (0.33), 3.665 (0.39), 3.681 (0.55), 3.698 (0.66), 3.723 (0.55), 3.750 (0.44), 3.763 (0.39) , 3.921 (0.39), 3.966 (0.33), 3.983 (0.39), 4.170 (0.39), 4.789 (0.89), 4.801 (1.27), 4.952 (5.04), 5.242 (0.39), 5.250 (0.39), 5.282 (0.33) , 5.327 (0.44), 5.344 (0.39), 5.359 (0.33), 5.386 (0.44), 5.395 (0.50), 5.412 (0.39), 5.425 (0.33), 5.453 (0.39), 5.491 (0.39), 6.802 (0.94) , 6,939 (2.05), 7,076 (1.00), 7,676 (1.38), 7,697 (1.88), 7,812 (1.27), 7,833 (1.00), 8,556 (2.10). Example 208 (5S)-2-{[6-(Difluoromethyl)pyridin-3-yl]methyl}-5-[(3,3-difluoropyrrolidin-1-yl)carbonyl]-5,6,7,8-tetra -hydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one

[01244] (5S)-2-{[6-(Difluoromethyl)pyridin-3-yl]methyl}-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4 ]triazolo[4,3-a]pyridine-5-carboxylic acid (100 mg, 25% purity, 77.1 μmol) was initially loaded into THF (800 μl) at room temperature. Subsequently, 3,3-difluoropyrrolidine (9.91 mg, 92.5 μmol), HATU (38.1 mg, 100 μmol), and triethylamine (54 μl, 390 μmol) were added. The reaction mixture was stirred at room temperature overnight. The reaction mixture was mixed with water and concentrated under reduced pressure. The residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: gradient (acetonitrile/water with 0.1% formic acid). The fractions containing the product were concentrated under reduced pressure and 24. 3 mg (74% possibility) of the title compound. LC-MS (Method 3): Rt = 1.20 min; MS (ESIpos): m / z = 414 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (1.38), 0.146 (1.30), 1.041 (1.65), 1.673 (1.23), 1.731 (1.69), 2.002 (1.76), 2.012 (1.88), 2.047 (1.38), 2,327 (1.50), 2,366 (1.73), 2,381 (1.04), 2,410 (1.27), 2,431 (1.11), 2,563 (3.80), 2,573 (3.95), 2,588 (3.80), 2,605 (3.84), 2,648 (1.30), 2,670 (2.00), 2,710 (1.92), 2,884 (1.00), 3,533 (1.38), 3,541 (1.61), 3,550 (2.19), 3,560 (2.42), 3,580 (1.19), 3,636 (0.50), 3,668 (1.46), 3,703 (1.69), 3,747 (0.88), 3,782 (2.30), 3,811 (2.57), 3,829 (0.81), 3,891 (0.77), 3,909 (1.61), 3,935 (1.15), 3,953 (0.50), 3,993 (0.96), 4,021 (0.77), 4,037 (0.92), 4,065 (0.61), 4,148 (0.58), 4,179 (0.92), 4,206 (0.92), 4,759 (1.27), 4,774 (1.88), 4,784 (1.38), 4,831 (1.27), 4,846 (1.76), 4,856 (1.27), 4,957 (16.00), 6,806 (3.72), 6,943 (7.10), 7,081 (3.41), 7,682 (4.87), 7,702 (6.71), 7,820 (3.84), 7,840 (2.95), 8,157 (0.81), 8,563 (5.14). Example 209 (5S)-2-{[6-(Difluoromethyl)pyridin-3-yl]methyl}-5-[(3-fluoroazetidin-1-yl)carbonyl]-5,6,7,8-tetrahydro [1,2,4]triazolo[4,3-a]pyridin-3(2H)-one

[01245] (5S)-2-{[6-(Difluoromethyl)pyridin-3-yl]methyl}-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4 ]triazolo[4,3-a]pyridine-5-carboxylic acid (100 mg, 25% purity, 77.1 μmol) was initially loaded into THF (800 μl) at room temperature. Subsequently, 3-fluoroazetidine (6.95 mg, 92.5 μmol), HATU (38.1 mg, 100 μmol), and triethylamine (54 μl, 390 μmol) were added. The reaction mixture was stirred at room temperature overnight. The reaction mixture was mixed with water and concentrated under reduced pressure. The residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: gradient (acetonitrile/water with 0.1% formic acid). The fractions containing the product were concentrated under reduced pressure and 23. 2 mg (77% possibility) of the title compound. LC-MS (Method 3): Rt = 1.01 min; MS (ESIpos): m / z = 382 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (1.89), -0.031 (0.40), -0.026 (0.55), -0.024 (0.65), -0.020 (0.84), -0.018 (1.09), -0.015 (1.39) , - 0.008 (16.00), -0.007 (12.42), 0.008 (15.60), 0.015 (1.74), 0.018 (0.94), 0.021 (0.70), 0.026 (0.45), 0.028 (0.40), 0.033 (0.35), 0.146 ( 1.94), 0.990 (0.55), 1.701 (1.19), 1.709 (1.24), 1.939 (0.60), 1.949 (0.75), 1.965 (0.80), 1.975 (0.80), 2.008 (0.70), 2.323 (1.64), 2.327 ( 2.43), 2.332 (1.84), 2.366 (1.79), 2.445 (0.45), 2.464 (0.70), 2.523 (5.42), 2.526 (4.02), 2.558 (2.09), 2.562 (1.94), 2.566 (1.44), 2.569 ( 1.19), 2.572 (1.19), 2.579 (1.84), 2.594 (2.34), 2.606 (1.29), 2.622 (0.75), 2.636 (0.80), 2.649 (0.45), 2.665 (1.79), 2.670 (2.34), 2.674 ( 1.84), Example 210 (5S)-2-(4-Bromobenzyl)-5-{[(3R,4S)-3,4-difluoropyrrolidin-1-yl]carbonyl}-5,6,7,8-tetra- hydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one

[01246] (5S)-2-(4-Bromobenzyl)-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine -5-carboxylic acid (134 mg, 47% purity, 179 μmol) was initially loaded into THF (2.6 mL) at room temperature. Subsequently, HBTU (88.1 mg, 232 μmol) and N,N-diisopropylethylamine (250 μl, 1.4 mmol) were added. After stirring for 5 minutes, (3R,4S)-3,4-difluoropyrrolidine hydrochloride (30.8 mg, 214 μmol) was added and the reaction mixture was stirred at room temperature overnight. The reaction mixture was mixed with water and ethyl acetate, and the organic phase was removed. The organic phase was washed with 10% citric acid solution and saturated aqueous sodium chloride solution, dried over sodium sulfate and filtered, and the filtrate was concentrated. The residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: gradient (acetonitrile/water with 0.1% formic acid). The fractions containing the product were concentrated under reduced pressure and 54. 3 mg (69% possibility) of the title compound. LC-MS (Method 3): Rt = 1.47 min; MS (ESIpos): m / z = 441 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ 1.725 (1.31), 1.925 (0.44), 1.959 2.029 (0.82), 2.038 (0.89), 2.046 2.073 (0.69), 2.081 (0.76), 2.089 2.569 (1.44), 2.583 (1.90), 2,596 2,639 (0.85) 89), 3,753 ( 0.84) .00), 5.254 5.285 ( 0.70) 08), 7.201 (5.37 ), 7,527 (7. Example 211 (5S)-2-(3-Bromobenzyl)-5-{[(3R,4S)- 5,6,7,8-tetrahydro[1,2,4]triazolo[ 4,3-a]pyridin-3(2H)-one

[01247] (5S)-2-(3-Bromobenzyl)-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine -5-carboxylic acid (128 mg, 59% purity, 215 μmol) was initially loaded into THF (3.1 mL) at room temperature. Subsequently, HBTU (106 mg, 279 μmol) and N,N-diisopropylethylamine (300 μl, 1.7 mmol) were added. After stirring for 5 minutes, (3R,4S)-3,4-difluoropyrrolidine hydrochloride (37.0 mg, 258 μmol) was added and the reaction mixture was stirred at room temperature overnight. The reaction mixture was mixed with water and ethyl acetate, and the organic phase was removed. The organic phase was washed with 10% aqueous citric acid solution and saturated aqueous sodium chloride solution, dried over sodium sulfate and filtered, and the filtrate was concentrated. The residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: gradient (acetonitrile/water with 0.1% formic acid). The fractions containing the product were concentrated under reduced pressure and 23. 2 mg (24% possibility) of the title compound. LC-MS (Method 3): Rt = 1.50 min; MS (ESIpos): m / z = 441 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: 1.670 (1.28), 1.695 (0.91), 1.730 (1.61), 1.928 (0.54), 1.962 (1.20), 2.011 (1.55), 2.019 (1.18), 2.036 (0.94), 2.046 (1.09), 2.054 (1.18), 2.062 (1.15), 2.073 (1.00), 2.081 (0.85), 2.089 (0.96), 2.096 (0.81), 2.327 (0.54), 2.560 (1.83) (1.65) (0.80) (1.54) (0.85) (0.65) (0.81) (0.83) (2.61), 7,308 (3.75), 7,311 (4.42), 7,327 (1.78), 7,331 (2.05), 7,435 (5.42), 7,476 (3.16), 7,495 (2.57). Example 212 (5S)-2-(4-Bromobenzyl)-5-{[(3S)-3-fluoropyrrolidin-1-yl]carbonyl}-5,6,7,8-tetrahydro[1,2,4 ]triazolo[4,3-a]pyridin-3(2H)-one

[01248] (5S)-2-(4-Bromobenzyl)-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine -5-carboxylic acid (134 mg, 47% purity, 179 μmol) was initially loaded into THF (2.6 mL) at room temperature. Subsequently, HBTU (88.1 mg, 232 μmol) and N,N-diisopropylethylamine (250 μl, 1.4 mmol) were added. After stirring for 5 minutes, (3S)-3-fluoropyrrolidine hydrochloride (26.9 mg, 214 μmol) was added and the reaction mixture was stirred at room temperature overnight. The reaction mixture was mixed with water and ethyl acetate, and the organic phase was removed. The organic phase was washed with 10% aqueous citric acid solution and saturated aqueous sodium chloride solution, dried over sodium sulfate and filtered, and the filtrate was concentrated. The residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: gradient (acetonitrile/water with 0.1% formic acid). The fractions containing the product were concentrated under reduced pressure and 51. 7 mg (66% possibility) of the title compound. LC-MS (Method 3): Rt = 1.40 min; MS (ESIpos): m / z = 423 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (1.20), -0.008 (9.55), 0.008 (10.75), 0.146 (1.20), 0.940 (0.85), 0.956 (0.80), 1.728 (4.00), 1.913 (0.90) , 2,027 (1.60), 2,085 (2.35), 2,133 (1.70), 2,267 (1.45), 2,327 (1.60), 2,366 (0.85), 2,558 (3.25), 2,573 (2.10), 2,600 (3.30), 2,642 (1.30) , 2,670 (1.75), 2,709 (0.90), 3,268 (0.95), 3,287 (2.35), 3,344 (1.60), 3,367 (1.10), 3,392 (1.15), 3,464 (0.90), 3,491 (1.10), 3,606 (0.70) , 3,633 (3.60), 3,651 (2.55), 3,657 (2.65), 3,675 (1.95), 3,700 (1.40), 3,722 (1.45), 3,742 (2.65), 3,765 (2.00), 3,786 (1.55), 3,855 (3.20) , 4,674 (1.50), 4,684 (1.85), 4,690 (1.95), 4,699 (1.55), 4,731 (1.90), 4,746 (3.25), 4,756 (1.90), 4,785 (16.00), 4,830 (0.70), 5,258 (1.70) , 5,389 (2.05), 5,510 (1.10), 7,175 (6.10), 7,181 (8.15), 7,196 (8.05), 7,202 (8.55), 7,520 (1.90), 7,526 (13.45), 7,547 (12.20). Example 213 (5S)-2-(3-Bromobenzyl)-5-{[(3S)-3-fluoropyrrolidin-1-yl]carbonyl}-5,6,7,8-tetrahydro[1,2,4 ]triazolo[4,3-a]pyridin-3(2H)-one

[01249] (5S)-2-(3-Bromobenzyl)-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine -5-carboxylic acid (128 mg, 59% purity, 215 μmol) was initially loaded into THF (3.1 mL) at room temperature. Subsequently, HBTU (106 mg, 279 μmol) and N,N-diisopropylethylamine (300 μl, 1.7 mmol) were added. After stirring for 5 minutes, (3S)-3-fluoropyrrolidine hydrochloride (32.4 mg, 258 μmol) was added and the reaction mixture was stirred at room temperature overnight. The reaction mixture was mixed with water and ethyl acetate, and the organic phase was removed. The organic phase was washed with 10% aqueous citric acid solution and saturated aqueous sodium chloride solution, dried over sodium sulfate and filtered, and the filtrate was concentrated. The residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: gradient (acetonitrile/water with 0.1% formic acid). The fractions containing the product were concentrated under reduced pressure and 55. 5 mg (61% possibility) of the title compound. LC-MS (Method 3): Rt = 1.40 min; MS (ESIpos): m / z = 423 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (0.62), 0.146 (0.65), 1.719 (3.49), 1.732 (4.21), 1.871 (0.78), 1.881 (0.75), 1.906 (1.01), 1.995 (1.21), 2,008 (1.21), 2,021 (1.76), 2,064 (1.67), 2,089 (2.48), 2,101 (2.74), 2,126 (1.76), 2,138 (2.02), 2,220 (1.08), 2,242 (1.08), 2,269 (1.47), 2,327 (0.95), 2,366 (0.69), 2,561 (2.45), 2,570 (2.78), 2,587 (2.12), 2,613 (3.46), 2,654 (1.34), 2,669 (1.50), 2,710 (0.82), 3,273 (0.85), 3,347 (1.21), 3,369 (1.14), 3,397 (1.18), 3,405 (1.14), 3,458 (0.85), 3,466 (0.88), 3,494 (1.14), 3,503 (1.08), 3,613 (0.69), 3,638 (3.89), 3,655 (2.61), 3,663 (2.81), 3,680 (2.06), 3,704 (1.50), 3,722 (1.60), 3,742 (3.23), 3,770 (2.06), 3,785 (2.06), 3,856 (3.33), 4,691 (1.53), 4,700 (1.86), 4,706 (1.99), 4,715 (1.57), 4,747 (1.96), 4,756 (2.25), 4,762 (2.58), 4,772 (1.99), 4,819 (16.00), 4,866 (0.88), 5,260 (1.63), 5,390 (2.22), 5,512 (1.21), 7,222 (2.94), 7,241 (4.70), 7,291 (4.70), 7,311 (7.93), 7,330 (3.69), 7,436 (7.09), 7,475 (4.34), 7,495 (3.56). Example 214 (5S)-2-(4-Bromo-2-fluorobenzyl)-5-{[(3S)-3-fluoropyrrolidin-1-yl]carbonyl}-5,6,7,8-tetrahydro[1 ,2,4]triazolo[4,3-a]pyridin-3(2H)-one

[01250] (5S)-2-(4-Bromo-2-fluorobenzyl)-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3 -a]pyridine-5-carboxylic acid (85.0 mg, 223 μmol) was initially loaded into THF (2.0 mL) at room temperature. Subsequently, HBTU (110 mg, 290 μmol) and N,N-diisopropylethylamine (190 μl, 1.1 mmol) were added. After stirring for 5 minutes, (3S)-3-fluoropyrrolidine hydrochloride (33.6 mg, 267 μmol) was added and the reaction mixture was stirred at room temperature over the weekend. The reaction mixture was mixed with water and ethyl acetate, and the organic phase was removed. The organic phase was washed with 10% aqueous citric acid solution and saturated aqueous sodium chloride solution, dried over sodium sulfate and filtered, and the filtrate was concentrated. The residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: gradient (acetonitrile/water with 0.1% formic acid). The fractions containing the product were concentrated under reduced pressure and 49. 1 mg (50% possibility) of the title compound. LC-MS (Method 3): Rt = 1.47 min; MS (ESIpos): m / z = 441 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (2.07), -0.008 (15.92), 0.008 (15.04), 0.146 (1.91), 1.722 (6.61), 1.861 (1.35), 1.895 (1.67), 2.021 (2.87) , 2,087 (3.82), 2,135 (2.63), 2,265 (2.31), 2,327 (3.26), 2,366 (2.55), 2,524 (9.47), 2,569 (3.42), 2,597 (5.17), 2,639 (1.99), 2,670 (3.34) , 2,710 (2.47), 3,364 (1.67), 3,391 (1.83), 3,462 (1.27), 3,488 (1.83), 3,604 (1.19), 3,630 (6.05), 3,655 (4.38), 3,673 (3.18), 3,693 (2.31) , 3,718 (2.55), 3,740 (4.38), 3,764 (3.42), 3,782 (2.79), 3,851 (5.25), 4,669 (2.55), 4,678 (3.34), 4,684 (3.50), 4,693 (2.71), 4,726 (3.18) , 4,735 (3.58), 4,741 (4.22), 4,750 (3.18), 4,772 (3.90), 4,811 (16.00), 4,837 (10.27), 4,877 (2.71), 5,257 (2.63), 5,388 (3.42), 5,509 (1.83 ) , 7,188 (3.98), 7,204 (7.08), 7,208 (8.68), 7,224 (4.06), 7,229 (4.70), 7,403 (8.36), 7,408 (8.60), 7,428 (7.24), 7,543 (7.56), 7,547 (7.16) , 7,567 (7.72), 7,572 (7.24), 8,559 (0.64). Example 215 (5S)-2-(4-Bromo-2-fluorobenzyl)-5-{[(3R,4S)-3,4-difluoropyrrolidin-1-yl]carbonyl}-5,6,7,8-tetra -hydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one

[01251] (5S)-2-(4-Bromo-2-fluorobenzyl)-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3 -a]pyridine-5-carboxylic acid (85.0 mg, 223 μmol) was initially loaded into THF (2.0 mL) at room temperature. Subsequently, HBTU (110 mg, 290 μmol) and N,N-diisopropylethylamine (190 μl, 1.1 mmol) were added. After stirring for 5 minutes, (3R,4S)-3,4-difluoropyrrolidine hydrochloride (38.4 mg, 267 μmol) was added and the reaction mixture was stirred at room temperature over the weekend. The reaction mixture was mixed with water and ethyl acetate, and the organic phase was removed. The organic phase was washed with 10% aqueous citric acid solution and saturated aqueous sodium chloride solution, dried over sodium sulfate and filtered, and the filtrate was concentrated. The residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: gradient (acetonitrile/water with 0.1% formic acid). The fractions containing the product were concentrated under reduced pressure and 50. 6 mg (49% possibility) of the title compound. LC-MS (Method 3): Rt = 1.54 min; MS (ESIpos): m / z = 459 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (0.70), -0.008 (5.71), 0.008 (5.79), 0.146 (0.63), 1.636 (2.03), 1.661 (2.64), 1.670 (2.35), 1.685 (1.84) , 1,699 (2.42), 1,711 (2.93), 1,720 (3.34), 1,734 (2.81), 1,911 (1.09), 1,953 (2.49), 1,962 (2.18), 1,978 (1.62), 1,998 (3.20), 2,022 (2.03) , 2,032 (2.28), 2,040 (2.49), 2,048 (2.42), 2,056 (1.91), 2,067 (1.82), 2,073 (2.20), 2,083 (1.69), 2,327 (0.99), 2,366 (0.68), 2,577 (4.65) , 2,591 (6.34), 2,603 (3.56), 2,621 (1.36), 2,633 (2.18), 2,646 (1.14), 2,665 (0.92), 2,670 (1.19), 2,674 (0.94), 2,710 (0.80), 3,448 (1.23) , 3.457 (0.77), 3.483 (2.13), 3.504 (1.55), 3.511 (1.57), 3.521 (1.84), 3.530 (2.59), 3.538 (2.37), 3.563 (1.09), 3.573 (1.60), 3.583 (1.02) , 3,611 (1.67), 3,624 (1.96), 3,643 (1.19), 3,657 (1.33), 3,666 (1.86), 3,680 (2.74), 3,698 (3.46), 3,713 (2.13), 3,722 (2.13), 3,731 (2.32) , 3,751 (2.06), 3,761 (2.03), 3,783 (1.16), 3,796 (1.14), 3,825 (0.75), 3,861 (1.65), 3,902 (1.23), 3,921 (1.62), 3,935 (1.89), 3,950 (1.14) , 3,971 (1.79), 3,985 (1.84), 4,000 (1.14), 4,013 (1.04), 4,124 (1.14), 4,138 (1.31), 4,152 (1.26), 4,166 (2.15), 4,179 (1.38), 4,192 (1.26) , 4,208 (1.14), 4,778 (7,46), 4,785 (7,24), 4,795 (4,72), 4,816 (16.00), 4,830 (9.08), 4,838 (9,27), 4,869 (1.48), 4,877 (2.25), 5,243 (1.14) , 5,252 (1.79), 5,265 (1.79), 5,274 (2.03), 5,283 (1.69), 5,295 (1.31), 5,327 (1.48), 5,336 (1.50), 5,348 (1.60), 5,363 (1.43), 5,375 (1.89) , 5,386 (2.25), 5,398 (1.86), 5,406 (1.91), 5,414 (1.69), 5,425 (1.23), 5,439 (1.23), 5,456 (1.52), 5,470 (1.57), 5,478 (1.62), 5,492 (1.21) , 5.501 (0.80), 7.180 (3.00), 7.188 (3.53), 7.200 (6.70), 7.208 (7.53), 7.221 (3.87), 7.228 (4.16), 7.405 (8.08), 7.425 (6.80), 7.545 (7.07) , 7,549 (4.96), 7,569 (7.21), 7,573 (4.99). Example 216 (5S)-5-{[(3S)-3-Fluoropyrrolidin-1-yl]carbonyl}-2-{(1RS)-1-[6-(trifluoromethyl)pyridin-3-yl]ethyl}-5 ,6,7,8-tetrahydro[1,2,4]triazolo[4,3- a]pyridin-3(2H)-one (isomer 1)

[01252] (5S)-3-Oxo-2-{(1RS)-1-[6-(trifluoromethyl)pyridin-3-yl]ethyl}-2,3,5,6,7,8-hexahydro [1,2,4]triazolo[4,3-a]pyridine-5-carboxylic acid (isomer 1) (75.0 mg, 210 μmol) was initially loaded into THF (2.0 mL) at room temperature. Subsequently, HBTU (104 mg, 274 μmol) and N,N-diisopropylethylamine (180 μl, 1.1 mmol) were added. After stirring for 5 minutes, (3S)-3-fluoropyrrolidine hydrochloride (31.7 mg, 253 μmol) was added and the reaction mixture was stirred at room temperature overnight. The reaction mixture was mixed with water and ethyl acetate, and the organic phase was removed. The organic phase was washed with 10% aqueous citric acid solution and saturated aqueous sodium chloride solution, dried over sodium sulfate and filtered, and the filtrate was concentrated. The residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: gradient (acetonitrile/water with 0.1% formic acid). The fractions containing the product were concentrated under reduced pressure and 32. 5 mg (36% possibility) of the title compound. LC-MS (Method 3): Rt = 1.36 min; MS (ESIpos): m / z = 428 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (0.57), -0.008 (4.90), 0.008 (5.76), 0.146 (0.57), 1.681 (15.40), 1.699 (16.00), 1.723 (3.24), 1.735 (4.02) , 1,747 (3.10), 1,851 (0.68), 1,861 (0.66), 1,887 (0.87), 1,960 (0.90), 1,972 (0.80), 1,985 (1.13), 1,995 (1.46), 2,009 (1.24), 2,061 (1.64) , 2.075 (1.83), 2.092 (2.11), 2.126 (1.21), 2.153 (0.79), 2.210 (0.88), 2.231 (0.83), 2.259 (1.15), 2.322 (0.79), 2.327 (1.06), 2.366 (0.60) , 2,523 (3.39), 2,569 (1.87), 2,586 (1.53), 2,593 (2.30), 2,609 (1.29), 2,648 (2.28), 2,656 (2.47), 2,669 (2.14), 2,689 (1.02), 2,697 (1.10) , 2.710 (1.06), 3.273 (0.63), 3.348 (0.74), 3.361 (0.69), 3.370 (0.74), 3.397 (0.79), 3.405 (0.82), 3.459 (0.61), 3.467 (0.66), 3.494 (0.93) , 3.503 (0.87), 3.590 (0.57), 3.616 (1.31), 3.638 (2.46), 3.661 (1.94), 3.689 (0.83), 3.704 (2.09), 3.728 (2.05), 3.750 (1.64), 3.769 (1.31) , 3,838 (2.57), 4,644 (1.23), 4,654 (1.51), 4,659 (1.64), 4,669 (1.23), 4,703 (1.53), 4,713 (1.84), 4,719 (2.05), 4,728 (1.56), 5,256 (1.31) , 5,388 (1.32), 5,468 (1.95), 5,477 (2.49), 5,486 (2.09), 5,495 (2.76), 7,883 (4.74), 7,903 (6.80), 7,999 (3.75), 8,019 (2.72), 8,705 (5.28) . Example 217 (5S)-5-{[(3S)-3-Fluoropyrrolidin-1-yl]carbonyl}-2-{(1RS)-1-[6-(trifluoromethyl)pyridin-3-yl]ethyl}-5 ,6,7,8-tetrahydro[1,2,4]triazolo[4,3- a]pyridin-3(2H)-one (isomer 2)

[01253] (5S)-3-Oxo-2-{(1RS)-1-[6-(trifluoromethyl)pyridin-3-yl]ethyl}-2,3,5,6,7,8-hexahydro [1,2,4]triazolo[4,3-a]pyridine-5-carboxylic acid (isomer 2) (65.0 mg, 177 μmol) was initially loaded into THF (2.0 mL) at room temperature. Subsequently, HBTU (87.2 mg, 230 μmol) and N,N-diisopropylethylamine (150 μl, 880 μmol) were added. After stirring for 5 minutes, (3S)-3-fluoropyrrolidine hydrochloride (26.7 mg, 212 μmol) was added and the reaction mixture was stirred at room temperature overnight. The reaction mixture was mixed with water and ethyl acetate, and the organic phase was removed. The organic phase was washed with 10% aqueous citric acid solution and saturated aqueous sodium chloride solution, dried over sodium sulfate and filtered, and the filtrate was concentrated. The residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: gradient (acetonitrile/water with 0.1% formic acid). The fractions containing the product were concentrated under reduced pressure and 30. 2 mg (40% possibility) of the title compound. LC-MS (Method 3): Rt = 1.35 min; MS (ESIpos): m / z = 428 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (0.56), -0.008 (4.61), 0.008 (4.37), 0.146 (0.49), 1.677 (15.68), 1.694 (16.00), 1.746 (1.65), 1.884 (0.49) , 1,924 (0.75), 2,010 (0.61), 2,084 (1.67), 2,104 (1.72), 2,259 (1.02), 2,327 (1.12), 2,367 (0.53), 2,586 (1.62), 2,602 (1.34), 2,612 (1.51) , 2.626 (1.26), 2.655 (1.99), 2.665 (1.94), 2.669 (1.96), 2.697 (0.78), 2.710 (0.80), 2.882 (0.51), 3.247 (0.49), 3.275 (0.90), 3.371 (0.65) , 3.379 (0.68), 3.441 (0.53), 3.468 (0.77), 3.618 (1.89), 3.634 (1.74), 3.646 (1.36), 3.676 (0.97), 3.715 (1.48), 3.738 (1.51), 3.759 (1.17) , 3,777 (1.00), 3,842 (2.06), 4,689 (1.02), 4,698 (1.24), 4,704 (1.33), 4,713 (0.99), 4,746 (1.26), 4,754 (1.46), 4,761 (1.69), 4,770 (1.26) , 5,245 (1.06), 5,377 (1.46), 5,489 (1.69), 5,498 (2.54), 5,506 (2.30), 5,515 (2.09), 7,900 (3.88), 7,920 (6.69), 7,974 (2.72), 7,994 (1.62) , 8,663 (4.90). Example 218 (5S)-5-{[(3R,4S)-3,4-Difluoropyrrolidin-1-yl]carbonyl}-2-{(1RS)-1-[6-(trifluoromethyl)pyridin-3-yl] ethyl}-5,6,7,8-tetrahydro[1,2,4]triazolo[4,3- a]pyridin-3(2H)-one (isomer 1)

[01254] (5S)-3-Oxo-2-{(1R)-1-[6-(trifluoromethyl)pyridin-3-yl]ethyl}-2,3,5,6,7,8-hexahydro [1,2,4]triazolo[4,3-a]pyridine-5-carboxylic acid (isomer 1) (75.0 mg, 210 μmol) was initially loaded into THF (2.0 mL) at room temperature. Subsequently, HBTU (104 mg, 274 μmol) and N,N-diisopropylethylamine (180 μl, 1.1 mmol) were added. After stirring for 5 minutes, (3R,4S)-3,4-difluoropyrrolidine hydrochloride (36.3 mg, 253 μmol) was added and the reaction mixture was stirred at room temperature overnight. The reaction mixture was mixed with water and ethyl acetate, and the organic phase was removed. The organic phase was washed with 10% aqueous citric acid solution and saturated aqueous sodium chloride solution, dried over sodium sulfate and filtered, and the filtrate was concentrated. The residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: gradient (acetonitrile/water with 0.1% formic acid). The fractions containing the product were concentrated under reduced pressure and 32. 4 mg (35% possibility) of the title compound. LC-MS (Method 3): Rt = 1.43 min; MS (ESIpos): m / z = 446 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (1.11), -0.008 (9.41), 0.008 (9.45), 0.146 (1.07), 1.406 (0.97), 1.679 (15.86), 1.697 (16.00), 1.719 (2.58) , 1,943 (1.32), 1,968 (0.93), 1,976 (1.29), 1,990 (1.29), 2,022 (1.15), 2,041 (1.25), 2,048 (1.29), 2,058 (1.22), 2,077 (1.00), 2,322 (1.65) , 2,327 (2.29), 2,332 (1.75), 2,523 (6.59), 2,569 (2.04), 2,584 (2.18), 2,595 (2.61), 2,606 (1.93), 2,619 (1.32), 2,652 (2.79), 2,665 (3.15) , 2,669 (3.04), 2,674 (2.51), 2,694 (1.36), 2,709 (1.32), 3,491 (1.18), 3,511 (0.89), 3,528 (1.04), 3,537 (1.43), 3,545 (1.32), 3,579 (0.93) , 3.617 (0.97), 3.630 (1.11), 3.673 (1.15), 3.687 (1.61), 3.703 (1.79), 3.722 (1.57), 3.736 (1.07), 3.753 (1.25), 3.766 (1.15), 3.801 (0.93) , 3.842 (1.04), 3.882 (0.79), 3.915 (0.93), 3.928 (1.15), 3.965 (1.04), 3.978 (1.00), 4.116 (0.79), 4.131 (0.75), 4.146 (1.00), 4.158 (0.79) , 4,744 (2.72), 4,758 (3.69), 4,768 (2.51), 5,251 (1.04), 5,262 (1.00), 5,272 (1.07), 5,303 (0.79), 5,312 (0.79), 5,319 (0.89), 5,329 (0.86) , 5.342 (0.89), 5.365 (0.89), 5.376 (1.07), 5.385 (1.07), 5.396 (1.07), 5.404 (1.04), 5.418 (1.04), 5.427 (0.79), 5.452 (1.36), 5.470 (2.86) , 5,485 (3.19), 5,500 (2.76), 5,516 (0.82), 7,884 (5.37), 7,904 (7.48), 8,002 (4.22), 8,023 (3.11), 8,705 (6.59). Example 219 (5S)-5-{[(3R,4S)-3,4-Difluoropyrrolidin-1-yl]carbonyl}-2-{(1RS)-1-[6-(trifluoromethyl)pyridin-3-yl] ethyl}-5,6,7,8-tetrahydro[1,2,4]triazolo[4,3- a]pyridin-3(2H)-one (isomer 2)

[01255] (5S)-3-Oxo-2-{(1RS)-1-[6-(trifluoromethyl)pyridin-3-yl]ethyl}-2,3,5,6,7,8-hexahydro [1,2,4]triazolo[4,3-a]pyridine-5-carboxylic acid (isomer 2) (65.0 mg, 177 μmol) was initially loaded into THF (2.0 mL) at room temperature. Subsequently, HBTU (87.2 mg, 230 μmol) and N,N-diisopropylethylamine (150 μl, 880 μmol) were added. After stirring for 5 minutes, (3R,4S)-3,4-difluoropyrrolidine hydrochloride (30.5 mg, 212 μmol) was added and the reaction mixture was stirred at room temperature overnight. The reaction mixture was mixed with water and ethyl acetate, and the organic phase was removed. The organic phase was washed with 10% aqueous citric acid solution and saturated aqueous sodium chloride solution, dried over sodium sulfate and filtered, and the filtrate was concentrated. The residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: gradient (acetonitrile/water with 0.1% formic acid). The fractions containing the product were concentrated under reduced pressure and 11. 6 mg (15% possibility) of the title compound. LC-MS (Method 3): Rt = 1.43 min; MS (ESIpos): m / z = 446 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (1.97), -0.050 (0.62), - 0.008 (16.00), 0.008 (15.32), 0.018 (0.68), 0.146 (1.66), 1.616 (0.94), 1.652 (1.25 ), 1677 (13.66), 1695 (13.30), 1741 (1.19), 1779 (0.83), 1976 (0.99), 2017 (1.51), 2027 (1.51), 2065 (1.04), 2093 (0.78), (0.78) , 2,322 (2.86), 2,327 (3.79), 2,332 (2.81), 2,366 (1.66), 2,392 (0.57), 2,404 (0.62), 2,523 (7.69), 2,567 (0.83), 2,583 (1.09), 2,594 (1.14) , 2,609 (1.56), 2,620 (1.14), 2,633 (1.40), 2,651 (2.08), 2,661 (2.44), 2,665 (3.48), 2,669 (4.00), 2,674 (3.01), 2,692 (0.68), 2,710 (1.51) , 3.462 (0.73), 3.483 (0.68), 3.501 (0.68), 3.508 (0.94), 3.517 (0.99), 3.605 (0.78), 3.645 (0.68), 3.660 (1.19), 3.673 (0.94), 3.695 (0.99) , 3.720 (0.83), 3.737 (0.83), 3.758 (0.62), 3.859 (0.57), 3.897 (0.57), 3.916 (0.78), 3.929 (0.83), 3.958 (0.57), 3.966 (0.78), 3.980 (0.62) , 4.145 (0.57), 4.157 (0.78), 4.186 (0.57), 4.796 (1.97), 4.810 (2.49), 4.820 (1.82), 5.247 (0.83), 5.255 (0.78), 5.264 (0.68), 5.311 (0.73) , 5.342 (0.73), 5.357 (0.94), 5.368 (0.94), 5.391 (0.88), 5.441 (0.73), 5.476 (1.04), 5.493 (1.66), 5.501 (1.82), 5.511 (1.56), 5.520 (1.66) , 7,897 (1.77), 7,901 (2.08), 7,916 (3.32), 7,920 (3.58), 7,966 (1.71), 7,979 (2.18), 7,993 (1.19), 8,551 (0.78), 8,660 (4.26). Example 220 (5RS,8RS)-5-{[(3S)-3-Fluoropyrrolidin-1-yl]carbonyl}-8-methyl-2-{[6-(trifluoromethyl)pyridin-3-yl]methyl}-5 ,6,7,8-tetrahydro[1,2,4]triazolo[4,3- a]pyridin-3(2H)-one (diastereomer mixture; 4 isomers)

[01256] (5RS,8RS)-8-Methyl-3-oxo-2-{[6-(trifluoromethyl)pyridin-3-yl]methyl}octahydro[1,2,4]triazolo[4,3- a]pyridine-5-carboxylic acid (diastereomer mixture; 4 isomers) (100 mg, 279 μmol) was initially loaded into dichloromethane (2.0 mL) and DMF (4.0 mL) at room temperature. Subsequently, 1-[bis(dimethylamino)methylene]-1H-benzotriazol-1-ium 3-oxide hexafluorophosphate (138 mg, 363 μmol) and N,N-diisopropylethylamine (120 μl, 670 μmol) were added. After stirring for 15 min, (3S)-3-fluoropyrrolidine hydrochloride (38.5 mg, 307 μmol) was added, and the reaction mixture was stirred at room temperature for 30 min. The solvent was removed under reduced pressure, and the residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/water gradient). HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/gradient water). The product-containing fractions were concentrated under reduced pressure and 76.0 mg (64% possibility) of the title compound were obtained as a diastereomer mixture. LC-MS (Method 3): Rt = 1.39 min; MS (ESIpos): m /z = 428 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.008 (0.95), 0.008 (0.84), 1.175 (11.85), 1.181 ( 12.64), 1.192 (12.80), 1.198 (12.36), 1.345 (0.79), 1.375 (1.07), 1.409 (1.13), 1.442 (0.85), 1.804 (1.52), 1.814 (1.61), 1.824 (1.65), ( 1.39), 1.965 (0.69), 1.999 (1.14), 2.033 (0.60), 2.040 (0.61), 2.078 (3.30), 2.088 (3.09), 2.103 (3.06), 2.111 (3.23), 2.126 (2.92), 2.135 ( 2.51), 2.153 (1.32), 2.172 (0.58), 2.227 (0.92), 2.237 (0.95), 2.258 (1.26), 2.524 (0.86), 2.707 (1.11), 2.722 (1.74), 2.737 (2.13), 2.752 ( 1.75), 2.766 (1.08), 3.276 (0.43), 3.357 (0.89), 3.367 (1.05), 3.387 (0.89), 3.397 (0.83), 3.414 (0.46), 3.463 (0.43), 3.490 (0.58), 3.498 ( 0.58), 3.520 (1.78), 3.543 (1.38), 3.550 (1.09), 3.569 (1.18), 3.599 (2.26), 3.625 (1.34), 3.641 (1.96), 3.648 (1.65), 3.671 (1.54), 3.700 ( 0.76), 3.714 (0.73), 3.736 (1.85), 3.758 (1.07), 3.766 (1.05), 3.776 (1.17), 3.844 (1.52), 3.910 (0.54), 3.932 (0.99), 3.952 (0.72), 3.980 ( 0.44), 4.006 (0.53), 4.038 (0.41), 4.725 (0.97), 4.738 (1.03), 4.773 (0.95), 4.782 (1.50), 4.793 (0.96), 4.854 (0.84), 4.860 (1.12), 4.872 ( 0.97) 1.28), 5.481 (0.68), 5.511 (0.56), 7.884 (0.66), 7.908 (16.00), 7.928 (0.87), 8.633 (6.30). Example 221 (5RS,8RS)-5-{[(3S)-3-Fluoropyrrolidin-1-yl]carbonyl}-8-methyl-2-{[6-(trifluoromethyl)pyridin-3-yl]methyl}-5 ,6,7,8-tetrahydro[1,2,4]triazolo[4,3- a]pyridin-3(2H)-one (isomer 1)

[01257] (5RS,8RS)-5-{[(3S)-3-Fluoropyrrolidin-1-yl]carbonyl}-8-methyl- 2-{[6-(trifluoromethyl)pyridin-3-yl]methyl}- 5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one (diastereomer mixture; 4 isomers) was separated by chiral preparatory HPLC [preparation sample: 60 mg dissolved in 1 mL of ethanol and 1 mL of acetonitrile; injection volume: 0.25 mL; column: Daicel Chiralpak® IA 5 μm, 250 x 20 mm; eluent: n-heptane/ethanol 50:50; flow rate: 20 ml/min; temperature 40°C; UV detection: 220 nm]. After separation, 18.4 mg of isomer 1, which elutes first, and 18.5 mg of isomer 2, which elutes later, were isolated. Isomer 1:

[01258] Analytical chiral HPLC: Rt = 1.95 min, de = 100% [column: Daicel Chiralcel® ID-3 50 x 4.6 mm; eluent: n-heptane/ethanol 70:30; flow rate: 1 ml/min; UV detection: 220 nm]. LC-MS (Method 3): Rt = 1.40 min; MS (ESIpos): m /z = 428 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.008 (2.11), 0.008 (1.73), 1.175 (15.58), 1.191 ( 16.00), 1.316 (0.40), 1.345 (1.10), 1.373 (1.14), 1.401 (0.52), 1.797 (0.87), 1.821 (1.22), 1.842 (0.80), 1.856 (0.67), 2.003 (0.50), 2.076 ( 3.92), 2.138 (1.06), 2.153 (0.81), 2.207 (0.68), 2.229 (0.70), 2.245 (0.70), 2.257 (0.97), 2.328 (0.43), 2.670 (0.47), 2.720 (1.03), 2.735 ( 1.32), 2.744 (1.35), 2.774 (0.60), 3.338 (0.78), 3.356 (0.70), 3.367 (1.10), 3.385 (1.09), 3.395 (0.76), 3.413 (0.61), 3.519 (2.55), 3.542 ( 1.99), 3.567 (1.70), 3.598 (2.78), 3.647 (0.57), 3.671 (0.60), 3.679 (0.60), 3.745 (0.48), 3.768 (0.62), 3.776 (0.61), 3.909 (0.78), 3.931 ( 1.41), 3.951 (1.04), 3.978 (0.66), 4.005 (0.77), 4.036 (0.62), 4.858 (1.59), 4.872 (1.35), 4.889 (1.29), 4.901 (1.72), 4.909 (1.15), 5.051 ( 13.02), 5.269 (0.97), 5.348 (0.97), 5.399 (0.99), 5.480 (0.97), 7.885 (0.47), 7.908 (12.03), 7.928 (0.69), 8.632 (5.68). Example 222 (5RS,8RS)-5-{[(3S)-3-Fluoropyrrolidin-1-yl]carbonyl}-8-methyl-2-{[6-(trifluoromethyl)pyridin-3-yl]methyl}-5 ,6,7,8-tetrahydro[1,2,4]triazolo[4,3- a]pyridin-3(2H)-one (isomer 2)

[01259] (5RS,8RS)-5-{[(3S)-3-Fluoropyrrolidin-1-yl]carbonyl}-8-methyl- 2-{[6-(trifluoromethyl)pyridin-3-yl]methyl}- 5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one (diastereomer mixture; 4 isomers) was separated by chiral preparatory HPLC [preparation sample: 60 mg dissolved in 1 mL of ethanol and 1 mL of acetonitrile; injection volume: 0.25 mL; column: Daicel Chiralpak® IA 5 μm, 250 x 20 mm; eluent: n-heptane/ethanol 50:50; flow rate: 20 ml/min; temperature 40°C; UV detection: 220 nm]. After separation, 18.4 mg of isomer 1, which elutes first, and 18.5 mg of isomer 2, which elutes later, were isolated. Isomer 2:

[01260] Analytical chiral HPLC: Rt = 2.22 min, de = 100% [column: Daicel Chiralcel® ID-3 50 x 4.6 mm; eluent: n-heptane/ethanol 70:30; flow rate: 1 ml/min; UV detection: 220 nm]. LC-MS (Method 3): Rt = 1.39 min; MS (ESIpos): m /z = 428 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.008 (1.59), 0.008 (1.32), 1.120 (0.68), 1.181 ( 15.77), 1,198 (16.00), 1,377 (0.51), 1,391 (0.56), 1,408 (1.21), 1,441 (1.17), 1,464 (0.45), 1,803 (1.39), 1,813 (1.24), 1,824 (1.15), 1.837 ( 1.13), 1.964 (0.73), 1.999 (1.22), 2.102 (2.42), 2.115 (3.09), 2.126 (3.14), 2.135 (2.50), 2.146 (1.27), 2.170 (0.54), 2.227 (0.65), 2.236 ( 0.75), 2.271 (0.93), 2.282 (0.84), 2.524 (0.99), 2.707 (1.01), 2.722 (1.52), 2.737 (1.78), 2.752 (1.45), 2.767 (0.89), 3.275 (0.76), 3.294 ( 1.15), 3.303 (1.69), 3.391 (1.53), 3.400 (1.29), 3.453 (0.67), 3.462 (0.68), 3.489 (0.84), 3.497 (0.79), 3.599 (0.51), 3.624 (1.85), 3.641 ( 2.31), 3.670 (1.69), 3.698 (1.02), 3.714 (1.01), 3.735 (2.25), 3.757 (1.43), 3.774 (1.16), 3.843 (2.15), 4.724 (1.36), 4.737 (1.44), 4.772 ( 1.34), 4.781 (2.09), 4.792 (1.37), 5.001 (0.77), 5.042 (8.22), 5.049 (6.72), 5.091 (0.65), 5.260 (1.10), 5.391 (1.28), 5.510 (0.78), 7.883 ( 0.53), 7.907 (12.15), 7.927 (0.85), 8.632 (4.85). Example 223 (5RS,8RS)-8-Methyl-2-(4-methylbenzyl)-5-(pyrrolidin-1-ylcarbonyl)-5,6,7,8-tetrahydro[1,2,4]triazolo[ 4,3-a]pyridin-3(2H)-one (mixture of diastereomer; 4 isomers)

[01261] (5RS,8RS)-8-Methyl-2-(4-methylbenzyl)-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4 ,3-a]pyridine-5-carboxylic acid (mixture of diastereomer; 4 isomers) (27.3 mg, 90.6 μmol) was initially loaded into DMF (1.5 mL) and dichloromethane (750 μL) at room temperature . Subsequently, 1-[bis(dimethylamino)methylene]-1H-benzotriazol-1-ium 3-oxide hexafluorophosphate (44.7 mg, 118 μmol) and N,N-diisopropylethylamine (22 μl, 130 μmol) were added. After stirring for 15 minutes, pyrrolidine (9.1 μl, 110 μmol) was added and the reaction mixture was stirred at room temperature overnight. The solvent was removed under reduced pressure, and the residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/water gradient). The product-containing fractions were concentrated under reduced pressure and 18.0 mg (55% possibility) of the title compound were obtained as a mixture of diastereomers. LC-MS (Method 1): Rt = 1.10 min; MS (ESIpos): m /z = 355 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.008 (0.89), 0.008 (0.80), 1.166 (8.74), 1.183 ( 9.03), 1.380 (0.42), 1.396 (1.31), 1.411 (0.71), 1.432 (0.51), 1.442 (0.50), 1.528 (1.03), 1.755 (1.12), 1.770 (2.91), 1.787 (4.30), 1.804 ( 3.36), 1.821 (0.86), 1.892 (0.84), 1.908 (2.40), 1.925 (2.98), 1.942 (1.80), 1.958 (0.48), 2.040 (1.84), 2.049 (2.25), 2.058 (1.75), 2.271 ( 16.00), 2.523 (0.60), 2.663 (0.69), 2.677 (0.96), 2.693 (1.06), 2.708 (0.93), 2.723 (0.55), 3.220 (0.49), 3.237 (1.05), 3.250 (1.04), 3.267 ( 1.83), 3.284 (0.98), 3.335 (2.01), 3.347 (0.81), 3.353 (1.05), 3.364 (1.12), 3.382 (0.52), 3.428 (0.55), 3.445 (1.19), 3.453 (0.91), 3.463 ( 0.75), 3.470 (1.52), 3.487 (0.68), 3.578 (0.69), 3.595 (1.41), 3.603 (0.76), 3.611 (0.84), 3.619 (1.12), 3.636 (0.52), 4.707 (1.64), 4.738 ( 1.56), 4,746 (5.65), 4,757 (1.42), 4,799 (3.57), 4,839 (1.59), 7,097 (1.28), 7,118 (10.61), 7,124 (9.75), 7,145 (1.25). Example 224 (5RS,7RS)-7-Methyl-2-(4-methylbenzyl)-5-(pyrrolidin-1-ylcarbonyl)-5,6,7,8-tetrahydro[1,2,4]triazolo[ 4,3-a]pyridin-3(2H)-one (mixture of diastereomer; 4 isomers)

[01262] (5RS,7RS)-7-Methyl-2-(4-methylbenzyl)-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4 ,3-a]pyridine-5-carboxylic acid (60.0 mg, 199 μmol) was initially loaded together with pyrrolidine (25 μl, 300 μmol) in pyridine/DMF (5/1) (3.0 mL) at temperature environment. Subsequently, O-(7-azabenzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate (121 mg, 319 μmol) was added, and the reaction mixture was stirred at room temperature for 5 hours. The solvent was removed under reduced pressure, and the residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/water gradient). The product-containing fractions were concentrated under reduced pressure and 23.0 mg (29% possibility) of the title compound were obtained as a diastereomer mixture. LC-MS (Method 1): Rt = 1.06 min; MS (ESIpos): m /z = 355 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: 1.013 (3.80), 1.030 (3.91), 1.106 (7.23), 1.329 (0.57 ), 1.359 (0.58), 1.771 (1.01), 1.788 (1.80), 1.805 (1.54), 1.814 (0.95), 1.860 (0.50), 1.882 (0.68), 1.899 (1.42), 1.916 (1.58), 1.931 (0.91 ), 2.111 (0.74), 2.141 (0.57), 2.151 (0.79), 2.181 (0.84), 2.270 (10.66), 2.611 (0.49), 2.616 (0.51), 2.646 (0.40), 2.651 (0.45), 2.657 (0.43 ), 3.076 (2.31), 3.226 (0.41), 3.243 (0.65), 3.256 (0.57), 3.273 (0.92), 3.290 (0.45), 3.339 (0.47), 3.356 (0.93), 3.374 (0.50), 3.386 (0.56 ), 3.468 (0.59), 3.476 (0.46), 3.493 (0.74), 3.634 (0.73), 3.651 (0.41), 3.659 (0.56), 4.601 (0.62), 4.617 (0.73), 4.628 (0.71), 4.643 (0.61 ), 4,718 (4.78), 7,128 (16.00). Example 225 (5RS,7RS)-2-(4-Methylbenzyl)-5-(pyrrolidin-1-ylcarbonyl)-7-(trifluoromethyl)-5,6,7,8-tetrahydro[1,2,4] triazolo[4,3-a]pyridin-3(2H)-one (diastereomer 1, racemate)

[01263] 5RS,7RS)-2-(4-Methylbenzyl)-3-oxo-7-(trifluoromethyl)- 2,3,5,6,7,8-hexahydro[1,2,4]triazolo[ 4,3-a]pyridine-5-carboxylic acid (diastereomer mixture; 4 isomers) (98.0 mg, 276 μmol) was initially loaded together with pyrrolidine (25 μl, 300 μmol) in pyridine/DMF (5/1 ) (2.0 mL) at room temperature. Subsequently, O-(7-azabenzotriazoM-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate (115 mg, 303 μmol) was added, and the reaction mixture was stirred at room temperature for 2 hours. The solvent was removed under reduced pressure, and the residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/water gradient). The fractions containing the product were concentrated under reduced pressure and 37.4 mg (33% possibility) of diastereomer 1 (racemate) and 8.7 mg (8% possibility) of diastereomer 2 (racemate) of the title compound were obtained. . LC-MS (Method 3): Rt = 1.69 min; MS (ESIpos): m /z = 409 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.008 (0.44), 0.008 (0.45), 1.777 (0.99), 1.794 ( 1.60), 1.806 (1.64), 1.822 (1.20), 1.839 (0.52), 1.907 (0.75), 1.924 (2.35), 1.941 (3.00), 1.958 (1.73), 1.975 (0.43), 2.167 (0.74), 2.182 ( 0.75), 2.197 (1.28), 2.210 (2.06), 2.272 (15.46), 2.523 (0.50), 2.643 (0.56), 2.676 (1.24), 2.687 (1.24), 2.719 (0.94), 3.379 (0.80), 3.396 ( 0.43), 3.534 (0.43), 3.551 (0.96), 3.559 (0.83), 3.568 (0.62), 3.576 (1.44), 3.593 (0.64), 3.631 (0.66), 3.648 (1.38), 3.655 (0.63), 3.665 ( 0.77), 3.673 (0.92), 4.723 (0.92), 4.762 (4.01), 4.782 (3.97), 4.820 (0.94), 4.937 (1.52), 4.947 (1.32), 7.104 (0.72), 7.112 (0.47), 7.127 ( 16.00), 7.150 (0.70). Example 226 (5RS,7RS)-2-(4-Methylbenzyl)-5-(pyrrolidin-1-ylcarbonyl)-7-(trifluoromethyl)-5,6,7,8-tetrahydro[1,2,4] triazolo[4,3-a]pyridin-3(2H)-one (diastereomer 2, racemate)

[01264] (5RS,7RS)-2-(4-Methylbenzyl)-3-oxo-7-(trifluoromethyl)- 2,3,5,6,7,8-hexahydro[1,2,4]triazole [4,3-a]pyridine-5-carboxylic acid (diastereomer mixture; 4 isomers) (98.0 mg, 276 μmol) was initially loaded together with pyrrolidine (25 μl, 300 μmol) in pyridine/DMF (5/ 1) (2.0 mL) at room temperature. Subsequently, O-(7-azabenzotriazol-1-yl)-N,N,N',N-tetramethyluronium hexafluorophosphate (115 mg, 303 μmol) was added, and the reaction mixture was stirred at room temperature for 2 hours. . The solvent was removed under reduced pressure, and the residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/water gradient). The fractions containing the product were concentrated under reduced pressure and 37.4 mg (33% possibility) of diastereomer 1 (racemate) and 8.7 mg (8% possibility) of diastereomer 2 (racemate) of the title compound were obtained. . LC-MS (Method 3): Rt = 1.62 min; MS (ESIpos): m /z = 409 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.008 (0.69), 0.008 (0.74), 1.665 (0.67), 1.692 ( 0.67), 1.779 (0.59), 1.785 (0.66), 1.797 (0.98), 1.802 (1.02), 1.817 (0.88), 1.910 (1.28), 1.927 (1.65), 1.944 (0.95), 2.274 (9.27), 2.634 ( 0.46), 2.665 (0.67), 2.674 (0.77), 2.706 (0.77), 2.863 (0.57), 3.263 (0.51), 3.276 (0.51), 3.293 (0.94), 3.354 (0.43), 3.371 (0.81), 3.389 ( 0.49), 3.401 (0.51), 3.555 (0.51), 3.562 (0.47), 3.579 (0.82), 3.637 (0.80), 3.654 (0.44), 3.661 (0.50), 4.710 (0.65), 4.724 (0.78), 4.745 ( 4.83), 7.141 (16.00). Example 227 (5RS,7RS)-2-[(6-Chloropyridin-3-yl)methyl]-5-(pyrrolidin-1-ylcarbonyl)-7-(trifluoromethyl)-5,6,7,8-tetrahydro [1,2,4]triazolo[4,3-a]pyridin-3(2H)-one (diastereomer 1, racemate)

[01265] (5RS,7RS)-2-[(6-Chloropyridin-3-yl)methyl]-3-oxo-7-(trifluoromethyl)-2,3,5,6,7,8-hexahydro[ 1,2,4]triazolo[4,3-a]pyridine-5-carboxylic acid (mixture of diastereomer; 4 isomers) (88.0 mg, 234 μmol) was initially loaded into THF (3.0 mL) at temperature environment. Subsequently, HBTU (115 mg, 304 μmol) and N,N-diisopropylethylamine (200 μl, 1.2 mmol) were added. After stirring for 15 minutes, pyrrolidine (23 μl, 280 μmol) was added and the reaction mixture was stirred at room temperature overnight. The reaction mixture was mixed with water and ethyl acetate, and the organic phase was removed. The organic phase was washed with saturated aqueous sodium chloride solution, dried over sodium sulfate and filtered, and the filtrate was concentrated. The residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: gradient (acetonitrile/water with 0.1% formic acid). After separation, 10.2 mg (10% possibility) of diastereomer 1 (racemate), which elutes first, and 43.7 mg (44% chance) of diastereomer 2 (racemate), which elutes later, were isolated. Diastereomer 1, racemate: LC-MS (Method 3): Rt = 1, 37 min; MS (ESIpos): m /z = 430 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (1.19), -0.008 (9.63), 0.008 (8.89) ), 0.146 (1.11), 1.635 (1.26), 1.666 (2.81), 1.693 (2.74), 1.726 (1.48), 1.778 (2.37), 1.785 (2.74), 1.795 (3.93), 1.802 (4.00), 1.818 (3.19 ), 1,893 (1.56), 1,909 (5.48), 1,926 (6.89), 1,944 (4.00), 2,327 (2.07), 2,366 (1.85), 2,523 (8.67), 2,657 (2.15), 2,669 (2.37), 2,688 (2.52 ), 2,697 (3.04), 2,710 (2.30), 2,729 (3.41), 2,876 (2.44), 2,911 (1.56), 3,012 (1.19), 3,264 (2.44), 3,276 (2.59), 3,351 (2.52), 3,369 (3.70 ), 3,386 (2.30), 3,399 (2.37), 3,417 (1.26), 3,569 (2.15), 3,586 (3.63), 3,611 (2.00), 3,627 (3.63), 3,652 (1.93), 4,711 (2.74), 4,725 (3.04 ), 4,738 (2.81), 4,753 (2.44), 4,884 (16.00), 7,516 (6.22), 7,536 (7.63), 7,720 (4.52), 7,727 (4.44), 7,741 (3.85), 7,747 (3.85), 8,328 (6.00 ), 8,334 (5.70). Example 228 (5RS,7RS)-2-[(6-Chloropyridin-3-yl)methyl]-5-(pyrrolidin-1-ylcarbonyl)-7-(trifluoromethyl)-5,6,7,8-tetrahydro [1,2,4]triazolo[4,3-a]pyridin-3(2H)-one (diastereomer 2, racemate)

[01266] (5RS,7RS)-2-[(6-Chloropyridin-3-yl)methyl]-3-oxo-7-(trifluoromethyl)-2,3,5,6,7,8-hexahydro[ 1,2,4]triazolo[4,3-a]pyridine-5-carboxylic acid (mixture of diastereomer; 4 isomers) (88.0 mg, 234 μmol) was initially loaded into THF (3.0 mL) at temperature environment. Subsequently, HBTU (115 mg, 304 μmol) and N,N-diisopropylethylamine (200 μl, 1.2 mmol) were added. After stirring for 15 minutes, pyrrolidine (23 μl, 280 μmol) was added and the reaction mixture was stirred at room temperature overnight. The reaction mixture was mixed with water and ethyl acetate, and the organic phase was removed. The organic phase was washed with saturated aqueous sodium chloride solution, dried over sodium sulfate and filtered, and the filtrate was concentrated. The residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: gradient (acetonitrile/water with 0.1% formic acid). After separation, 10.2 mg (10% possibility) of diastereomer 1 (racemate), which elutes first, and 43.7 mg (44% chance) of diastereomer 2 (racemate), which elutes later, were isolated. Diastereomer 2, racemate: LC-MS (Method 3): Rt = 1, 45 min; MS (ESIpos): m /z = 430 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (0.54), -0.008 (4.44), 0.008 (3.96) ), 0.146 (0.54), 1.778 (2.01), 1.795 (3.23), 1.805 (3.35), 1.822 (2.59), 1.906 (1.50), 1.923 (4.73), 1.939 (5.81), 1.957 (3.32), 2.173 (1.47 ), 2,189 (1.53), 2,203 (1.92), 2,218 (4.02), 2,327 (1.02), 2,366 (0.70), 2,523 (3.03), 2,667 (1.95), 2,694 (2.49), 2,705 (2.59), 2,734 (2.08 ), 2,962 (3.00), 3,000 (1.92), 3,010 (1.47), 3,250 (0.86), 3,268 (1.72), 3,280 (2.27), 3,297 (5.91), 3,331 (3.03), 3,349 (3.32), 3,366 (2.17 ), 3.377 (1.72), 3.395 (0.99), 3.532 (0.93), 3.549 (1.98), 3.557 (1.79), 3.574 (3.10), 3.591 (1.31), 3.625 (1.44), 3.641 (2.87), 3.658 (1.63 ), 3.666 (1.85), 3.683 (0.93), 4.914 (16.00), 4.949 (3.26), 4.964 (2.78), 7.510 (5.78), 7.530 (7.41), 7.692 (4.12), 7.699 (4.12), 7.713 (3.32 ), 7,719 (3.29), 8,299 (5.72), 8,305 (5.52). Example 229 (5RS,7RS)-2-[(6-Chloropyridin-3-yl)methyl]-5-(pyrrolidin-1-ylcarbonyl)-7-(trifluoromethyl)-5,6,7,8-tetrahydro [1,2,4]triazolo[4,3-a]pyridin-3(2H)-one (enantiomer 1)

[01267] (5RS,7RS)-2-[(6-Chloropyridin-3-yl)methyl]-5-(pyrrolidin-1-ylcarbonyl)-7-(trifluoromethyl)-5,6,7,8-tetra- hydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one (diastereomer 2, racemate) was separated by chiral preparatory HPLC [sample preparation: 42 mg dissolved in 2 mL of ethanol and 2 mL of n-heptane; injection volume: 0.40 mL; column: Daicel Chiralpak® IB 5 μm, 250 x 20 mm; eluent: n-heptane/ethanol 50:50; flow rate: 15 ml/min; temperature 40°C; UV detection: 220 nm]. After separation, 14.7 mg of enantiomer 1, which elutes first, and 16.1 mg of enantiomer 2, which elutes later, were isolated. Enantiomer 1:

[01268] Analytical chiral HPLC: Rt = 4.99 min, ee = 99% [column: Daicel Chiralpak® IB, 250 x 4.6 mm; eluent: i-hexane/ethanol 50:50; flow rate: 1 ml/min; UV detection: 220 nm]. LC-MS (Method 3): Rt = 1.47 min; MS (ESIpos): m /z = 430 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (1.30), -0.008 (11.16), 0.008 (10.55), 0.146 (1.30) (1.47) (2.25), 2734 (2.16), 2962 (3.11), 2998 (1.90), 3010 (1.47), 3250 (1.12), 3267 (2.34), 3279 (2.77), 3348 (4.67), 3365 (2.59), 3377 (2.08) (1.99) (2.94), 8,298 (4.15), 8,304 (4.24). Example 230 (5RS,7RS)-2-[(6-Chloropyridin-3-yl)methyl]-5-[(3,3-difluoropyrrolidin-1-yl)carbonyl]-7-(trifluoromethyl)-5,6, 7,8-tetrahydro[1,2,4]triazolo[4,3- a]pyridin-3(2H)-one (diastereomer 2, racemate)

[01269] (5RS,7RS)-2-[(6-Chloropyridin-3-yl)methyl]-3-oxo-7-(trifluoromethyl)-2,3,5,6,7,8-hexahydro[ 1,2,4]triazolo[4,3-a]pyridine-5-carboxylic acid (mixture of diastereomer; 4 isomers) (88.0 mg, 234 μmol) was initially loaded into THF (3.0 mL) at temperature environment. Subsequently, HBTU (115 mg, 304 μmol) and N,N-diisopropylethylamine (200 μl, 1.2 mmol) were added. After stirring for 15 minutes, 3,3-difluoropyrrolidine hydrochloride (40.2 mg, 280 μmol) was added and the reaction mixture was stirred at room temperature overnight. The reaction mixture was mixed with water and ethyl acetate, and the organic phase was removed. The organic phase was washed with saturated aqueous sodium chloride solution, dried over sodium sulfate and filtered, and the filtrate was concentrated. The residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: gradient (acetonitrile/water with 0.1% formic acid). After separation, 10.2 mg of diastereomer 1 (racemate) (9% of possibility), which elutes first, and 48 mg (44% possibility) of diastereomer 2 (racemate), which elutes later, were isolated. Diastereomer 2, racemate: LC-MS (Method 3): Rt = 1.56 min; MS (ESIpos): m /z = 466 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.008 (2.62), 0.008 (2.46), 2.112 (0.44), 2.129 ( 0.51), 2.148 (1.03), 2.164 (1.01), 2.179 (1.06), 2.189 (1.30), 2.205 (0.97), 2.220 (0.94), 2.236 (0.90), 2.259 (1.65), 2.278 (1.76), 2.311 ( 0.92), 2.327 (0.61), 2.366 (0.55), 2.374 (0.59), 2.394 (1.16), 2.412 (1.03), 2.424 (1.45), 2.440 (1.32), 2.461 (0.88), 2.523 (1.85), 2.563 ( 1.83), 2.581 (1.41), 2.601 (0.99), 2.619 (0.50), 2.678 (1.36), 2.686 (1.10), 2.707 (1.76), 2.716 (2.61), 2.725 (1.52), 2.747 (1.89), 2.755 ( 1.78), 2.901 (1.23), 2.970 (2.55), 3.010 (1.85), 3.534 (0.50), 3.545 (1.25), 3.565 (2.55), 3.578 (1.94), 3.596 (1.23), 3.609 (0.42), 3.710 ( 1.16), 3.750 (1.54), 3.779 (1.76), 3.814 (1.21), 3.889 (0.72), 3.897 (1.17), 3.914 (2.90), 3.932 (3.03), 3.951 (1.12), 4.130 (1.03), 4.157 ( 0.84), 4.173 (1.56), 4.200 (1.63), 4.234 (0.97), 4.878 (0.59), 4.920 (16.00), 4.951 (2.06), 4.964 (2.22), 5.029 (1.98), 5.042 (1.91), 7.512 ( 6.06), 7,532 (7.69), 7,695 (3.71), 7,701 (3.78), 7,715 (3.16), 7,722 (3.16), 8,299 (5.17), 8,305 (5.08). Example 231 (5RS,7RS)-2-[(6-Chloropyridin-3-yl)methyl]-5-[(3,3-difluoropyrrolidin-1-yl)carbonyl]-7-(trifluoromethyl)-5,6, 7,8-tetrahydro[1,2,4]triazolo[4,3- a]pyridin-3(2H)-one (enantiomer 1)

[01270] (5RS,7RS)-2-[(6-Chloropyridin-3-yl)methyl]-5-[(3,3-difluoropyrrolidin-1-yl)carbonyl]-7-(trifluoromethyl)-5,6 ,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one (diastereomer 2, racemate) was separated by chiral preparatory HPLC [sample preparation: 48 mg dissolved in 2 mL of ethanol and 1.5 mL of n-heptane; injection volume: 0.5 mL; column: Daicel Chiralpak® IE 5 μm, 250 x 20 mm; eluent: n-heptane/ethanol 40:60; flow rate: 15 ml/min; temperature 40°C; UV detection: 220 nm]. After separation, 16.7 mg of enantiomer 1, which elutes first, and 17.5 mg of enantiomer 2, which elutes later, were isolated. Enantiomer 1:

[01271] Analytical chiral HPLC: Rt = 5.80 min, ee = 99% [column: Daicel Chiralpak® IE 5 μm, 250 x 4.6 mm; eluent: i-hexane/ethanol 40:60; flow rate: 1 ml/min; UV detection: 220 nm]. LC-MS (Method 3): Rt = 1.56 min; MS (ESIpos): m /z = 466 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (1.25), -0.008 (10.99), 0.008 (10.43), 0.146 (1.25) (1.74) (1.18) (1.18) (1.81) (0.90) (3.83), 7,716 (3.20), 7,722 (3.20), 8,299 (5.29), 8,305 (5.08). Example 232 (5RS,7RS)-2-[(6-Chloropyridin-3-yl)methyl]-5-[(3,3-difluoropyrrolidin-1-yl)carbonyl]-7-(trifluoromethyl)-5,6, 7,8-tetrahydro[1,2,4]triazolo[4,3- a]pyridin-3(2H)-one (enantiomer 2)

[01272] (5RS,7RS)-2-[(6-Chloropyridin-3-yl)methyl]-5-[(3,3-difluoropyrrolidin-1-yl)carbonyl]-7-(trifluoromethyl)-5,6 ,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one (diastereomer 2, racemate) was separated by chiral preparatory HPLC [sample preparation: 48 mg dissolved in 2 mL of ethanol and 1.5 mL of n-heptane; injection volume: 0.5 mL; column: Daicel Chiralpak® IE 5 μm, 250 x 20 mm; eluent: n-heptane/ethanol 40:60; flow rate: 15 ml/min; temperature 40°C; UV detection: 220 nm]. After separation, 16.7 mg of enantiomer 1, which elutes first, and 17.5 mg of enantiomer 2, which elutes later, were isolated. Enantiomer 2:

[01273] Analytical chiral HPLC: Rt = 6.78 min, ee = 99% [column: Daicel Chiralpak® IE 5 μm, 250 x 4.6 mm; eluent: i-hexane/ethanol 40:60; flow rate: 1 ml/min; UV detection: 220 nm]. LC-MS (Method 3): Rt = 1.56 min; MS (ESIpos): m /z = 466 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (1.77), -0.008 (16.00), 0.008 (12.99), 0.146 (1.77) (6.75) (1.25) (2.18) (4.47), 7,533 (5.82), 7,695 (2.70), 7,701 (2.70), 7,716 (2.29), 7,722 (2.29), 8,299 (3.95), 8,305 (3.84). Example 233 (5RS,7RS)-5-[(3-Hydroxyazetidin-1-yl)carbonyl]-7-(trifluoromethyl)-2-{[6-(trifluoromethyl)pyridin-3-yl]methyl}-5,6 ,7,8-tetrahydro[1,2,4]triazolo[4,3- a]pyridin-3(2H)-one (diastereomer 1; 2 isomers)

[01274] (5RS,7RS)-3-Oxo-7-(trifluoromethyl)-2-{[6-(trifluoromethyl)pyridin-3-yl]methyl}-2,3,5,6,7,8-hexa -hydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylic acid (mixture of diastereomer; 4 isomers) (53.0 mg, 129 μmol) was initially loaded into dichloromethane (1.0 mL ) and DMF (2.0 mL) at 0°C. Subsequently, 1-[bis(dimethylamino)methylene]-1H-benzotriazol- 1-yl 3-oxide hexafluorophosphate (63.7 mg, 168 μmol) and N,N-diisopropylethylamine (59 μl, 340 μmol) were added. After stirring at 0°C for 60 minutes, azetidin-3-ol hydrochloride (17.0 mg, 155 μmol) was added and the reaction mixture was stirred at room temperature overnight. The solvent was removed under reduced pressure, and the residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/water gradient). The fractions containing the product were concentrated under reduced pressure and 20.5 mg (34% possibility) of the title compound were obtained. LC-MS (Method 3): Rt = 1.32 min; MS (ESIpos): m /z = 466 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.008 (2.82), 0.008 (2.65), 1.236 (0.44), 2.073 ( 0.95), 2.126 (0.46), 2.145 (1.11), 2.163 (1.78), 2.177 (3.07), 2.190 (4.53), 2.199 (4.11), 2.231 (0.66), 2.328 (0.52), 2.523 (1.78), 2.657 ( 1.32), 2.666 (1.33), 2.686 (1.72), 2.695 (2.51), 2.704 (1.73), 2.726 (1.98), 2.875 (0.84), 2.905 (1.25), 2.966 (3.44), 2.975 (2.41), 3.005 ( 2.56), 3.017 (2.01), 3.650 (2.51), 3.659 (1.87), 3.669 (1.95), 3.677 (2.75), 4.027 (1.52), 4.040 (1.57), 4.074 (2.71), 4.089 (2.90), 4.114 ( 1.38), 4.129 (1.25), 4.144 (1.26), 4.153 (1.29), 4.170 (1.07), 4.461 (0.99), 4.479 (2.15), 4.498 (3.22), 4.520 (2.29), 4.542 (3.24), 4.562 ( 1.86), 4,579 (0.71), 4,728 (2.11), 4,741 (3.29), 4,749 (2.58), 4,760 (1.45), 5,018 (1.29), 5,043 (10,99), 5,049 (11,28), 5,787 (0.60), 5,801 ( 0.60), 5.830 (3.51), 5.835 (3.85), 5.844 (4.03), 5.850 (3.07), 7.917 (16.00), 7.948 (0.54), 8.645 (5.51), 8.681 (0.49). Example 234 (5RS,7RS)-5-[(3-Hydroxyazetidin-1-yl)carbonyl]-7-(trifluoromethyl)-2-{[6-(trifluoromethyl)pyridin-3-yl]methyl}-5,6 ,7,8-tetrahydro[1,2,4]triazolo[4,3- a]pyridin-3(2H)-one (isomer 2)

[01275] (5RS,7RS)-5-[(3-Hydroxiazetidin-1-yl)carbonyl]-7-(trifluoromethyl)-2-{[6-(trifluoromethyl)pyridin-3-yl]methyl}-5, 6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one (diastereomer 1; 2 isomers) was separated by chiral preparatory HPLC [sample preparation: 20.5 mg dissolved in 1 mL of ethanol and 1 mL of isopropanol; injection volume: 0.5 mL; column: Daicel Chiralpak® IB 5 μm, 250 x 20 mm; eluent: n-heptane/ethanol 50:50; flow rate: 20 ml/min; temperature 25°C; UV detection: 220 nm]. After separation, 6.1 mg of isomer 1, which elutes first, and 7.4 mg of isomer 2, which elutes later, were isolated. Isomer 2:

[01276] Analytical chiral HPLC: Rt = 2.34 min, de = 100% [column: Daicel Chiralpak® IB-3-3 μm, 50 x 4.6 mm; eluent: i-hexane/i-propanol 50:50; flow rate: 1 ml/min; UV detection: 220 nm]. LC-MS (Method 3): Rt = 1.31 min; MS (ESIpos): m /z = 466 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: 1.456 (0.65), 2.145 (1.08), 2.162 (1.77), 2.189 (4.32 ), 2.230 (0.66), 2.328 (0.77), 2.366 (0.54), 2.657 (1.22), 2.665 (1.38), 2.694 (2.29), 2.704 (1.66), 2.726 (1.80), 2.916 (1.19), 2.965 (3.27 ), 2,994 (1.08), 3,005 (2.36), 3,017 (1.85), 3,650 (2.33), 3,659 (1.80), 3,677 (2.57), 4,026 (1.47), 4,039 (1.45), 4,073 (2.54), 4,089 (2.75 ), 4,113 (1.31), 4,129 (1.19), 4,144 (1.21), 4,153 (1.22), 4,170 (1.01), 4,460 (0.89), 4,478 (2.03), 4,498 (3.01), 4,521 (2.19), 4,542 (3.08 ), 4.561 (1.75), 4.578 (0.70), 4.728 (2.01), 4.740 (3.10), 5.019 (1.22), 5.042 (10.30), 5.049 (10.63), 5.784 (0.61), 5.798 (0.56), 5.831 (4.09 ), 5,841 (4.20), 7,917 (16.00), 8,645 (6.64), 8,682 (0.65). Example 235 (5RS,7RS)-5-{[(3S)-3-Fluoropyrrolidin-1-yl]carbonyl}-7-(trifluoromethyl)-2-{[6-(trifluoromethyl)pyridin-3-yl]methyl} -5,6,7,8-tetrahydro[1,2,4]triazolo[4,3- a]pyridin-3(2H)-one (mixture of diastereomer 1; 2 isomers)

[01277] (5RS,7RS)-3-Oxo-7-(trifluoromethyl)-2-{[6-(trifluoromethyl)pyridin-3-yl]methyl}-2,3,5,6,7,8-hexa -hydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylic acid (mixture of diastereomer; 4 isomers) (100 mg, 244 μmol) and (3S)-3-fluoropyrrolidine hydrochloride (33, 7 mg, 268 μmol) were initially loaded into dichloromethane (2.0 mL) and DMF (4.0 mL) at room temperature. Subsequently, N,N-diisopropylethylamine (100 μl, 580 μmol) and HBTU (120 mg, 317 μmol) were added. After stirring at room temperature for 30 minutes, saturated aqueous ammonium chloride solution and diethyl ether were added. The organic phase was removed and the aqueous phase was extracted twice with diethyl ether. The combined organic phases were washed with saturated aqueous sodium chloride solution, dried over sodium sulfate and filtered, and the filtrate was concentrated. The residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/gradient water). The fractions containing the product were concentrated under reduced pressure and 9.5 mg (8% possibility) of mixture of diastereomer 1 (2 isomers), which elutes first, and 81.0 mg (69% possibility) of mixture of diastereomer 2 (2 isomers), which elutes later, were isolated. Mixture of diastereomer 1 (2 isomers): LC-MS (Method 3): Rt = 1.52 min; MS (ESIpos): m /z = 482 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: 0.146 (0.42), 1.629 (0.89), 1.660 (1.92), 1.689 (2.14 ), 1,739 (1.24), 2,096 (1.31), 2,156 (1.24), 2,230 (1.52), 2,260 (1.60), 2,327 (1.24), 2,366 (0.89), 2,679 (2.18), 2,711 (3.02), 2,719 (3.47 ), 2.751 (3.40), 2.891 (3.33), 2.930 (2.23), 3.027 (1.55), 3.137 (0.61), 3.400 (0.80), 3.440 (0.66), 3.509 (0.80), 3.564 (0.92), 3.611 (1.71 ), 3.661 (1.60), 3.687 (2.09), 3.714 (1.57), 3.747 (1.20), 3.828 (0.82), 3.855 (0.84), 3.877 (1.66), 3.900 (1.67), 3.932 (1.62), 3.955 (1.78 ), 3.980 (0.98), 4.011 (0.71), 4.044 (0.52), 4.675 (0.85), 4.689 (0.85), 4.702 (0.96), 4.716 (0.89), 4.726 (0.92), 4.741 (2.04), 4.754 (2.02 ), 4.768 (1.95), 4.782 (1.10), 4.808 (0.89), 4.822 (0.98), 4.834 (1.01), 4.849 (0.80), 5.015 (16.00), 5.269 (1.05), 5.349 (0.71), 5.402 (1.38 ), 5.481 (0.75), 5.527 (0.75), 7.908 (3.10), 7.928 (10.34), 7.944 (6.14), 7.963 (1.78), 8.112 (0.42), 8.677 (8.03). Example 236 (5RS,7RS)-5-{[(3S)-3-Fluoropyrrolidin-1-yl]carbonyl}-7-(trifluoromethyl)-2-{[6-(trifluoromethyl)pyridin-3-yl]methyl} -5,6,7,8-tetrahydro[1,2,4]triazolo[4,3- a]pyridin-3(2H)-one (mixture of diastereomer 2; 2 isomers)

[01278] (5RS,7RS)-3-Oxo-7-(trifluoromethyl)-2-{[6-(trifluoromethyl)pyridin-3-yl]methyl}-2,3,5,6,7,8-hexa -hydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylic acid (mixture of diastereomer; 4 isomers) (100 mg, 244 μmol) and (3S)-3-fluoropyrrolidine hydrochloride (33, 7 mg, 268 μmol) were initially loaded into dichloromethane (2.0 mL) and DMF (4.0 mL) at room temperature. Subsequently, N,N-diisopropylethylamine (100 μl, 580 μmol) and 1-[bis(dimethylamino)methylene]-1H-benzotriazol-1-yl 3-oxide hexafluorophosphate (120 mg, 317 μmol) were added. After stirring at room temperature for 30 minutes, saturated aqueous ammonium chloride solution and diethyl ether were added. The organic phase was removed and the aqueous phase was extracted twice with diethyl ether. The combined organic phases were washed with saturated aqueous sodium chloride solution, dried over sodium sulfate and filtered, and the filtrate was concentrated. The residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/gradient water). The fractions containing the product were concentrated under reduced pressure and 9.5 mg (8% possibility) of mixture of diastereomer 1 (2 isomers), which elutes first, and 81.0 mg (69% possibility) of mixture of diastereomer 2 (2 isomers), which elutes later, were isolated. Mixture of diastereomer 2 (2 isomers): LC-MS (Method 3): Rt = 1.59 min; MS (ESIpos): m /z = 482 [M+H]+ ¹H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.008 (1.65), 0.008 (1.33), 2.125 (0.90), 2.141 ( 1.33), 2.160 (1.40), 2.171 (1.70), 2.205 (1.37), 2.215 (1.80), 2.227 (2.15), 2.236 (2.62), 2.248 (2.33), 2.277 (1.60), 2.293 (1.58), 2.328 ( 0.94), 2.366 (0.44), 2.518 (1.76), 2.523 (1.38), 2.670 (0.51), 2.675 (0.45), 2.686 (0.78), 2.695 (0.80), 2.710 (1.42), 2.724 (2.01), 2.734 ( 1.28), 2.755 (1.22), 2.763 (1.34), 2.890 (0.98), 2.925 (0.89), 2.981 (2.29), 3.019 (1.52), 3.354 (0.76), 3.380 (0.82), 3.408 (0.70), 3.434 ( 0.43), 3.443 (0.41), 3.519 (0.48), 3.530 (0.61), 3.541 (0.44), 3.570 (0.90), 3.592 (0.74), 3.620 (1.36), 3.643 (1.74), 3.672 (1.58), 3.689 ( 0.92), 3.700 (0.92), 3.738 (0.40), 3.765 (0.48), 3.796 (0.63), 3.831 (0.52), 3.852 (1.09), 3.884 (0.51), 3.892 (0.68), 3.930 (0.43), 3.964 ( 0.61), 3.990 (1.28), 4.017 (0.63), 4.054 (0.48), 4.922 (0.72), 4.937 (0.76), 4.971 (1.02), 4.986 (1.01), 5.017 (0.52), 5.048 (12.85), 5.073 ( 0.76), 5.084 (1.10), 5.269 (0.96), 5.358 (0.56), 5.403 (1.14), 5.490 (0.53), 5.524 (0.47), 7.919 (16.00), 8.644 (4.92). Example 237 (5S,7R)-5-{[(3S)-3-Fluoropyrrolidin-1-yl]carbonyl}-7-(trifluoromethyl)-2-{[6-(trifluoromethyl)pyridin-3-yl]methyl} -5,6,7,8-tetrahydro[1,2,4]triazolo[4,3- a]pyridin-3(2H)-one (isomer 1)

[01279] (5RS,7RS)-5-{[(3S)-3-Fluoropyrrolidin-1-yl]carbonyl}-7-(trifluoromethyl)-2-{[6-(trifluoromethyl)pyridin-3-yl]methyl }-5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one (mixture of diastereomer 2; 2 isomers) was separated by preparatory HPLC chiral [sample preparation: 66 mg dissolved in 6 mL isopropanol; injection volume: 0.5 mL; column: Daicel Chiralpak® IB 5 μm, 250 x 20 mm; eluent: n-heptane/isopropanol 40:60; flow rate: 15 ml/min; temperature 25°C; UV detection: 210 nm]. After separation, 28.8 mg of (5S,7R)-5-{[(3S)-3-fluoropyrrolidin-1-yl]carbonyl}-7-(trifluoromethyl)-2-{[6-(trifluoromethyl) were isolated )pyridin-3-yl]methyl}-5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one (isomer 1), which elutes first and 28.8 mg of isomer 2, which elutes later. Isomer 1: Specific rotation: +42.51 (589 nm, 0.5450 g/100 cm3 MeOH)

[01280] Analytical chiral HPLC: Rt = 1.38 min, de = 100% [column: Daicel Chiralpak® IB-3-3 μm, 50 x 4.6 mm; eluent: i-hexane/i-propanol 50:50; flow rate: 1 ml/min; UV detection: 220 nm]. LC-MS (Method 3): Rt = 1.59 min; MS (ESIpos): m /z = 482 [M+H]+ ¹H-NMR (400 MHz, DMSO-d6) δ [ppm]: 0.008 (2.13), 1.261 (0.42), 2.108 (0.76), 2.120 (0.83 ), 2,143 (1.30), 2,172 (2.16), 2,204 (1.57), 2,215 (1.43), 2,235 (1.93), 2,250 (1.89), 2,295 (2.57), 2,328 (1.22), 2,523 (1.13), 2,682 (1.10 ), 2.697 (0.67), 2.710 (1.91), 2.721 (2.02), 2.735 (1.15), 2.750 (1.64), 2.764 (1.04), 2.925 (1.09), 2.934 (1.13), 2.946 (1.01), 2.954 (0.95 ), 2.981 (3.14), 3.018 (1.94), 3.029 (1.47), 3.346 (0.77), 3.356 (1.00), 3.375 (0.96), 3.384 (0.72), 3.402 (0.97), 3.434 (0.80), 3.443 (0.80 ), 3.497 (0.57), 3.505 (0.62), 3.533 (0.87), 3.541 (0.80), 3.623 (0.85), 3.646 (2.19), 3.674 (2.40), 3.691 (1.42), 3.700 (1.79), 3.716 (0.76 ), 3.738 (0.78), 3.766 (0.41), 3.774 (0.45), 3.799 (0.64), 3.806 (0.65), 3.831 (0.97), 3.853 (1.74), 3.877 (0.84), 3.893 (0.73), 3.901 (0.69 ), 3.930 (0.83), 3.960 (0.62), 3.987 (0.87), 4.019 (0.51), 4.924 (1.35), 4.937 (1.45), 4.972 (2.03), 4.986 (2.00), 5.004 (0.50), 5.016 (0.79 ), 5,045 (14.11), 5,269 (1.26), 5,394 (1.60), 5,401 (1.65), 5,524 (0.88), 7,919 (16.00), 7,943 (0.44), 8,644 (5.11). Example 238 (5RS,7RS)-2-[(6-Chloropyridin-3-yl)methyl]-5-[(3-fluoroazetidin-1-yl)carbonyl]-7-(trifluoromethyl)-5,6,7, 8-tetrahydro[1,2,4]triazolo[4,3- a]pyridin-3(2H)-one (diastereomer 1, racemate)

[01281] (5RS,7RS)-2-[(6-Chloropyridin-3-yl)methyl]-3-oxo-7-(trifluoromethyl)-2,3,5,6,7,8-hexahydro[ 1,2,4]triazolo[4,3-a]pyridine-5-carboxylic acid (mixture of diastereomer; 4 isomers) (88.0 mg, 234 μmol) was initially loaded into THF (3.0 mL) at temperature environment. Subsequently, HBTU (115 mg, 304 μmol) and N,N-diisopropylethylamine (200 μl, 1.2 mmol) were added. After stirring for 15 minutes, 3-fluoroazetidine hydrochloride (31.3 mg, 280 μmol) was added and the reaction mixture was stirred at room temperature overnight. The reaction mixture was mixed with water and ethyl acetate, and the organic phase was removed. The organic phase was washed with saturated aqueous sodium chloride solution, dried over sodium sulfate and filtered, and the filtrate was concentrated. The residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: gradient (acetonitrile/water with 0.1% formic acid). After separation, 7.90 mg (8% possibility) of diastereomer 1 (racemate), which elutes first, and 31 mg (30% chance) of diastereomer 2 (racemate), which elutes later, were isolated Diastereomer 1, racemate: LC-MS (Method 4): Rt = 0.72 min. ; MS (ESIpos): m /z = 434 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (1.51), -0.008 (16.00), 0.008 (12.99), 0.146 (1.62), 1.679 (1.16), 1.708 (1.86), 1.739 (1.28), 2.323 (1.86), 2.328 (2.20), 2.332 (1.62), 2.366 (2.43), 2.456 (1.39), 2.523 (7.77), 2,665 (1.97), 2,670 (2.55), 2,675 (2.09), 2,710 (3.94), 2,752 (2.32), 2,867 (2.32), 2,902 (1.28), 2,992 (0.93), 3,969 (0.70), 4,450 (2.67), 4,463 (2.55), 4,478 (2.90), 4,492 (2.09), 4,669 (0.70), 4,902 (6.96), 5,382 (0.70), 5,513 (0.70), 7,517 (3.13), 7,538 (4.06), 7,734 (2.32), 7,754 (1.97), 8,340 (3.36). Example 239 (5RS,7RS)-2-[(6-Chloropyridin-3-yl)methyl]-5-[(3-fluoroazetidin-1-yl)carbonyl]-7- (trifluoromethyl)-5,6,7,8-tetrahydro[1,2,4]triazolo[4,3- a]pyridin-3(2H)-one (diastereomer 2, racemate)

[01282] (5RS,7RS)-2-[(6-Chloropyridin-3-yl)methyl]-3-oxo-7-(trifluoromethyl)-2,3,5,6,7,8-hexahydro[ 1,2,4]triazolo[4,3-a]pyridine-5-carboxylic acid (mixture of diastereomer; 4 isomers) (88.0 mg, 234 μmol) was initially loaded into THF (3.0 mL) at temperature environment. Subsequently, HBTU (115 mg, 304 μmol) and N,N-diisopropylethylamine (200 μl, 1.2 mmol) were added. After stirring for 15 minutes, 3-fluoroazetidine hydrochloride (31.3 mg, 280 μmol) was added and the reaction mixture was stirred at room temperature overnight. The reaction mixture was mixed with water and ethyl acetate, and the organic phase was removed. The organic phase was washed with saturated aqueous sodium chloride solution, dried over sodium sulfate and filtered, and the filtrate was concentrated. The residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: gradient (acetonitrile/water with 0.1% formic acid). After separation, 7.90 mg (8% possibility) of diastereomer 1 (racemate), which elutes first, and 31 mg (30% possibility) of diastereomer 2 (racemate), which elutes later, were isolated Diastereomer 2, racemate: LC-MS (Method 4): Rt = 0.74 min. ; MS (ESIpos): m /z = 434 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.150 (1.12), -0.008 (9.92), 0.008 (7.26), 0.146 (0.94), 2.187 (2.13), 2.221 (2.54), 2.253 (3.31), 2.327 (1.83), 2.366 (1.59), 2.524 (5.08), 2.670 (2.24), 2.684 (3.19), 2.696 (3.25), 2,710 (1.83), 2,725 (2.60), 2,968 (5.90), 3,003 (3.66), 3,017 (2.36), 3,978 (1.59), 4,039 (1.83), 4,287 (1.71), 4,427 (2.13), 4,460 (1.83), 4,488 (2.07), 4,737 (5.90), 4,751 (5.49), 4,919 (16.00), 5,358 (1.30), 5,502 (1.24), 7,510 (6.85), 7,531 (8.56), 7,701 (5.73), 7,708 (3.31), 7,721 (4.84), 8,307 (9.03). Example 240 (5RS,7RS)-2-[(6-Chloropyridin-3-yl)methyl]-5-[(3-fluoroazetidin-1-yl)carbonyl]-7- (trifluoromethyl)-5,6,7,8-tetrahydro[1,2,4]triazolo[4,3- a]pyridin-3(2H)-one (enantiomer 1)

[01283] (5RS,7RS)-2-[(6-Chloropyridin-3-yl)methyl]-5-[(3-fluoroazetidin-1-yl)carbonyl]-7-(trifluoromethyl)-5,6,7 ,8-tetrahydro[1,2,4]triazolo[4,3- a]pyridin-3(2H)-one (diastereomer 2, racemate) was separated by chiral preparatory HPLC [sample preparation: 30 mg dissolved in 2.5 mL of ethanol and 1.5 mL of n-heptane; injection volume: 0.7 mL; column: Daicel Chiralpak® IB 5 μm, 250 x 20 mm; eluent: n-heptane/ethanol 40:60; flow rate: 15 ml/min; temperature 40°C; UV detection: 220 nm]. After separation, 8 mg of enantiomer 1, which elutes first, and 8.8 mg of enantiomer 2, which elutes later, were isolated. Enantiomer 1:

[01284] Analytical chiral HPLC: Rt = 4.56 min, ee = 99% [column: Daicel Chiralpak® IB 5 μm, 250 x 4.6 mm; eluent: i-hexane/ethanol 50:50; flow rate: 1 ml/min; UV detection: 220 nm]. LC-MS (Method 3): Rt = 1.36 min; MS (ESIpos): m /z = 434 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.150 (1.23), 0.008 (9.60), 0.146 (0.98), 1.234 ( 0.80), 2.104 (0.74), 2.121 (0.98), 2.138 (1.85), 2.155 (2.34), 2.169 (2.22), 2.186 (2.15), 2.223 (2.58), 2.252 (3.32), 2.283 (1.23), 2.327 ( 2.28), 2.366 (2.15), 2.523 (9.23), 2.610 (0.49), 2.669 (2.71), 2.685 (3.38), 2.695 (3.38), 2.709 (2.65), 2.725 (2.58), 2.934 (1.91), 2.943 ( 2.09), 2.968 (5.97), 3.002 (3.57), 3.013 (2.40), 3.374 (0.68), 3.402 (0.55), 3.950 (1.29), 3.977 (1.60), 4.006 (1.48), 4.039 (1.91), 4.207 ( 0.92), 4.219 (0.98), 4.235 (1.60), 4.251 (1.78), 4.261 (1.54), 4.279 (1.42), 4.287 (1.72), 4.304 (1.54), 4.333 (0.68), 4.398 (1.66), 4.423 ( 2.15), 4.459 (1.72), 4.484 (2.03), 4.621 (0.80), 4.633 (0.98), 4.645 (0.86), 4.671 (1.42), 4.687 (1.60), 4.713 (1.60), 4.736 (6.09), 4.751 ( 5.29) 8.25), 7,701 (5.54), 7,721 (4.49), 7,727 (2.77), 8,307 (8.31). Example 241 (5RS,7RS)-2-[(6-Chloropyridin-3-yl)methyl]-5-{[(3S)-3-fluoropyrrolidin-1-yl]carbonyl}-7-(trifluoromethyl)-5, 6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one (mixture of diastereomer 1; 2 isomers)

[01285] (5RS,7RS)-2-[(6-Chloropyridin-3-yl)methyl]-3-oxo-7-(trifluoromethyl)-2,3,5,6,7,8-hexahydro[ 1,2,4]triazolo[4,3-a]pyridine-5-carboxylic acid (mixture of diastereomer; 4 isomers) (88.0 mg, 234 μmol) was initially loaded into THF (3.0 mL) at temperature environment. Subsequently, HBTU (115 mg, 304 μmol) and N,N-diisopropylethylamine (200 μl, 1.2 mmol) were added. After stirring for 15 minutes, (3S)-3-fluoropyrrolidine hydrochloride (35.2 mg, 280 μmol) was added and the reaction mixture was stirred at room temperature overnight. The reaction mixture was mixed with water and ethyl acetate, and the organic phase was removed. The organic phase was washed with 10% aqueous citric acid solution and saturated aqueous sodium chloride solution, dried over sodium sulfate and filtered, and the filtrate was concentrated. The residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: gradient (acetonitrile/water with 0.1% formic acid). After separation, 11.2 mg (30% possibility) of mixture of diastereomer 1 (2 isomers), which elutes first, and 54 mg (30% possibility) of mixture of diastereomer 2 (2 isomers), which elutes later, were isolated Mixture of diastereomer 1 (2 isomers): LC-MS (. Method 4): Rt = 0.74 min; MS (ESIpos): m /z = 448 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (1.86), - 0.033 (0.47), -0.025 (0.56), -0.022 (0.65), -0.008 (16.00), 0.008 (14.19), 0.018 (0.98), 0.146 (1.86), 1.620 (0.42), 1.651 (1.07), 1.664 ( 0.37), 1.681 (1.07), 1.695 (0.70), 1.704 (0.74), 1.711 (0.60), 1.731 (0.65), 2.051 (0.33), 2.094 (0.65), 2.111 (0.65), 2.124 (0.65), 2.156 ( 0.56), 2.211 (0.60), 2.226 (0.70), 2.259 (0.79), 2.323 (1.21), 2.327 (1.58), 2.332 (1.16), 2.366 (1.35), 2.523 (5.30), 2.578 (0.60), 2.589 ( 0.56), 2.594 (0.56), 2.670 (2.70), 2.702 (1.49), 2.710 (3.26), 2.742 (1.86), 2.882 (1.77), 2.922 (1.21), 2.999 (0.74), 3.019 (0.93), 3.043 ( 0.60), 3.271 (0.51), 3.351 (0.88), 3.368 (0.74), 3.379 (0.47), 3.399 (0.51), 3.426 (0.42), 3.436 (0.37), 3.506 (0.42), 3.514 (0.42), 3.525 ( 0.42), 3.534 (0.37), 3.556 (0.56), 3.583 (0.47), 3.608 (0.98), 3.622 (0.74), 3.636 (0.65), 3.649 (0.74), 3.656 (0.88), 3.682 (1.07), 3.690 ( 0.70), 3.707 (0.70), 3.718 (0.60), 3.745 (0.60), 3.792 (0.37), 3.824 (0.60), 3.832 (0.37), 3.849 (0.47), 3.871 (0.74), 3.894 (0.84), 3.910 ( 0.47), 3.919 (0.70), 3.927 (0.88), 3.954 (0.88), 3.974 (0.51), 4.005 (0.37), 4.664 (0.42), 4.678 (0.51), 4.691 (0.47), 4.706 (0.51), 4.714 ( 0.60), 4.729 (1.07), 4.743 (1.02), 4.756 (1.07), 4.771 (0.56), 4.796 (0.51), 4.810 (0.56), 4.823 (0.56), 4.838 (0.60), 4.890 (9.02), 4.930 ( 0.37) 2.47), 7,733 (1.81), 7,739 (1.40), 7,746 (2.09), 7,754 (1.44), 8,332 (3.49). Example 242 (5RS,7RS)-2-[(6-Chloropyridin-3-yl)methyl]-5-{[(3S)-3-fluoropyrrolidin-1-yl]carbonyl}-7-(trifluoromethyl)-5, 6,7,8-tetrahydro[1,2,4]triazolo[4,3- a]pyridin-3(2H)-one (mixture of diastereomer 2; 2 isomers)

[01286] (5RS,7RS)-2-[(6-Chloropyridin-3-yl)methyl]-3-oxo-7-(trifluoromethyl)-2,3,5,6,7,8-hexahydro[ 1,2,4]triazolo[4,3-a]pyridine-5-carboxylic acid (mixture of diastereomer; 4 isomers) (88.0 mg, 234 μmol) was initially loaded into THF (3.0 mL) at temperature environment. Subsequently, HBTU (115 mg, 304 μmol) and N,N-diisopropylethylamine (200 μl, 1.2 mmol) were added. After stirring for 15 minutes, (3S)-3-fluoropyrrolidine hydrochloride (35.2 mg, 280 μmol) was added and the reaction mixture was stirred at room temperature overnight. The reaction mixture was mixed with water and ethyl acetate, and the organic phase was removed. The organic phase was washed with 10% aqueous citric acid solution and saturated aqueous sodium chloride solution, dried over sodium sulfate and filtered, and the filtrate was concentrated. The residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: gradient (acetonitrile/water with 0.1% formic acid). After separation, 11.2 mg (30% possibility) of mixture of diastereomer 1 (2 isomers), which elutes first, and 54 mg (30% possibility) of mixture of diastereomer 2 (2 isomers), which elutes later, were isolated Mixture of diastereomer 2 (2 isomers): LC-MS (. Method 4): Rt = 0.77 min; MS (ESIpos): m /z = 448 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (0.48), - 0.008 (4.34), 0.008 (3.69), 0.146 (0.48), 2.132 (1.45), 2.150 (1.72), 2.161 (2.14), 2.196 (1.69), 2.205 (2.00), 2.226 (3.10), 2.239 (2.31), 2,278 (2.03), 2,322 (1.03), 2,327 (1.07), 2,332 (0.72), 2,366 (0.52), 2,523 (2.31), 2,674 (1.48), 2,685 (0.86), 2,714 (2.38), 2,724 (1.38), 2,744 (1.41), 2,753 (1.45), 2,908 (1.03), 2,973 (2.66), 3,011 (1.69), 3,356 (1.03), 3,373 (1.00), 3,402 (0.83), 3,437 (0.55), 3,512 (0.55), 3,520 (0.62), 3,564 (1.07), 3,586 (0.86), 3,613 (1.62), 3,631 (1.83), 3,667 (1.90), 3,695 (1.14), 3,728 (0.45), 3,761 (0.52), 3,793 (0.66), 3.824 (0.55), 3.847 (1.21), 3.866 (0.62), 3.889 (0.72), 3.925 (0.45), 3.958 (0.59), 3.986 (1.45), 4.012 (0.76), 4.050 (0.55), 4.875 (0.45), 4,921 (16.00), 4,957 (1.34), 4,969 (1.21), 5,013 (1.00), 5,025 (0.97), 5,067 (1.07), 5,265 (1.03), 5,355 (0.62), 5,399 (1.31), 5,487 (0.59), 5,522 (0.52), 7,511 (6.45), 7,532 (8.07), 7,691 (2.24), 7,698 (4.55), 7,705 (2.69), 7,712 (2.00), 7,719 (3.76), 7,725 (2.14), 8,304 (5.21). Example 243 (5RS,7RS)-2-[(6-Chloropyridin-3-yl)methyl]-5-{[(3S)-3-fluoropyrrolidin-1-yl]carbonyl}-7-(trifluoromethyl)-5, 6,7,8-tetrahydro[1,2,4]triazolo[4,3- a]pyridin-3(2H)-one (isomer 1)

[01287] (5RS,7RS)-2-[(6-Chloropyridin-3-yl)methyl]-5-{[(3S)-3-fluoropyrrolidin-1-yl]carbonyl}-7-(trifluoromethyl)-5 ,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one (mixture of diastereomer 2; 2 isomers) was separated by chiral preparatory HPLC [preparation sample: 54 mg dissolved in 1 mL of ethanol and 1 mL of acetonitrile; injection volume: 0.01 mL; column: Daicel Chiralpak® IE 5 μm, 250 x 20 mm; eluent: n-heptane/ethanol 50:50; flow rate: 20 ml/min; temperature 30°C; UV detection: 220 nm]. After separation, 15.1 mg of isomer 1, which elutes first, and 15.9 mg of isomer 2, which elutes later, were isolated. Isomer 1:

[01288] Analytical chiral HPLC: Rt = 2.65 min, de = 99% [column: Daicel Chiralpak® IE, 50 x 4.6 mm; eluent: n-heptane/ethanol 50:50; flow rate: 1 ml/min; UV detection: 220 nm]. LC-MS (Method 3): Rt = 1.44 min; MS (ESIpos): m /z = 448 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (1.26), -0.008 (10.67), 0.008 (11.41), 0.147 (1.43) (1.84) (4.65) (2.12) (1.09) (1.43) (10.67), 7,692 (2.87), 7,698 (6.02), 7,705 (3.73), 7,712 (2.29), 7,719 (5.16), 7,725 (2.92), 8,300 (7.80). Example 244 (5RS,7RS)-2-[(6-Chloropyridin-3-yl)methyl]-5-{[(3S)-3-fluoropyrrolidin-1-yl]carbonyl}-7-(trifluoromethyl)-5, 6,7,8-tetrahydro[1,2,4]triazolo[4,3- a]pyridin-3(2H)-one (isomer 2)

[01289] (5RS,7RS)-2-[(6-Chloropyridin-3-yl)methyl]-5-{[(3S)-3-fluoropyrrolidin-1-yl]carbonyl}-7-(trifluoromethyl)-5 ,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one (mixture of diastereomer 2; 2 isomers) was separated by chiral preparatory HPLC [preparation sample: 54 mg dissolved in 1 mL of ethanol and 1 mL of acetonitrile; injection volume: 0.01 mL; column: Daicel Chiralpak® IE 5 μm, 250 x 20 mm; eluent: n-heptane/ethanol 50:50; flow rate: 20 ml/min; temperature 30°C; UV detection: 220 nm]. After separation, 15.1 mg of isomer 1, which elutes first, and 15.9 mg of isomer 2, which elutes later, were isolated. Isomer 2:

[01290] Analytical chiral HPLC: Rt = 3.15 min, d = 93% [Daicel Chiralpak® IE column, 50 x 4.6 mm; eluent: n-heptane/ethanol 50:50 flow rate: 1 ml/min; UV detection: 220 nm]. LC-MS (Method 3): Rt = 1.45 min; MS (ESIpos): m /z = 448 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ 2.116 (1.14), 2.132 (1.25), 2.150 2.196 (1.36), 2.205 (1.97), 2.226 2.327 (0.75), 2.366 (0.56), 2.523 2.684 (0.93), 2.705 (1.33), 2.715 2.753 (1.41), 2.895 (0.95), 2.964 3.014 (1.31), 3.355 (2.49), 3.373 3. 512 (0.76), 3.521 (0.79) .53), 5.027 5.274 (0.94), 5356 (0.94), 5406 7532 (5.71), 7691 (1.70), 7698 7719 (2.69), 7726 (1.59), 8304 (3. -3-yl)methyl]-5-{[(3R)-3-fluoropyrrolidin-1-yl]carbonyl}-7-(trifluoromethyl)-5,6,7,8-tetrahydro[1,2,4 ]triazolo[4,3- a]pyridin-3(2H)-one (mixture of diastereomer 2; 2 isomers)

[01291] (5RS,7RS)-2-[(6-Chloropyridin-3-yl)methyl]-3-oxo-7-(trifluoromethyl)-2,3,5,6,7,8-hexahydro[ 1,2,4]triazolo[4,3-a]pyridine-5-carboxylic acid (mixture of diastereomer; 4 isomers) (88.0 mg, 234 μmol) was initially loaded into THF (3.0 mL) at temperature environment. Subsequently, HBTU (115 mg, 304 μmol) and N,N-diisopropylethylamine (200 μl, 1.2 mmol) were added. After stirring for 15 minutes, (3R)-3-fluoropyrrolidine hydrochloride (35.2 mg, 280 μmol) was added and the reaction mixture was stirred at room temperature overnight. The reaction mixture was mixed with water and ethyl acetate, and the organic phase was removed. The organic phase was washed with 10% aqueous citric acid solution and saturated aqueous sodium chloride solution, dried over sodium sulfate and filtered, and the filtrate was concentrated. The residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: gradient (acetonitrile/water with 0.1% formic acid). After separation, 20.1 mg (10% possibility) of mixture of diastereomer 1 (2 isomers), which elutes first, and 46 mg (44% possibility) of mixture of diastereomer 2 (2 isomers), which elutes later, were isolated Mixture of diastereomer 2 (2 isomers): LC-MS (. Method 4): Rt = 0.77 min; MS (ESIpos): m /z = 448 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.150 (1.12), - 0.008 (10.52), 0.008 (7.16), 0.146 (1.12), 2.115 (1.37), 2.162 (2.24), 2.181 (1.43), 2.205 (2.05), 2.227 (3.24), 2.272 (1.99), 2.323 (1.99), 2,328 (2.18), 2,337 (0.93), 2,366 (1.06), 2,523 (4.54), 2,670 (2.30), 2,711 (2.49), 2,724 (1.43), 2,741 (1.43), 2,754 (1.49), 2,895 (1.18), 2,972 (2.61), 3,011 (1.74), 3,372 (1.31), 3,400 (0.93), 3,437 (0.62), 3,487 (0.81), 3,512 (0.75), 3,524 (0.81), 3,564 (1.18), 3,586 (1.00), 3,613 (1.74), 3,633 (1.87), 3,667 (1.99), 3,696 (1.18), 3,713 (0.68), 3,734 (0.62), 3,763 (0.56), 3,793 (0.87), 3,825 (0.56), 3,848 (1.25), 3,867 (0.75), 3,889 (0.68), 3,917 (0.56), 3,966 (0.68), 3,986 (1.56), 4,018 (0.75), 4,047 (0.81), 4,082 (0.56), 4,921 (16.00), 4,958 (1.31), 4,969 (1.25), 5,011 (1.25), 5,026 (1.25), 5,064 (1.06), 5,273 (1.06), 5,345 (0.68), 5,353 (0.75), 5,401 (1.56), 5,493 (0.68), 5,521 (0.68), 7,511 (6.91), 7,532 (8.53), 7,692 (2.24), 7,698 (4.61), 7,705 (2.86), 7,712 (2.12), 7,719 (3.98), 7,725 (2.49), 8,305 (6.16). Example 246 (5RS,7RS)-2-[(6-Chloropyridin-3-yl)methyl]-5-{[(3R)-3-fluoropyrrolidin-1-yl]carbonyl}-7-(trifluoromethyl)-5, 6,7,8-tetrahydro[1,2,4]triazolo[4,3- a]pyridin-3(2H)-one (isomer 1)

[01292] (5RS,7RS)-2-[(6-Chloropyridin-3-yl)methyl]-5-{[(3R)-3-fluoropyrrolidin-1-yl]carbonyl}-7-(trifluoromethyl)-5 ,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one (mixture of diastereomer 2; 2 isomers) was separated by chiral preparatory HPLC [preparation sample: 45.8 mg dissolved in 2.5 mL of ethanol, 2.5 mL of n-heptane and 1 mL of dichloromethane; injection volume: 0.4 mL; column: Daicel Chiralpak® IE 5 μm, 250 x 20 mm; eluent: n-heptane/ethanol 50:50; flow rate: 15 ml/min; temperature 40°C; UV detection: 220 nm]. After separation, 19.8 mg of isomer 1, which elutes first, and 16 mg of isomer 2, which elutes later, were isolated. Isomer 1:

[01293] Analytical chiral HPLC: Rt = 7.02 min, de = 99% [column: Daicel Chiralpak® IE 5 μm, 250 x 4.6 mm; eluent: n-heptane/ethanol 50:50; flow rate: 1 ml/min; UV detection: 220 nm]. LC-MS (Method 3): Rt = 1.42 min; MS (ESIpos): m /z = 448 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (0.66), -0.008 (6.74), 0.008 (5.83), 0.146 (0.71), 0.846 (0.63), 0.862 (0.58), 1.086 (0.66), 1.102 (0.79), 1.236 (0.76), 2.115 (1.06), 2.131 (1.22) (1.85) (1.01) (1.09) (0.94), 3683 (0.51), 3759 (0.51), 3783 (0.66), 3857 (0.48), 3880 (0.63), 3964 (0.76), 3986 (1.93), 4020 (0.74), 4046 (0.86), 4080 (0.61) (6.03), 7,691 (1.85), 7,698 (3.37), 7,705 (2.03), 7,712 (1.70), 7,719 (2.87), 7,726 (1.67), 8,304 (4.13). Example 247 (5RS,7RS)-2-[(6-Chloropyridin-3-yl)methyl]-5-{[(3R)-3-fluoropyrrolidin-1-yl]carbonyl}-7-(trifluoromethyl)-5, 6,7,8-tetrahydro[1,2,4]triazolo[4,3- a]pyridin-3(2H)-one (isomer 2)

[01294] (5RS,7RS)-2-[(6-Chloropyridin-3-yl)methyl]-5-{[(3R)-3-fluoropyrrolidin-1-yl]carbonyl}-7-(trifluoromethyl)-5 ,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one (mixture of diastereomer 2; 2 isomers) was separated by chiral preparatory HPLC [preparation sample: 45.8 mg dissolved in 2.5 mL of ethanol, 2.5 mL of n-heptane and 1 mL of dichloromethane; injection volume: 0.4 mL; column: Daicel Chiralpak® IE 5 μm, 250 x 20 mm; eluent: n-heptane/ethanol 50:50; flow rate: 15 ml/min; temperature 40°C; UV detection: 220 nm]. After separation, 19.8 mg of isomer 1, which elutes first, and 16 mg of isomer 2, which elutes later, were isolated. Isomer 2:

[01295] Analytical chiral HPLC: Rt = 9.14 min, de = 99% [column: Daicel Chiralpak® IE 5 μm, 250 x 4.6 mm; eluent: n-heptane/ethanol 50:50; flow rate: 1 ml/min; UV detection: 220 nm]. LC-MS (Method 3): Rt = 1.42 min; MS (ESIpos): m /z = 448 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (1.57), 0.008 (11.20), (0.73), 1.102 (0.59 ), 1.234 (1.22), (0.63), 2.108 (1.22), 2.133 (1.91), (2.23), 2.233 (2.40), 2.241 (2.71), (1.46), 2.590 (1.08), 2.672 (3.41), ( 3.83), 2.725 (1.81), 2.741 (2.26), (4.52), 3.010 (2.92), 3.021 (2.23), (1.53), 3.395 (1.60), 3.427 (1.46), (1.29), 3.536 (1.32), 3,618 (1.18), (2.78), 3,712 (1.04), 3,730 (1.43), (1.46), 3,847 (2.54), 3,869 (1.39), (0.80), 3,980 (1.36), 4,011 (0.97), (3.23) , 4,971 (3.06), 5,268 (1.74), (8.10), 7,532 (10.33), 7,698 (5.46), 7,704 (3.72), 7,719 (4.49), 7,725 (2.96), 8,301 (7.48), 17,633 (0.52). Example 248 (5RS,7RS)-2-[(6-Chloropyridin-3-yl)methyl]-5-{[(3R,4S)-3,4-difluoropyrrolidin-1-yl]carbonyl}-7-(trifluoromethyl )-5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one (diastereomer 1, racemate)

[01296] (5RS,7RS)-2-[(6-Chloropyridin-3-yl)methyl]-3-oxo-7-(trifluoromethyl)-2,3,5,6,7,8-hexahydro[ 1,2,4]triazolo[4,3-a]pyridine-5-carboxylic acid (mixture of diastereomer; 4 isomers) (88.0 mg, 234 μmol) was initially loaded into THF (3.0 mL) at temperature environment. Subsequently, HBTU (115 mg, 304 μmol) and N,N-diisopropylethylamine (200 μl, 1.2 mmol) were added. After stirring for 15 minutes, (3R,4S)-3,4-difluoropyrrolidine hydrochloride (40.2 mg, 280 μmol) was added and the reaction mixture was stirred at room temperature overnight. The reaction mixture was mixed with water and ethyl acetate, and the organic phase was removed. The organic phase was washed with 10% citric acid solution and saturated aqueous sodium chloride solution, dried over sodium sulfate and filtered, and the filtrate was concentrated. The residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: gradient (acetonitrile/water with 0.1% formic acid). After separation, 15.5 mg (13% possibility) of diastereomer 1 (racemate), which elutes first, and 59 mg (54% chance) of diastereomer 2 (racemate), which elutes later, were isolated Diastereomer 1, racemate: LC-MS (Method 4): Rt = 0.77 min. ; MS (ESIpos): m /z = 466 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.150 (1.14), -0.008 (10.54), 0.007 (8.83), 0.145 (1.14), 1.635 (1.97), 1.663 (2.16), 1.697 (1.84), 1.728 (1.65), 2.327 (1.84), 2.366 (1.40), 2.522 (7.49), 2.559 (3.05), 2.669 (2.16), 2,679 (2.60), 2,711 (4.06), 2,719 (3.43), 2,752 (3.94), 2,884 (3.43), 2,924 (2.41), 2,992 (1.65), 3,002 (1.78), 3,011 (1.84), 3,507 (1.27), 3,517 (1.52), 3,551 (1.71), 3,559 (1.84), 3,570 (1.27), 3,605 (1.33), 3,614 (1.02), 3,638 (1.52), 3,651 (1.46), 3,671 (1.14), 3,684 (1.02), 3,696 (1.40), 3,709 (1.33), 3,729 (1.40), 3,743 (1.40), 3,766 (1.08), 3,779 (1.40), 3,792 (1.59), 3,805 (1.71), 3,818 (1.40), 3,826 (1.46), 3,839 (1.40), 3,867 (1.21), 3,906 (1.08), 4,083 (1.14), 4,097 (1.27), 4,110 (1.65), 4,125 (2.10), 4,143 (1.33), 4,153 (1.97), 4,169 (1.52), 4,709 (2.03), 4,723 (2.60), 4,735 (2.79), 4,751 (2.29), 4,760 (1.59), 4,890 (16.00), 4,920 (3.68), 5,245 (1.27), 5,273 (1.40), 5,283 (1.27), 5.306 (0.95), 5.319 (1.02), 5.325 (1.02), 5.340 (1.08), 5.368 (1.27), 5.378 (1.52), 5.391 (1.40), 5.404 (1.46), 5.413 (1.21), 5.426 (0.89), 5,435 (0.95), 5,449 (1.14), 5,458 (1.02), 5,469 (1.02), 5,483 (0.95), 7,514 (6.16), 7,535 (7.43), 7,698 (0.89), 7,716 (3.05), 7,723 (3.11), 7,727 (3.43), 7,734 (3.75), 7,743 (2.48), 7,748 (2.73), 7,754 (2.54), 8,302 (1.21), 8,325 (3.62), 8,331 (6.92), 8,338 (4.00). Example 249 (5RS,7RS)-2-[(6-Chloropyridin-3-yl)methyl]-5-{[(3R,4S)-3,4-difluoropyrrolidin-1-yl]carbonyl}-7-(trifluoromethyl )-5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one (diastereomer 2, racemate)

[01297] (5RS,7RS)-2-[(6-Chloropyridin-3-yl)methyl]-3-oxo-7-(trifluoromethyl)-2,3,5,6,7,8-hexahydro[ 1,2,4]triazolo[4,3-a]pyridine-5-carboxylic acid (mixture of diastereomer; 4 isomers) (88.0 mg, 234 μmol) was initially loaded into THF (3.0 mL) at temperature environment. Subsequently, HBTU (115 mg, 304 μmol) and N,N-diisopropylethylamine (200 μl, 1.2 mmol) were added. After stirring for 15 minutes, (3R,4S)-3,4-difluoropyrrolidine hydrochloride (40.2 mg, 280 μmol) was added and the reaction mixture was stirred at room temperature overnight. The reaction mixture was mixed with water and ethyl acetate, and the organic phase was removed. The organic phase was washed with 10% aqueous citric acid solution and saturated aqueous sodium chloride solution, dried over sodium sulfate and filtered, and the filtrate was concentrated. The residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: gradient (acetonitrile/water with 0.1% formic acid). After separation, 15.5 mg (13% possibility) of diastereomer 1 (racemate), which elutes first, and 59 mg (54% chance) of diastereomer 2 (racemate), which elutes later, were isolated Diastereomer 2, racemate: LC-MS (Method 4): Rt = 0.80 min. ; MS (ESIpos): m /z = 466 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.008 (3.00), 0.008 (2.78), 1.030 (0.77), 1.045 (0.77) (1.85) (2.23) (1.27) (0.72) (0.99) (0.69) (0.94) (1.05) (2.97), 7,705 (2.86), 7,709 (2.01), 7,719 (2.51), 7,725 (2.26), 8,295 (2.73), 8,301 (5.34), 8,307 (3.33). Example 250 (5RS,7RS)-2-[(6-Chloropyridin-3-yl)methyl]-5-{[(3R,4S)-3,4-difluoropyrrolidin-1-yl]carbonyl}-7-(trifluoromethyl )-5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one (enantiomer 1)

[01298] (5RS,7RS)-2-[(6-Chloropyridin-3-yl)methyl]-5-{[(3R,4S)-3,4-difluoropyrrolidin-1-yl]carbonyl}-7-( trifluoromethyl)-5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one (diastereomer 2, racemate) was separated by chiral preparatory HPLC [ sample preparation: 59 mg dissolved in 3 mL of ethanol; injection volume: 0.05 mL; column: Daicel Chiralpak® IE 5 μm, 250 x 20 mm; eluent: n-heptane/ethanol 50:50; flow rate: 20 ml/min; temperature 30°C; UV detection: 220 nm]. After separation, 13.8 mg of enantiomer 1, which elutes first, and 15.8 mg of enantiomer 2, which elutes later, were isolated. Enantiomer 1:

[01299] Analytical chiral HPLC: Rt = 1.89 min, ee = 99% [column: Daicel Chiralpak® IE, 50 x 4.6 mm; eluent: n-heptane/ethanol 50:50; flow rate: 1 ml/min; UV detection: 220 nm]. LC-MS (Method 3): Rt = 1.48 min; MS (ESIpos): m /z = 466 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (0.93), -0.008 (9.80), 0.008 (7.71), 0.146 (0.93), 0.859 (0.96), 1.135 (1.58), 1.153 (3.15), 1.171 (1.61), 2.156 (1.16), 2.171 (1.23), 2.187 (1.37) (2.36) (2.81) (1.92) (1.03) (4.52) (7.57), 7,688 (2.09), 7,698 (3.19), 7,704 (3.25), 7,719 (2.81), 7,725 (2.57), 8,301 (7.02). Example 251 (5RS,7RS)-5-[(3,3-Difluoropyrrolidin-1-yl)carbonyl]-2-{[3-fluoro-2-(trifluoromethyl)pyridin-4-yl]methyl}-7-( trifluoromethyl)-5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one (diastereomer 2, racemate)

[01300] (5RS,7RS)-2-{[3-Fluoro-2-(trifluoromethyl)pyridin-4-yl]methyl}-3-oxo-7-(trifluoromethyl)-2,3,5,6,7 ,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylic acid (mixture of diastereomer; 4 isomers) (93.0 mg, 217 μmol) was initially loaded into THF ( 2.0 mL) at room temperature. Subsequently, HBTU (107 mg, 282 μmol) and N,N-diisopropylethylamine (190 μl, 1.1 mmol) were added. After stirring for 15 minutes, 3,3-difluoropyrrolidine hydrochloride (37.4 mg, 261 μmol) was added and the reaction mixture was stirred at room temperature overnight. The reaction mixture was mixed with water and ethyl acetate, and the organic phase was removed. The organic phase was washed with 10% aqueous citric acid solution and saturated aqueous sodium chloride solution, dried over sodium sulfate and filtered, and the filtrate was concentrated. The residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: gradient (acetonitrile/water with 0.1% formic acid). After separation, 9.3 mg (6% possibility) of diastereomer 1 (racemate), which elutes first, and 75.8 mg (66% possibility) of diastereomer 2 (racemate), which elutes later, were isolated LC-MS (Method 3): Rt = 1.91 min (MS). ESIpos): m /z = 518 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.008 (2.21), 0.008 (2.19), 1.030 (0.81), 1.045 (0.81) , 2.073 (0.62), 2.130 (0.89), 2.146 (1.06), 2.165 (2.14), 2.171 (1.67), 2.177 (1.87), 2.182 (2.05), 2.196 (2.25), 2.206 (2.48), 2.212 (2.38) , 2,222 (1.95), 2,237 (1.87), 2,252 (1.71), 2,279 (3.19), 2,300 (3.44), 2,328 (2.21), 2,332 (2.35), 2,366 (0.89), 2,377 (1.24), 2,397 (2.11) , 2.427 (2.79), 2.443 (2.48), 2.462 (1.67), 2.473 (1.67), 2.523 (2.87), 2.565 (3.40), 2.583 (2.73), 2.603 (1.84), 2.622 (0.92), 2.665 (0.62) , 2.670 (0.78), 2.674 (0.62), 2.702 (2.40), 2.709 (2.86), 2.731 (3.35), 2.740 (4.75), 2.749 (3.10), 2.771 (3.90), 2.778 (3.67), 2.920 (2.35) , 2.993 (4.94), 3.025 (2.56), 3.033 (3.68), 3.041 (2.21), 3.520 (0.62), 3.539 (1.16), 3.550 (2.35), 3.569 (6.00), Example 252 (5RS,7RS)-5 -[(3,3-Difluoropyrrolidin-1-yl)carbonyl]-2-{[3-fluoro-2-(trifluoromethyl)pyridin-4-yl]methyl}-7-(trifluoromethyl)-5,6,7, 8-tetrahydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one (enantiomer 2)

[01301] (5RS,7RS)-5-[(3,3-Difluoropyrrolidin-1-yl)carbonyl]-2-{[3-fluoro-2-(trifluoromethyl)pyridin-4-yl]methyl}-7- (trifluoromethyl)-5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one (diastereomer 2; racemate) was separated by chiral preparatory HPLC [sample preparation: 75.8 mg dissolved in 3 mL of isopropanol in an ultrasound bath, then 3 mL of n-heptane was added; injection volume: 0.8 mL; column: Daicel Chiralpak® IA 5 μm, 250 x 20 mm; eluent: n-heptane/isopropanol 50:50; flow rate: 15 ml/min; temperature 30°C; UV detection: 220 nm]. After separation, 11.4 mg of enantiomer 1, which elutes first, and 13.3 mg of enantiomer 2, which elutes later, were isolated. Enantiomer 2:

[01302] Analytical chiral HPLC: Rt = 7.07 min, ee = 99% [column: Daicel Chiralpak® IA 5 μm, 250 x 4.6 mm; eluent: i-hexane/isopropanol 50:50; flow rate: 1 ml/min; UV detection: 220 nm]. LC-MS (Method 3): Rt = 1.77 min; MS (ESIpos): m /z = 518 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (1.82), -0.008 (16.00), 0.008 (15.76), 0.146 (1.87) (1.96) (0.81), 2710 (2.30), 2731 (1.10), 2739 (1.49), 2770 (1.20), 2778 (1.15), 2928 (0.81), 2993 (1.63), 3033 (1.15), 3550 (0.77), 3.569 (1.96) (0.72) (5.08), 5,158 (1.49), 7,560 (1.68), 7,573 (3.16), 7,586 (1.72), 8,568 (4.02), 8,580 (3.98). Example 253 (5RS,7RS)-5-[(3-Fluoroazetidin-1-yl)carbonyl]-2-{[3-fluoro-2-(trifluoromethyl)pyridin-4-yl]methyl}-7-(trifluoromethyl) -5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one (diastereomer 1, racemate)

[01303] (5RS,7RS)-2-{[3-Fluoro-2-(trifluoromethyl)pyridin-4-yl]methyl}-3-oxo-7-(trifluoromethyl)-2,3,5,6,7 ,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylic acid (mixture of diastereomer; 4 isomers) (93.0 mg, 217 μmol) was initially loaded into THF ( 2.0 mL) at room temperature. Subsequently, HBTU (107 mg, 282 μmol) and N,N-diisopropylethylamine (190 μl, 1.1 mmol) were added. After stirring for 15 minutes, 3-fluoroazetidine hydrochloride (29.1 mg, 261 μmol) was added and the reaction mixture was stirred at room temperature overnight. The reaction mixture was mixed with water and ethyl acetate, and the organic phase was removed. The organic phase was washed with 10% aqueous citric acid solution and saturated aqueous sodium chloride solution, dried over sodium sulfate and filtered, and the filtrate was concentrated. The residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: gradient (acetonitrile/water with 0.1% formic acid). After separation, 6.7 mg (6% possibility) of diastereomer 1 (racemate), which elutes first, and 65.5 mg (62% chance) of diastereomer 2 (racemate), which elutes later, were isolated. Diastereomer 1, racemate: LC-MS (Method 3): Rt = 1, 70 min; MS (ESIpos): m /z = 486 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.150 (1.81), -0.009 (15.15), 0.007 (16.00 ), 0.146 (1.64), 1.667 (0.62), 1.698 (1.81), 1.728 (2.83), 1.757 (2.04), 1.790 (0.79), 2.327 (2.83), 2.365 (2.54), 2.457 (2.09), 2.522 (8.37 ), 2.664 (1.87), 2.669 (2.49), 2.709 (2.94), 2.737 (2.37), 2.745 (2.49), 2.776 (2.77), 2.888 (3.11), 2.917 (1.70), 2.928 (1.87), 2.968 (0.62 ), 3.004 (1.36), 3.017 (1.36), 3.246 (0.51), 3.905 (0.62), 3.943 (1.07), 3.971 (1.36), 4.006 (1.02), 4.041 4.178 (0.62), 4.190 (0.62), 4.211 ( 0.79), 4.230 (0.96), 4.255 (0.96), 4.282 (0.73), 4.307 (0.73), 4.321 (0.51), 4.338 (0.62), 4.355 (0.85), 4.384 (1.30), 4.412 (1.24), 4.443 ( 1.58), 4.471 (3.39), 4.485 (3.00), 4.498 (2.88), 4.512 (2.54), 4.587 (0.57), 4.602 (0.73), 4.639 (1.13), 4.658 (1.24), 4.696 (0.62), 4.727 ( 0.68), 4.742 (0.51), 5.070 (9.78), 5.079 (10.06), 5.380 (1.24), 5.517 (1.24), 7.635 (3.45), 7.649 (6.05), 7.661 (3.39), 8.579 (5.82), 8.590 ( 5.48). Example 254 (5RS,7RS)-5-[(3-Fluoroazetidin-1-yl)carbonyl]-2-{[3-fluoro-2-(trifluoromethyl)pyridin-4-yl]methyl}-7-(trifluoromethyl) -5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one (diastereomer 2, racemate)

[01304] (5RS,7RS)-2-{[3-Fluoro-2-(trifluoromethyl)pyridin-4-yl]methyl}-3-oxo-7-(trifluoromethyl)-2,3,5,6,7 ,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylic acid (mixture of diastereomer; 4 isomers) (93.0 mg, 217 μmol) was initially loaded into THF ( 2.0 mL) at room temperature. Subsequently, HBTU (107 mg, 282 μmol) and N,N-diisopropylethylamine (190 μl, 1.1 mmol) were added. After stirring for 15 minutes, 3-fluoroazetidine hydrochloride (29.1 mg, 261 μmol) was added and the reaction mixture was stirred at room temperature overnight. The reaction mixture was mixed with water and ethyl acetate, and the organic phase was removed. The organic phase was washed with 10% citric acid solution and saturated aqueous sodium chloride solution, dried over sodium sulfate and filtered, and the filtrate was concentrated. The residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: gradient (acetonitrile/water with 0.1% formic acid). After separation, 6.7 mg (6% possibility) of diastereo - mer 1 (racemate), which elutes first, and 65.5 mg (62% possibility) of diastereomer 2 (racemate), which elutes later, were isolated. 1.75 min; MS (ESIpos): m /z = 486 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (0.51), -0.008 (3.67), 0.008 (3.01), 1030 (0.61), 1045 (0.71), 2073 (0.61), 2137 (1.68), 2156 (2.90), 2173 (3.62), 2187 (3.57), 2203 (3.16), 2219 (1.73), 2240 (3.67) (8.76) (1.12) (2.09) (1.78), 5,408 (1.73), 5,505 (1.78), 5,551 (1.68), 7,567 (5.61), 7,579 (10.90), 7,592 (5.91), 8,568 (11.87), 8,580 (11.87). Example 255 (5RS,7RS)-5-[(3-Fluoroazetidin-1-yl)carbonyl]-2-{[3-fluoro-2-(trifluoromethyl)pyridin-4-yl]methyl}-7-(trifluoromethyl) -5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one (enantiomer 2)

[01305] (5RS,7RS)-5-[(3-Fluoroazetidin-1-yl)carbonyl]-2-{[3-fluoro-2-(trifluoromethyl)pyridin-4-yl]methyl}-7-(trifluoromethyl )-5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one (diastereomer 2; racemate) was separated by chiral preparatory HPLC [preparation sample: 65.5 mg dissolved in 3 mL of isopropanol, then 1 mL of dichloromethane and 2 mL of n-heptane were added; injection volume: 0.4 mL; column: Daicel Chiralpak® IA 5 μm, 250 x 20 mm; eluent: n-heptane/isopropanol 50:50; flow rate: 15 ml/min; temperature 30°C; UV detection: 220 nm]. After separation, 5.7 mg of enantiomer 1, which elutes first, and 5.4 mg of enantiomer 2, which elutes later, were isolated. Enantiomer 2:

[01306] Analytical chiral HPLC: Rt = 7.09 min, ee = 99% [column: Daicel Chiralpak® IA 5 μm, 250 x 4.6 mm; eluent: n-heptane/isopropanol 50:50; flow rate: 1 ml/min; UV detection: 220 nm]. LC-MS (Method 3): Rt = 1.64 min; MS (ESIpos): m /z = 486 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.150 (1.04), -0.009 (16.00), 0.007 (7.79), 0.017 (0.39) (0.32) (0.27) (1.28) (0.37) (0.37) (0.37), 5.361 (0.27), 5.408 (0.25), 5.505 (0.30), 5.753 (1.97), 7.565 (0.89), 7.578 (1.53), 7.591 (0.84), 8.567 (1.73), 8.579 (1.65). Example 256 (5RS,7RS)-5-{[(3S)-3-Fluoropyrrolidin-1-yl]carbonyl}-2-{[3-fluoro-2-(trifluoromethyl)pyridin-4-yl]methyl}-7 -(trifluoromethyl)-5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one (mixture of diastereomer 2; 2 isomers)

[01307] (5RS,7RS)-2-{[3-Fluoro-2-(trifluoromethyl)pyridin-4-yl]methyl}-3-oxo-7-(trifluoromethyl)-2,3,5,6,7 ,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylic acid (mixture of diastereomer; 4 isomers) (93.0 mg, 217 μmol) was initially loaded into THF ( 2.0 mL) at room temperature. Subsequently, HBTU (107 mg, 282 μmol) and N,N-diisopropylethylamine (190 μl, 1.1 mmol) were added. After stirring for 15 minutes, (3S)-3-fluoropyrrolidine hydrochloride (32.7 mg, 261 μmol) was added and the reaction mixture was stirred at room temperature overnight. The reaction mixture was mixed with water and ethyl acetate, and the organic phase was removed. The organic phase was washed with 10% aqueous citric acid solution and saturated aqueous sodium chloride solution, dried over sodium sulfate and filtered, and the filtrate was concentrated. The residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: gradient (acetonitrile/water with 0.1% formic acid). After separation, 8.8 mg (7% possibility) of mixture of diastereomer 1 (2 isomers), which elutes first, and 68.3 mg (63% possibility) of mixture of diastereomer 2 (2 isomers), which elutes later, were isolated Mixture of diastereomer 2, 2 isomers: LC-MS. (Method 3): Rt = 1.76 min; MS (ESIpos): m /z = 500 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (0.68), -0.008 (5.73), 0.008 (6.83), 0.146 (0.68), 2.000 (0.94), 2.117 (2.71), 2.149 (4.64), 2.167 (4.38), 2.183 (4.43), 2.213 (4.27), 2.224 (6.57) , 2,234 (6.88), 2,245 (8.96), 2,282 (4.59), 2,323 (2.24), 2,328 (2.87), 2,333 (2.76), 2,366 (2.29), 2,523 (7.35), 2,670 (2.35), 2,675 (1.77) , 2,700 (2.55), 2,710 (4.59), 2,730 (3.65), 2,738 (6.41), 2,749 (4.07), 2,768 (3.96), 2,778 (4.48), 2,927 (2.97), 2,995 (7.71), 3,033 (5.00) , 3,163 (14.80), 3,173 (14.85), 3,360 (8.08), 3,378 (5.73), 3,388 (4.07), 3,406 (3.75), 3,436 (2.14), 3,446 (2.03), 3,508 (1.41), 3,527 (1.93 ) , 3,572 (3.07), 3,596 (2.55), 3,621 (4.74), 3,643 (6.41), 3,662 (3.44), 3,671 (5.32), 3,687 (3.18), 3,696 (3.07), 3,713 (1.30), 3,736 (1.30) , 3,763 (1.72), 3,794 (2.14), 3,832 (1.62), 3,853 (3.70), 3,891 (2.24), 3,928 (1.30), 3,963 (2.14), 3,990 (4.38), 4,023 (1.88), 4,087 (4.38) , 4,938 (2.29), 4,950 (2.35), 4,986 (3.23), 4,999 (3.13), 5,045 (5.16), 5,087 (11.41), 5,095 (14.85), 5,117 (15.84), 5,159 (4.12), 5,269 (3.1 3) , 5,358 (1.77), 5,402 (3.75), 5,489 (1.72), 5,524 (1.41), 7,562 (5.73), 7,574 (10.32), 7,587 (5.37), 8,136 (13.29), 8,568 (16.00), 8,580 (16. 00) . Example 257 (5RS,7RS)-5-{[(3S)-3-Fluoropyrrolidin-1-yl]carbonyl}-2-{[3-fluoro-2-(trifluoromethyl)pyridin-4-yl]methyl}-7 -(trifluoromethyl)-5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one (isomer 1)

[01308] (5RS,7RS)-5-{[(3S)-3-Fluoropyrrolidin-1-yl]carbonyl}-2-{[3-fluoro-2-(trifluoromethyl)pyridin-4-yl]methyl}- 7-(trifluoromethyl)-5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one (mixture of diastereomer 2; 2 isomers) was separated by chiral preparatory HPLC [sample preparation: 68.3 mg dissolved in 3 mL of acetonitrile and 2 mL of ethanol (heated); injection volume: 0.25 mL; column: Daicel Chiralpak® IB 5 μm, 250 x 20 mm; eluent: n-heptane/isopropanol 50:50; flow rate: 15 ml/min; temperature 25°C; UV detection: 210 nm]. After separation, 30.7 mg of isomer 1, which elutes first, and 27.2 mg of isomer 2, which elutes later, were isolated. Isomer 1:

[01309] Analytical chiral HPLC: Rt = 2.17 min, d = 99% [column: Daicel Chiraltek® IB 3 μm, 50 x 4.6 mm; eluent: i-hexane/ethanol 50:50; flow rate: 1 ml/min; UV detection: 220 nm]. LC-MS (Method 4): Rt = 0.89 min; MS (ESIpos): m /z = 500 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (1.69), -0.008 (15.64), 0.008 (16.00), 0.145 (1.87) (4.00) (3.64) (2.22) (1.60) (3.29), 5,400 (4.18), 5,523 (2.31), 7,561 (4.89), 7,573 (9.87), 7,587 (5.42), 8,568 (13.42), 8,580 (13.60). Example 258 (5RS,7RS)-5-{[(3S)-3-Fluoropyrrolidin-1-yl]carbonyl}-2-{[3-fluoro-2-(trifluoromethyl)pyridin-4-yl]methyl}-7 -(trifluoromethyl)-5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one (isomer 2)

[01310] (5RS,7RS)-5-{[(3S)-3-Fluoropyrrolidin-1-yl]carbonyl}-2-{[3-fluoro-2-(trifluoromethyl)pyridin-4-yl]methyl}- 7-(trifluoromethyl)-5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one (mixture of diastereomer 2; 2 isomers) was separated by chiral preparatory HPLC [sample preparation: 68.3 mg dissolved in 3 mL of acetonitrile and 2 mL of ethanol (heated); injection volume: 0.25 mL; column: Daicel Chiralpak® IB 5 μm, 250 x 20 mm; eluent: n-heptane/isopropanol 50:50; flow rate: 15 ml/min; temperature 25°C; UV detection: 210 nm]. After separation, 30.7 mg of isomer 1, which elutes first, and 27.2 mg of isomer 2, which elutes later, were isolated. Isomer 2:

[01311] Analytical chiral HPLC: Rt = 3.68 min, d = 97.8% [column: Daicel Chiraltek® IB 3 μm, 50 x 4.6 mm; eluent: i-hexane/ethanol 50:50; flow rate: 1 ml/min; UV detection: 220 nm]. LC-MS (Method 4): Rt = 0.89 min; MS (ESIpos): m /z = 500 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (1.67), -0.008 (14.33), 0.008 (12.71), 0.146 (1.67) (2.23) (2.73), 2738 (4.22), 2749 (2.42), 2770 (3.22), 2778 (3.10), 2910 (1.98), 2987 (4.65), 3025 (3.41), 3037 (2.85), 3361 (2.36), 3379 (2.29) (1.43) (2.05), 5,359 (1.98), 5,407 (1.86), 5,490 (1.86), 7,556 (2.67), 7,569 (5.33), 7,576 (5.52), 7,588 (2.79), 8,569 (9.92), 8,581 (9.67). Example 259 (5RS,7RS)-5-{[(3R,4S)-3,4-Difluoropyrrolidin-1-yl]carbonyl}-2-{[3-fluoro-2-(trifluoromethyl)pyridin-4-yl] methyl}-7-(trifluoromethyl)-5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one (diastereomer 1, racemate)

[01312] (5RS,7RS)-2-{[3-Fluoro-2-(trifluoromethyl)pyridin-4-yl]methyl}-3-oxo-7-(trifluoromethyl)-2,3,5,6,7 ,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylic acid (mixture of diastereomer; 4 isomers) (93.0 mg, 217 μmol) was initially loaded into THF ( 2.0 mL) at room temperature. Subsequently, HBTU (107 mg, 282 μmol) and N,N-diisopropylethylamine (190 μl, 1.1 mmol) were added. After stirring for 15 minutes, (3R,4S)-3,4-difluoropyrrolidine hydrochloride (37.4 mg, 261 μmol) was added and the reaction mixture was stirred at room temperature overnight. The reaction mixture was mixed with water and ethyl acetate, and the organic phase was removed. The organic phase was washed with 10% citric acid solution and saturated aqueous sodium chloride solution, dried over sodium sulfate and filtered, and the filtrate was concentrated. The residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: gradient (acetonitrile/water with 0.1% formic acid). After separation, 8.5 mg (8% possibility) of diastereomer 1 (racemate), which elutes first, and 72 mg (64% chance) of diastereomer 2 (racemate), which elutes later, were isolated Diastereomer 1, racemate: LC-MS (Method 3): Rt = 1.75 min. ; MS (ESIpos): m /z = 518 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.150 (2.18), -0.009 (16.00), 0.007 (13.45), 0.145 (2.18), 1.652 (1.09), 1.682 (1.09), 1.713 (1.09), 1.747 (1.09), 2.322 (4.36), 2.327 (6.18), 2.331 (4.36), 2.365 (4.00), 2.412 (1.09), 2,444 (1.82), 2,450 (1.82), 2,523 (14.18), 2,558 (3.27), 2,560 (1.82), 2,564 (2.18), 2,566 (1.82), 2,571 (1.45), 2,576 (1.82), 2,581 (1.45), 2,585 (1.45), 2,592 (1.45), 2,596 (1.45), 2,664 (4.73), 2,669 (5.82), 2,673 (4.00), 2,689 (3.27), 2,709 (4.36), 2,737 (1.82), 2,776 (2.18), 2,906 (2.18), 2,947 (1.45), 2,989 (1.45), 3,024 (1.45), 3,180 (0.73), 3,189 (0.73), 3,201 (1.09), 3,218 (1.82), 3,223 (1.45), 3,234 (1.82), 3,246 (2.55), 3,251 (2.18), 3,358 (0.73), 3,520 (0.73), 3,565 (1.09), 3,639 (0.73), 3,699 (0.73), 3,730 (0.73), 3,788 (1.09), 3,802 (0.73), 3.823 (0.73), 4.139 (1.09), 4.744 (1.45), 4.757 (1.45), 4.764 (1.09), 4.772 (1.45), 5.070 (8.00), 5.249 (0.73), 5.256 (0.73), 5.361 (0.73), 5,394 (1.09), 5,450 (0.73), 5,470 (0.73), 5,753 (13.09), 7,623 (1.82), 7,637 (4.00), 7,650 (2.18), 8,578 (3.64), 8,589 (3.27). Example 260 (5RS,7RS)-5-{[(3R,4S)-3,4-Difluoropyrrolidin-1-yl]carbonyl}-2-{[3-fluoro-2-(trifluoromethyl)pyridin-4-yl] methyl}-7-(trifluoromethyl)-5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one (diastereomer 2, racemate)

[01313] (5RS,7RS)-2-{[3-Fluoro-2-(trifluoromethyl)pyridin-4-yl]methyl}-3-oxo-7-(trifluoromethyl)-2,3,5,6,7 ,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylic acid (mixture of diastereomer; 4 isomers) (93.0 mg, 217 μmol) was initially loaded into THF ( 2.0 mL) at room temperature. Subsequently, HBTU (107 mg, 282 μmol) and N,N-diisopropylethylamine (190 μl, 1.1 mmol) were added. After stirring for 15 minutes, (3R,4S)-3,4-difluoropyrrolidine hydrochloride (37.4 mg, 261 μmol) was added and the reaction mixture was stirred at room temperature overnight. The reaction mixture was mixed with water and ethyl acetate, and the organic phase was removed. The organic phase was washed with 10% aqueous citric acid solution and saturated aqueous sodium chloride solution, dried over sodium sulfate and filtered, and the filtrate was concentrated. The residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: gradient (acetonitrile/water with 0.1% formic acid). After separation, 8.5 mg (8% possibility) of diastereomer 1 (racemate), which elutes first, and 72 mg (64% chance) of diastereomer 2 (racemate), which elutes later, were isolated Diastereomer 2, racemate: LC-MS (Method 3): Rt = 1.81 min. ; MS (ESIpos): m /z = 518 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (0.52), -0.008 (6.19), (1.22), 2.154 (1.44) , (2.78), 2.769 (4.56), 2.780 (3.37), (4.70), 3.025 (4.78), 3.036 (3.78), (3.11), 3.526 (2.63), 3.536 (4.07), (1.93), 3.588 (2.93 ), 3,599 (2.07), (1.70), 3,697 (1.93), 3,707 (3.44), (2.30), 3,767 (1.56), 3,780 (1.59), (1.81), 3,871 (2.85), 3,884 (2.52), ( 2.70), 4.074 (2.41), 4.091 (3.07), (1.63), 4.150 (1.26), 4.166 (1.44), (1.52), 4.224 (1.22), 4.238 (1.19), (5.93), 5.087 (11.19), 5,110 (8.48), (3.00), 5,260 (1.96), 5,270 (2.15), 5,285 (2.07), 5,296 (2.07), 5,329 (1.67), 5,337 (1.74), 5,350 (1.81), 5,384 (2.52), 5,407 (2.04) (7.70), 7,588 (3.63), 8,167 (0.89), 8,569 (11.81), 8,581 (11.26). Example 261 (5RS,7RS)-5-{[(3R,4S)-3,4-Difluoropyrrolidin-1-yl]carbonyl}-2-{[3-fluoro-2-(trifluoromethyl)pyridin-4-yl] methyl}-7-(trifluoromethyl)-5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one (enantiomer 1)

[01314] (5RS,7RS)-5-{[(3R,4S)-3,4-Difluoropyrrolidin-1-yl]carbonyl}-2-{[3-fluoro-2-(trifluoromethyl)pyridin-4-yl ]methyl}-7-(trifluoromethyl)-5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one (diastereomer 2; racemate) was separated by chiral preparatory HPLC [sample preparation: 72.2 mg dissolved in 3 mL of acetonitrile and 2 mL of ethanol (heated); injection volume: 0.25 mL; column: Daicel Chiralpak® IB 5 μm, 250 x 20 mm; eluent: n-heptane/ethanol 50:50; flow rate: 15 ml/min; temperature 25°C; UV detection: 210 nm]. After separation, 31.3 mg of enantiomer 1, which elutes first, and 31.2 mg of enantiomer 2, which elutes later, were isolated. Enantiomer 1:

[01315] Analytical chiral HPLC: Rt = 2.08 min, ee = 99% [column: Daicel Chiraltek® IB, 3 μm, 50 x 4.6 mm; Laufmittel: i-Hexane/Ethanol 50:50; Flow: 1 ml/min; UV detection: 220 nm]. LC-MS (Method 4): Rt = 0.90 min; MS (ESIpos): m /z = 518 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (1.73), -0.008 (16.00), 0.008 (12.80), 0.146 (1.73) (2.94) (2.42) (1.56) (1.38) (1.47) (1.04) (1.04), 7,554 (1.73), 7,566 (4.06), 7,576 (4.93), 7,589 (2.25), 8,569 (7.26), 8,581 (7.26). Example 262 (5RS,7RS)-5-{[(3R,4S)-3,4-Difluoropyrrolidin-1-yl]carbonyl}-2-{[3-fluoro-2-(trifluoromethyl)pyridin-4-yl] methyl}-7-(trifluoromethyl)-5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one (enantiomer 2)

[01316] (5RS,7RS)-5-{[(3R,4S)-3,4-Difluoropyrrolidin-1-yl]carbonyl}-2-{[3-fluoro-2-(trifluoromethyl)pyridin-4-yl ]methyl}-7-(trifluoromethyl)-5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one (diastereomer 2; acemate) was separated by chiral preparatory HPLC [sample preparation: 72.2 mg dissolved in 3 mL of acetonitrile and 2 mL of ethanol (heated); injection volume: 0.25 mL; column: Daicel Chiralpak® IB 5 µm, 250 x 20 mm; eluent: n-heptane/ethanol 50:50; flow rate: 15 ml/min; temperature 25ºC; UV detection: 210 nm]. After separation, 31.3 mg of enantiomer 1, which elutes first, and 31.2 mg of enantiomer 2, which elutes later, were isolated. Enantiomer 2:

[01317] Analytical chiral HPLC: Rt = 4.11 min, ee = 99% [column: Daicel Chiraltek® IB 3 μm, 50 x 4.6 mm; eluent: i-hexane/ethanol 50:50; flow rate: 1 ml/min; UV detection: 220 nm]. LC-MS (Method 4): Rt = 0.90 min; MS (ESIpos): m /z = 518 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (1.71), 0.008 (15.86), 0.147 (1.71), 0.853 ( 0.96), 1.234 (2.39), 2.138 (1.78), 2.153 (1.78), 2.173 (3.49), 2.189 (3.21), 2.204 (3.42), 2.221 (6.97), 2.229 (6.63), 2.239 (6.50), 2.293 ( 5.40), 2327 (5.40), 2366 (2.80), 2519 (10.60), 2523 (8.27), 2670 (2.53), 2700 (3.56), 2711 (4.79), 2730 (5.06), 2741 (7.52), 2751 ( 3.76), 2.769 (6.02), 2.781 (4.51), 2.915 (3.42), 2.986 (8.62), 2.997 (6.22), 3.026 (6.56), 3.038 (5.20), 3.502 (3.28), 3.526 (2.67), 3.536 ( 4.85), 3.546 (4.03), 3.556 (3.01), 3.590 (3.69), 3.650 (2.53), 3.664 (2.46), 3.684 (1.98), 3.707 (4.51), 3.720 (4.44), 3.740 (3.35), 3.753 ( 3.01), 3.767 (1.98), 3.780 (1.85), 3.802 (1.37), 3.814 (1.44), 3.870 (3.69), 3.892 (3.56), 4.048 (1.85), 4.061 (2.67), 4.075 (1.71), 4.091 ( 3.01) 1.57) 1 ( 2.94), 5.298 (2.87), 5.329 (2.12), 5.350 (2.39), 5.384 (3.35), 5.408 (2.67), 5.418 (2.94), 5.430 (2.80), 5.441 (1.71), 5.457 (2.19), 5.480 ( 2.26), 5,492 (2.32), 7,555 (3.83), 7,566 (9.37), 7,577 (10.87), 7,589 (5.20), 8,569 (16.00), 8,581 (15.93). Example 263 (5RS,7RS)-2-[(5-Chloro-3-fluoropyridin-3-yl)methyl]-5-{[(3S)-3-fluoropyrrolidin-1-yl]carbonyl}-7-(trifluoromethyl )-5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one (mixture of diastereomer 1; 2 isomers) CL

[01318] (5RS,7RS)-2-[(5-Chloro-3-fluoropyridin-3-yl)methyl]-3-oxo-7- (trifluoromethyl)-2,3,5,6,7,8- hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylic acid (mixture of diastereomer; 4 isomers) (55.0 mg, 139 μmol) was initially loaded into THF (2.0 mL) at room temperature. Subsequently, HBTU (68.7 mg, 181 μmol) and N,N-diisopropylethylamine (120 μl, 700 μmol) were added. After stirring for 5 minutes, (3S)-3-fluoropyrrolidine hydrochloride (21.0 mg, 167 μmol) was added and the reaction mixture was stirred at room temperature overnight. The reaction mixture was mixed with water and ethyl acetate, and the organic phase was removed. The organic phase was washed with 10% aqueous citric acid solution and saturated aqueous sodium chloride solution, dried over sodium sulfate and filtered, and the filtrate was concentrated. The residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: gradient (acetonitrile/water with 0.1% formic acid). After separation, 10.5 mg (16% possibility) of mixture of diastereomer 1 (2 isomers), which elutes first, and 37 mg (51% possibility) of mixture of diastereomer 2 (2 isomers), which elutes later, were isolated Mixture of diastereomer 1, 2 isomers: LC-MS (Method. 1): Rt = 1.06 min; MS (ESIpos): m /z = 466 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (1.70), -0.033 (0.53) , 1.713 (0.53), 1.739 (0.53), 2.097 (0.32), 2.109 (0.32), 2.131 (0.32), 2.212 (0.32), 2.231 (0.32), 2.257 (0.32), 2.323 (1.70), 2.327 (2.33) , 2.332 (1.80), 2.366 (1.91), 2.460 (0.32), 2.523 (7.31), 2.559 (2.44), 2.574 (1.27), 2.581 (0.85), 2.586 (0.74), 2.598 (0.74), 2.604 (0.53) , 2.637 (0.95), 2.665 (2.44), 2.670 (3.60), 2.674 (2.75), 2.710 (3.18), 2.760 (0.21), 2.862 (1.06), 2.898 (0.74), 2.987 (0.42), 3.011 (0.42) , 3.359 (1.59), 3.435 (0.74), 3.468 (0.53), 3.499 (0.64), 3.534 (0.42), 3.554 (0.53), 3.588 (0.53), 3.619 (0.64), 3.636 (0.64), 3.657 (0.64) , 3.674 (0.74), 3.703 (0.53), 3.721 (0.42), 3.743 (0.32), 3.787 (0.32), 3.795 (0.32), 3.826 (0.42), 3.859 (0.53), 3.887 (0.42), 3.931 (0.64) , 3.957 (0.74), 3.986 (0.42), 4.677 (0.32), 4.690 (0.42), 4.704 (0.32), 4.716 (0.42), 4.731 (0.42), 4.742 (0.42), 4.755 (0.42), 4.767 (0.42) , 4.781 (0.32), 4.798 (0.42), 4.812 (0.32), 4.825 (0.32), 4.971 (4.77), 5.284 (0.32), 5.354 (0.32), 5.396 (0.53), 5.417 (0.32), 5.481 (0.32) , 5,524 (0.32), 8,104 (1.17), 8,109 (1.27), 8,129 (1.17), 8,133 (1.27), 8,489 (1.70). Example 264 (5RS,7RS)-2-[(5-Chloro-3-fluoropyridin-3-yl)methyl]-5-{[(3S)-3-fluoropyrrolidin-1-yl]carbonyl}-7-(trifluoromethyl )-5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one (mixture of diastereomer 2; 2 isomers)

[01319] (5RS,7RS)-2-[(5-Chloro-3-fluoropyridin-3-yl)methyl]-3-oxo-7- (trifluoromethyl)-2,3,5,6,7,8- hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylic acid (mixture of diastereomer; 4 isomers) (55.0 mg, 139 μmol) was initially loaded into THF (2.0 mL) at room temperature. Subsequently, HBTU (68.7 mg, 181 μmol) and N,N-diisopropylethylamine (120 μl, 700 μmol) were added. After stirring for 5 minutes, (3S)-3-fluoropyrrolidine hydrochloride (21.0 mg, 167 μmol) was added and the reaction mixture was stirred at room temperature overnight. The reaction mixture was mixed with water and ethyl acetate, and the organic phase was removed. The organic phase was washed with 10% aqueous citric acid solution and saturated aqueous sodium chloride solution, dried over sodium sulfate and filtered, and the filtrate was concentrated. The residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: gradient (acetonitrile/water with 0.1% formic acid). After separation, 10.5 mg (16% possibility) of mixture of diastereomer 1 (2 isomers), which elutes first, and 37 mg (51% possibility) of mixture of diastereomer 2 (2 isomers), which elutes later, were isolated Mixture of diastereomer 2, 2 isomers: LC-MS (Method. 1): Rt = 1.10 min; MS (ESIpos): m /z = 466 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -1.950 (1.23), -1.643 (1.23), - 1.565 (0.92), -1.154 (1.23), -0.149 (5.54), -0.039 (1.85), 0.146 (5.23), 1.883 (1.23), 1.954 (1.23), 1.989 (1.54), 1.999 ( 1.54), 2.039 (1.23), 2.120 (4.31), 2.149 (7.38), 2.186 (6.77), 2.199 (6.46), 2.216 (6.15), 2.268 (5.54), 2.297 (3.69), 2.327 (10.46), 2.367 ( 6.15), 2,413 (1.54), 2,610 (2.15), 2,635 (3.38), 2,670 (15.38), 2,710 (10.15), 2.801 (1.23), 2,815 (1.23), 2,83 (1.54), 2,948 (9,85), 2,982 ( 7.08), 3.025 (1.23), 3.084 (1.23), 3.119 (1.23), 3.204 (1.54), 3.361 (5.85), 3.388 (3.38), 3.426 (2.46), 3.474 (1.54), 3.499 (1.85), 3.510 ( 2.15), 3.524 (1.85), 3.534 (2.15), 3.567 (4.00), 3.597 (4.00), 3.605 (3.08), 3.628 (4.92), 3.668 (4.62), 3.691 (4.00), 3.726 (1.85), 3.762 ( 1.23), 3.790 (2.46), 3.798 (1.85), 3.820 (2.46), 3.843 (3.08), 3.865 (2.15), 3.887 (2.15), 3.919 (1.85), 3.976 (2.77), 3.996 (3.08), 4.019 ( 2.77), 4.049 (1.85), 4.076 (1.54), 4.904 (2.46), 4.931 (5.85), 4.970 (16.00), 4.995 (3.69), 5.017 (9.54), 5.056 (6.15), 5.265 (3.08), 5.303 ( 1.23) ( 1.23) .493 ( 1.23), 15.243 (0.92), 16.225 (0.92).Example 265 (5RS,7RS)-2-[(5-Chloro-3-fluoropyridin-3-yl)methyl]-5-{[(3S)-3- fluoropyrrolidin-1-yl]carbonyl}-7-(trifluoromethyl)-5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one ( isomer 2)

[01320] (5RS,7RS)-2-[(5-Chloro-3-fluoropyridin-3-yl)methyl]-5-{[(3S)-3-fluoropyrrolidin-1-yl]carbonyl}-7-( trifluoromethyl)-5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one (mixture of diastereomer 2, 2 isomers) was separated by HPLC chiral preparatory [sample preparation: 37 mg dissolved in 2 mL of n-heptane and 2 mL of ethanol; injection volume: 0.9 mL; column: Daicel Chiralpak® IC 5 μm, 250 x 20 mm; eluent: n-heptane/ethanol 50:50; flow rate: 15 ml/min; temperature 50°C; UV detection: 220 nm]. After separation, 14.3 mg of isomer 1, which elutes first, and 15.1 mg of isomer 2, which elutes later, were isolated. Isomer 2:

[01321] Analytical chiral HPLC: Rt = 6.52 min, de = 99% [column: Daicel Chiralpak® IC 5 μm, 250 x 4.6 mm; eluent: i-hexane/ethanol 50:50; flow rate: 1 ml/min; UV detection: 220 nm]. LC-MS (Method 3): Rt = 1.49 min; MS (ESIpos): m /z = 466 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (1.56), -0.008 (16.00), 0.008 (15.94), 0.146 (1.50) (2.00) (1.62) (2.25) (1.88), 5,266 (1.56), 5,394 (2.37), 5,525 (1.12), 8,102 (4.75), 8,107 (4.81), 8,126 (4.81), 8,131 (4.94), 8,483 (6.12). Example 266 (5RS,7RS)-2-[(5-Chloro-3-fluoropyridin-3-yl)methyl]-5-{[(3R,4S)-3,4-difluoropyrrolidin-1-yl]carbonyl}- 7-(trifluoromethyl)-5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one (diastereomer 2, racemate)

[01322] (5RS,7RS)-2-[(5-Chloro-3-fluoropyridin-3-yl)methyl]-3-oxo-7- (trifluoromethyl)-2,3,5,6,7,8- hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylic acid (mixture of diastereomer; 4 isomers) (55.0 mg, 139 μmol) was initially loaded into THF (2.0 mL) at room temperature. Subsequently, HBTU (68.7 mg, 181 μmol) and N,N-diisopropylethylamine (120 μl, 700 μmol) were added. After stirring for 5 minutes, (3R,4S)-3,4-difluoropyrrolidine hydrochloride (24.0 mg, 167 μmol) was added and the reaction mixture was stirred at room temperature overnight. The reaction mixture was mixed with water and ethyl acetate, and the organic phase was removed. The organic phase was washed with 10% aqueous citric acid solution and saturated aqueous sodium chloride solution, dried over sodium sulfate and filtered, and the filtrate was concentrated. The residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: gradient (acetonitrile/water with 0.1% formic acid). After separation, 23.9 mg (35% possibility) of diastereomer 2 (racemate), which elutes later, were isolated. LC-MS (Method 1): Rt = 1.13 min; DMSO-d6) δ [ppm]: -0.150 (1.73), -0.031 (0.56), - 0.008 (16.00), 0.008 (13.67), 0.146 (1.63), 2.073 (0.42), 2.145 (0.47), 2.161 (0.47 ), 2.193 (1.17), 2.256 (0.84), 2.295 (0.56), 2.322 (1.45), 2.327 (1.96), 2.332 (1.45), 2.366 (0.56), 2.439 (0.42), 2.648 (0.42), 2.665 (1.77 ), 2.669 (2.33), 2.684 (1.21), 2.695 (0.65), 2.710 (0.84), 2.728 (0.56), 2.942 (1.77), 2.976 (1.17), 2.988 (0.75), 3.491 (0.37), 3.527 (0.61 ), 3.535 (0.56), 3.578 (0.61), 3.640 (0.37), 3.653 (0.33), 3.698 (0.56), 3.709 (0.51), 3.729 (0.42), 3.746 (0.37), 3.851 (0.42), 3.870 (0.51 ), 3.888 (0.51), 3.897 (0.47), 4.058 (0.37), 4.088 (0.47), 4.102 (0.33), 4.201 (0.47), 4.933 (0.89), 4.971 (2.47), 4.993 (1.77), 5.008 (1.21 ), 5.024 (1.40), 5.028 (1.35), 5.047 (0.47), 5.064 (0.56), 5.267 (0.42), 5.288 (0.47), 5.342 (0.37), 5.382 (0.56), 5.394 (0.47), 5.403 (0.42 ), 5.426 (0.37), 5.454 (0.33), 5.486 (0.37), 8.103 (1.40), 8.107 (1.49), 8.126 (1.49), 8.131 (1.45), 8.477 (2.19). Example 267 (5RS,7RS)-2-[(5-Chloro-3-fluoropyridin-3-yl)methyl]-5-{[(3R,4S)-3,4-difluoropyrrolidin-1-yl]carbonyl}- 7-(trifluoromethyl)-5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one (enantiomer 1)

[01323] (5RS,7RS)-2-[(5-Chloro-3-fluoropyridin-3-yl)methyl]-5-{[(3R,4S)- 3,4-difluoropyrrolidin-1-yl]carbonyl} -7-(trifluoromethyl)-5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one (diastereomer 2, racemate) was separated by Chiral preparatory HPLC [sample preparation: 23.9 mg dissolved in 1.5 mL of n-heptane and 2 mL of ethanol; injection volume: 1.2 mL; column: Daicel Chiralpak® IE 5 μm, 250 x 20 mm; eluent: n-heptane/ethanol 50:50; flow rate: 15 ml/min; temperature 40°C; UV detection: 220 nm]. After separation, 8.6 mg of enantiomer 1, which elutes first, and 9.4 mg of enantiomer 2, which elutes later, were isolated. Enantiomer 1:

[01324] Analytical chiral HPLC: Rt = 1.86 min, ee = 99% [column: Daicel Chiralpak® IE, 3 μm, 50 x 4.6 mm; eluent: n-heptane/ethanol 50:50; flow rate: 1 ml/min; UV detection: 220 nm]. LC-MS (Method 3): Rt = 1.55 min; MS (ESIpos): m /z = 484 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (1.69), -0.008 (16.00), 0.008 (14.89), 0.146 (1.85) (1.07) (0.95) (0.45) (0.58) (3.13) (0.86) (4.40), 8.481 (4.40). Example 268 (5RS,7RS)-2-[(5-Chloropyridin-3-yl)methyl]-5-{[(3R,4S)-3,4-difluoropyrrolidin-1-yl]carbonyl}-7-(trifluoromethyl )-5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one (diastereomer 1, racemate)

[01325] (5RS,7RS)-2-[(5-Chloropyridin-3-yl)methyl]-3-oxo-7-(trifluoromethyl)-2,3,5,6,7,8-hexahydro[ 1,2,4]triazolo[4,3-a]pyridine-5-carboxylic acid (mixture of diastereomer; 4 isomers) (70.0 mg, 75% purity, 139 μmol) was initially loaded into THF (2, 0 mL) at room temperature. Subsequently, HBTU (68.7 mg, 181 μmol) and N,N-diisopropylethylamine (120 μl, 700 μmol) were added. After stirring for 5 minutes, (3R,4S)-3,4-difluoropyrrolidine hydrochloride (24.0 mg, 167 μmol) was added and the reaction mixture was stirred at room temperature overnight. The reaction mixture was mixed with water and ethyl acetate, and the organic phase was removed. The organic phase was washed with 10% aqueous citric acid solution and saturated aqueous sodium chloride solution, dried over sodium sulfate and filtered, and the filtrate was concentrated. The residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: gradient (acetonitrile/water with 0.1% formic acid). After separation, 12.6 mg (19% possibility) of diaste - rheomer 1 (racemate), which elutes first, and 9 mg (14% possibility) of diastereomer 2 (racemate), which elutes later, were isolated Diastereomer 1, racemate: LC-MS (Method 3): Rt = 1, 41 min; 1.09), -0.008 (12.36), 0.008 (16.00), 0.146 (1.58), 1.642 (1.27), 1.670 (1.39), 1.703 (1.27), 1.735 (1.03), 2.323 (1.27), 2.327 (1.76), 2.332 (1.39) (1.52) (1.15) (0.91) (1.45) (7.94) (0.97) (2.61), 8,453 (4.12), 8,458 (3.15), 8,576 (3.88), 8,581 (3.45), 9,265 (3.45). Example 269 (5RS,7RS)-2-[(5-Chloropyridin-3-yl)methyl]-5-{[(3R,4S)-3,4-difluoropyrrolidin-1-yl]carbonyl}-7-(trifluoromethyl )-5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one (diastereomer 2, racemate)

[01326] (5RS,7RS)-2-[(5-Chloropyridin-3-yl)methyl]-3-oxo-7-(trifluoromethyl)-2,3,5,6,7,8-hexahydro[ 1,2,4]triazolo[4,3-a]pyridine-5-carboxylic acid (mixture of diastereomer; 4 isomers) (70.0 mg, 75% purity, 139 μmol) was initially loaded into THF (2, 0 mL) at room temperature. Subsequently, HBTU (68.7 mg, 181 μmol) and N,N-diisopropylethylamine (120 μl, 700 μmol) were added. After stirring for 5 minutes, (3R,4S)-3,4-difluoropyrrolidine hydrochloride (24.0 mg, 167 μmol) was added and the reaction mixture was stirred at room temperature overnight. The reaction mixture was mixed with water and ethyl acetate, and the organic phase was removed. The organic phase was washed with 10% aqueous citric acid solution and saturated aqueous sodium chloride solution, dried over sodium sulfate and filtered, and the filtrate was concentrated. The residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: gradient (acetonitrile/water with 0.1% formic acid). After separation, 12.6 mg (19% possibility) of diastereomer 1 (racemate), which elutes first, and 9 mg (14% chance) of diastereomer 2 (racemate), which elutes later, were isolated Diastereomer 2, racemate: LC-MS (Method 3): Rt = 1.46 min. ; MS (ESIpos): m /z = 466 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (1.95), -0.008 (16.00), 0.008 (14.42), 0.146 (1.86), 2.166 (1.21), 2.182 (1.16), 2.197 (1.44), 2.208 (2.27), 2.218 (2.69), 2.228 (2.13), 2.241 (1.11), 2.277 (1.95), 2.312 (1.16), 2,323 (1.90), 2,327 (2.64), 2,332 (1.90), 2,366 (1.81), 2,523 (5.43), 2,665 (2.04), 2,670 (2.64), 2,674 (1.95), 2,693 (1.44), 2,703 (1.21), 2,710 (2.09), 2,723 (1.95), 2,733 (2.97), 2,743 (1.44), 2,762 (2.37), 2,772 (1.81), 2,889 (1.30), 2,904 (1.25), 2,977 (3.11), 2,988 (2.27), 3,016 (2.27), 3,027 (1.81), 3,500 (1.02), 3,533 (1.58), 3,542 (1.44), 3,552 (1.25), 3,563 (0.74), 3,578 (1.07), 3,586 (1.58), 3,596 (0.97), 3,646 (0.97), 3,660 (0.79), 3,678 (0.79), 3,695 (0.79), 3,703 (1.44), 3,718 (1.53), 3,738 (1.07), 3,752 (1.07), 3,766 (0.79), 3,780 (0.74), 3,800 (0.65), 3,847 (0.83), 3,866 (1.34), 3,895 (1.34), 3,930 (0.70), 4,043 (0.74), 4,057 (0.93), 4,071 (0.65), 4,087 (1.11), 4,104 (0.97), 4,119 (0.70), 4,134 (0.70), 4,157 (0.70), 4,173 (0.74), 4,201 (1.21), 4,230 (0.70), 4,911 (0.74), 4,952 (13.22), 5,007 (3.06), 5,020 (4.31), 5.273 (1.02), 5.296 (1.07), 5.328 (0.65), 5.351 (0.74), 5.386 (1.30), 5.397 (1.16), 5.407 (1.02), 5.418 (1.07), 5.427 (1.07), 5.439 (0.65), 5,458 (0.83), 5,480 (0.83), 5,490 (0.93), 7,750 (1.81), 7,763 (4.50), 8,425 (7.14), 8,429 (4.73), 8,570 (4.87). Example 270 (5RS,8RS)-5-{[(3R,4S)-3,4-Difluoropyrrolidin-1-yl]carbonyl}-8-(trifluoromethyl)-2-{[6-(trifluoromethyl)pyridin-3- yl]methyl}-5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one (diastereomer mixture; 4 isomers)

[01327] Under argon: 5-{[(3RS,4RS)-3,4-Difluoropyrrolidin-1-yl]carbonyl}-8-(trifluoromethyl)-2-{[6-(trifluoromethyl)pyridin-3-yl] methyl}[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one (23.0 mg, 46.4 μmol) and palladium on charcoal (50.0 mg, 10% palladium ) were suspended in ethanol (5.0 mL), and the mixture was stirred at room temperature in a hydrogen atmosphere (1 atm) overnight. The reaction mixture was filtered through Celite. The filtrate was concentrated, and the residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: gradient (acetonitrile/water with 0.1% formic acid). The fractions containing the product were concentrated under pressure reduced and 10.6 mg (46% possibility) of the title compound were obtained. LC-MS (Method 4): Rt = 0.85 min (ESIpos): m / z = 500 [M+H]+ 1H; -NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (1.36), -0.008 (12.38), 0.008 (12.98), 0.146 (1.36), 1.724 (0.83), 1.755 (1.81), 1.781 (1.89 ), 1.807 (0.83), 2.067 (1.81), 2.084 (2.34), 2.120 (1.66), 2.167 (3.40), 2.229 (0.83), 2.323 (2.11), 2.327 (2.87), 2.332 (2.19), 2.366 (1.36 ), 2.665 (2.04), 2.669 (2.72), 2.674 (2.26), 2.710 (1.36), 3.477 (0.98), 3.486 (0.91), 3.498 (0.83), 3.511 (1.58), 3.520 (1.74), 3.532 (1.96 ), 3.541 (1.21), 3.567 (1.43), 3.574 (1.43), 3.632 (1.06), 3.645 (1.21), 3.666 (0.75), 3.690 (1.43), 3.704 (1.89), 3.726 (1.51), 3.736 (1.58 ), 3.757 (1.66), 3.771 (1.36), 3.794 (1.06), 3.804 (0.98), 3.840 (0.53), 3.873 (1.06), 3.892 (0.60), 3.909 (0.91), 3.935 (1.06), 3.949 (1.21 ), 3.964 (0.91), 3.986 (1.21), 4.000 (1.06), 4.015 (0.68), 4.028 (0.60), 4.104 (1.81), 4.136 (1.51), 4.152 (1.13), 4.166 (0.91), 4.179 (1.21 ), 4.191 (0.98), 4.205 (0.83), 4.220 (0.68), 4.892 (3.92), 4.901 (4.91), 5.065 (2.11), 5.106 (10.57), 5.120 (5.81), 5.126 (6.34), 5.167 (1.43 ), 5.257 (1.28), 5.270 (1.28), 5.280 (1.43), 5.289 (1.28), 5.300 (0.75), 5.318 (0.91), 5.335 (1.06), 5.346 (0.98), 5.357 (1.06), 5.370 (1.06 ), 5.381 (1.43), 5.393 (1.43), 5.402 (1.21), 5.412 (1.28), 5.421 (1.13), 5.433 (0.83), 5.447 (0.91), 5.455 (0.91), 5.464 (0.91), 5.479 (0.98 ), 5,486 (1.06), 5,500 (0.83), 7,922 (16.00), 7,941 (1.28), 8,634 (7.09). Example 271 (5RS,8RS)-5-{[(3S)-3-Fluoropyrrolidin-1-yl]carbonyl}-8-(trifluoromethyl)-2-{[6-(trifluoromethyl)pyridin-3-yl]methyl} -5,6,7,8-tetrahydro[1,2,4]triazolo[4,3- a]pyridin-3(2H)-one (diastereomer mixture; 4 isomers)

[01328] Under argon: 5-{[(3S)-3-Fluoropyrrolidin-1-yl]carbonyl}-8-(trifluoromethyl)-2-{[6-(trifluoromethyl)pyridin-3-yl]methyl}[1 ,2,4]triazolo[4,3- a]pyridin-3(2H)-one (165 mg, 346 μmol) and palladium on charcoal (50.0 mg, 10% palladium) were suspended in ethanol (29 mL ) and stirred at room temperature in a hydrogen atmosphere (1 atm). The reaction mixture was filtered through Celite. The filtrate was concentrated, and the residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: gradient (acetonitrile/water with 0.1% formic acid). The fractions containing the product were concentrated under pressure reduced and 21.3 mg (74% possibility) of the title compound were obtained. Diastereomer mixture (4 isomers): LC-MS (Method 3): Rt = 1.51 min MS (ESIpos): m /z = 482 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.150 (1.89), -0.034 (0.38), - 0.009 (16.00), 0.007 (15.87), 0.146 (2.02) , 1.742 (0.63), 1.772 (0.76), 1.799 (0.63), 1.827 (0.50), 2.078 (1.51), 2.104 (1.76), 2.152 (1.39), 2.178 (1.76), 2.222 (1.26), 2.251 (0.76) , 2,322 (3.15), 2,327 (4.16), 2,331 (3.02), 2,365 (2,39), 2,522 (10.20), 2,587 (0.88), 2,639 (0.50), 2,664 (3.28), 2,669 (4,54), 2,674 (3.28) , 2,700 (0.38), 2,709 (2.27), 2,731 (0.50), 2,890 (0.50), 3,366 (1.51), 3,384 (1.39), 3,396 (0.88), 3,412 (1.01), 3,424 (0.50), 3,439 (0.38) , 3.467 (0.50), 3.520 (0.76), 3.535 (1.26), 3.559 (1.01), 3.588 (0.88), 3.609 (1.64), 3.629 (1.13), 3.656 (1.01), 3.676 (0.76), 3.737 (0.76) , 3.757 (0.76), 3.779 (0.88), 3.804 (0.50), 3.869 (0.88), 3.926 (0.50), 3.948 (0.63), 3.964 (0.63), 4.022 (0.50), 4.053 (0.63), 4.091 (1.01) , 4.097 (1.01), 4.778 (0.50), 4.791 (0.63), 4.837 (0.63), 4.846 (0.63), 4.921 (0.76), 4.933 (0.76), 4.956 (0.88), 5.059 (0.63), 5.069 (0.50) , 5,099 (2.52), 5,110 (3.02), 5,122 (4.28), 5,162 (0.88), 5,268 (0.88), 5,355 (0.50), 5,402 (0.88), 5,490 (0.63), 7,897 (0.50), 7,921 (9.57) , 7,941 (0.63), 8,635 (3.78). Example 272 (5RS,8RS)-5-{[(3S)-3-Fluoropyrrolidin-1-yl]carbonyl}-8-(trifluoromethyl)-2-{[6-(trifluoromethyl)pyridin-3-yl]methyl} -5,6,7,8-tetrahydro[1,2,4]triazolo[4,3- a]pyridin-3(2H)-one (isomer 2)

[01329] (5RS,8RS)-5-{[(3S)-3-Fluoropyrrolidin-1-yl]carbonyl}-8-(trifluoromethyl)-2-{[6-(trifluoromethyl)pyridin-3-yl]methyl }-5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one (diastereomer mixture; 4 isomers) was separated by chiral preparatory HPLC [sample preparation: 93 mg was dissolved in 3 mL of ethanol and 3 mL of n-heptane; injection volume: 0.58 mL; column: Daicel Chiralpak® IA 5 μm, 250 x 20 mm; eluent: n-heptane/ethanol 60:40; flow rate: 15 ml/min; temperature 40°C; UV detection: 220 nm]. After separation, 46 mg of isomer 1, which elutes first, and 32.7 mg of isomer 2, which elutes later, were isolated. Isomer 2:

[01330] Analytical chiral HPLC: Rt = 1.95 min, d = 98.4% [column: Daicel Chiralpak® IA, 3 μm, 50 x 4.6 mm; eluent: n-heptane/ethanol 50:50; flow rate: 1 ml/min; UV detection: 220 nm]. LC-MS (Method 3): Rt = 1.54 min; MS (ESIpos): m /z = 482 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (0.71), -0.008 (6.13), 0.008 (5.87), 0.146 (0.71), 1806 (1.01), 1827 (1.52), 1850 (1.06), 2078 (2.58), 2095 (2.28), 2105 (3.14), 2142 (2.03), 2152 (1.92), 2177 (1.77), 2192 (1.52) (1.27) (0.81), 3633 (2.94), 3651 (2.18), 3676 (1.57), 3699 (1.22), 3736 (2.03), 3761 (1.92), 3781 (1.57), 3806 (1.16), 3869 (2.38), 4089 (1.37) (1.42), 5,399 (1.62), 5,520 (0.91), 7,921 (16.00), 7,941 (0.96), 8,637 (7.04). Example 273 (5RS,8RS)-2-[(3-Fluoropyridin-2-yl)methyl]-5-{[(3S)-3-fluoropyrrolidin-1-yl]carbonyl}-8-(trifluoromethyl)-5, 6,7,8-tetrahydro[1,2,4]triazolo[4,3- a]pyridin-3(2H)-one (mixture of diastereomer; 4 isomers)

[01331] Under argon, 2-[(5-chloro-3-fluoropyridin-2-yl)methyl]-5-{[(3S)-3-fluoropyrrolidin-1-yl]carbonyl}-8-(trifluoromethyl)[ 1,2,4]triazolo[4,3-a]pyridin-3(2H)-one (50.0 mg, 62% purity, 67.1 μmol) and palladium on charcoal (10.0 mg, palladium a 10%) were suspended in ethanol (5.0 mL) and stirred at room temperature in a hydrogen atmosphere (1 atm) over the weekend. The reaction mixture was filtered through Celite. The filtrate was concentrated, and the residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: gradient (acetonitrile/water with 0.1% formic acid). The fractions containing the product were concentrated under pressure reduced and 0.5 mg (1.7% possibility) of the title compound was obtained. LC-MS (Method 3): Rt = 1.18 min (ESIpos): m / z = 432 [M+H] +1H-NMR (500 MHz, DMSO-d6) δ [ppm]: -0.120 (1.33), -0.009 (5.54), - 0.007 (16.00), 0.007 (11.08), 0.117 (1.28), 1.330 (0.87), 1,343 (0.82), 1,768 (1.90), 1,796 (2.56), 1,815 (1.79), 1,823 (2.10), 1,856 (2.36), 1,880 (2.10), 1,901 (0.77), 2,010 (2.82), 2,019 (3.54), 2,027 (3.85), 2,037 (5.03), 2,050 (6.10), 2,072 (4.97), 2,081 (4.26), 2,101 (3.49), 2,121 (4.51), 2,152 (9.44), 2,164 (5.90), 2,182 (4.36), 2,230 (3.18), 2,258 (2.36), 2,271 (2.31), 2,354 (1.18), 2,358 (2.31), 2,361 (3.08), 2,365 (2.21), 2,369 (1.08), 2,518 (5.38), 2,522 (3.79), 2,628 (1.03), 2,631 (2.15), 2,635 (2.97), 2,639 (2.10), 2,643 (0.87), 3,348 (6.56), 3,358 (4.92), 3,371 (3.74), 3,380 (3.13), 3,390 (2.36), 3,411 (1.74), 3,418 (1.69), 3,461 (1.18), 3,468 (1.23), 3,488 (1.95), 3,495 (1.74), 3,516 (1.90), 3,522 (1.95), 3,543 (4.67), 3,563 (4.87), 3,577 (3.03), 3,585 (3.28), 3,590 (3.18), 3,598 (5.03), 3,615 (1.23), 3,633 (3.79), 3,650 (3.95), 3,656 (2.97), 3,670 (2.92), 3,686 (2.72), 3,711 (1.33), 3,738 (2.62), 3,746 (1.54), 3,756 (3.38), 3,764 (2.05), 3,772 (2.05), 3,783 (1.38), 3,789 (1.33), 3,812 (1.59), 3,837 (0.77), 3,861 (3.33), 3,936 (1.59), 3,954 (2.87), 3,972 (2.51), 3,994 (1.28), 4,015 (1.44), 4,041 (1.74), 4,079 (3.95), 4,772 (2.00), 4,776 (2.26), 4,785 (2.36), 4,825 (2.62), 4,830 (3.33), 4,838 (2.72), 4,842 (2.51), 4,896 (2.51), 4,900 (2.97), 4,908 (2.82), 4,912 (2.62), 4,936 (2.51), 4,943 (3.85), 4,953 (2.62), 4,965 (3.90), 4,970 (8.05), 4,973 (7.33), 4,997 (5.59), 5,001 (11.64), 5,005 (10.67), 5,114 (4.26), 5,118 (7.54), 5,122 (6.82), 5,127 (7.74), 5,131 (4.36), 5,146 (2.87), 5,149 (4.97), 5,154 (4.46), 5,159 (5.13), 5,163 (2.77), 5,279 (3.13), 5,285 (2.97), 5,368 (2.05), 5,385 (3.23), 5,393 (3.44), 5,474 (1.85), 5,507 (1.33), 7,422 (6.10), 7,431 (11,08), 7,439 (12,26), 7,448 (12,77), 7,457 (7,08), 7,711 (8.15), 7,713 (6,41), 7,729 (12.10), 7,733 (6,97), 7,748 (7,23), 8,360 (8,05), 8,363 (13,28), 8,369 (8,67), 8,372 (12,87), 8,524 (5,03). Example 274 (5RS,8RS)-5-{[(3R,4S)-3,4-Difluoropyrrolidin-1-yl]carbonyl}-2-[(3-fluoropyridin-2-yl)methyl]-8-(trifluoromethyl )-5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one (diastereomer mixture; 4 isomers)

[01332] Under argon: 2-[(5-Chloro-3-fluoropyridin-2-yl)methyl]-5-{[(3R,4S)- 3,4-difluoropyrrolidin-1-yl]carbonyl}-8- (trifluoromethyl)[1,2,4]triazolo[4,3- a]pyridin-3(2H)-one (95.0 mg, 47% purity, 93.1 μmol) and palladium on charcoal (10.0 mg, 10% palladium) were suspended in ethanol (5.0 mL) and stirred at room temperature in a hydrogen atmosphere (1 atm) overnight. The reaction mixture was filtered through Celite. The filtrate was concentrated, and the residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: gradient (acetonitrile/water with 0.1% formic acid). The fractions containing the product were concentrated under pressure reduced and 17 mg (41% possibility) of the title compound were obtained LC-MS (Method 3): Rt = 1.25 min (ESIpos): m /z = 450 [M+H]+ 1H-NMR; (400 MHz, DMSO-d6) δ [ppm]: -0.149 (2.00), 1.747 (1.83), 1.780 (4.50), 1.808 (5.17), 1.839 (2.50), 2.024 (4.67), 2.034 (5.67), 2.049 (5.67) (2.83) (2.17) (2.67) (4.83) (14.33), 4,971 (9.67), 5,010 (16.00), 5,065 (3.00), 5,114 (9,33), 5,127 (10.00), 5,154 (4,83), 5,00), 5,247 (2.50), 5,257 (3.50), 5,268 (3.67) (3.67) (12.17), 7,450 (12.83), 7,461 (7.00), 7,706 (8.50), 7,731 (13.17), 7,753 (7.83), 8,360 (13.00), 8,371 (12.83). Example 275 (5S,8RS)-5-{[(3S)-3-Fluoropyrrolidin-1-yl]carbonyl}-8-hydroxy-2-{[6-(trifluoromethyl)pyridin-3-yl]methyl}-5 ,6,7,8-tetrahydro[1,2,4]triazolo[4,3- a]pyridin-3(2H)-one (diastereomer mixture; 2 isomers)

[01333] (5S)-5-{[(3S)-3-Fluoropyrrolidin-1-yl]carbonyl}-2-{[6-(trifluoromethyl)pyridin-3-yl]methyl}-5,6,7, 8-tetrahydro[1,2,4]triazolo[4,3- a]pyridin-3(2H)-one (150 mg, 363 μmol) was initially loaded under argon into dichloromethane (1.5 mL) at temperature environment. Subsequently, at 0°C, hydrogen tetrafluoroborate (ethyl ether adduct) (55 μl, 400 μmol) was added dropwise, and the reaction mixture was stirred at 0°C for 30 min and at room temperature for 60 min. The reaction mixture was concentrated and dried under high vacuum overnight. The residue was dissolved in acetonitrile (600 μl) and, at room temperature, a solution of iron(II) (S,S-(2-({(S)-2-[(S)-1- (pyridin-2 -ylmethyl)pyrrolidin-2-yl]pyrrolidin-1-yl}methyl)pyridine)(bis-acetonitrile) hexafluoroantimonate (16.9 mg, 18.1 μmol) and acetic acid (10 μl, 180 μmol) in acetonitrile (0 .36 mL) was slowly added dropwise. Subsequently, at room temperature, hydrogen peroxide (27 μL, 50% solution in water, 440 μmol) in acetonitrile (3.3 mL) was slowly added dropwise, and the mixture was mixed. was stirred for 10 min. Hydrogen peroxide (27 μl, 50% solution by weight in water, 440 μmol) in acetonitrile (3.3 mL) was added dropwise again, and the mixture was stirred for another 10 minutes. of hydrogen (27 μl, 50% solution in water, 440 μmol) in acetonitrile (3.3 mL) was added dropwise again, and the mixture was stirred at room temperature for a further 40 minutes. aqueous sodium hydroxide solution and stirred vigorously at room temperature for 20 minutes. The mixture was diluted again with aqueous sodium hydroxide solution, and the aqueous phase was extracted with dichloromethane. The organic phase was washed with saturated aqueous sodium chloride solution, dried over sodium sulfate and filtered, and the filtrate was concentrated. The residue was purified via preparatory HPLC (Method 11). The fractions containing the product were concentrated under reduced pressure and 15.0 mg (9% possibility) of the title compound were obtained. LC-MS (Method 3): Rt = 1.09 min; MS (ESIpos): m /z = 430 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (1.25), -0.008 (16.00), 0.008 (8.87), 0.015 (0.77) (1.17) (0.85), 2323 (1.25), 2327 (1.53), 2331 (1.21), 2366 (2.10), 2389 (0.97), 2405 (1.01), 2425 (0.77), 2523 (7.70), 2525 (6.85), 2558 (1.21) (0.28) (0.64) (1.37) (0.60) (0.36) (0.93) (0.60), 7,920 (7.58), 8,650 (2.66), 8,663 (1.37). Alternative method:

[01334] (5S)-5-{[(3S)-3-Fluoropyrrolidin-1-yl]carbonyl}-2-{[6-(trifluoromethyl)pyridin-3-yl]methyl}-5,6,7, 8-tetrahydro[1,2,4]triazolo[4,3- a]pyridin-3(2H)-one (400 mg, 968 μmol) and cerium(IV) sulfate (1.29 g, 3, 87 mmol) were suspended in tert-butanol (1.3 mL) at room temperature. Subsequently, 1N aqueous sulfuric acid (1.3 mL, 24 mmol) was added, and the reaction mixture was stirred at 70 ° C overnight. The reaction mixture was cooled to room temperature and adjusted to pH 9 with 2 N aqueous sodium hydroxide solution. The suspension was filtered and the filtrate was extracted three times with dichloromethane. The combined organic phases were dried over sodium sulfate and filtered, and the filtrate was concentrated. 270 mg (59% chance) of the title compound was obtained. LC-MS (Method 3): Rt = 1.03 min; MS (ESIpos): m /z = 430 [M+H]+ Example 276 (5S)-5-{[(3S)-3-Fluoropyrrolidin-1-yl]carbonyl}-2-{[6-(trifluoromethyl) pyridin-3-yl]methyl}-5,6-dihydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one

[01335] (5S,8RS)-5-{[(3S)-3-Fluoropyrrolidin-1-yl]carbonyl}-8-hydroxy-2- {[6-(trifluoromethyl)pyridin-3-yl]methyl}- 5,6,7,8-tetrahydro[1,2,4]triazolo[4,3- a]pyridin-3(2H)-one (diastereomer mixture; 2 isomers) (200 mg, 70% purity , 326 μmol) was initially loaded in THF (4.8 mL) at room temperature. Subsequently, 3,3,3-triethyl-1-(methoxycarbonyl)diazathian-3-io-1-oxide 2,2-dioxide (233 mg, 978 μmol) was added, and the mixture was stirred in the microwave. at 90°C for 45 min. 3,3,3-Triethyl-1-(methoxycarbonyl)diazathian-3-io-1-oxide 2,2-dioxide (78 mg, 326 μmol) was added again, and the mixture was stirred in the microwave at 90° C for another 2 hours. The reaction mixture was concentrated under reduced pressure and the residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 40mm; eluent: acetonitrile/water with 0.1% formic acid gradient). The fractions containing the product were concentrated under reduced pressure and 9.60 mg (7% possibility) of the title compound were obtained. LC-MS (Method 3): Rt = 1.28 min; MS (ESIpos): m /z = 412 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (1.80), -0.032 (0.48), - 0.027 (0.60), -0.024 (0.72), -0.019 (0.96), -0.016 (1.20), -0.009 (16.00), 0.007 (15.52), 0.018 (0.96), 0.022 (0.60), 0.027 (0.60), 0.146 (1.80), 2.091 (0.60) (0.36) (3.61) (0.84) (3.25) (0.60), 2994 (0.60), 3008 (0.72), 3032 (0.48), 3047 (0.36), 3055 (0.48), 3208 (0.36), 3220 (0.36), 3246 (0.72), 3255 (0.72), 3357 (0.72) (0.96) (0.96), 6.278 (0.60), 6.307 (1.68), 6.315 (1.80), 6.334 (0.84), 6.340 (0.84), 7.922 (7.58), 8.559 (0.36), 8.664 (2.41), 17.706 (0.36). Example 278 (5S)-8,8-Difluoro-5-{[(3S)-3-fluoropyrrolidin-1-yl]carbonyl}-2-{[6-(trifluoromethyl)pyridin-3-yl]methyl}-5 ,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one

[01336] (5S)-5-{[(3S)-3-Fluoropyrrolidin-1-yl]carbonyl}-2-{[6-(trifluoromethyl)pyridin-3-yl]methyl}-6,7-di- hydro[1,2,4]triazolo[4,3-a]pyridine-3,8(2H,5H)-dione (isomer 1) (33.5 mg, 62% purity, 48.6 μmol) was initially charged under argon in dichloromethane (5.0 mL) at room temperature. Subsequently, diethylamino sulfur trifluoride (19 μl, 150 μmol) was added, and the mixture was stirred at 40°C overnight. The reaction mixture was mixed with water and saturated aqueous sodium hydrogen carbonate solution. The aqueous phase was extracted four times with dichloromethane, and the combined organic phases were dried over sodium sulfate and filtered, and the filtrate was concentrated. The residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: gradient (acetonitrile/water with 0.1% formic acid). The fractions containing the product were concentrated under reduced pressure and 7. 10 mg (31% possibility) of the title compound. LC-MS (Method 3): Rt = 1.52 min; MS (ESIpos): m / z = 450 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (1.80), -0.008 (15.78), 0.008 (16.00), 0.027 (0.58), 0.146 (1.66), 1.096 (1.30), 1.113 (3.17), 1.131 (1.51) , 2,119 (0.94), 2,148 (1.37), 2,169 (1.01), 2,177 (0.94), 2,237 (1.15), 2,284 (2.02), 2,323 (3.24), 2,327 (3.68), 2,332 (3.10), 2,352 (1.73) , 2,366 (3.17), 2,381 (1.37), 2,407 (0.94), 2,435 (1.30), 2,446 (1.08), 2,523 (6.92), 2,568 (0.58), 2,591 (0.58), 2,665 (1.95), 2,670 (2.67) , 2.674 (1.95), 2.710 (2.31), 3.184 (0.58), 3.201 (0.65), 3.243 (0.72), 3.346 (1.51), 3.357 (1.08), 3.375 (0.65), 3.395 (0.65), 3.420 (0.58) , 3.428 (0.58), 3.518 (0.58), 3.527 (0.65), 3.614 (0.58), 3.655 (1.59), 3.679 (1.66), 3.707 (1.15), 3.758 (0.94), 3.780 (1.37), 3.801 (1.15) , 3,825 (0.79), 3,890 (1.51), 4,864 (0.72), 4,878 (1.15), 4,940 (1.51), 5,172 (9,87), 5,277 (1.08), 5,407 (1.15), 5,531 (0.58), 7,946 (14,49) , 7,949 (9.37), 8,677 (4.25). Example 279 (5S,8RS)-2-[(5-Chloropyridin-3-yl)methyl]-5-{[(3S)-3-fluoropyrrolidin-1-yl]carbonyl}-8-hydroxy-5,6, 7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one (mixture of diastereomer; 2 isomers)

[01337] (5S)-2-[(5-Chloropyridin-3-yl)methyl]-5-{[(3S)-3-fluoropyrrolidin-1-yl]carbonyl}-5,6,7,8-tetra -hydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one (15.2 mg, 38.8 μmol) and cerium(IV) sulfate (51.6 mg, 155 μmol) were suspended in tert-butanol (52 μl) at room temperature. Subsequently, 1 N aqueous sulfuric acid (52 μl, 970 μmol) was added, and the reaction mixture was stirred at 70°C overnight. Cerium (IV) sulfate (25.8 mg, 77.6 μmol) was added again, and the mixture was stirred once more at 70°C overnight. The reaction mixture was cooled to room temperature and adjusted to pH 9 with 2N aqueous sodium hydroxide solution. The solids were filtered with suction and the filtrate was extracted three times with dichloromethane. The combined organic phases were dried over sodium sulfate and filtered, and the filtrate was concentrated. The residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: gradient (acetonitrile/water with 0.1% formic acid). The fractions containing the product were concentrated under reduced pressure and 7. 10 mg (46% possibility) of the title compound. LC-MS (Method 4): Rt = 0.48 min; MS (ESIpos): m / z = 396 [M+H]+ 1H-NMR (600 MHz, DMSO-d6) δ [ppm]: 1.443 (2.53), 1.446 (2.51), 1.727 (1.43), 1.743 (2.23), 1.749 (2.12), 1.757 (2.29), 1.791 (1.45), 1.796 (1.26), 1.811 (2.25) (2.12) (2.40) (2.68) (2.25) (1.39) (2.77), 8,355 (1.36), 8,431 (4.78), 8,446 (3.55), 8,569 (7.77), 8,572 (7.90). Example 280 (5RS,6RS)-5-{[(3S)-3-Fluoropyrrolidin-1-yl]carbonyl}-2-{[3-fluoro-2-(trifluoromethyl)pyridin-4-yl]methyl}-6 -(trifluoromethyl)-5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one (mixture of diastereomer, 2 isomers)

[01338] (5RS,6RS)-2-{[3-Fluoro-2-(trifluoromethyl)pyridin-4-yl]methyl}-3-oxo-6-(trifluoromethyl)-2,3,5,6,7 ,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylic acid (mixture of diastereomer; 4 isomers) (96.0 mg, 224 μmol) was initially loaded into THF/ 2.0 mL), THF (120 μl, 2.0 mL) and HBTU (111 mg, 291 μmol) and N,N-diisopropylethylamine (120 μl, 670 μmol) were added subsequently. After stirring at room temperature for 15 minutes, (3S)-3-fluoropyrrolidine hydrochloride (33.8 mg, 269 μmol) was added and the reaction mixture was stirred at room temperature for 72 hours. The solvent was removed under reduced pressure, and the residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/water gradient). The fractions containing the product were concentrated under reduced pressure and 72.0 mg (64% possibility) of the title compound were obtained. LC-MS (Method 3): Rt = 1.64 min; MS (ESIpos): m /z = 500 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (1.82), -0.008 (16.00), 0.008 (13.07), 0.146 (1.70) (0.70), 3.538 (1.41), 3.619 (0.70), 3.668 (0.94), 3.768 (0.76), 4.135 (0.70), 4.840 (0.82) (0.88) (1.70), 7,587 (1.11), 8,572 (3.52), 8,584 (3.40). Example 281 (5RS,6RS)-5-{[(3S)-3-Fluoropyrrolidin-1-yl]carbonyl}-2-{[3-fluoro-2-(trifluoromethyl)pyridin-4-yl]methyl}-6 -(trifluoromethyl)-5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one (isomer 1)

[01339] (5RS,6RS)-5-{[(3S)-3-Fluoropyrrolidin-1-yl]carbonyl}-2-{[3-fluoro-2-(trifluoromethyl)pyridin-4-yl]methyl}- 6-(trifluoromethyl)-5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one (diastereomer mixture; 2 isomers) was separated by chiral preparatory HPLC [sample preparation: 68 mg dissolved in 6 mL of acetonitrile/ethanol (2:1); injection volume: 0.4 mL; column: Daicel Chiralcel® OD-H 5 μm, 250 x 20 mm; eluent: n-heptane/ethanol 70:30; flow rate: 15 ml/min; temperature 25°C; UV detection: 210 nm]. After separation, 26.8 mg of isomer 1, which eluted first, and 27.2 mg of isomer 2, which eluted later, were isolated. Isomer 1:

[01340] Analytical chiral HPLC: Rt = 10.33 min, de = 100% [column: Daicel Chiralcel® OD-3 50 x 4.6 mm; eluent: n-heptane/ethanol 90:10; flow rate: 1 ml/min; UV detection: 220 nm]. LC-MS (Method 4): Rt = 0.86 min; MS (ESIpos): m /z = 500 [M+H]+ ¹H-NMR (500 MHz, DMSO-d6) δ [ppm]: -0.120 (0.91), -0.007 (10.14), 0.006 (7.74), 0.117 (0.91), 0.845 (0.57), 1.234 (1.37), 1.961 (2.73), 1.978 (2.79), 1989 (2.33), 2036 (3.36), 2047 (6.89), 2062 (6.89), 2073 (3.93), 2095 (2.11) (3.13) (2.79) (2.51) (2.79) (1.77), 5,054 (2.28), 5,067 (8.54), 5,082 (10.65), 5,087 (13.04), 5,098 (12.19), 5,115 (1.82), 5,132 (1.94), 5,293 (2.96), 5,399 (3.02), 5,02) (1.99), 5.946 (0.51), 7.549 (3.87), 7.559 (7.12), 7.569 (4.21), 7.575 (3.25), 7.585 (5.41), 7.596 (2.73), 8.572 (16.00), 8.582 (15.43). Example 282(5RS,6RS)-2-[(3,5-Dichloropyridin-2-yl)methyl]-5-{[(3S)-3-fluoropyrrolidin-1-yl]carbonyl}-6-(trifluoromethyl)- 5,6,7,8-tetrahydro[1,2,4]triazolo[4,3- a]pyridin-3(2H)-one (diastereomer mixture; 2 isomers)

[01341] (5RS,6RS)-2-[(3,5-Dichloropyridin-2-yl)methyl]-3-oxo-6-(trifluoromethyl)-2,3,5,6,7,8-hexa- hydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylic acid (mixture of diastereomer; 4 isomers) (50.0 mg, 122 μmol) was initially loaded into THF (2.0 mL) , and HBTU (60.0 mg, 158 μmol) and N,N-diisopropylethylamine (64 μl, 360 μmol) were subsequently added. After stirring at room temperature for 15 minutes, (3S)-3-fluoropyrrolidine hydrochloride (18.3 mg, 146 μmol) was added and the reaction mixture was stirred at room temperature for 72 hours. The solvent was removed under reduced pressure, and the residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/water gradient). The fractions containing the product were concentrated under reduced pressure and 46.4 mg (79% possibility) of the title compound were obtained. LC-MS (Method 4): Rt = 0.84 min; MS (ESIpos): m /z = 482 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (0.64), -0.008 (5.30), 0.008 (4.77), 0.146 (0.64), 1038 (0.42), 1055 (0.95), 1073 (0.53), 1944 (1.80), 1964 (1.80), 1978 (1.48), 2003 (1.80), 2026 (2.23), 2041 (2.75), 2055 (2.23) (1.06) (1.70) (1.38) (0.74) (1.06), 5.021 (10.91), 5.026 (16.00), 5.045 (6.46), 5.067 (0.74), 5.085 (1.59), 5.279 (1.70), 5.409 (2.01) (8.26), 8,259 (8.90), 8,558 (6.15), 8,560 (6.78), 8,563 (6.68). Example 283 (5RS,6RS)-2-[(3,5-Dichloropyridin-2-yl)methyl]-5-{[(3S)-3-fluoropyrrolidin-1-yl]carbonyl}-6-(trifluoromethyl)- 5,6,7,8-tetrahydro[1,2,4]triazolo[4,3- a]pyridin-3(2H)-one (isomer 1)

[01342] (5RS,7RS)-2-[(3,5-Dichloropyridin-2-yl)methyl]-5-{[(3S)-3-fluoropyrrolidin-1-yl]carbonyl}-6-(trifluoromethyl) -5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one (diastereomer mixture; 2 isomers) was separated by chiral preparatory HPLC [ sample preparation: 43 mg dissolved in 5 mL of acetonitrile/isopropanol (3:2); injection volume: 0.5 mL; column: Daicel Chiralcel® OD-H 5 μm, 250 x 20 mm; eluent: n-heptane/isopropanol 50:50; flow rate: 15 ml/min; temperature 25°C; UV detection: 210 nm]. After separation, 19.2 mg of isomer 1, which eluted first, and 18.3 mg of isomer 2, which eluted later, were isolated. Isomer 1:

[01343] Analytical chiral HPLC: Rt = 3.97 min, de = 100% [column: Daicel Chiralcel® ID-3 50 x 4.6 mm; eluent: n-heptane/isopropanol 50:50; flow rate: 1 ml/min; UV detection: 220 nm]. LC-MS (Method 3): Rt = 1.61 min; MS (ESIpos): m /z = 482 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (1.20), -0.008 (14.40), 0.008 (9.18), 0.146 (1.16) (2.41) (2.57) (2.81) (0.92) (8.82) (7.06), 8.566 (4.81). Example 284 (5RS,6RS)-5-{[(3S)-3-Fluoropyrrolidin-1-yl]carbonyl}-6-(trifluoromethyl)-2- {[6-(trifluoromethyl)pyridin-3-yl]methyl} -5,6,7,8-tetrahydro[1,2,4]triazolo[4,3- a]pyridin-3(2H)-one (diastereomer mixture; 2 isomers)

[01344] (5RS,6RS)-3-Oxo-6-(trifluoromethyl)-2-{[6-(trifluoromethyl)pyridin-3-yl]methyl}-2,3,5,6,7,8-hexa -hydro[1,2,4]triazolo[4,3- a]pyridine-5-carboxylic acid (mixture of diastereomer; 4 isomers) (54.0 mg, 132 μmol) was initially loaded into THF (2.0 mL ), and HBTU (64.9 mg, 171 μmol) and N,N-diisopropylethylamine (69 μl, 390 μmol) were subsequently added. After stirring at room temperature for 15 minutes, (3S)-3-fluoropyrrolidine hydrochloride (19.8 mg, 158 μmol) was added and the reaction mixture was stirred at room temperature overnight. The solvent was removed under reduced pressure, and the residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/water gradient). The fractions containing the product were concentrated under reduced pressure and 51.4 mg (81% possibility) of the title compound were obtained. LC-MS (Method 3): Rt = 1.55 min; MS (ESIpos): m /z = 482 [M+H]+ Example 285 (5RS,6RS)-5-{[(3S)-3-Fluoropyrrolidin-1-yl]carbonyl}-6-(trifluoromethyl)-2 - {[6-(trifluoromethyl)pyridin-3-yl]methyl}-5,6,7,8-tetrahydro[1,2,4]triazolo[4,3- a]pyridin-3(2H)- one (isomer 1)

[01345] (5RS,6RS)-5-{[(3S)-3-Fluoropyrrolidin-1-yl]carbonyl}-6-(trifluoromethyl)-2-{[6-(trifluoromethyl)pyridin-3-yl]methyl }-5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one (diastereomer mixture; 2 isomers) was separated by chiral preparatory HPLC [sample preparation: 200 mg dissolved in 5 mL of acetonitrile/isopropanol (1:1); injection volume: 0.15 mL; column: Daicel Chiralcel® IB 5 μm, 250 x 30 mm; eluent: n-heptane/isopropanol 50:50; flow rate: 60 ml/min; temperature 28°C; UV detection: 220 nm]. After separation, 69.8 mg of isomer 1, which eluted first, and 71.7 mg of isomer 2, which eluted later, were isolated. Isomer 1:

[01346] Analytical chiral HPLC: Rt = 1.79 min, de = 100% [column: Daicel Chiralcel® IB-3 50 x 4.6 mm; eluent: n-heptane/isopropanol 50:50; flow rate: 1 ml/min; UV detection: 220 nm]. LC-MS (Method 3): Rt = 1.54 min; MS (ESIpos): m /z = 482 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (1.40), -0.008 (16.00), 5.035 (4.08), 5.278 (0.64), 5,405 (0.75), 7,919 (7.30), 8,643 (1.83). Example 286 (5RS,6RS)-5-{[(3S)-3-Fluoropyrrolidin-1-yl]carbonyl}-6-(trifluoromethyl)-2-{[6-(trifluoromethyl)pyridin-3-yl]methyl} -5,6,7,8-tetrahydro[1,2,4]triazolo[4,3- a]pyridin-3(2H)-one (isomer 2)

[01347] (5RS,6RS)-5-{[(3S)-3-Fluoropyrrolidin-1-yl]carbonyl}-6-(trifluoromethyl)-2-{[6-(trifluoromethyl)pyridin-3-yl]methyl }-5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one (diastereomer mixture; 2 isomers) was separated by chiral preparatory HPLC [sample preparation: 200 mg dissolved in 5 mL of acetonitrile/isopropanol (1:1); injection volume: 0.15 mL; column: Daicel Chiralcel® IB 5 μm, 250 x 30 mm; eluent: n-heptane/isopropanol 50:50; flow rate: 60 ml/min; temperature 28°C; UV detection: 220 nm]. After separation, 69.8 mg of isomer 1, which eluted first, and 71.7 mg of isomer 2, which eluted later, were isolated. Isomer 2:

[01348] Analytical chiral HPLC: Rt = 2.10 min, de = 100% [column: Daicel Chiralcel® IB-3 50 x 4.6 mm; eluent: n-heptane/isopropanol 50:50; flow rate: 1 ml/min; UV detection: 220 nm]. LC-MS (Method 3): Rt = 1.54 min; MS (ESIpos): m /z = 482 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (1.85), -0.008 (16.00), 0.008 (14.32), 0.146 (1.85) (1.85) (1.18) (1.01), 5,413 (1.01), 5,514 (1.01), 7,918 (15.16), 7,921 (16.00), 8,644 (4.04). Example 287 (5RS,6RS)-2-[(3,5-Dichloropyridin-2-yl)methyl]-5-{[(3R,4S)-3,4-difluoropyrrolidin-1-yl]carbonyl}-6- (trifluoromethyl)-5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one (diastereomer 1; racemate)

[01349] (5RS,6RS)-2-[(3,5-Dichloropyridin-2-yl)methyl]-3-oxo-6-(trifluoromethyl)-2,3,5,6,7,8-hexa- hydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylic acid (mixture of diastereomer; 4 isomers) (50.0 mg, 122 μmol) was initially loaded into THF (2.0 mL) , and HBTU (60.0 mg, 158 μmol) and N,N-diisopropylethylamine (64 μl, 360 μmol) were subsequently added. After stirring at room temperature for 15 minutes, (3R,4S)-3,4-difluoropyrrolidine hydrochloride (20.9 mg, 146 μmol) was added and the reaction mixture was stirred at room temperature overnight. The solvent was removed under reduced pressure, and the residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/water gradient). The fractions containing the product were concentrated under reduced pressure and 41.0 mg (67% possibility) of the title compound were obtained. LC-MS (Method 3): Rt = 1.66 min; MS (ESIpos): m /z = 500 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (1.74), -0.008 (16.00), 0.008 (14.26), 0.146 (1.74) (2.29) (4.14) (6.64), 8.557 (5.22). Example 288 (5RS,6RS)-2-[(3,5-Dichloropyridin-2-yl)methyl]-5-{[(3R,4S)-3,4-difluoropyrrolidin-1-yl]carbonyl}-6- (trifluoromethyl)-5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one (enantiomer 2)

[01350] (5RS,6RS)-2-[(3,5-Dichloropyridin-2-yl)methyl]-5-{[(3R,4S)-3,4-difluoropyrrolidin-1-yl]carbonyl}-6 -(trifluoromethyl)-5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one (diastereomer 1; racemate) was separated by preparatory HPLC chiral [sample preparation: 40 mg dissolved in 3.5 mL of ethanol (in an ultrasound bath); injection volume: 0.80 mL; column: Daicel Chiralcel® OX-H 5 μm, 250 x 20 mm; eluent: ethanol + 0.2% diethylamine; flow rate: 15 ml/min; temperature 55°C; UV detection: 220 nm]. After separation, 19.5 mg of enantiomer 1, which eluted first, and 18.4 mg of enantiomer 2, which eluted later, were isolated. Enantiomer 2:

[01351] Analytical chiral HPLC: Rt = 8.73 min, ee = 100% [column: Daicel Chiralcel® OX-H-3 250 x 4.6 mm; eluent: ethanol + 0.2% diethylamine; flow rate: 1 ml/min; UV detection: 220 nm]. LC-MS (Method 3): Rt = 1.70 min; MS (ESIpos): m /z = 500 [M+H]+ ¹H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.150 (0.79), 0.146 (0.79), 1.234 (0.93), 1.936 ( 1.08), 2.006 (2.14), 2.022 (2.59), 2.077 (1.22), 2.327 (1.45), 2.366 (1.24), 2.605 (1.53), 2.626 (1.90), 2.670 (2.67), 2.710 (1.61), 2.741 ( 2.78), 2.756 (1.72), 2.784 (1.48), 3.504 (1.59), 3.524 (1.43), 3.586 (1.24), 3.632 (1.19), 3.651 (1.45), 3.699 (1.27), 3.717 (1.48), 3.732 ( 1.40), 3.783 (0.90), 3.830 (1.24), 3.848 (0.95), 3.901 (0.85), 4.102 (0.85), 4.396 (1.00), 4.918 (5.32), 4.933 (3.09), 4.989 (1.22), 5.027 ( 16.00), 5.047 (5.71), 5.086 (1.22), 5.264 (1.19), 5.355 (1.48), 5.447 (1.06), 8.255 (6.88), 8.260 (7.17), 8.559 (6.72). Example 289 (5RS,6RS)-2-[(3,5-Dichloropyridin-2-yl)methyl]-5-[(3,3-difluoropyrrolidin-1-yl)carbonyl]-6-(trifluoromethyl)-5, 6,7,8-tetrahydro[1,2,4]triazolo[4,3- a]pyridin-3(2H)-one (diastereomer 1, racemate)

[01352] (5RS,6RS)-2-[(3,5-Dichloropyridin-2-yl)methyl]-3-oxo-6-(trifluoromethyl)-2,3,5,6,7,8-hexa- hydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylic acid (mixture of diastereomer; 4 isomers) (50.0 mg, 122 μmol) was initially loaded into THF (2.0 mL) , and HBTU (60.0 mg, 158 μmol) and N,N-diisopropylethylamine (64 μl, 360 μmol) were subsequently added. After stirring at room temperature for 15 minutes, 3,3-difluoropyrrolidine hydrochloride (20.9 mg, 146 μmol) was added and the reaction mixture was stirred at room temperature overnight. The solvent was removed under reduced pressure, and the residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/water gradient). The fractions containing the product were concentrated under reduced pressure and 43.0 mg (71% possibility) of the title compound were obtained. LC-MS (Method 3): Rt = 1.75 min; MS (ESIpos): m /z = 500 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (1.23), -0.008 (10.09), 0.008 (9.95), 0.146 (1.15) (1.80) (2.81) (2.88) (2.02) (4.18), 4,991 (1.95), 5,031 (16.00), 5,039 (13.91), 5,080 (1.73), 5,489 (0.50), 8,256 (7.86), 8,261 (8.65), 8,557 (9.01), 8,562 (8.86). Example 290 (5RS,6RS)-2-[(3,5-Dichloropyridin-2-yl)methyl]-5-[(3,3-difluoropyrrolidin-1-yl)carbonyl]-6-(trifluoromethyl)-5, 6,7,8-tetrahydro[1,2,4]triazolo[4,3- a]pyridin-3(2H)-one (enantiomer 2)

[01353] (5RS,6RS)-2-[(3,5-Dichloropyridin-2-yl)methyl]-5-[(3,3-difluoropyrrolidin-1-yl)carbonyl]-6-(trifluoromethyl)-5 ,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one (diastereomer 1, racemate) was separated by chiral preparatory HPLC [sample preparation: 42 mg dissolved in 3.5 mL of ethanol (in an ultrasound bath); injection volume: 0.80 mL; column: Daicel Chiralcel® OX-H 5 μm, 250 x 20 mm; eluent: ethanol + 0.2% diethylamine; flow rate: 15 ml/min; temperature 55°C; UV detection: 220 nm]. After separation, 17.9 mg of enantiomer 1, which eluted first, and 17.0 mg of enantiomer 2, which eluted later, were isolated. Enantiomer 2:

[01354] Analytical chiral HPLC: Rt = 9.89 min, ee = 100% [column: Daicel Chiralcel® OZ-H-3 250 x 4.6 mm; eluent: n-heptane/ethanol 70:30 + 0.2% diethylamine; flow rate: 1 ml/min; UV detection: 220 nm]. LC-MS (Method 3): Rt = 1.74 min; MS (ESIpos): m /z = 500 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (1.99), 0.008 (16.00), 0.146 (2.21), 1.235 ( 1.40), 1.955 (2.06), 1.974 (2.36), 1.991 (2.36), 2.007 (1.84), 2.057 (2.21), 2.327 (3.24), 2.366 (3.61), 2.573 (2.80), 2.594 (2.29), 2.610 ( 2.29), 2.637 (2.29), 2.669 (4.87), 2.710 (3.17), 2.742 (2.58), 3.407 (2.14), 3.571 (3.32), 3.588 (3.69), 3.606 (1.55), 3.674 (3.10), 3.707 ( 2.95), 3.739 (1.84), 3.767 (1.18), 3.800 (2.51), 3.835 (2.43), 3.867 (1.92), 3.909 (1.33), 4.117 (1.92), 4.143 (1.92), 4.395 (1.25), 4.897 ( 3.47), 4,910 (3.61), 4,947 (4.13), 4,961 (4.13), 4,991 (2.06), 5,030 (15,48), 5,039 (13,20), 5,079 (1.47), 8,256 (8,85), 8,261 (9.00), 8,557 ( 9.88), 8.562 (9.51). Example 291 (5RS,6RS)-2-[(5-Chloro-3-fluoropyridin-2-yl)methyl]-5-{[(3R,4S)-3,4-difluoropyrrolidin-1-yl]carbonyl}- 6-(trifluoromethyl)-5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one (diastereomer 1, racemate)

[01355] (5RS,6RS)-2-[(5-Chloro-3-fluoropyridin-2-yl)methyl]-3-oxo-6- (trifluoromethyl)-2,3,5,6,7,8- hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylic acid (mixture of diastereomer; 4 isomers) (50.0 mg, 127 μmol) was initially loaded into THF (2.0 mL), and HBTU (62.5 mg, 165 μmol) and N,N-diisopropylethylamine (66 μl, 380 μmol) were subsequently added. After stirring at room temperature for 15 minutes, (3R,4S)-3,4-difluoropyrrolidine hydrochloride (21.8 mg, 152 μmol) was added and the reaction mixture was stirred at room temperature overnight. The solvent was removed under reduced pressure, and the residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/water gradient). The fractions containing the product were concentrated under reduced pressure and 45.0 mg (73% possibility) of the title compound were obtained. LC-MS (Method 3): Rt = 1.56 min; MS (ESIpos): m /z = 484 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (1.28), -0.008 (16.00), 0.008 (8.30), 0.146 (1.22) (2.36) (3.31) (1.69) (1.08) (1.35) (4.59) (5.60), 8,103 (5.74), 8,122 (5.67), 8,127 (5.60), 8,476 (6.35). Example 292 (5RS,6RS)-2-[(5-Chloro-3-fluoropyridin-2-yl)methyl]-5-{[(3R,4S)-3,4-difluoropyrrolidin-1-yl]carbonyl}- 6-(trifluoromethyl)-5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one (enantiomer 1)

[01356] (5RS,6RS)-2-[(5-Chloro-3-fluoropyridin-2-yl)methyl]-5-{[(3R,4S)- 3,4-difluoropyrrolidin-1-yl]carbonyl} -6-(trifluoromethyl)-5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one (diastereomer 1, racemate) was separated by Chiral preparatory HPLC [sample preparation: 44 mg dissolved in 2 mL acetonitrile/ethanol (1:1) + 0.2% diethylamine; injection volume: 0.15 mL; column: Daicel Chiralcel® IB 5 μm, 250 x 20 mm; eluent: n-heptane/ethanol 50:50; flow rate: 20 ml/min; temperature 30°C; UV detection: 220 nm]. After separation, 9.9 mg of enantiomer 1, which eluted first, and 11.9 mg of enantiomer 2, which eluted later, were isolated. Enantiomer 1:

[01357] Analytical chiral HPLC: Rt = 1.66 min, ee = 100% [column: Daicel Chiralcel® IE-3 50 x 4.6 mm; eluent: n-heptane/ethanol 50:50 + 0.2% diethylamine; flow rate: 1 ml/min; UV detection: 220 nm]. LC-MS (Method 3): Rt = 1.55 min; MS (ESIpos): m /z = 484 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (1.91), 0.008 (16.00), 0.146 (1.91), 1.109 ( 0.41), 1.236 (0.81), 1.904 (0.93), 1.926 (1.04), 1.961 (0.64), 1.997 (1.86), 2.013 (2.20), 2.057 (0.99), 2.327 (1.86), 2.366 (1.86), 2.596 ( 0.87), 2.620 (1.33), 2.635 (1.10), 2.670 (2.38), 2.710 (2.55), 2.734 (2.14), 2.749 (1.39), 2.777 (1.22), 3.269 (0.70), 3.399 (0.87), 3.468 ( 0.58), 3.501 (1.04), 3.556 (1.10), 3.600 (0.93), 3.628 (0.75), 3.650 (1.04), 3.663 (1.10), 3.698 (1.04), 3.713 (0.87), 3.736 (0.93), 3.770 ( 0.64), 3.790 (0.75), 3.826 (0.99), 3.840 (0.87), 3.854 (0.64), 3.881 (0.58), 3.895 (0.64), 3.908 (0.58), 4.054 (0.64), 4.100 (0.58), 4.356 ( 0.46), 4.372 (0.70), 4.398 (0.87), 4.410 (0.70), 4.438 (0.52), 4.903 (3.19), 4.909 (4.06), 4.925 (2.84), 4.941 (0.87), 4.979 (9.10), 5.002 ( 3.19), 5.037 (0.64), 5.260 (0.99), 5.362 (1.16), 5.401 (1.04), 5.481 (0.81), 8.098 (3.36), 8.103 (3.59), 8.122 (3.65), 8.127 (3.54), 8.477 ( 4.29). Example 293 (5RS,6RS)-2-[(5-Chloro-3-fluoropyridin-2-yl)methyl]-5-{[(3R,4S)-3,4-difluoropyrrolidin-1-yl]carbonyl}- 6-(trifluoromethyl)-5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one (enantiomer 2) (5RS,6RS)-2-[(5-Chloro-3-fluoropyridin-2-yl)methyl]-5-{[(3R,4S)-3,4-difluoropyrrolidin-1-yl]carbonyl}-6- (trifluoromethyl)-5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one (diastereomer 1, racemate) was separated by chiral preparatory HPLC [sample preparation: 44 mg dissolved in 2 mL of acetonitrile/ethanol (1:1) + 0.2% diethylamine; injection volume: 0.15 mL; column: Daicel Chiralcel® IB 5 μm, 250 x 20 mm; eluent: n-heptane/ethanol 50:50; flow rate: 20 ml/min; temperature 30°C; UV detection: 220 nm]. After separation, 9.9 mg of enantiomer 1, which eluted first, and 11.9 mg of enantiomer 2, which eluted later, were isolated. Enantiomer 2:

[01358] Analytical chiral HPLC: Rt = 1.92 min, ee = 97% [column: Daicel Chiralcel® IE-3 50 x 4.6 mm; eluent: n-heptane/ethanol 50:50 + 0.2% diethylamine; flow rate: 1 ml/min; UV detection: 220 nm]. LC-MS (Method 3): Rt = 1.55 min; MS (ESIpos): m /z = 484 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (1.80), -0.008 (16.00), 0.008 (14.88), 0.146 (1.80), 1074 (1.91), 1091 (3.99), 1110 (2.08), 1233 (0.90), 1904 (1.12), 1925 (1.46), 1961 (0.90), 1997 (2.30), 2013 (2.75), 2057 (1.12) (2.25) (1.35) (0.79) (1.35), 5,363 (1.52), 5,402 (1.40), 5,481 (1.07), 8,098 (4.94), 8,103 (5.16), 8,122 (5.00), 8,127 (5.33), 8,478 (7.02). Example 294 (5RS,6RS)-2-[(5-Chloro-3-fluoropyridin-2-yl)methyl]-5-{[(3S)-3-fluoropyrrolidin-1-yl]carbonyl}-6-(trifluoromethyl )-5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one (diastereomer mixture; 2 isomers)

[01359] (5RS,6RS)-2-[(5-Chloro-3-fluoropyridin-2-yl)methyl]-3-oxo-6- (trifluoromethyl)-2,3,5,6,7,8- hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylic acid (mixture of diastereomer; 4 isomers) (50.0 mg, 127 μmol) was initially loaded into THF (2.0 mL), and HBTU (62.5 mg, 165 μmol) and N,N-diisopropylethylamine (66 μl, 380 μmol) were subsequently added. After stirring at room temperature for 15 minutes, (3S)-3-fluoropyrrolidine hydrochloride (19.1 mg, 152 μmol) was added and the reaction mixture was stirred at room temperature overnight. The solvent was removed under reduced pressure, and the residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/water gradient). The fractions containing the product were concentrated under reduced pressure and 39.0 mg (66% possibility) of the title compound were obtained. LC-MS (Method 3): Rt = 1.50 min; MS (ESIpos): m /z = 466 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (0.51), -0.008 (4.55), 0.008 (4.09), 0.146 (0.51) (1.44) (0.88) (5.80) (1.18) (16.00) (1.83) (11.24) (6.01), 8,121 (5.76), 8,126 (6.04), 8,478 (7.30). Example 295 (5RS,6RS)-2-[(5-Chloro-3-fluoropyridin-2-yl)methyl]-5-{[(3S)-3-fluoropyrrolidin-1-yl]carbonyl}-6-(trifluoromethyl )-5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one (isomer 1)

[01360] (5RS,6RS)-2-[(5-Chloro-3-fluoropyridin-2-yl)methyl]-5-{[(3S)-3-fluoropyrrolidin-1-yl]carbonyl}-6-( trifluoromethyl)-5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one (diastereomer mixture; 2 isomers) was separated by preparative HPLC chiral [sample preparation: 38 mg dissolved in 2 mL of acetonitrile/ethanol (1:1); injection volume: 0.15 mL; column: Daicel Chiralcel® ID 5 μm, 250 x 20 mm; eluent: n-heptane/ethanol 35:65 + 0.2% diethylamine; flow rate: 20 ml/min; temperature 25°C; UV detection: 220 nm]. After separation, 11.3 mg of isomer 1, which eluted first, and 13.0 mg of isomer 2, which eluted later, were isolated. Isomer 1:

[01361] Analytical chiral HPLC: Rt = 1.57 min, de = 100% [column: Daicel Chiralcel® ID-3 50 x 4.6 mm; eluent: n-heptane/ethanol 50:50 + 0.2% diethylamine; flow rate: 1 ml/min; UV detection: 220 nm]. LC-MS (Method 3): Rt = 1.50 min; MS (ESIpos): m /z = 466 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (1.91), -0.008 (16.00), 0.008 (14.39), 0.146 (1.76), 0.866 (0.88), 0.886 (1.17), 0.904 (0.73), 1.933 (2.20), 1.947 (1.91), 2.003 (1.76), 2.108 (3.08) (4.11) (2.50) (1.32) (7.05) (1.91), 8,097 (7.93), 8,102 (8.37), 8,121 (8.22), 8,126 (8.51), 8,478 (8.51). Example 296 (5RS,6RS)-2-[(5-Chloro-3-fluoropyridin-2-yl)methyl]-5-[(3,3-difluoropyrrolidin-1-yl)carbonyl]-6-(trifluoromethyl)- 5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one (diastereomer 1, racemate)

[01362] (5RS,6RS)-2-[(5-Chloro-3-fluoropyridin-2-yl)methyl]-3-oxo-6- (trifluoromethyl)-2,3,5,6,7,8- hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylic acid (mixture of diastereomer; 4 isomers) (50.0 mg, 127 μmol) was initially loaded into THF (1.6 mL), and HBTU (62.5 mg, 165 μmol) and N,N-diisopropylethylamine (66 μl, 380 μmol) were subsequently added. After stirring at room temperature for 15 minutes, 3,3-difluoropyrrolidine hydrochloride (21.8 mg, 152 μmol) was added and the reaction mixture was stirred at room temperature overnight. The solvent was removed under reduced pressure, and the residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/water gradient). The fractions containing the product were concentrated under reduced pressure and 48.0 mg (78% possibility) of the title compound were obtained. LC-MS (Method 4): Rt = 0.86 min; MS (ESIpos): m /z = 484 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (0.59), -0.008 (4.82), 0.008 (4.82), 0.146 (0.57), 1,253 (13.91), 1,269 (16.00), 1,279 (10.17), 1,294 (8.34), 1,928 (0.59), 1,947 (0.89), 1,963 (0.97), 1,981 (0.93), 1,997 (0.65), 2.049 (0.91) (1.07) (1.28) (1.07) (0.59) (4.23) (2.98), 8.481 (2.84). Example 297 (5RS,6RS)-2-[(5-Chloro-3-fluoropyridin-2-yl)methyl]-5-[(3,3-difluoropyrrolidin-1-yl)carbonyl]-6-(trifluoromethyl)- 5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one (enantiomer 2)

[01363] (5RS,6RS)-2-[(5-Chloro-3-fluoropyridin-2-yl)methyl]-5-[(3,3-difluoropyrrolidin-1-yl)carbonyl]-6-(trifluoromethyl) -5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one (diastereomer 1, racemate) was separated by chiral preparatory HPLC [preparation of sample: 48 mg dissolved in 2 mL of acetonitrile/methanol (1:1); injection volume: 0.20 mL; column: Daicel Chiralcel® IC 5 μm, 250 x 20 mm; eluent: n-heptane/ethanol 50:50; flow rate: 20 ml/min; temperature 30°C; UV detection: 220 nm]. After separation, 13.9 mg of enantiomer 1, which eluted first, and 16.2 mg of enantiomer 2, which eluted later, were isolated. Enantiomer 2:

[01364] Analytical chiral HPLC: Rt = 1.67 min, ee = 100% [column: Daicel Chiralcel® IC-3 50 x 4.6 mm; eluent: n-heptane/ethanol 50:50; flow rate: 1 ml/min; UV detection: 220 nm]. LC-MS (Method 3): Rt = 1.64 min; MS (ESIpos): m /z = 484 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.150 (3.80), 0.146 (2.40), 0.866 (1.00), 0.885 ( 1.40), 0.904 (0.80), 1.235 (1.00), 1.313 (0.80), 1.946 (1.80), 1.961 (1.80), 1.980 (1.80), 1.998 (1.60), 2.064 (2.20), 2.327 (12.60), 2.365 ( 16.00), 2590 (3.00), 2605 (2.80), 2626 (2.60), 2669 (6.80), 2709 (7.60), 2736 (2.00), 2781 (1.20), 3397 (2.60), 3569 (2.20), 3591 ( 2.00), 3.611 (1.40), 3.640 (1.00), 3.672 (2.00), 3.706 (2.60), 3.773 (1.00), 3.804 (1.80), 3.836 (1.80), 3.861 (1.40), 3.903 (1.20), 3.998 ( 1.20), 4.117 (1.40), 4.143 (1.40), 4.391 (1.20), 4.415 (1.00), 4.888 (2.60), 4.902 (2.60), 4.941 (3.80), 4.953 (2.60), 4.985 (6.80), 5.031 ( 1.00), 8,103 (3.00), 8,127 (3.20), 8,482 (3.40). Example 298 (5RS,6RS)-2-[(5-Chloropyridin-2-yl)methyl]-5-{[(3S)-3-fluoropyrrolidin-1-yl]carbonyl}-6-(trifluoromethyl)-5, 6,7,8-tetrahydro[1,2,4]triazolo[4,3- a]pyridin-3(2H)-one (mixture of diastereomer; 2 isomers)

[01365] (5RS,6RS)-2-[(5-Chloropyridin-2-yl)methyl]-3-oxo-6-(trifluoromethyl)-2,3,5,6,7,8-hexahydro[ 1,2,4]triazolo[4,3-a]pyridine-5-carboxylic acid (mixture of diastereomer; 4 isomers) (47.0 mg, 125 μmol) was initially loaded into THF (2.0 mL), and HBTU (61.5 mg, 162 μmol) and N,N-diisopropylethylamine (65 μl, 370 μmol) were subsequently added. After stirring at room temperature for 15 minutes, (3S)-3-fluoropyrrolidine hydrochloride (18.8 mg, 150 μmol) was added and the reaction mixture was stirred at room temperature overnight. The solvent was removed under reduced pressure, and the residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/water gradient). The fractions containing the product were concentrated under reduced pressure and 31.0 mg (55% possibility) of the title compound were obtained. LC-MS (Method 3): Rt = 1.44 min; MS (ESIpos): m /z = 448 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (1.01), -0.008 (8.66), 0.008 (8.56), 0.146 (1.01) (1.52) (1.16) (1.06) (16.00) (4.66), 7.218 (3.29), 7.227 (7.80), 7.239 (3.34), 7.249 (3.09), 7.920 (5.57), 7.926 (6.38), 7.941 (5.42), 7.947 (6.08), 8.574 (9.52), 8.580 (8.46). Example 299 (5RS,6RS)-2-[(5-Chloropyridin-2-yl)methyl]-5-{[(3S)-3-fluoropyrrolidin-1-yl]carbonyl}-6-(trifluoromethyl)-5, 6,7,8-tetrahydro[1,2,4]triazolo[4,3- a]pyridin-3(2H)-one (isomer 2)

[01366] (5RS,7RS)-2-[(5-Chloropyridin-2-yl)methyl]-5-{[(3S)-3-fluoropyrrolidin-1-yl]carbonyl}-6-(trifluoromethyl)-5 ,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one (diastereomer mixture; 2 isomers) was separated by chiral preparatory HPLC [preparation of sample: 30 mg dissolved in 3 mL of methanol/tert-butyl methyl ether (2:1); injection volume: 1.00 mL; column: Daicel Chiralcel® IB 5 μm, 250 x 20 mm; eluent: methanol/tert-butyl methyl ether 10:90; flow rate: 20 ml/min; temperature 30°C; UV detection: 270 nm]. After separation, 11.1 mg of isomer 1, which eluted first, and 11.3 mg of isomer 2, which eluted later, were isolated. Isomer 2:

[01367] Analytical chiral HPLC: Rt = 6.44 min, de = 100% [column: Daicel Chiralcel® IB 50 x 4.6 mm; eluent: methanol/tert-butyl methyl ether 10:90; flow rate: 1 ml/min; UV detection: 220 nm]. LC-MS (Method 4): Rt = 0.77 min; MS (ESIpos): m /z = 448 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (1.82), -0.008 (16.00), 0.008 (15.36), 0.146 (1.87) (1.82) (1.06) (0.98) (1.36) (4.37) (4.20), 7,228 (7.60), 7,249 (3.44), 7,922 (4.12), 7,928 (4.07), 7,943 (3.95), 7,949 (3.90), 8,573 (5.26), 8,579 (5.22). Example 300 (5RS,6RS)-2-[(5-Chloropyridin-2-yl)methyl]-5-{[(3R,4S)-3,4-difluoropyrrolidin-1-yl]carbonyl}-6-(trifluoromethyl )-5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one (diastereomer 1; racemate)

[01368] (5RS,6RS)-2-[(5-Chloropyridin-2-yl)methyl]-3-oxo-6-(trifluoromethyl)-2,3,5,6,7,8-hexahydro[ 1,2,4]triazolo[4,3-a]pyridine-5-carboxylic acid (mixture of diastereomer; 4 isomers) (47.0 mg, 125 μmol) was initially loaded into THF (2.0 mL), and HBTU (61.5 mg, 162 μmol) and N,N-diisopropylethylamine (65 μl, 370 μmol) were subsequently added. After stirring at room temperature for 15 minutes, (3R,4S)-3,4-difluoropyrrolidine hydrochloride (21.5 mg, 150 μmol) was added and the reaction mixture was stirred at room temperature overnight. The solvent was removed under reduced pressure, and the residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/water gradient). The fractions containing the product were concentrated under reduced pressure and 34.0 mg (59% possibility) of the title compound were obtained. LC-MS (Method 3): Rt = 1.50 min; MS (ESIpos): m /z = 466 [M+H]+ ¹H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (0.67), -0.008 (6.04), 0.008 (5.59), 0.146 (0.67) (1.21) (0.79), 2767 (2.37), 2782 (1.58), 2811 (1.28), 2825 (0.70), 3399 (0.97), 3411 (1.00), 3423 (1.00), 3436 (0.97), 3473 (0.88), 3508 (1.28) (1.03) (0.61) (0.76) (0.43) (0.91) (4.61), 8.579 (4.37). Example 301 (5RS,6RS)-2-[(5-Chloropyridin-2-yl)methyl]-5-{[(3R,4S)-3,4-difluoropyrrolidin-1-yl]carbonyl}-6-(trifluoromethyl )-5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one (enantiomer 2)

[01369] (5RS,6RS)-2-[(5-Chloropyridin-2-yl)methyl]-3-oxo-6-(trifluoromethyl)-2,3,5,6,7,8-hexahydro[ 1,2,4]triazolo[4,3-a]pyridine-5-carboxylic acid (diastereomer 1, racemate) was separated by chiral preparatory HPLC [sample preparation: 34 mg dissolved in 3 mL methanol/tert-butyl methyl ether (3:1); injection volume: 1.00 mL; column: Daicel Chiralcel® IB 5 μm, 250 x 20 mm; eluent: methanol/tert-butyl methyl ether 10:90; flow rate: 15 ml/min; temperature 30°C; UV detection: 270 nm]. After separation, 15.3 mg of enantiomer 1, which eluted first, and 14.3 mg of enantiomer 2, which eluted later, were isolated. Enantiomer 2: analytical chiral HPLC: Rt = 5.58 min, ee = 100% [column: Daicel Chiralcel® IB 50 x 4.6 mm; eluent: methanol/tert-butyl methyl ether 10:90; flow rate: 1 ml/min; UV detection: 220 nm]. LC-MS (Method 4): Rt = 0.80 min; MS (ESIpos): m /z = 466 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (1.57), -0.008 (13.32), 0.008 (12.83), 0.146 (1.53) 1.57), 2.078 (0.97), 2.327 (1.11), 2.366 (0.90), 2.593 (0.56), 2.612 (0.90), 2.636 (0.90), 2.655 (1.60), 2.670 (2.02), 2.695 (0.90), 2.710 ( 2.26), 2.769 (2.19), 2.783 (1.43), 2.812 (1.18), 3.423 (0.97), 3.437 (0.90), 3.472 (0.80), 3.508 (1.18), 3.555 (1.25), 3.593 (1.04), 3.632 ( 0.87), 3.653 (1.18), 3.668 (1.18), 3.687 (0.70), 3.702 (1.11), 3.718 (0.94), 3.727 (0.80), 3.739 (1.22), 3.761 (0.63), 3.774 (0.70), 3.793 ( 0.80), 3.805 (0.80), 3.828 (1.01), 3.846 (0.80), 3.860 (0.73), 3.885 (0.63), 3.900 (0.80), 3.914 (0.63), 4.061 (0.63), 4.098 (0.66), 4.367 ( 0.56), 4,380 (0.70), 4,392 (0.70), 4,408 (0.87), 4,418 (0.73), 4,430 (0.70), 4,446 (0.56), 4,923 (11.65), 4,935 (1600), 4,946 (6,99), 5,244 ( 0.90), 5.256 (0.97), 5.266 (1.08), 5.322 (0.77), 5.358 (1.25), 5.389 (0.97), 5.440 (0.66), 5.463 (0.87), 5.479 (0.83), 7.211 (3.41), 7.225 ( 3.58), 7.231 (3.90), 7.246 (3.62), 7.924 (3.44), 7.927 (3.41), 7.930 (3.34), 7.945 (3.27), 7.949 (3.23), 7.951 (3.20), 8.573 (5.39), 8.579 ( 5.25). Example 302 (5RS,6RS)-5-[(3-Fluoroazetidin-1-yl)carbonyl]-2-{[3-fluoro-2-(trifluoromethyl)pyridin-4-yl]methyl}-6-(trifluoromethyl) -5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one (diastereomer 1, racemate)

[01370] (5RS,6RS)-2-{[3-Fluoro-2-(trifluoromethyl)pyridin-4-yl]methyl}-3-oxo-6-(trifluoromethyl)-2,3,5,6,7 ,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylic acid (mixture of diastereomer; 4 isomers) (96.0 mg, 224 μmol) was initially loaded into THF/ 2.0 mL), THF (120 μl, 2.0 mL) and HBTU (111 mg, 291 μmol) and N,N-diisopropylethylamine (120 μl, 670 μmol) were added subsequently. After stirring at room temperature for 15 minutes, 3-fluoroazetidine hydrochloride (30.0 mg, 269 μmol) was added and the reaction mixture was stirred at room temperature overnight. The solvent was removed under reduced pressure, and the residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/water gradient). The fractions containing the product were concentrated under reduced pressure and 25.0 mg (23% possibility) of the title compound were obtained. LC-MS (Method 3): Rt = 1.61 min; MS (ESIpos): m /z = 486 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (1.95), -0.008 (16.00), 0.008 (14.87), 0.146 (2.03) (1.05) (2.63) (5.11). Example 303 (5RS,6RS)-5-[(3-Fluoroazetidin-1-yl)carbonyl]-2-{[3-fluoro-2-(trifluoromethyl)pyridin-4-yl]methyl}-6-(trifluoromethyl) -5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one (enantiomer 1)

[01371] (5RS,6RS)-5-[(3-Fluoroazetidin-1-yl)carbonyl]-2-{[3-fluoro-2-(trifluoromethyl)pyridin-4-yl]methyl}-6-(trifluoromethyl )-5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one (diastereomer 1; racemate) was separated by chiral preparatory HPLC [preparation sample: 23 mg dissolved in isopropanol/dichloromethane/n-heptane (3:1:2); injection volume: 0.50 mL; column: Daicel Chiralcel® IB 5 μm, 250 x 30 mm; eluent: n-heptane/isopropanol 60:40; flow rate: 60 ml/min; temperature 40°C; UV detection: 220 nm]. After separation, 10.5 mg of enantiomer 1, which eluted first, and 11.8 mg of enantiomer 2, which eluted later, were isolated. Enantiomer 1:

[01372] Analytical chiral HPLC: Rt = 4.70 min, ee = 100% [column: Daicel Chiralcel® IB-3 50 x 4.6 mm; eluent: n-heptane/isopropanol 60:40; flow rate: 1 ml/min; UV detection: 220 nm]. LC-MS (Method 3): Rt = 1.59 min; MS (ESIpos): m /z = 486 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (1.52), -0.008 (16.00), 0.146 (1.68), 1.994 (2.48) (1.44) (8.16), 5,369 (1.12), 5,560 (0.96), 7,566 (3.52), 7,579 (6.40), 7,592 (3.84), 8,571 (6.48), 8,583 (6.40). Example 304 (5RS,6RS)-5-[(3-Fluoroazetidin-1-yl)carbonyl]-6-(trifluoromethyl)-2-{[6-(trifluoromethyl)pyridin-3-yl]methyl}-5,6 ,7,8-tetrahydro[1,2,4]triazolo[4,3- a]pyridin-3(2H)-one (diastereomer 1, racemate)

[01373] (5RS,6RS)-3-Oxo-6-(trifluoromethyl)-2-{[6-(trifluoromethyl)pyridin-3-yl]methyl}-2,3,5,6,7,8-hexa -hydro[1,2,4]triazolo[4,3- a]pyridine-5-carboxylic acid (mixture of diastereomer; 4 isomers) (54.0 mg, 132 μmol) was initially loaded into THF (2.0 mL ), and HBTU (64.9 mg, 171 μmol) and N,N-diisopropylethylamine (69 μl, 390 μmol) were subsequently added. After stirring at room temperature for 15 minutes, 3-fluoroazetidine hydrochloride (17.6 mg, 158 μmol) was added and the reaction mixture was stirred at room temperature overnight. The solvent was removed under reduced pressure, and the residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/water gradient). The fractions containing the product were concentrated under reduced pressure and 47.9 mg (78% possibility) of the title compound were obtained. LC-MS (Method 3): Rt = 1.52 min; MS (ESIpos): m /z = 468 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (1.77), -0.008 (16.00), 0.008 (12.72), 0.146 (1.77) (3.12) (1.18) (0.67), 7,921 (12.46), 8,652 (4.63). Example 305 (5RS,6RS)-5-[(3-Fluoroazetidin-1-yl)carbonyl]-6-(trifluoromethyl)-2-{[6-(trifluoromethyl)pyridin-3-yl]methyl}-5,6 ,7,8-tetrahydro[1,2,4]triazolo[4,3- a]pyridin-3(2H)-one (enantiomer 2) (5RS,6RS)-5-[(3-Fluoroazetidin-1-yl)carbonyl]-6-(trifluoromethyl)-2-{[6-(trifluoromethyl)pyridin-3-yl]methyl}-5,6,7 ,8-tetrahydro[1,2,4]triazolo[4,3- a]pyridin-3(2H)-one (diastereomer 1; racemate) was separated by chiral preparatory HPLC [sample preparation: 46 mg dissolved in acetonitrile/ethanol (3:1); injection volume: 0.30 mL; column: Daicel Chiralcel® IE 5 μm, 250 x 30 mm; eluent: n-heptane/ethanol 50:50; flow rate: 15 ml/min; temperature 30°C; UV detection: 210 nm]. After separation, 16.9 mg of isomer 1, which eluted first, and 21.7 mg of isomer 2, which eluted later, were isolated. Enantiomer 2:

[01374] Analytical chiral HPLC: Rt = 2.09 min, ee = 100% [column: Daicel Chiralcel® IE-3 50 x 4.6 mm; eluent: n-heptane/ethanol 50:50; flow rate: 1 ml/min; UV detection: 220 nm]. LC-MS (Method 4): Rt = 0.80 min; MS (ESIpos): m /z = 468 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (0.84), 0.008 (5.48), 0.146 (0.75), 1.100 ( 0.66), 1.235 (1.33), 1.950 (1.51), 1.968 (1.99), 1.984 (2.44), 2.001 (1.63), 2.040 (1.99), 2.327 (1.45), 2.366 (1.36), 2.524 (6.48), 2.670 ( 3.22), 2.710 (1.51), 2.738 (1.60), 2.754 (2.71), 2.771 (1.66), 2.797 (1.33), 2.813 (0.69), 3.936 (0.75), 3.967 (1.27), 3.998 (1.36), 4.030 ( 1.18), 4.061 (0.84), 4.224 (1.39), 4.244 (1.54), 4.274 (1.66), 4.304 (1.51), 4.471 (0.75), 4.485 (0.78), 4.526 (0.72), 4.540 (0.69), 4.567 ( 0.96), 4.595 (0.72), 4.643 (3.59), 4.655 (5.06), 4.666 (3.28), 4.821 (0.72), 4.849 (0.72), 4.873 (0.66), 5.030 (9.94), 5.045 (9.76), 5.372 ( 0.90), 5.418 (0.87), 5.515 (0.90), 5.561 (0.87), 7.922 (16.00), 8.653 (6.24). Example 306 (5RS,6RS)-2-[(3,5-Dichloropyridin-2-yl)methyl]-5-[(3-fluoroazetidin-1-yl)carbonyl]-6-(trifluoromethyl)-5,6, 7,8-tetrahydro[1,2,4]triazolo[4,3- a]pyridin-3(2H)-one (diastereomer 1, racemate)

[01375] (5RS,6RS)-2-[(3,5-Dichloropyridin-2-yl)methyl]-3-oxo-6-(trifluoromethyl)-2,3,5,6,7,8-hexa- hydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylic acid (mixture of diastereomer; 4 isomers) (50.0 mg, 122 μmol) was initially loaded into THF (2.0 mL) , and HBTU (60.0 mg, 158 μmol) and N,N-diisopropylethylamine (64 μl, 360 μmol) were subsequently added. After stirring at room temperature for 15 minutes, 3-fluoroazetidine hydrochloride (16.3 mg, 146 μmol) was added and the reaction mixture was stirred at room temperature for 72 hours. The solvent was removed under reduced pressure, and the residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/water gradient). The fractions containing the product were concentrated under reduced pressure and 45.3 mg (80% possibility) of the title compound were obtained. LC-MS (Method 4): Rt = 0.82 min; MS (ESIpos): m /z = 468 [M+H]+ Example 307 (5RS,6RS)-2-[(3,5-Dichloropyridin-2-yl)methyl]-5-[(3-fluoroazetidin-1 - yl)carbonyl]-6-(trifluoromethyl)-5,6,7,8-tetrahydro[1,2,4]triazolo[4,3- a]pyridin-3(2H)-one (enantiomer 1)

[01376] (5RS,6RS)-2-[(3,5-Dichloropyridin-2-yl)methyl]-5-[(3-fluoroazetidin-1-yl)carbonyl]-6-(trifluoromethyl)-5,6 ,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one (diastereomer 1; racemate) was separated by chiral preparatory HPLC [sample preparation: 40 mg dissolved in acetonitrile/ethanol (3:1); injection volume: 0.40 mL; column: Daicel Chiralcel® IE 5 μm, 250 x 30 mm; eluent: n-heptane/ethanol 50:50; flow rate: 15 ml/min; temperature 25°C; UV detection: 210 nm]. After separation, 17.6 mg of enantiomer 1, which eluted first, and 18.1 mg of enantiomer 2, which eluted later, were isolated. Enantiomer 1:

[01377] Analytical chiral HPLC: Rt = 2.65 min, ee = 100% [column: Daicel Chiralcel® IE-3 50 x 4.6 mm; eluent: n-heptane/ethanol 50:50; flow rate: 1 ml/min; UV detection: 220 nm]. LC-MS (Method 4): Rt = 0.82 min; MS (ESIpos): m /z = 468 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (1.90), -0.008 (16.00), 0.008 (14.18), 0.146 (1.90) (1.21) (0.69), 5.037 (9.51), 5.046 (7.26), 5.411 (0.78), 5.548 (0.69), 8.258 (5.97), 8.263 (6.31), 8.556 (4.06). 2,728 (2.25), 2,745 (1.21), 2,772 (1.21), 3,958 (1.12), 3,984 (1.04), 4,018 (1.04), 4,243 (1.73), 4,543 (0.86), 4,609 (3.03), 4,623 (3.55), 4,631 (2.77), 4,800 (0.69), 5,037 (9.51), 5,046 (7.26), 5,411 (0.78), 5,548 (0.69), 8,258 (5.97), 8,263 (6.31), 8,556 (4.06). Example 308 (5RS,6RS)-2-[(5-Chloro-3-fluoropyridin-2-yl)methyl]-5-[(3-fluoroazetidin-1-yl)carbonyl]-6-(trifluoromethyl)-5, 6,7,8-tetrahydro[1,2,4]triazolo[4,3- a]pyridin-3(2H)-one (diastereomer 1; racemate)

[01378] (5RS,6RS)-2-[(5-Chloro-3-fluoropyridin-2-yl)methyl]-3-oxo-6- (trifluoromethyl)-2,3,5,6,7,8- hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylic acid (mixture of diastereomer; 4 isomers) (50.0 mg, 127 μmol) was initially loaded into THF (2.0 mL), and HBTU (62.5 mg, 165 μmol) and N,N-diisopropylethylamine (66 μl, 380 μmol) were subsequently added. After stirring at room temperature for 15 minutes, 3-fluoroazetidine hydrochloride (17.0 mg, 152 μmol) was added and the reaction mixture was stirred at room temperature overnight. The solvent was removed under reduced pressure, and the residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/water gradient). The fractions containing the product were concentrated under reduced pressure and 37.0 mg (65% possibility) of the title compound were obtained. LC-MS (Method 3): Rt = 1.46 min; MS (ESIpos): m /z = 452 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (1.64), -0.008 (15.18), 0.008 (15.69), 0.146 (1.85) (4.31) (2.36) (1.33) (11.59). Example 309 (5RS,6RS)-2-[(5-Chloro-3-fluoropyridin-2-yl)methyl]-5-[(3-fluoroazetidin-1-yl)carbonyl]-6-(trifluoromethyl)-5, 6,7,8-tetrahydro[1,2,4]triazolo[4,3- a]pyridin-3(2H)-one (enantiomer 2)

[01379] (5RS,6RS)-2-[(5-Chloro-3-fluoropyridin-2-yl)methyl]-5-[(3-fluoroazetidin-1-yl)carbonyl]-6-(trifluoromethyl)-5 ,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one (diastereomer 1, racemate) was separated by chiral preparatory HPLC [sample preparation: 36 mg dissolved in 3 mL of ethanol; injection volume: 0.80 mL; column: Daicel Chiralcel® OX-H 5 μm, 250 x 20 mm; eluent: ethanol + 0.2% diethylamine; flow rate: 15 ml/min; temperature 55°C; UV detection: 235 nm]. After separation, 13.7 mg of enantiomer 1, which eluted first, and 11.7 mg of enantiomer 2, which eluted later, were isolated. Enantiomer 2:

[01380] Analytical chiral HPLC: Rt = 7.56 min, ee = 100% [column: Daicel Chiralcel® OZ-H 50 x 4.6 mm; eluent: n-heptane/ethanol 70:30 + 0.2% diethylamine; flow rate: 1 ml/min; UV detection: 220 nm]. LC-MS (Method 3): Rt = 1.46 min; MS (ESIpos): m /z = 452 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (1.44), -0.008 (13.25), 0.146 (1.40), 1.236 (0.90) (3.70) (2.34) (1.26) (8.88) (1.58), 5,513 (1.53), 5,556 (1.49), 8,104 (6.81), 8,128 (6.99), 8,476 (8.16). Example 310 (5RS,6RS)-2-[(5-Chloropyridin-2-yl)methyl]-5-[(3-fluoroazetidin-1-yl)carbonyl]-6-(trifluoromethyl)-5,6,7, 8-tetrahydro[1,2,4]triazolo[4,3- a]pyridin-3(2H)-one (diastereomer 1, racemate)

[01381] (5RS,6RS)-2-[(5-Chloropyridin-2-yl)methyl]-3-oxo-6-(trifluoromethyl)-2,3,5,6,7,8-hexahydro[ 1,2,4]triazolo[4,3-a]pyridine-5-carboxylic acid (mixture of diastereomer; 4 isomers) (47.0 mg, 125 μmol) was initially loaded into THF (2.0 mL), and HBTU (61.5 mg, 162 μmol) and N,N-diisopropylethylamine (65 μl, 370 μmol) were subsequently added. After stirring at room temperature for 15 minutes, 3-fluoroazetidine hydrochloride (16.7 mg, 150 μmol) was added and the reaction mixture was stirred at room temperature overnight. The solvent was removed under reduced pressure, and the residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/water gradient). The fractions containing the product were concentrated under reduced pressure and 30.0 mg (55% possibility) of the title compound were obtained. LC-MS (Method 3): Rt = 1.40 min; MS (ESIpos): m /z = 434 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (2.09), -0.008 (15.63), 0.008 (16.00), 0.146 (2.02) (3.29) (1.64) (5.23) (9.05), 7,248 (9.87), 7,928 (4.64), 7,944 (4.26), 8,575 (7.03), 8,581 (3.96). Example 311 (5RS,6RS)-2-[(5-Chloropyridin-2-yl)methyl]-5-[(3-fluoroazetidin-1-yl)carbonyl]-6-(trifluoromethyl)-5,6,7, 8-tetrahydro[1,2,4]triazolo[4,3- a]pyridin-3(2H)-one (enantiomer 2)

[01382] (5RS,6RS)-2-[(5-Chloropyridin-2-yl)methyl]-5-[(3-fluoroazetidin-1-yl)carbonyl]-6-(trifluoromethyl)-5,6,7 ,8-tetrahydro[1,2,4]triazolo[4,3- a]pyridin-3(2H)-one (diastereomer 1; racemate) was separated by chiral preparatory HPLC [sample preparation: 30 mg dissolved in 3 mL of ethanol/acetonitrile (1:2); injection volume: 0.25 mL; column: Daicel Chiralcel® IC 5 μm, 250 x 20 mm; eluent: n-heptane/ethanol (50:50); flow rate: 15 ml/min; temperature 25°C; UV detection: 210 nm]. After separation, 12.30 mg of enantiomer 1, which eluted first, and 12.1 mg of enantiomer 2, which eluted later, were isolated. Enantiomer 2:

[01383] Analytical chiral HPLC: Rt = 2.51 min, ee = 100% [column: Daicel Chiralcel® IC-3 50 x 4.6 mm; eluent: n-heptane/ethanol 50:50; flow rate: 1 ml/min; UV detection: 220 nm]. LC-MS (Method 3): Rt = 140.00 min; MS (ESIpos): m /z = 433 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (0.76), -0.008 (7.47), 0.008 (6.94), 0.146 (0.88) (2.18) (2.00) (5.59) 5 (9.65). Example 312 (5RS,7RS)-5-[(3,3-Difluoropyrrolidin-1-yl)carbonyl]-7-(trifluoromethyl)-2-{[6-(trifluoromethyl)pyridin-3-yl]methyl}-5 ,6,7,8-tetrahydro[1,2,4]triazolo[4,3- a]pyridin-3(2H)-one (diastereomer 1; racemate)

[01384] (5RS,7RS)-3-Oxo-7-(trifluoromethyl)-2-{[6-(trifluoromethyl)pyridin-3-yl]methyl}-2,3,5,6,7,8-hexa -hydro[1,2,4]triazolo[4,3- a]pyridine-5-carboxylic acid (mixture of diastereomer; 4 isomers) (100 mg, 90% purity, 219 μmol) was initially loaded into THF (3 .0 mL), and HBTU (108 mg, 285 μmol) and N,N-diisopropylethylamine (110 μl, 660 μmol) were subsequently added. After stirring at room temperature for 15 minutes, 3,3-difluoropyrrolidine hydrochloride (37.7 mg, 263 μmol) was added and the reaction mixture was stirred at room temperature overnight. The solvent was removed under reduced pressure, and the residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/gradient water) and diastereomer 1 was isolated. The fractions containing the product were concentrated under reduced pressure and 78.2 mg (71% possibility) of the title compound were obtained. LC-MS (Method 3): Rt = 1.69 min; MS (ESIpos): m /z = 500 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (0.71), -0.008 (5.74), 0.146 (0.71), 2.138 (0.40) (0.51) 2,726 (2.30), 2,735 (1.48), 2,757 (1.63), 2,764 (1.68), 2,895 (1.15), 2,927 (1.08), 2,979 (2.12), 3,019 (1.61), 3,541 (0.44), 3,552 (1.04), 3,571 (2.21), 3,586 (2.16), 3,603 (1.28), 3,714 (0.99), 3,756 (1.28), 3,786 (1.52), 3,821 (1.17), 3,901 (1.04), 3,919 (2.36), 3,936 (2.58), 3,955 (1.06), 4,135 (0.88), 4,163 (0.73), 4,178 (1.28), 4,205 (1.35), 4,238 (0.90), 4,968 (1.70), 4,982 (1.63), 5,019 (1.74), 5,048 (16.00), 7,920 (15.23), 7,943 (0.93), 8,642 (5.16), 8,678 (0.77). Example 313 (5RS,7RS)-5-[(3,3-Difluoropyrrolidin-1-yl)carbonyl]-7-(trifluoromethyl)-2-{[6-(trifluoromethyl)pyridin-3-yl]methyl}-5 ,6,7,8-tetrahydro[1,2,4]triazolo[4,3- a]pyridin-3(2H)-one (enantiomer 1)

[01385] (5RS,7RS)-5-[(3,3-Difluoropyrrolidin-1-yl)carbonyl]-7-(trifluoromethyl)-2-{[6-(trifluoromethyl)pyridin-3-yl]methyl}- 5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one (diastereomer 1; racemate) was separated by chiral preparatory HPLC [sample preparation : 77 mg dissolved in 2 mL of ethanol; injection volume: 0.50 mL; column: Daicel Chiralcel® OX-H 5 μm, 250 x 20 mm; eluent: n-heptane/ethanol (50:50); flow rate: 20 ml/min; temperature 40°C; UV detection: 220 nm]. After separation, 24.0 mg of isomer 1, which eluted first, and 28.8 mg of isomer 2, which eluted later, were isolated. Isomer 1:

[01386] Analytical chiral HPLC: Rt = 1.33 min, ee = 100% [column: Daicel Chiralcel® IE-3 50 x 4.6 mm; eluent: n-heptane/ethanol 50:50; flow rate: 1 ml/min; UV detection: 220 nm]. LC-MS (Method 3): Rt = 1.69 min; MS (ESIpos): m /z = 500 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.150 (0.83), -0.008 (6.23), 0.008 (6.13), 0.146 (0.65) (1.26) (2.16), 2734 (1.33), 2756 (1.66), 2764 (1.45), 2902 (1.02), 2979 (2.00), 3018 (1.48), 3551 (1.02), 3570 (2.03), 3584 (1.54), 3602 (1.02) (0.71), 4.179 (1.17), 4.205 (1.29), 4.237 (0.77), 4.968 (1.54), 4.982 (1.57), 5.047 (16.00), 7.917 (14.49), 7.920 (15.35), 8.642 (5.15). Example 314 (5RS,7RS)-2-[(5-Chloropyridin-2-yl)methyl]-5-{[(3S)-3-fluoropyrrolidin-1-yl]carbonyl}-7-(trifluoromethyl)-5, 6,7,8-tetrahydro[1,2,4]triazolo[4,3- a]pyridin-3(2H)-one (mixture of diastereomer; 4 isomers)

[01387] (5RS,7RS)-2-[(5-Chloropyridin-2-yl)methyl]-3-oxo-7-(trifluoromethyl)-2,3,5,6,7,8-hexahydro[ 1,2,4]triazolo[4,3-a]pyridine-5-carboxylic acid (mixture of diastereomer; 4 isomers) (206 mg, 546 μmol) was initially loaded into THF (8.0 mL), and HBTU ( 269 mg, 710 μmol) and N,N-diisopropylethylamine (290 μl, 1.6 mmol) were subsequently added. After stirring at room temperature for 15 minutes, (3S)-3-fluoropyrrolidine hydrochloride (82.3 mg, 656 μmol) was added and the reaction mixture was stirred at room temperature overnight. The solvent was removed under reduced pressure, and the residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/water gradient). The fractions containing the product were concentrated under reduced pressure and 221 mg (90% possibility) of the title compound were obtained. LC-MS (Method 3): Rt = 1.44 min; MS (ESIpos): m /z = 448 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.150 (1.37), -0.009 (12.42), 4.890 (1.37), 4.932 (7.20), 4,940 (10.49), 4,947 (10.33), 4,951 (10.20), 4,974 (1.76), 4,991 (2.90), 5,025 (1.43), 5,40), 5,081 (1.50), 5,267 (1.60), 5,358 (0.91) (6.65), 8,580 (6.71). Example 315 (5RS,7RS)-2-[(5-Chloropyridin-2-yl)methyl]-5-{[(3S)-3-fluoropyrrolidin-1-yl]carbonyl}-7-(trifluoromethyl)-5, 6,7,8-tetrahydro[1,2,4]triazolo[4,3- a]pyridin-3(2H)-one (isomer 2)

[01388] 5RS,7RS)-2-[(5-Chloropyridin-2-yl)methyl]-5-{[(3S)-3-fluoropyrrolidin-1-yl]carbonyl}-7-(trifluoromethyl)-5, 6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one (diastereomer mixture; 4 isomers) was separated by chiral preparatory HPLC [sample preparation : 218 mg dissolved in 5 mL of ethanol/n-heptane (3:2); injection volume: 0.23 mL; column: Daicel Chiralcel® IC 5 μm, 250 x 20 mm; eluent: n-heptane/ethanol (50:50); flow rate: 15 ml/min; temperature 40°C; UV detection: 220 nm]. After separation, 100 mg of isomer 1, which eluted first, and 90 mg of isomer 2, which eluted later, were isolated. Isomer 2:

[01389] Analytical chiral HPLC: Rt = 4.14 min, de = 100% [column: Daicel Chiralcel® IC-3 50 x 4.6 mm; eluent: n-heptane/ethanol 50:50; flow rate: 1 ml/min; UV detection: 220 nm]. LC-MS (Method 3): Rt = 1.44 min; MS (ESIpos): m /z = 448 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (1.94), -0.008 (16.00), 0.008 (15.60), 0.146 (1.94) (2.64) (1.72) (3.83) (1.23) (1.94) (7.58). Example 316 (5RS,7RS)-2-[(5-Chloropyridin-3-yl)methyl]-5-{[(3S)-3-fluoropyrrolidin-1-yl]carbonyl}-7-(trifluoromethyl)-5, 6,7,8-tetrahydro[1,2,4]triazolo[4,3- a]pyridin-3(2H)-one (mixture of diastereomer; 2 isomers)

[01390] (5RS,7RS)-2-[(5-Chloropyridin-3-yl)methyl]-3-oxo-7-(trifluoromethyl)-2,3,5,6,7,8-hexahydro[ 1,2,4]triazolo[4,3-a]pyridine-5-carboxylic acid (mixture of diastereomer; 4 isomers) (625 mg, 1.66 mmol) was initially loaded into THF (3.0 mL), and HBTU (818 mg, 2.16 mmol) and N,N-diisopropylethylamine (870 μl, 5.0 mmol) were subsequently added. After stirring at room temperature for 15 minutes, (3S)-3-fluoropyrrolidine hydrochloride (250 mg, 1.99 mmol) was added and the reaction mixture was stirred at room temperature overnight. The solvent was removed under reduced pressure, and the residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/water gradient). The fractions containing the product were concentrated under reduced pressure and 296 mg (38% possibility) of the title compound were obtained. LC-MS (Method 3): Rt = 1.44 min; MS (ESIpos): m /z = 448 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (1.08), -0.008 (8.89), 0.008 (9.13), 0.146 (1.10), 2004 (0.47), 2073 (1.57), 2171 (2.52), 2190 (1.50), 2212 (2.41), 2235 (3.70), 2284 (2.39), 2323 (1.44), 2327 (1.52), 2366 (0.68) (2.99) (1.13) (1.50) (1.44) (0.58), 7,761 (5.30), 7,766 (3.83), 8,428 (6.82), 8,454 (0.50), 8,568 (5.72), 8,574 (5.77). Example 317 (5RS,7RS)-2-[(5-Chloropyridin-3-yl)methyl]-5-{[(3S)-3-fluoropyrrolidin-1-yl]carbonyl}-7-(trifluoromethyl)-5, 6,7,8-tetrahydro[1,2,4]triazolo[4,3- a]pyridin-3(2H)-one (isomer 1)

[01391] (5RS,7RS)-2-[(5-Chloropyridin-3-yl)methyl]-5-{[(3S)-3-fluoropyrrolidin-1-yl]carbonyl}-7-(trifluoromethyl)-5 ,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one (diastereomer mixture; 2 isomers) was separated by chiral preparatory HPLC [preparation of sample: 296 mg dissolved in 9 mL of ethanol/n-heptane (7:2); injection volume: 0.20 mL; column: Daicel Chiralcel® IE 5 μm, 250 x 20 mm; eluent: n-heptane/ethanol (30:70); flow rate: 15 ml/min; temperature 40°C; UV detection: 220 nm]. After separation, 110 mg of isomer 1, which eluted first, and 101 mg of isomer 2, which eluted later, were isolated. Isomer 1:

[01392] Analytical chiral HPLC: Rt = 3.16 min, de = 100% [column: Daicel Chiralcel® IE 50 x 4.6 mm; eluent: n-heptane/ethanol 50:50; flow rate: 1 ml/min; UV detection: 220 nm]. LC-MS (Method 3): Rt = 1.40 min; MS (ESIpos): m /z = 448 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (1.59), -0.008 (12.81), 0.008 (13.77), 0.146 (1.59) (3.57) (1.85) (0.83) (1.34) (8.67), 8,568 (6.82), 8,574 (6.95). Example 318 (5RS,7RS)-2-[(5-Chloropyridin-3-yl)methyl]-5-{[(3S)-3-fluoropyrrolidin-1-yl]carbonyl}-7-(trifluoromethyl)-5, 6,7,8-tetrahydro[1,2,4]triazolo[4,3- a]pyridin-3(2H)-one (isomer 2)

[01393] (5RS,7RS)-2-[(5-Chloropyridin-3-yl)methyl]-5-{[(3S)-3-fluoropyrrolidin-1-yl]carbonyl}-7-(trifluoromethyl)-5 ,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one (diastereomer mixture; 2 isomers) was separated by chiral preparatory HPLC [preparation of sample: 296 mg dissolved in 9 mL of ethanol/n-heptane (7:2); injection volume: 0.20 mL; column: Daicel Chiralcel® IE 5 μm, 250 x 20 mm; eluent: n-heptane/ethanol (30:70); flow rate: 15 ml/min; temperature 40°C; UV detection: 220 nm]. After separation, 110 mg of isomer 1, which eluted first, and 101 mg of isomer 2, which eluted later, were isolated. Isomer 1:

[01394] Analytical chiral HPLC: Rt = 4.32 min, de = 100% [column: Daicel Chiralcel® IE 50 x 4.6 mm; eluent: n-heptane/ethanol 50:50; flow rate: 1 ml/min; UV detection: 220 nm]. LC-MS (Method 3): Rt = 1.40 min; MS (ESIpos): m /z = 448 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (1.14), -0.008 (8.84), 0.008 (8.27), 0.146 (1.03) (0.99) (1.71) (1.03) (1.64) (4.42), 8.574 (4.42). Example 319 (5RS,8RS)-2-(3-Chloro-4-fluorobenzyl)-5-{[(3R,4S)-3,4-difluoropyrrolidin-1-yl]carbonyl}-8-methyl-5,6 ,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one (diastereomer mixture; 4 isomers)

[01395] (5RS,8RS)-2-(3-Chloro-4-fluorobenzyl)-8-methyl-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4 ]triazolo[4,3-a]pyridine-5-carboxylic acid (diastereomer mixture; 4 isomers) (100 mg, 79% purity, 233 μmol) was initially loaded into THF (2.0 mL), and HBTU ( 115 mg, 302 μmol) and N,N-diisopropylethylamine (120 μl, 700 μmol) were subsequently added. After stirring at room temperature for 15 minutes, (3R,4S)-3,4-difluoropyrrolidine hydrochloride (40.1 mg, 279 μmol) was added and the reaction mixture was stirred at room temperature overnight. The solvent was removed under reduced pressure, and the residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/water gradient). The fractions containing the product were concentrated under reduced pressure and 44.0 mg (44% possibility) of the title compound were obtained. LC-MS (Method 4): Rt = 0.87 min; MS (ESIpos): m /z = 429 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (0.92), -0.008 (7.38), 0.008 (7.15), 0.146 (0.83) (1.29) (1.15) (1.06) (1.01) (1.61) (0.69) (2.44), 7,242 (2.31), 7,374 (3.00), 7,395 (4.80), 7,419 (2.72), 7,429 (3.46), 7,447 (3.37). Example 320 (5RS,8RS)-2-(3-Chloro-4-fluorobenzyl)-5-{[(3S)-3-fluoropyrrolidin-1-yl]carbonyl}-8-methyl-5,6,7,8 -tetrahydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one (mixture of diastereomer; 4 isomers)

[01396] (5RS,8RS)-2-(3-Chloro-4-fluorobenzyl)-8-methyl-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4 ]triazolo[4,3-a]pyridine-5-carboxylic acid (diastereomer mixture; 4 isomers) (100 mg, 79% purity, 233 μmol) was initially loaded into THF (2.0 mL), and HBTU ( 115 mg, 302 μmol) and N,N-diisopropylethylamine (120 μl, 700 μmol) were subsequently added. After stirring at room temperature for 15 minutes, (3S)-3-fluoropyrrolidine hydrochloride (35.0 mg, 279 μmol) was added and the reaction mixture was stirred at room temperature overnight. The solvent was removed under reduced pressure, and the residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/water gradient). The fractions containing the product were concentrated under reduced pressure and 55.0 mg (58% possibility) of the title compound were obtained. LC-MS (Method 3): Rt = 1.57 min; MS (ESIpos): m /z = 411 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (1.83), -0.008 (16.00), 0.008 (13.96), 0.146 (1.88) (1.33) (0.92) (2.04), 7,431 (2.04), 7,448 (2.21). Example 321 (5RS,8RS)-2-(3-Chloro-4-fluorobenzyl)-5-[(3-fluoroazetidin-1-yl)carbonyl]-8-methyl-5,6,7,8-tetrahydro [1,2,4]triazolo[4,3-a]pyridin-3(2H)-one (diastereomer mixture; 4 isomers)

[01397] (5RS,8RS)-2-(3-Chloro-4-fluorobenzyl)-8-methyl-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4 ]triazolo[4,3-a]pyridine-5-carboxylic acid (diastereomer mixture; 4 isomers) (100 mg, 79% purity, 233 μmol) was initially loaded into THF (2.0 mL), and HBTU ( 115 mg, 302 μmol) and N,N-diisopropylethylamine (120 μl, 700 μmol) were subsequently added. After stirring at room temperature for 15 minutes, 3-fluoroazetidine hydrochloride (31.1 mg, 279 μmol) was added and the reaction mixture was stirred at room temperature overnight. The solvent was removed under reduced pressure, and the residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/water gradient). The fractions containing the product were concentrated under reduced pressure and 48.0 mg (52% possibility) of the title compound were obtained. LC-MS (Method 3): Rt = 1.53 min; MS (ESIpos): m /z = 397 [M+H]+ ¹H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (0.45), -0.008 (4.06), 0.008 (3.98), 0.146 (0.44) (1.14) (1.48) (0.96) (0.51) (2.92) (2.20), 7.451 (2.21). Example 322 (5RS,8RS)-5-{[(3R,4S)-3,4-Difluoropyrrolidin-1-yl]carbonyl}-2-{[3-fluoro-2-(trifluoromethyl)pyridin-4-yl] methyl}-8-methyl-5,6,7,8-tetrahydro[1,2,4]triazolo[4,3- a]pyridin-3(2H)-one (diastereomer mixture; 4 isomers)

[01398] (5RS,8RS)-2-{[3-Fluoro-2-(trifluoromethyl)pyridin-4-yl]methyl}-8-methyl-3-oxo-2,3,5,6,7,8 -hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylic acid (mixture of diastereomer; 4 isomers) (80.0 mg, 214 μmol) was initially loaded into THF (2. 0 mL), and HBTU (105 mg, 278 μmol) and N,N-diisopropylethylamine (110 μl, 640 μmol) were subsequently added. After stirring at room temperature for 15 minutes, (3R,4S)-3,4-difluoropyrrolidine hydrochloride (36.8 mg, 256 μmol) was added and the reaction mixture was stirred at room temperature overnight. The solvent was removed under reduced pressure, and the residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/water gradient). The fractions containing the product were concentrated under reduced pressure and 38.0 mg (38% possibility) of the title compound were obtained. LC-MS (Method 4): Rt = 0.82 min; MS (ESIpos): m /z = 464 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (1.67), -0.008 (16.00), 0.008 (12.74), 0.146 (1.71) (4.34) (0.56) (0.80), 5.091 (2.75), 5.116 (1.75), 5.124 (1.79), 5.166 (0.56), 7.509 (1.19), 7.518 (1.31), 7.530 (0.64), 8.561 (1.83), 8.573 (1.79). Example 323 (5RS,8RS)-2-(3-Chloro-4-fluorobenzyl)-5-[(3,3-difluoropyrrolidin-1-yl)carbonyl]-8-methyl-5,6,7,8-tetra -hydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one (mixture of diastereomer; 4 isomers)

[01399] (5RS,8RS)-2-(3-Chloro-4-fluorobenzyl)-8-methyl-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4 ]triazolo[4,3-a]pyridine-5-carboxylic acid (diastereomer mixture; 4 isomers) (100 mg, 79% purity, 233 μmol) was initially loaded into THF, and HBTU (115 mg, 302 μmol) and N,N-diisopropylethylamine (120 μl, 700 μmol) were subsequently added. After stirring at room temperature for 15 minutes, 3,3-difluoropyrrolidine hydrochloride (40.1 mg, 279 μmol) was added and the reaction mixture was stirred at room temperature overnight. The solvent was removed under reduced pressure, and the residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/water gradient). The fractions containing the product were concentrated under reduced pressure and 14.0 mg (14% possibility) of the title compound were obtained. LC-MS (Method 3): Rt = 1.72 min; MS (ESIpos): m /z = 429 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (1.90), -0.008 (16.00), 0.008 (14.19), 0.146 (1.90) (1.52) (1.52) (3.90), 7,396 (5.33), 7,418 (3.24), 7,427 (3.24), 7,450 (2.95). Example 324 (5RS,8RS)-2-(2,4-Difluorobenzyl)-5-{[(3R,4S)-3,4-difluoropyrrolidin-1-yl]carbonyl}-8-methyl-5,6,7 ,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one (diastereomer mixture; 4 isomers)

[01400] (5RS,8RS)-2-(2,4-Difluorobenzyl)-8-methyl-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazole [4,3-a]pyridine-5-carboxylic acid (diastereomer mixture; 4 isomers) (80.0 mg, 247 μmol) was initially loaded into THF (2.0 mL), and HBTU (122 mg, 322 μmol ) and N,N-diisopropylethylamine (130 μl, 740 μmol) were subsequently added. After stirring at room temperature for 15 minutes, (3R, 4S)-3,4-difluoropyrrolidine hydrochloride (42.6 mg, 297 μmol) was added and the reaction mixture was stirred at room temperature for 72 hours. The solvent was removed under reduced pressure, and the residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/water gradient). The fractions containing the product were concentrated under reduced pressure and 46.0 mg (45% possibility) of the title compound were obtained. LC-MS (Method 4): Rt = 0.80 min; MS (ESIpos): m /z = 413 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (0.68), -0.008 (6.34), 0.008 (6.42), 0.146 (0.75), 1165 (15.62), 1182 (16.00), 1337 (1.36), 1370 (1.51), 1398 (0.68), 1810 (1.36), 2041 (2.19), 2072 (2.72), 2328 (1.28), 2366 (0.98) (1.13) (1.74) (0.53) (0.68) (0.83) (3.47), 7,262 (1.89), 7,272 (3.25), 7,289 (1.96), 7,310 (0.91). Example 325 (5RS,8RS)-5-{[(3R,4S)-3,4-Difluoropyrrolidin-1-yl]carbonyl}-8-methyl-2-{[6-(trifluoromethyl)pyridin-3-yl] methyl}-5,6,7,8-tetrahydro[1,2,4]triazolo[4,3- a]pyridin-3(2H)-one (diastereomer mixture; 4 isomers)

[01401] (5RS,8RS)-8-Methyl-3-oxo-2-{[6-(trifluoromethyl)pyridin-3-yl]methyl}-2,3,5,6,7,8-hexahydro [1,2,4]triazolo[4,3-a]pyridine-5-carboxylic acid (mixture of diastereomer; 4 isomers) (80.0 mg, 225 μmol) was initially loaded into THF (2.0 mL), and HBTU (111 mg, 292 μmol) and N,N-diisopropylethylamine (120 μl, 670 μmol) were subsequently added. After stirring at room temperature for 15 minutes, (3R,4S)-3,4-difluoropyrrolidine hydrochloride (38.7 mg, 269 μmol) was added and the reaction mixture was stirred at room temperature overnight. The solvent was removed under reduced pressure, and the residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/water gradient). The fractions containing the product were concentrated under reduced pressure and 70.0 mg (70% possibility) of the title compound were obtained. LC-MS (Method 4): Rt = 0.78 min; MS (ESIpos): m /z = 446 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.150 (0.54), -0.008 (4.71), 0.008 (5.18), 0.146 (0.58) (1.47) (0.77) (1.04) (0.77) (0.50) (0.58) (12.83) (0.93), 5.432 (0.62), 5.456 (0.73), 5.464 (0.77), 5.476 (0.73), 7.904 (9.12), 7.908 (11.32), 7.926 (1.00), 8.628 (5.80). Example 326 (5RS,8RS)-2-(2,4-Difluorobenzyl)-5-{[(3S)-3-fluoropyrrolidin-1-yl]carbonyl}-8-methyl-5,6,7,8-tetra -hydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one (mixture of diastereomer; 4 isomers)

[01402] (5RS,8RS)-2-(2,4-Difluorobenzyl)-8-methyl-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazole [4,3-a]pyridine-5-carboxylic acid (diastereomer mixture; 4 isomers) (80.0 mg, 247 μmol) was initially loaded into THF, and HBTU (122 mg, 322 μmol) and N,N- diisopropylethylamine (130 μl, 740 μmol) were subsequently added. After stirring at room temperature for 15 minutes, (3S)-3-fluoropyrrolidine hydrochloride (37.3 mg, 297 μmol) was added and the reaction mixture was stirred at room temperature overnight. The solvent was removed under reduced pressure, and the residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/water gradient). The fractions containing the product were concentrated under reduced pressure and 50.0 mg (51% possibility) of the title compound were obtained. LC-MS (Method 3): Rt = 1.43 min; MS (ESIpos): m /z = 395 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (0.66), -0.008 (6.12), 0.008 (5.45), 0.146 (0.66) 0 (1.46) (3.59) (2.53) (0.71), 3490 (0.80), 3515 (1.99), 3542 (1.60), 3560 (1.37), 3592 (2.61), 3619 (1.73), 3640 (2.13), 3664 (1.95), 3687 (0.93), 3.704 (0.93) (0.53) (1.51), 4890 (5.81), 4930 (2.66), 5258 (1.42), 5346 (0.84), 5391 (1.60), 5477 (0.80), 5509 (0.66), 5943 (0.44), 7054 (1.91), 7060 (2.04) (4.70), 7,284 (2.70), 7,290 (3.50), 7,305 (1.11), 7,312 (1.20). Example 327 (5RS,8RS)-2-(2,4-Difluorobenzyl)-5-[(3,3-difluoropyrrolidin-1-yl)carbonyl]-8-methyl-5,6,7,8-tetrahydro [1,2,4]triazolo[4,3-a]pyridin-3(2H)-one (diastereomer mixture; 4 isomers)

[01403] (5RS,8RS)-2-(2,4-Difluorobenzyl)-8-methyl-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazole [4,3-a]pyridine-5-carboxylic acid (diastereomer mixture; 4 isomers) (80.0 mg, 247 μmol) was initially loaded into THF (2.0 mL), and HBTU (122 mg, 322 μmol ) and N,N-diisopropylethylamine (130 μl, 740 μmol) were subsequently added. After stirring at room temperature for 15 minutes, 3,3-difluoropyrrolidine hydrochloride (42.6 mg, 297 μmol) was added and the reaction mixture was stirred at room temperature overnight. The solvent was removed under reduced pressure, and the residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/water gradient). The fractions containing the product were concentrated under reduced pressure and 30.0 mg (29% possibility) of the title compound were obtained. LC-MS (Method 3): Rt = 1.57 min; MS (ESIpos): m /z = 413 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.150 (1.37), -0.008 (11.75), 0.008 (10.16), 0.146 (1.30) (1.59) (2.38) (2.67) (0.58) (1.87), 7,221 (2.09), 7,227 (1.87), 7,247 (4.68), 7,269 (4.97), 7,276 (2.52), 7,285 (3.39), 7,306 (1.37). Example 328 (5RS,8RS)-5-[(3-Fluoroazetidin-1-yl)carbonyl]-8-methyl-2-{[6-(trifluoromethyl)pyridin-3-yl]methyl}-5,6,7 ,8-tetrahydro[1,2,4]triazolo[4,3- a]pyridin-3(2H)-one (diastereomer mixture; 4 isomers)

[01404] (5RS,8RS)-8-Methyl-3-oxo-2-{[6-(trifluoromethyl)pyridin-3-yl]methyl}-2,3,5,6,7,8-hexahydro [1,2,4]triazolo[4,3-a]pyridine-5-carboxylic acid (diastereomer mixture; 4 isomers) (50.0 mg, 140 μmol) was initially loaded into THF (500 μl), and HBTU (69.2 mg, 182 μmol) and N,N-diisopropylethylamine (73 μl, 420 μmol) were subsequently added. After stirring at room temperature for 15 minutes, 3-fluoroazetidine hydrochloride (18.8 mg, 168 μmol) was added and the reaction mixture was stirred at room temperature overnight. The solvent was removed under reduced pressure, and the residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/water gradient). The fractions containing the product were concentrated under reduced pressure and 35.0 mg (60% possibility) of the title compound were obtained. LC-MS (Method 3): Rt = 1.34 min; MS (ESIpos): m /z = 414 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.008 (3.37), 0.008 (3.14), 0.146 (0.42), 1.168 ( 15.69), 1,185 (16.00), 1,325 (0.46), 1,365 (0.98), 1,385 (1.02), 1,396 (1.08), 1,425 (0.50), 1,813 (1.06), 1,822 (1.08), 2.057 (2.54), 2.328 ( 0.66), 2.332 (0.52), 2.366 (0.56), 2.523 (2.02), 2.670 (0.75), 2.700 (0.79), 2.711 (1.35), 2.730 (1.41), 2.744 (1.21), 2.759 (0.69), 3.908 ( 0.44), 3.930 (0.77), 3.958 (0.75), 3.991 (0.83), 4.017 (0.52), 4.177 (0.44), 4.220 (0.71), 4.234 (0.71), 4.275 (0.79), 4.303 (0.77), 4.341 ( 0.48), 4.363 (0.79), 4.386 (0.56), 4.423 (0.44), 4.448 (0.58), 4.530 (0.44), 4.569 (0.44), 4.584 (0.48), 4.619 (3.03), 4.673 (0.44), 5.004 ( 0.56), 5.046 (7.13), 5.096 (0.39), 5.349 (0.52), 5.411 (0.52), 5.493 (0.52), 5.554 (0.52), 7.906 (11.32), 8.635 (4.70). Example 329 (5RS,8RS)-2-(2,4-Difluorobenzyl)-5-[(3-fluoroazetidin-1-yl)carbonyl]-8-methyl-5,6,7,8-tetrahydro[1 ,2,4]triazolo[4,3-a]pyridin-3(2H)-one (mixture of diastereomer; 4 isomers)

[01405] (5RS,8RS)-2-(2,4-Difluorobenzyl)-8-methyl-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazole [4,3-a]pyridine-5-carboxylic acid (diastereomer mixture; 4 isomers) (80.0 mg, 247 μmol) was initially loaded into THF (2.0 mL), and HBTU (122 mg, 322 μmol ) and N,N-diisopropylethylamine (130 μl, 740 μmol) were subsequently added. After stirring at room temperature for 15 minutes, 3-fluoroazetidine hydrochloride (33.1 mg, 297 μmol) was added and the reaction mixture was stirred at room temperature overnight. The solvent was removed under reduced pressure, and the residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/water gradient). The fractions containing the product were concentrated under reduced pressure and 55.0 mg (58% possibility) of the title compound were obtained. LC-MS (Method 3): Rt = 1.46 min; MS (ESIpos): m /z = 381 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (1.04), -0.008 (13.04), 0.008 (7.58), 0.146 (1.08) (1.55) (0.94) (0.57) (0.94). Example 330 (5RS,8RS)-5-[(3,3-Difluoropyrrolidin-1-yl)carbonyl]-8-methyl-2-{[6-(trifluoromethyl)pyridin-3-yl]methyl}-5,6 ,7,8-tetrahydro[1,2,4]triazolo[4,3- a]pyridin-3(2H)-one (mixture of diastereomer; 4 isomers)

[01406] (5RS,8RS)-8-Methyl-3-oxo-2-{[6-(trifluoromethyl)pyridin-3-yl]methyl}-2,3,5,6,7,8-hexahydro [1,2,4]triazolo[4,3-a]pyridine-5-carboxylic acid (diastereomer mixture; 4 isomers) (100 mg, 281 μmol) was initially loaded into THF (2.0 mL), and HBTU (138 mg, 365 μmol) and N,N-diisopropylethylamine (150 μl, 840 μmol) were subsequently added. After stirring at room temperature for 15 minutes, 3,3-difluoropyrrolidine hydrochloride (48.4 mg, 337 μmol) was added and the reaction mixture was stirred at room temperature overnight. The solvent was removed under reduced pressure, and the residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/water gradient). The fractions containing the product were concentrated under reduced pressure and 60.0 mg (48% possibility) of the title compound were obtained. LC-MS (Method 4): Rt = 0.81 min; MS (ESIpos): m /z = 446 [M+H]+ ¹H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.008 (3.55), 0.008 (3.57), 0.146 (0.46), 1.175 ( 15.46), 1,191 (16.00), 1,317 (0.44), 1,335 (0.95), 1,349 (1.15), 1,364 (1.25), 1,379 (1.25), 1,395 (0.88), 1.407 (0.64), 1.805 (1.66), 1.817 ( 1.52), 1.827 (1.39), 1.839 (1.39), 2.073 (3.67), 2.105 (2.42), 2.115 (2.28), 2.328 (0.61), 2.366 (0.76), 2.381 (0.95), 2.390 (0.76), 2.408 ( 1.25), 2.427 (1.22), 2.451 (0.78), 2.518 (4.01), 2.572 (1.81), 2.589 (1.27), 2.607 (0.66), 2.670 (0.71), 2.696 (0.42), 2.711 (1.52), 2.728 ( 1.91), 2.743 (2.30), 2.758 (1.81), 2.773 (1.17), 3.533 (1.79), 3.552 (2.69), 3.566 (1.42), 3.573 (1.37), 3.633 (0.46), 3.667 (1.49), 3.701 ( 1.74), 3.736 (1.03), 3.742 (0.95), 3.756 (0.66), 3.775 (2.98), 3.801 (1.96), 3.807 (1.76), 3.818 (0.91), 3.841 (0.44), 3.882 (0.78), 3.901 ( 1.64), 3.920 (0.95), 3.927 (1.22), 3.947 (0.93), 3.977 (0.98), 3.992 (0.56), 4.005 (0.71), 4.021 (0.91), 4.048 (0.59), 4.151 (0.61), 4.183 ( 0.93), 4.206 (0.93), 4.238 (0.46), 4.805 (1.37), 4.812 (1.96), 4.824 (1.49), 4.868 (1.39), 4.875 (2.15), 4.887 (1.47), 5.006 (0.59), 5.050 ( 12.84), 5.093 (0.66), 7.881 (0.71), 7.906 (15.24), 7.927 (1.35), 8.629 (5.70). Example 331 (5RS,7RS)-2-(3-Chloro-4-fluorobenzyl)-5-[(3,3-difluoropyrrolidin-1-yl)carbonyl]-7-methyl-5,6,7,8-tetra -hydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one (mixture of diastereomer; 4 isomers)

[01407] (5RS,7RS)-2-(3-Chloro-4-fluorobenzyl)-7-methyl-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4 ]triazolo[4,3-a]pyridine-5-carboxylic acid (mixture of diastereomer; 4 isomers) (70.0 mg, 206 μmol) was initially loaded into THF (2.0 mL), and HBTU (102 mg, 268 μmol) and N,N-diisopropylethylamine (110 μl, 620 μmol) were subsequently added. After stirring at room temperature for 15 minutes, 3,3-difluoropyrrolidine hydrochloride (35.5 mg, 247 μmol) was added and the reaction mixture was stirred at room temperature overnight. The solvent was removed under reduced pressure, and the residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/water gradient). The fractions containing the product were concentrated under reduced pressure and 47.8 mg (54% possibility) of the title compound were obtained. LC-MS (Method 3): Rt = 1.69 min; MS (ESIpos): m /z = 429 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (1.30), -0.008 (11.60), 0.008 (9.50), 0.146 (1.20) (3.60) (1.40) (1.20) (16.00), 7240 (1.70), 7256 (2.50), 7262 (2.40), 7268 (2.20), 7376 (4.10), 7399 (5.60), 7421 (3.10), 7443 (3.20), 7448 (3.30), 7461 (3.20), 7,466 (3.10). Example 332 (5RS,7RS)-5-[(3,3-Difluoropyrrolidin-1-yl)carbonyl]-7-methyl-2-{[6-(trifluoromethyl)pyridin-3-yl]methyl}-5,6 ,7,8-tetrahydro[1,2,4]triazolo[4,3- a]pyridin-3(2H)-one (mixture of diastereomer; 4 isomers)

[01408] (5RS,7RS)-7-Methyl-3-oxo-2-{[6-(trifluoromethyl)pyridin-3-yl]methyl}-2,3,5,6,7,8-hexahydro [1,2,4]triazolo[4,3-a]pyridine-5-carboxylic acid (diastereomer mixture; 4 isomers) (100 mg, 281 μmol) was initially loaded into THF (2.0 mL), and HBTU (138 mg, 365 μmol) and N,N-diisopropylethylamine (150 μl, 840 μmol) were subsequently added. After stirring at room temperature for 15 minutes, 3,3-difluoropyrrolidine hydrochloride (48.4 mg, 337 μmol) was added and the reaction mixture was stirred at room temperature overnight. The solvent was removed under reduced pressure, and the residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/water gradient). The fractions containing the product were concentrated under reduced pressure and 106 mg (85% possibility) of the title compound were obtained. LC-MS (Method 4): Rt = 0.79 min; MS (ESIpos): m /z = 446 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (0.75), -0.008 (7.11), 0.008 (6.34), 0.146 (0.75) (0.62) (0.96) (1.76) (1.53) (1.00) (1.35), 4,732 (1.23), 4,747 (1.16), 4,988 (16.00), 7,900 (1.03), 7,920 (14.02), 7,946 (0.73), 8,665 (5.02). Example 333 (5RS,7RS)-5-{[(3R,4S)-3,4-Difluoropyrrolidin-1-yl]carbonyl}-2-{[3-fluoro-2-(trifluoromethyl)pyridin-4-yl] methyl}-7-methyl-5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one (mixture of diastereomer; 4 isomers)

[01409] (5RS,7RS)-2-{[3-Fluoro-2-(trifluoromethyl)pyridin-4-yl]methyl}-7-methyl-3-oxo-2,3,5,6,7,8 -hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylic acid (mixture of diastereomer; 4 isomers) (81.4 mg, 90% purity, 196 μmol) was initially loaded in THF (2.0 mL), and HBTU (96.5 mg, 254 μmol) and N,N-diisopropylethylamine (100 μl, 590 μmol) were subsequently added. After stirring at room temperature for 15 minutes, (3R,4S)-3,4-difluoropyrrolidine hydrochloride (33.7 mg, 235 μmol) was added and the reaction mixture was stirred at room temperature overnight. The solvent was removed under reduced pressure, and the residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/water gradient). The fractions containing the product were concentrated under reduced pressure and 41.5 mg (46% possibility) of the title compound were obtained. LC-MS (Method 3): Rt = 1.49 min; MS (ESIpos): m /z = 464 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (1.08), -0.008 (9.90), 0.008 (8.58), 0.146 (1.08) 2 (1.76) (0.88), 2523 (3.99), 2661 (3.15), 2665 (3.27), 2690 (3.87), 2697 (2.51), 3463 (0.84), 3472 (0.60), 3497 (1.32), 3508 (1.28), 3517 (1.16) (1.36) (0.84) (1.56) (16.00) (1.20) (3.55), 8,568 (5.87), 8,579 (5.67). Example 334 (5RS,7RS)-5-[(3,3-Difluoropyrrolidin-1-yl)carbonyl]-2-{[3-fluoro-2-(trifluoromethyl)pyridin-4-yl]methyl}-7-methyl -5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one (diastereomer mixture; 4 isomers)

[01410] (5RS,7RS)-2-{[3-Fluoro-2-(trifluoromethyl)pyridin-4-yl]methyl}-7-methyl-3-oxo-2,3,5,6,7,8 -hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylic acid (mixture of diastereomer; 4 isomers) (81.4 mg, 90% purity, 196 μmol) was initially loaded in THF (2.0 mL), and HBTU (96.5 mg, 254 μmol) and N,N-diisopropylethylamine (100 μl, 590 μmol) were subsequently added. After stirring at room temperature for 15 minutes, 3,3-difluoropyrrolidine hydrochloride (33.7 mg, 235 μmol) was added and the reaction mixture was stirred at room temperature overnight. The solvent was removed under reduced pressure, and the residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/water gradient). The fractions containing the product were concentrated under reduced pressure and 36.3 mg (40% possibility) of the title compound were obtained. LC-MS (Method 3): Rt = 1.56 min; MS (ESIpos): m /z = 464 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (0.84), -0.008 (7.15), 0.008 (6.47), 0.146 (0.84) (0.65) (0.99) (1.15) (1.58) (1.02) (1.15), 5,042 (16.00), 7,591 (2.54), 7,603 (4.80), 7,616 (2.72), 8,568 (5.29), 8,580 (5.20). Example 335 (5RS,7RS)-5-[(3-Fluoroazetidin-1-yl)carbonyl]-2-{[3-fluoro-2-(trifluoromethyl)pyridin-4-yl]methyl}-7-methyl-5 ,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one (mixture of diastereomer 1, racemate)

[01411] (5RS,7RS)-2-{[3-Fluoro-2-(trifluoromethyl)pyridin-4-yl]methyl}-7-methyl-3-oxo-2,3,5,6,7,8 -hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylic acid (mixture of diastereomer; 4 isomers) (81.4 mg, 90% purity, 196 μmol) was initially loaded in THF (2.0 mL), and HBTU (96.5 mg, 254 μmol) and N,N-diisopropylethylamine (100 μl, 590 μmol) were subsequently added. After stirring at room temperature for 15 minutes, 3-fluoroazetidine hydrochloride (26.2 mg, 235 μmol) was added and the reaction mixture was stirred at room temperature overnight. The solvent was removed under reduced pressure, and the residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/water gradient). The fractions containing the product were concentrated under reduced pressure and 38.9 mg (55% possibility) of the title compound were obtained. LC-MS (Method 4): Rt = 0.75 min; MS (ESIpos): m /z = 432 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (1.79), -0.008 (16.00), 0.008 (13.81), 0.146 (1.79) (3.78) (1.09) (3.98) (1.19), 5,523 (1.09), 7,603 (3.48), 7,616 (6.56), 7,628 (3.78), 8,567 (6.06), 8,579 (5.96). Example 336 (5RS,7RS)-5-{[(3R,4S)-3,4-Difluoropyrrolidin-1-yl]carbonyl}-7-methyl-2-{[6-(trifluoromethyl)pyridin-3-yl] methyl}-5,6,7,8-tetrahydro[1,2,4]triazolo[4,3- a]pyridin-3(2H)-one (mixture of diastereomer 1; racemate)

[01412] (5RS,7RS)-7-Methyl-3-oxo-2-{[6-(trifluoromethyl)pyridin-3-yl]methyl}-2,3,5,6,7,8-hexahydro [1,2,4]triazolo[4,3-a]pyridine-5-carboxylic acid (mixture of diastereomer; 4 isomers) (78.8 mg, 221 μmol) was initially loaded into THF (2.0 mL), and HBTU (109 mg, 288 μmol) and N,N-diisopropylethylamine (150 μl, 880 μmol) were subsequently added. After stirring at room temperature for 15 minutes, (3R,4S)-3,4-difluoropyrrolidine hydrochloride (38.1 mg, 265 μmol) was added and the reaction mixture was stirred at room temperature overnight. The solvent was removed under reduced pressure, and the residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/water gradient). The fractions containing the product were concentrated under reduced pressure and 78.9 mg (80% possibility) of the title compound were obtained. LC-MS (Method 4): Rt = 0.76 min; MS (ESIpos): m /z = 446 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (0.58), 0.146 (0.52), 1.023 (10.88), 1.027 ( 11.14), 1,039 (11.23), 1,290 (0.61), 1,322 (1.50), 1,354 (2.20), 1,385 (1.56), 1,417 (0.75), 1,874 (3.65), 2.157 (2.89), 2.187 (2.52), 2.197 ( 3.39), 2.228 (3.41), 2.246 (1.76), 2.260 (1.56), 2.278 (1.62), 2.327 (0.78), 2.366 (0.46), 2.642 (2.43), 2.683 (2.20), 2.710 (0.61), 3.461 ( 0.93), 3.495 (1.24), 3.504 (1.33), 3.513 (1.33), 3.548 (1.68), 3.598 (1.04), 3.617 (0.90), 3.631 (1.13), 3.651 (0.72), 3.664 (0.90), 3.674 ( 0.98), 3.687 (1.13), 3.697 (1.16), 3.709 (1.42), 3.721 (1.10), 3.731 (1.24), 3.744 (1.22), 3.772 (1.71), 3.807 (1.36), 3.842 (0.81), 3.884 ( 0.69), 3.982 (0.75), 3.997 (0.84), 4.010 (0.72), 4.027 (1.07), 4.043 (0.72), 4.056 (0.64), 4.070 (0.55), 4.115 (0.67), 4.130 (0.81), 4.143 ( 0.69), 4.158 (1.36), 4.174 (0.81), 4.187 (0.78), 4.202 (0.78), 4.648 (1.68), 4.654 (1.82), 4.663 (2.05), 4.671 (2.34), 4.682 (1.91), 4.690 ( 1.74) 1.36), 5.407 (1.30), 5.460 (1.16), 5.486 (0.81), 6.088 (0.95), 7.917 (12.88), 8.663 (6.37). Example 337 (5S,7S)-5-{[(3R,4S)-3,4-Difluoropyrrolidin-1-yl]carbonyl}-7-methyl-2-{[6-(trifluoromethyl)pyridin-3-yl] methyl}-5,6,7,8-tetrahydro[1,2,4]triazolo[4,3- a]pyridin-3(2H)-one (enantiomer 1)

[01413] (5RS,7RS)-5-{[(3R,4S)-3,4-Difluoropyrrolidin-1-yl]carbonyl}-7-methyl-2-{[6-(trifluoromethyl)pyridin-3-yl ]methyl}-5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one (diastereomer 1; racemate) was separated by chiral preparatory HPLC [sample preparation: 66.7 mg dissolved in 7 mL of ethanol; injection volume: 0.15 mL; column: Daicel Chiralcel® OD-H 5 μm, 250 x 20 mm; eluent: n-heptane/ethanol (60:40); flow rate: 15 ml/min; temperature 25°C; UV detection: 220 nm]. After separation, 21.7 mg of enantiomer 1, which eluted first, and 26.4 mg of enantiomer 2, which eluted later, were isolated. Enantiomer 1:

[01414] Analytical chiral HPLC: Rt = 2.78 min, ee = 100% [column: Daicel Chiralcel® IB-3 50 x 4.6 mm; eluent: n-heptane/ethanol 50:50; flow rate: 1 ml/min; UV detection: 220 nm]. LC-MS (Method 15): Rt = 1.31 min; MS (ESIpos): m /z = 446 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (1.09), -0.008 (10.72), 0.008 (11.52), 0.146 (1.20) 8 (0.73) (2.48) (0.95) (1.28) (0.69) (1.75) (1.24), 5.322 (1.02), 5.340 (0.98), 5.406 (1.28), 5.461 (1.02), 6.086 (0.98), 7.916 (12.46), 7.919 (12.28), 8.664 (5.94). Example 338 (5RS,7RS)-5-{[(3R,4S)-3,4-Difluoropyrrolidin-1-yl]carbonyl}-7-methyl-2-{[6-(trifluoromethyl)pyridin-3-yl] methyl}-5,6,7,8-tetrahydro[1,2,4]triazolo[4,3- a]pyridin-3(2H)-one (enantiomer 2)

[01415] (5RS,7RS)-5-{[(3R,4S)-3,4-Difluoropyrrolidin-1-yl]carbonyl}-7-methyl-2-{[6-(trifluoromethyl)pyridin-3-yl ]methyl}-5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one (diastereomer 1) was separated by chiral preparatory HPLC [preparation sample: 66.7 mg dissolved in 7 mL of ethanol; injection volume: 0.15 mL; column: Daicel Chiralcel® OD-H 5 μm, 250 x 20 mm; eluent: n-heptane/ethanol (60:40); flow rate: 15 ml/min; temperature 25°C; UV detection: 220 nm]. After separation, 21.7 mg of enantiomer 1, which eluted first, and 26.4 mg of enantiomer 2, which eluted later, were isolated. Enantiomer 2:

[01416] Analytical chiral HPLC: Rt = 2.98 min, ee = 100% [column: Daicel Chiralcel® IB-3 50 x 4.6 mm; eluent: n-heptane/ethanol 50:50; flow rate: 1 ml/min; UV detection: 220 nm]. LC-MS (Method 4): Rt = 0.76 min; MS (ESIpos): m /z = 446 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (1.26), -0.008 (10.77), 0.008 (10.65), 0.146 (1.26), 1.023 (10.81), 1.028 (11.26), 1.039 (11.65), 1.044 (11.19), 1.235 (1.03), 1.290 (0.76), 1.320 (1.49), 1.355 Example 339 (5RS,7RS)-2- (3-Chloro-4-fluorobenzyl)-5-{[(3R,4S)-3,4-difluoropyrrolidin-1-yl]carbonyl}-7-methyl-5,6,7,8-tetrahydro[1 ,2,4]triazolo[4,3-a]pyridin- 3(2H)-one (mixture of diastereomer; 4 isomers)

[01417] (5RS,7RS)-2-(3-Chloro-4-fluorobenzyl)-7-methyl-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4 ]triazolo[4,3-a]pyridine-5-carboxylic acid (diastereomer mixture; 4 isomers) (70.0 mg, 206 μmol) was initially loaded into THF (2.0 mL), and HBTU (85.9 mg, 227 μmol) and N,N-diisopropylethylamine (110 μl, 620 μmol) were subsequently added. After stirring at room temperature for 15 minutes, (3R,4S)-3,4-difluoropyrrolidine hydrochloride (35.5 mg, 247 μmol) was added and the reaction mixture was stirred at room temperature overnight. The solvent was removed under reduced pressure, and the residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/water gradient). The fractions containing the product were concentrated under reduced pressure and 54.2 mg (61% possibility) of the title compound were obtained. LC-MS (Method 3): Rt = 1.62 min; MS (ESIpos): m /z = 429 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (1.33), 0.008 (11.11), 0.146 (1.21), 1.026 ( 10.32), 1,038 (10.57), 1,317 (1.39), 1,348 (1.69), 1,385 (1.39), 1,414 (0.78), 1,885 (1.39), 2,073 (3.68), 2,154 (2.84), 2.185 (2.23), 2.195 ( 3.26), 2.226 (3.62), 2.328 (2.29), 2.367 (1.39), 2.648 (2.23), 2.670 (2.66), 2.710 (1.51), 3.512 (1.21), 3.548 (1.39), 3.629 (1.03), 3.710 ( 1.33), 3.759 (1.57), 3.806 (1.27), 3.851 (0.91), 4.020 (1.03), 4.162 (1.33), 4.653 (1.69), 4.673 (2.17), 4.801 (16.00), 5.270 (1.03), 5.406 ( 1.09), 5.458 (0.97), 7.256 (2.35), 7.377 (2.96), 7.398 (4.35), 7.418 (2.11), 7.444 (3.50), 7.462 (3.50). Example 340 (5RS,7RS)-2-(3-Chloro-4-fluorobenzyl)-5-[(3-fluoroazetidin-1-yl)carbonyl]-7-methyl-5,6,7,8-tetrahydro [1,2,4]triazolo[4,3-a]pyridin-3(2H)-one (diastereomer mixture; 4 isomers)

[01418] (5RS,7RS)-2-(3-Chloro-4-fluorobenzyl)-7-methyl-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4 ]triazolo[4,3-a]pyridine-5-carboxylic acid (diastereomer mixture; 4 isomers) (70.0 mg, 206 μmol) was initially loaded into THF (2.0 mL), and HBTU (85.9 mg, 227 μmol) and N,N-diisopropylethylamine (110 μl, 620 μmol) were subsequently added. After stirring at room temperature for 15 minutes, 3-fluoroazetidine hydrochloride (27.6 mg, 247 μmol) was added and the reaction mixture was stirred at room temperature overnight. The solvent was removed under reduced pressure, and the residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/water gradient). The fractions containing the product were concentrated under reduced pressure and 57.2 mg (69% possibility) of the title compound were obtained. LC-MS (Method 3): Rt = 1.53 min; MS (ESIpos): m /z = 397 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: 0.008 (2.93), 1.017 (15.46), 1.033 (16.00), 1.340 (0.54 ), 1,370 (1.55), 1,400 (1.84), 1,420 (1.72), 1,451 (0.70), 1,876 (1.86), 2,072 (4.68), 2,119 (1.08), 2,152 (4.88), 2,182 (3.65), 2,192 (4.50 ), 2.223 (2.93), 2.327 (0.62), 2.366 (0.44), 2.630 (3.05), 2.636 (3.11), 2.670 (3.23), 2.709 (0.56), 3.878 (0.75), 3.906 (0.97), 3.936 (1.30 ), 3.965 (1.55), 3.997 (0.71), 4.026 (0.85), 4.136 (0.63), 4.149 (0.72), 4.165 (0.58), 4.185 (0.85), 4.201 (0.82), 4.233 (1.94), 4.251 (1.38 ), 4.262 (1.43), 4.291 (1.59), 4.319 (1.46), 4.385 (4.37), 4.400 (4.82), 4.413 (5.10), 4.428 (3.90), 4.448 (0.69), 4.480 (1.31), 4.496 (0.86 ), 4.533 (0.78), 4.549 (0.82), 4.573 (0.46), 4.644 (0.59), 4.661 (0.68), 4.686 (0.63), 4.698 (0.69), 4.713 (0.73), 4.738 (0.54), 4.806 (14.39 ), 5,377 (1.22), 5,519 (1.21), 7,264 (3.03), 7,375 (3.36), 7,398 (5.54), 7,420 (2.62), 7,452 (3.55), 7,470 (3.56). Example 341 (5RS,7RS)-5-[(3-Fluoroazetidin-1-yl)carbonyl]-7-methyl-2-{[6-(trifluoromethyl)pyridin-3-yl]methyl}-5,6,7 ,8-tetrahydro[1,2,4]triazolo[4,3- a]pyridin-3(2H)-one (diastereomer mixture; 4 isomers)

[01419] (5RS,7RS)-7-Methyl-3-oxo-2-{[6-(trifluoromethyl)pyridin-3-yl]methyl}-2,3,5,6,7,8-hexahydro [1,2,4]triazolo[4,3-a]pyridine-5-carboxylic acid (mixture of diastereomer; 4 isomers) (39.8 mg, 112 μmol) was initially loaded into THF (2.0 mL), and HBTU (55.1 mg, 145 μmol) and N,N-diisopropylethylamine (78 μl, 450 μmol) were subsequently added. After stirring at room temperature for 15 minutes, 3-fluoroazetidine hydrochloride (15.0 mg, 134 μmol) was added and the reaction mixture was stirred at room temperature overnight. The solvent was removed under reduced pressure, and the residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/water gradient). The fractions containing the product were concentrated under reduced pressure and 7.20 mg (16% possibility) of the title compound were obtained. LC-MS (Method 4): Rt = 0.71 min; MS (ESIpos): m /z = 414 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (0.80), -0.008 (6.70), 0.008 (6.25), 0.146 (0.88) (3.31) (0.95) (1.41) (0.72), 4.712 (0.76), 4.990 (13.22), 5.381 (1.26), 5.515 (1.26), 7.900 (1.98), 7.920 (11.85), 7.949 (1.49), 8.673 (7.35). Example 342 (5S)-2-{2-[3-Chloro-5-(trifluoromethyl)pyridin-2-yl]ethyl}-5-{[(3S)-3-fluoropyrrolidin-1-yl]carbonyl}-5 ,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one

[01420] (5S)-2-{2-[3-Chloro-5-(trifluoromethyl)pyridin-2-yl]ethyl}-3-oxo-2,3,5,6,7,8-hexahydro [1,2,4]triazolo[4,3-a]pyridine-5-carboxylic acid (75.0 mg, 72% purity, 138 μmol) was initially loaded into THF (1.5 mL), and HBTU ( 99.6 mg, 263 μmol) and N,N-diisopropylethylamine (110 μl, 620 μmol) were subsequently added. After stirring at room temperature for 15 minutes, (3S)-3-fluoropyrrolidine hydrochloride (29.5 mg, 235 μmol) was added and the reaction mixture was stirred at room temperature overnight. The solvent was removed under reduced pressure, and the residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/water gradient). The fractions containing the product were concentrated under reduced pressure and 50.9 mg (80% possibility) of the title compound were obtained. LC-MS (Method 3): Rt = 1.45 min; MS (ESIpos): m /z = 462 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (0.83), -0.008 (7.76), 0.008 (7.06), 0.146 (0.83) (7.83) (0.69), 3606 (2.98), 3631 (2.15), 3705 (1.87), 3727 (1.87), 3751 (1.59), 3769 (1.25), 3836 (2.56), 3975 (0.83), 3995 (1.45), 4011 (2.63) (1.66), 4,666 (1.87), 4,673 (2.01), 4,681 (1.45), 5,250 (1.25), 5,380 (1.52), 5,502 (0.97), 5,934 (0.48), 8,410 (5.96), 8,877 (5.96). Example 343 (5S)-2-{2-[3-Chloro-5-(trifluoromethyl)pyridin-2-yl]ethyl}-5-[(3,3-difluoropyrrolidin-1-yl)carbonyl]-5,6 ,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one

[01421] (5S)-2-{[3-Chloro-5-(trifluoromethyl)pyridin-2-yl]ethyl}-3-oxo-2,3,5,6,7,8-hexahydro[1 ,2,4]triazolo[4,3-a]pyridine-5-carboxylic acid (65.0 mg, 166 μmol) was initially loaded into THF (2.5 mL) at room temperature. Subsequently, HBTU (82.0 mg, 216 μmol) and N,N-diisopropylethylamine (87 μl, 500 μmol) were added. After stirring for 15 minutes, 3,3-difluoropyrrolidine hydrochloride (28.7 mg, 200 μmol) was added and the reaction mixture was stirred at room temperature overnight. HBTU (82.0 mg, 216 μmol) and 3,3-difluoropyrrolidine hydrochloride (28.7 mg, 200 μmol) were added again, and the mixture was stirred overnight. The reaction mixture was mixed with water and ethyl acetate. The organic phase was removed and the aqueous phase was extracted three times with ethyl acetate. The combined organic phases were washed with saturated aqueous sodium chloride solution, dried over sodium sulfate and filtered, and the filtrate was concentrated. The residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/gradient water). The fractions containing the product were concentrated under reduced pressure and 33.3 mg (42% possibility) of the title compound were obtained. LC-MS (Method 3): Rt = 1.59 min; MS (ESIpos): m /z = 480 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (1.01), 0.008 (7.50), 0.146 (0.97), 1.225 ( 1.31), 1.243 (7.46), 1.258 (8.43), 1.273 (4.85), 1.689 (5.30), 1.702 (7.20), 1.714 (6.68), 1.915 (2.16), 1.947 (3.24), 1.960 (3.10), 1.973 ( 4.07), 1,988 (3.13), 2,004 (2.39), 2,013 (2.65), 2,028 (2.87), 2,038 (2.91), 2,047 (2.28), 2,063 (2.20), 2,073 (16.00), 2,328 (1.75), 2,350 ( 1.19), 2.367 (3.32), 2.398 (2.76), 2.418 (2.65), 2.438 (1.79), 2.523 (11.00), 2.565 (5.41), 2.573 (4.03), 2.593 (6.97), 2.639 (2.39), 2.670 ( 1.94), 2.710 (1.57), 3.130 (0.71), 3.140 (0.75), 3.159 (0.67), 3.280 (8.47), 3.511 (5.45), 3.530 (9.44), 3.549 (5.00), 3.618 (1.42), 3.652 ( 3.24), 3.686 (3.54), 3.705 (2.01), 3.721 (1.79), 3.738 (3.88), 3.769 (4.92), 3.793 (3.69), 3.811 (1.83), 3.856 (1.83), 3.875 (3.58), 3.895 ( 2.05), 3,901 (2.46), 3,920 (1.12), 3,953 (1.04), 3,981 (3.66), 4,000 (3.28), 4,017 (6,94), 4,035 (11,93), 4,056 (11,75), 4,075 (5,93), 4,092 ( 2.80), 4.103 (1.75), 4.131 (2.24), 4.161 (2.09), 4.193 (0.90), 4.656 (2.87), 4.672 (4.03), 4.681 (2.87), 4.735 (3.06), 4.750 (3.99), 4.760 ( 2.91), 4.823 (0.71), 6.509 (1.19), 8.410 (11.82), 8.875 (12.16). Example 344 (5S)-5-{[(3R,4S)-3,4-Difluoropyrrolidin-1-yl]carbonyl}-2-[2-(4-fluorophenyl)ethyl]-5,6,7,8- tetrahydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one

[01422] (5S)-2-[2-(4-Fluorophenyl)ethyl]-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4, 3-a]pyridine-5-carboxylic acid (73.1 mg, 240 μmol) was initially loaded into THF (2.0 mL), and HBTU (118 mg, 311 μmol) and N,N-diisopropylethylamine (130 μl, 720 μmol) were subsequently added. After stirring at room temperature for 15 minutes, (3R,4S)-3,4-difluoropyrrolidine hydrochloride (41.3 mg, 287 μmol) was added and the reaction mixture was stirred at room temperature overnight. HBTU (90 mg, 240 μmol), (3R,4S)-3,4-difluoropyrrolidine hydrochloride (34.4 mg, 239 μmol), and N,N-diisopropylethylamine (43 μl, 240 μmol) were added again and the mixture was stirred at room temperature overnight. The solvent was removed under reduced pressure, and the residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/water gradient). The fractions containing the product were concentrated under reduced pressure and 62.3 mg (66% possibility) of the title compound were obtained. LC-MS (Method 4): Rt = 0.76 min; MS (ESIpos): m /z = 395 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (1.11), -0.008 (9.50), 0.008 (9.19), 0.146 (1.15) (1.74) (1.11) (1.39) (2.14) (1.74) (3.45) (1.47) (1.19) (5.27) (1.86) (7.29), 7.082 (13.35), 7.086 (14.61), 7.104 (9.23), 7.109 (8.63), 7.198 (6.34), 7.212 (9.74), 7.221 (10.69), 7.229 (8.44), 7.243 (5.54). Example 345 (5S)-5-[(3,3-Difluoroazetidin-1-yl)carbonyl]-2-[2-(4-fluorophenyl)ethyl]-5,6,7,8-tetrahydro[1, 2,4]triazolo[4,3-a]pyridin-3(2H)-one

[01423] (5S)-2-[2-(4-Fluorophenyl)ethyl]-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4, 3-a]pyridine-5-carboxylic acid (73.1 mg, 240 μmol) was initially loaded into THF (2.0 mL), and HBTU (118 mg, 311 μmol) and N,N-diisopropylethylamine (130 μl, 720 μmol) were subsequently added. After stirring at room temperature for 15 minutes, 3,3-difluoroazetidine hydrochloride (37.2 mg, 287 μmol) was added and the reaction mixture was stirred at room temperature for 72 hours. The solvent was removed under reduced pressure, and the residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/water gradient). The fractions containing the product were concentrated under reduced pressure and 56.0 mg (61% possibility) of the title compound were obtained. LC-MS (Method 3): Rt = 1.40 min; MS (ESIpos): m /z = 381 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (1.79), 0.146 (1.90), 1.709 (4.36), 1.721 ( 6.60), 1735 (5.71), 1950 (2.35), 1961 (3.58), 1974 (3.36), 1997 (1.79), 2012 (2.69), 2032 (3.02), 2046 (2.24), 2073 (6.60), 2327 ( 2.80), 2.366 (2.35), 2.523 (10.85), 2.564 (4.36), 2.584 (4.92), 2.600 (5.82), 2.613 (6.83), 2.627 (3.36), 2.642 (1.23), 2.656 (2.24), 2.670 ( 3.58) ( 4.81), 4.513 (7.94), 4.526 (4.70), 4.662 (2.35), 4.694 (2.69), 4.770 (1.12), 4.799 (2.46), 4.830 (2.24), 7.062 (7.16), 7.084 (16.00), 7.106 ( 10.29), 7,207 (9.40), 7,221 (10.85), 7,228 (9.17), 7,242 (7.05). Example 346 (5S)-5-[(3,3-Difluoropyrrolidin-1-yl)carbonyl]-2-[2-(4-methoxyphenyl)ethyl]-5,6,7,8-tetrahydro[1, 2,4]triazolo[4,3-a]pyridin-3(2H)-one

[01424] (5S)-2-[2-(4-Methoxyphenyl)ethyl]-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4, 3-a]pyridine-5-carboxylic acid (92.0 mg, 290 μmol) was initially loaded into THF (2.0 mL), and HBTU (143 mg, 377 μmol) and N,N-diisopropylethylamine (150 μl, 870 μmol) were subsequently added. After stirring at room temperature for 15 minutes, 3,3-difluoropyrrolidine hydrochloride (49.9 mg, 348 μmol) was added and the reaction mixture was stirred at room temperature for 72 hours. The solvent was removed under reduced pressure, and the residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/water gradient). The fractions containing the product were concentrated under reduced pressure and 51.6 mg (92% purity, 40% chance) of the title compound were obtained. LC-MS (Method 4): Rt = 0.75 min; MS (ESIpos): m /z = 407 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: 0.008 (2.58), 1.701 (2.94), 1.713 (4.02), 1.724 (3.77 ), 1,909 (0.73), 1,957 (1.87), 1,970 (1.77), 1,981 (2.06), 1,995 (2.06), 2,005 (1.63), 2,015 (1.54), 2,031 (1.60), 2,041 (1.55), 2,051 (1.14 ), 2.066 (1.03), 2.073 (1.41), 2.085 (0.51), 2.328 (0.87), 2.354 (0.71), 2.371 (1.17), 2.403 (1.47), 2.421 (1.42), 2.442 (1.09), 2.523 (4.27 ), 2.573 (3.78), 2.580 (3.40), 2.596 (2.90), 2.609 (2.10), 2.620 (3.47), 2.631 (1.84), 2.664 (1.65), 2.690 (0.57), 2.710 (0.63), 2.731 (0.98 ), 2,830 (5.18), 2,849 (10.41), 2,867 (5.46), 2,890 (1.30), 3.519 (15.11), 3,539 (11.03), 3.557 (6.77), 3,659 (1.93), 3,691 (2.71), 3,724 (5.71 ), 3.743 (6.41), 3.761 (4.83), 3.766 (6.69), 3.787 (4.86), 3.821 (1.36), 3.869 (0.93), 3.887 (1.96), 3.913 (1.36), 3.932 (0.62), 3.956 (0.62 ), 3.984 (1.22), 3.997 (0.65), 4.013 (0.85), 4.025 (1.11), 4.055 (0.62), 4.119 (0.74), 4.150 (1.12), 4.178 (1.12), 4.208 (0.51), 4.464 (0.46 ), 4,671 (1.50), 4,687 (2.17), 4,696 (1.57), 4,749 (1.55), 4,758 (1.90), 4,764 (2.10), 4,773 (1.54), 6,826 (13,56), 6,848 (16.00), 7,100 (14,23 ), 7,121 (12.19). Example 347 (5S)-5-[(3-Fluoroazetidin-1-yl)carbonyl]-2-[2-(4-methoxyphenyl)ethyl]-5,6,7,8-tetrahydro[1,2, 4]triazolo[4,3-a]pyridin-3(2H)-one

[01425] (5S)-2-[2-(4-Methoxyphenyl)ethyl]-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4, 3-a]pyridine-5-carboxylic acid (92.0 mg, 290 μmol) was initially loaded into THF (2.0 mL), and HBTU (143 mg, 377 μmol) and N,N-diisopropylethylamine (150 μl, 870 μmol) were subsequently added. After stirring at room temperature for 15 minutes, 3-fluoroazetidine hydrochloride (38.8 mg, 348 μmol) was added and the reaction mixture was stirred at room temperature for 72 hours. The solvent was removed under reduced pressure, and the residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/water gradient). The fractions containing the product were concentrated under reduced pressure and 58.3 mg (54% possibility) of the title compound were obtained. LC-MS (Method 4): Rt = 0.67 min; MS (ESIpos): m /z = 375 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (0.49), 0.146 (0.54), 1.717 (7.02), 1.909 ( 1.85), 1922 (2.69), 1934 (2.88), 1943 (2.71), 1955 (2.23), 1977 (2.25), 1995 (3.16), 2012 (2.77), 2029 (1.85), 2047 (0.94), 2072 ( 7.93), 2.327 (0.82), 2.366 (0.75), 2.572 (5.35), 2.594 (3.84), 2.610 (5.84), 2.624 (3.07), 2.639 (1.24), 2.652 (2.00), 2.665 (1.61), 2.710 ( 0.97), 2.834 (5.71), 2.852 (11.15), 2.871 (6.06), 3.368 (1.09), 3.531 (6.66), 3.751 (6.68), 3.761 (8.12), 3.769 (6.74), 3.780 (4.30), 3.891 ( 1.38), 3.906 (1.68), 3.935 (1.59), 3.970 (1.85), 3.994 (1.27), 4.138 (0.90), 4.154 (1.01), 4.168 (0.80), 4.225 (2.17), 4.252 (2.10), 4.282 ( 1.85), 4.293 (1.55), 4.316 (1.82), 4.345 (1.31), 4.384 (0.88), 4.407 (1.31), 4.430 (1.05), 4.450 (6.06), 4.465 (8.68), 4.476 (6.14), 4.498 ( 1.18), 4.523 (0.71), 4.601 (0.80), 4.616 (0.94), 4.654 (0.90), 4.670 (0.94), 4.680 (0.88), 4.694 (0.69), 5.327 (1.14), 5.387 (1.14), 5.469 ( 1.18), 5,530 (1.16), 6,827 (13.64), 6,848 (16.00), 7,105 (10.12), 7,121 (8.80). Example 348 (5S)-2-{[1-(6-Chloropyridin-2-yl)cyclopropyl]methyl}-5-[(3-fluoroazetidin-1-yl)carbonyl]-5,6,7,8-tetra -hydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one

[01426] (5S)-2-{[1-(6-Chloropyridin-2-yl)cyclopropyl]methyl}-3-oxo-2,3,5,6,7,8-hexahydro[1,2 ,4]triazolo[4,3-a]pyridine-5-carboxylic acid (60.0 mg, 172 μmol) was initially loaded into THF (3.0 mL), and HBTU (84.8 mg, 224 μmol) and N,N-Diisopropylethylamine (90 μl, 520 μmol) was subsequently added. After stirring at room temperature for 15 minutes, 3-fluoroazetidine hydrochloride (23.0 mg, 206 μmol) was added and the reaction mixture was stirred at room temperature overnight. The solvent was removed under reduced pressure, and the residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/water gradient). The fractions containing the product were concentrated under reduced pressure and 12.1 mg (17% possibility) of the title compound were obtained. LC-MS (Method 3): Rt = 1.35 min; MS (ESIpos): m /z = 406 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (0.72), -0.008 (6.41), 0.008 (5.61), 0.146 (0.68) (5.99) (1.18) (0.95) (0.64) (1.78), 7,718 (2.84), 7,729 (2.65), 7,738 (1.33), 7,749 (1.10). Example 349 (5S)-2-{[1-(6-Chloropyridin-2-yl)cyclopropyl]methyl}-5-[(3,3-difluoropyrrolidin-1-yl)carbonyl]-5,6,7,8 -tetrahydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one

[01427] (5S)-2-{[1-(6-Chloropyridin-2-yl)cyclopropyl]methyl}-3-oxo-2,3,5,6,7,8-hexahydro[1,2 ,4]triazolo[4,3-a]pyridine-5-carboxylic acid (60.0 mg, 172 μmol) was initially loaded into THF (3.0 mL), and HBTU (84.8 mg, 224 μmol) and N,N-Diisopropylethylamine (90 μl, 520 μmol) was subsequently added. After stirring at room temperature for 15 minutes, 3,3-difluoropyrrolidine hydrochloride (29.6 mg, 206 μmol) was added and the reaction mixture was stirred at room temperature overnight. The solvent was removed under reduced pressure, and the residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/water gradient). The fractions containing the product were concentrated under reduced pressure and 19.6 mg (26% possibility) of the title compound were obtained. LC-MS (Method 4): Rt = 0.81 min; MS (ESIpos): m /z = 438 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (1.50), -0.008 (14.75), 0.008 (12.25), 0.146 (1.75) (15.00) (1.50) (2.50), 4,796 (2.50), 7,242 (8.75), 7,262 (9.75), 7,569 (7.75), 7,589 (10.25), 7,701 (7.00), 7,721 (11.50), 7,740 (5.00). Example 350 (5S)-2-{[1-(6-Chloropyrrolidin-2-yl)cyclopropyl]methyl}-5-{[(3S)-3-fluoropyrrolidin-1-yl]carbonyl}-5,6,7 ,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one

[01428] (5S)-2-{[1-(6-Chloropyridin-2-yl)cyclopropyl]methyl}-3-oxo-2,3,5,6,7,8-hexahydro[1,2 ,4]triazolo[4,3-a]pyridine-5-carboxylic acid (60.0 mg, 172 μmol) was initially loaded into THF (3.0 mL), and HBTU (84.8 mg, 224 μmol) and N,N-Diisopropylethylamine (90 μl, 520 μmol) was subsequently added. After stirring at room temperature for 15 minutes, (3S)-3-fluoropyrrolidine hydrochloride (25.9 mg, 206 μmol) was added and the reaction mixture was stirred at room temperature overnight. The solvent was removed under reduced pressure, and the residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/water gradient). The fractions containing the product were concentrated under reduced pressure and 22.5 mg (31% possibility) of the title compound were obtained. LC-MS (Method 4): Rt = 0.74 min; MS (ESIpos): m /z = 420 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (1.70), -0.008 (14.64), 0.008 (12.26), 0.146 (1.70) (2.04) (3.74) (2.04) (5.79) (2.38) (5.79), 7,724 (7.49), 7,738 (2.72), 7,744 (3.06). Example 351 (5S)-5-[(3-Fluoroazetidin-1-yl)carbonyl]-2-{[1-(4-fluorophenyl)cyclopropyl]methyl}-5,6,7,8-tetrahydro[1 ,2,4]triazolo[4,3- a]pyridin-3(2H)-one

[01429] (5S)-2-{[1-(4-Fluorophenyl)cyclopropyl]methyl}-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazole [4,3-a]pyridine-5-carboxylic acid (80.0 mg, 241 μmol) was initially loaded into THF (4.0 mL), and HBTU (119 mg, 314 μmol) and N,N-diisopropylethylamine ( 130 μl, 720 μmol) were subsequently added. After stirring at room temperature for 15 minutes, 3-fluoroazetidine hydrochloride (32.3 mg, 290 μmol) was added and the reaction mixture was stirred at room temperature overnight. The solvent was removed under reduced pressure, and the residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/water gradient). The fractions containing the product were concentrated under reduced pressure and 40.8 mg (44% possibility) of the title compound were obtained. LC-MS (Method 3): Rt = 1.43 min; MS (ESIpos): m /z = 389 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (1.23), -0.008 (16.00), 0.008 (9.89), 0.146 (1.12) (2.64) (0.95) (3.73), 7,243 (4.79), 7,260 (2.72). Example 352 (5S)-2-{[1-(4-Fluorophenyl)cyclopropyl]methyl}-5-{[(3S)-3-fluoropyrrolidin-1-yl]carbonyl}-5,6,7,8-tetra -hydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one

[01430] (5S)-2-{[1-(4-Fluorophenyl)cyclopropyl]methyl}-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazole [4,3-a]pyridine-5-carboxylic acid (80.0 mg, 241 μmol) was initially loaded into THF (4.0 mL), and HBTU (119 mg, 314 μmol) and N,N-diisopropylethylamine ( 130 μl, 720 μmol) were subsequently added. After stirring at room temperature for 15 minutes, (3S)-3-fluoropyrrolidine hydrochloride (36.4 mg, 290 μmol) was added and the reaction mixture was stirred at room temperature overnight. The solvent was removed under reduced pressure, and the residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/water gradient). The fractions containing the product were concentrated under reduced pressure and 44.6 mg (46% possibility) of the title compound were obtained. LC-MS (Method 3): Rt = 1.47 min; MS (ESIpos): m /z = 403 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (1.34), -0.008 (16.00), 0.008 (9.57), 0.146 (1.23) (1.18) (1.18) (1.03) (1.95) (1.95) (11.63), 7,058 (6.38), 7,221 (4.73), 7,228 (6.23), 7,234 (6.48), 7,242 (8.95), 7,250 (5.86), 7,257 (4.17), 7,264 (4.22). Example 353 (5S)-5-[(3,3-Difluoropyrrolidin-1-yl)carbonyl]-2-{[1-(4-fluorophenyl)cyclopropyl]methyl}-5,6,7,8-tetrahydro [1,2,4]triazolo[4,3- a]pyridin-3(2H)-one

[01431] (5RS)-2-{[1-(4-Fluorophenyl)cyclopropyl]methyl}-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazole [4,3-a]pyridine-5-carboxylic acid (80.0 mg, 241 μmol) was initially loaded into THF (4.0 mL), and HBTU (119 mg, 314 μmol) and N,N-diisopropylethylamine ( 130 μl, 720 μmol) were subsequently added. After stirring at room temperature for 15 minutes, 3,3-difluoropyrrolidine hydrochloride (41.6 mg, 290 μmol) was added and the reaction mixture was stirred at room temperature overnight. The solvent was removed under reduced pressure, and the residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/water gradient). The fractions containing the product were concentrated under reduced pressure and 46.1 mg (45% possibility) of the title compound were obtained. LC-MS (Method 3): Rt = 1.61 min; MS (ESIpos): m /z = 421 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (0.60), -0.008 (5.39), 0.008 (4.70), 0.146 (0.62) (3.94), 0.996 (11.00), 1.013 (3.41), 1.024 (1.20), 1.037 (1.04), 1.649 (1.59), 1.662 (2.05), 1.695 (3.09) (2.95) (1.52) (1.78) (2.65) (8.00) (0.85) (1.91) (8.88), 7,256 (3.53), 7,261 (7.56). Example 354 (5S)-5-[(3-Hydroxyazetidin-1-yl)carbonyl]-2-{[1-(4-methylphenyl)cyclopropyl]methyl}-5,6,7,8-tetrahydro[1 ,2,4]triazolo[4,3-a]pyridin-3(2H)-one

[01432] (5S)-2-{[1-(4-Methylphenyl)cyclopropyl]methyl}-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazole [4,3-a]pyridine-5-carboxylic acid (45.0 mg, 137 μmol) was initially loaded into THF (2.0 mL), and HBTU (67.8 mg, 179 μmol) and N,N- diisopropylethylamine (72 μl, 410 μmol) were subsequently added. After stirring at room temperature for 15 minutes, azetidin-3-ol hydrochloride (18.1 mg, 165 μmol) was added and the reaction mixture was stirred at room temperature overnight. The solvent was removed under reduced pressure, and the residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/water gradient). The fractions containing the product were concentrated under reduced pressure and 19.1 mg (36% possibility) of the title compound were obtained. LC-MS (Method 3): Rt = 1.32 min; MS (ESIpos): m /z = 383 [M+H]+ ¹H-NMR (400 MHz, DMSO-d6) δ [ppm]: 0.008 (1.07), 0.711 (0.96), 0.777 (1.56), 0.802 (0.80 ), 0.930 (0.49), 0.944 (0.73), 0.969 (2.84), 0.984 (1.24), 0.994 (0.48), 1.681 (1.53), 1.691 (1.56), 1.878 (0.47), 1.903 (1.19), 1.914 (1.15 ), 1.944 (0.79), 1.954 (0.79), 2.236 (16.00), 2.451 (0.40), 2.565 (1.96), 2.577 (1.01), 2.594 (0.50), 2.607 (0.81), 3.572 (0.54), 3.582 (0.58 ), 3.606 (1.21), 3.618 (0.65), 3.631 (0.67), 3.643 (0.72), 3.654 (1.10), 3.692 (1.94), 3.730 (1.42), 3.879 (1.86), 3.900 (1.83), 3.915 (1.14 ), 3.936 (1.03), 3.956 (0.55), 3.968 (0.60), 3.979 (0.65), 3.992 (1.11), 4.009 (0.68), 4.036 (0.52), 4.076 (0.51), 4.092 (0.65), 4.116 (0.47 ), 4.242 (0.53), 4.261 (0.84), 4.281 (0.54), 4.395 (0.64), 4.410 (1.18), 4.418 (1.24), 4.430 (1.31), 4.440 (1.31), 4.456 (1.31), 4.476 (1.35 ), 5,779 (1.94), 5,793 (1.32), 7,026 (3.34), 7,045 (5.44), 7,103 (3.59), 7,110 (3.97), 7,123 (2.43), 7,130 (2.29). Example 355 (5S)-5-[(3-Fluoroazetidin-1-yl)carbonyl]-2-{[1-(4-methylphenyl)cyclopropyl]methyl}-5,6,7,8-tetrahydro[1 ,2,4]triazolo[4,3-a]pyridin-3(2H)-one

[01433] (5S)-2-{[1-(4-Methylphenyl)cyclopropyl]methyl}-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazole [4,3-a]pyridine-5-carboxylic acid (45.0 mg, 137 μmol) was initially loaded into THF (2.0 mL), and HBTU (67.8 mg, 179 μmol) and N,N- diisopropylethylamine (72 μl, 410 μmol) were subsequently added. After stirring at room temperature for 15 minutes, 3-fluoroazetidine hydrochloride (1:1) (18.4 mg, 165 μmol) was added and the reaction mixture was stirred at room temperature overnight. The solvent was removed under reduced pressure, and the residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/water gradient). The fractions containing the product were concentrated under reduced pressure and 17.3 mg (33% possibility) of the title compound were obtained. LC-MS (Method 3): Rt = 1.57 min; MS (ESIpos): m /z = 385 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.008 (2.15), 0.008 (1.85), 0.734 (1.36), 0.773 ( 1.76), 0.798 (0.79), 0.926 (0.52), 0.935 (0.45), 0.966 (3.73), 0.982 (1.21), 0.993 (0.45), 1.690 (1.97), 1.931 (1.03), 1.967 (0.82), 1.982 ( 0.70), 2.002 (0.48), 2.234 (16.00), 2.327 (0.70), 2.366 (0.52), 2.523 (3.12), 2.570 (1.58), 2.614 (0.58), 2.669 (0.76), 2.709 (0.55), 3.693 ( 1.12), 3.735 (1.61), 3.874 (2.30), 3.911 (1.61), 3.957 (0.58), 4.187 (0.67), 4.213 (0.70), 4.243 (0.52), 4.255 (0.55), 4.282 (0.67), 4.429 ( 1.52), 4.443 (2.30), 4.455 (1.55), 7.025 (2.88), 7.044 (4.61), 7.109 (3.64), 7.124 (2.42). Example 356 (5S)-5-{[(3S)-3-Fluoropyrrolidin-1-yl]carbonyl}-2-({1-[4-(trifluoromethyl)phenyl]cyclopropyl}methyl)-5,6,7, 8-tetrahydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one

[01434] (5S)-3-Oxo-2-({1-[4-(trifluoromethyl)phenyl]cyclopropyl}methyl)- 2,3,5,6,7,8-hexahydro[1,2, 4]triazolo[4,3-a]pyridine-5-carboxylic acid (57.4 mg, 151 μmol) was initially loaded into THF (1.4 mL), and HBTU (74.2 mg, 196 μmol) and N N-diisopropylethylamine (79 μl, 450 μmol) was added subsequently. After stirring at room temperature for 15 minutes, (3S)-3-fluoropyrrolidine hydrochloride (1:1) (22.7 mg, 181 μmol) was added and the reaction mixture was stirred at room temperature overnight. The solvent was removed under reduced pressure, and the residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/water gradient). The fractions containing the product were concentrated under reduced pressure and 38.5 mg (55% possibility) of the title compound were obtained. LC-MS (Method 4): Rt = 0.94 min; MS (ESIpos): m /z = 453 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (1.70), -0.008 (16.00), 0.146 (1.70), 0.858 (2.30), 0.939 (1.53), 1.112 (4.68), 1.709 (1.79), 1.871 (0.51), 1.999 (1.28), 2.073 (1.45), 2.251 (0.60), 2.327 (2.64), 2.366 (2.21), 2.589 (1.45) (2.21) (0.51), 7,430 (2.81), 7,449 (3.66), 7,571 (4.77), 7,592 (3.66). Example 357 (5S)-5-[(3-Fluoroazetidin-1-yl)carbonyl]-2-{[1-(4-methoxyphenyl)cyclopropyl]methyl}-5,6,7,8-tetrahydro[1 ,2,4]triazolo[4,3- a]pyridin-3(2H)-one

[01435] (5S)-2-{[1-(4-Methoxyphenyl)cyclopropyl]methyl}-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazole [4,3-a]pyridine-5-carboxylic acid (93.2 mg, 50% purity, 136 μmol) was initially loaded into THF (1.2 mL), and HBTU (134 mg, 353 μmol) and N N-diisopropylethylamine (140 μl, 810 μmol) was added subsequently. After stirring at room temperature for 15 minutes, 3-fluoroazetidine hydrochloride (18.2 mg, 163 μmol) was added and the reaction mixture was stirred at room temperature overnight. The solvent was removed under reduced pressure, and the residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/water gradient). The fractions containing the product were concentrated under reduced pressure and 38.1 mg (70% possibility) of the title compound were obtained. LC-MS (Method 4): Rt = 0.77 min; MS (ESIpos): m /z = 401 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (0.69), -0.008 (6.04), 0.008 (5.43), 0.147 (0.65), 0.705 (0.82) (1.38) (2.20), 6,796 (2.46), 7,131 (1.73), 7,146 (1.60). Example 358 (5S)-2-{[1-(2,4-Difluorophenyl)cyclopropyl]methyl}-5-{[(3S)-3-fluoropyrrolidin-1-yl]carbonyl}-5,6,7,8 -tetrahydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one

[01436] (5S)-2-{[1-(2,4-Difluorophenyl)cyclopropyl]methyl}-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4 ]triazolo[4,3-a]pyridine-5-carboxylic acid (78.0 mg, 223 μmol) was initially loaded into THF (2.0 mL), and HBTU (110 mg, 290 μmol) and N,N- diisopropylethylamine (120 μl, 670 μmol) were subsequently added. After stirring at room temperature for 15 minutes, (3S)-3-fluoropyrrolidine hydrochloride (28.0 mg, 223 μmol) was added and the reaction mixture was stirred at room temperature overnight. The solvent was removed under reduced pressure, and the residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/water gradient). The fractions containing the product were concentrated under reduced pressure and 42.3 mg (45% possibility) of the title compound were obtained. LC-MS (Method 3): Rt = 1.52 min; MS (ESIpos): m /z = 421 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (1.76), -0.008 (16.00), 0.008 (12.28), 0.146 (1.76) (1.76) (1.83). Example 359 (5S)-2-{[1-(2,4-Difluorophenyl)cyclopropyl]methyl}-5-[(3,3-difluoropyrrolidin-1-yl)carbonyl]-5,6,7,8-tetra -hydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one

[01437] (5S)-2-{[1-(2,4-Difluorophenyl)cyclopropyl]methyl}-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4 ]triazolo[4,3-a]pyridine-5-carboxylic acid (78.0 mg, 100% purity, 223 μmol) was initially loaded into THF (2.0 mL), and HBTU (110 mg, 290 μmol) and N,N-diisopropylethylamine (120 μl, 670 μmol) were subsequently added. After stirring at room temperature for 15 minutes, 3,3-difluoropyrrolidine hydrochloride (32.1 mg, 223 μmol) was added and the reaction mixture was stirred at room temperature overnight. The solvent was removed under reduced pressure, and the residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/water gradient). The fractions containing the product were concentrated under reduced pressure and 42.2 mg (43% possibility) of the title compound were obtained. LC-MS (Method 3): Rt = 1.66 min; MS (ESIpos): m /z = 439 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (1.72), -0.008 (16.00), 0.008 (12.30), 0.146 (1.63), 0.712 (1.03), 0.735 (3.44), 0.764 (3.78), 0.788 (1.12), 1.001 (7.83), 1.679 (1.81), 1.969 (1.63), 2.073 (8.09), 2.327 (2.41), 2.366 (2.67) (1.72) (2.15) (1.20), 7,091 (1.20), 7,112 (1.89), 7,134 (1.81), 7,150 (2.06), 7,171 (1.98), 7,189 (0.77). Example 360 (5S)-2-{[1-Ethyl-3-(trifluoromethyl)-1H-pyrazol-5-yl]methyl}-5-{[(3S)-3-fluoropyrrolidin-1-yl]carbonyl}- 5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one

[01438] (5S)-2-{[1-Ethyl-3-(trifluoromethyl)-1H-pyrazol-5-yl]methyl}-3-oxo- 2,3,5,6,7,8-hexa- hydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylic acid (99.9 mg, 91% purity, 254 μmol) was initially loaded into THF (2.0 mL), and HBTU (125 mg, 330 μmol) and N,N-diiSopropylethylamine (130 μl, 760 μmol) were subsequently added. After stirring at room temperature for 15 minutes, (3S)-3-fluoropyrrolidine hydrochloride (1:1) (38.2 mg, 304 μmol) was added and the reaction mixture was stirred at room temperature overnight. The solvent was removed under reduced pressure, and the residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/water gradient). The fractions containing the product were concentrated under reduced pressure and 49.2 mg (45% possibility) of the title compound were obtained. LC-MS (Method 3): Rt = 1.39 min; MS (ESIpos): m /z = 431 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.008 (2.11), 0.008 (1.84), (7.75), 1.716 (2.42 ), 1.729 (2.81), (0.50), 1.897 (0.67), 1.968 (0.55), (0.79), 2.054 (1.06), 2.064 (1.33), (1.51), 2.134 (1.15), 2.170 (0.42), ( 0.94), 2.327 (0.51), 2.366 (0.50), (2.16), 2.650 (0.82), 2.664 (0.58), (0.51), 3.287 (0.87), 3.343 (0.65), (0.70), 3.401 (0.73), 3.454 (0.51), (0.72), 3.623 (1.74), 3.635 (1.32), (1.11), 3.685 (1.06), 3.721 (1.60), (1.09), 3.785 (1.18), 3.854 (2.16), (7.28) , 4.240 (2.37), 4.665 (1.06), (1.09), 4.723 (1.42), 4.732 (1.58), (10.29), 4.792 (7.03), 4.796 (7.44), .47), 5.511 (0.79), 6.626 ( 7.19). Example 361 (5S)-5-{[(3R,4S)-3,4-Difluoropyrrolidin-1-yl]carbonyl}-2-{[1-ethyl-3-(trifluoromethyl)-1H-pyrazol-5-yl ]methyl}-5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one

[01439] (5S)-2-{[1-Ethyl-3-(trifluoromethyl)-1H-pyrazol-5-yl]methyl}-3-oxo- 2,3,5,6,7,8-hexa- hydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylic acid (99.9 mg, 91% purity, 254 μmol) was initially loaded into THF (2.0 mL), and HBTU (125 mg, 330 μmol) and N,N-diisopropylethylamine (130 μl, 760 μmol) were subsequently added. After stirring at room temperature for 15 minutes, (3R,4S)-3,4-difluoropyrrolidine hydrochloride (43.7 mg, 304 μmol) was added and the reaction mixture was stirred at room temperature overnight. The solvent was removed under reduced pressure, and the residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/water gradient). The fractions containing the product were concentrated under reduced pressure and 45.8 mg (40% possibility) of the title compound were obtained. LC-MS (Method 3): Rt = 1.46 min; MS (ESIpos): m /z = 449 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: 0.008 (3.10), 1.244 (0.66), 1.259 (0.70), 1.274 (0.45 ), 1,351 (7.19), 1,369 (14.93), 1,387 (7.30), 1,669 (1.28), 1,705 (1.30), 1,717 (1.51), 1,726 (1.67), 1,921 (0.54), 1,956 (1.24), 2,002 (1.57 ), 2.026 (0.97), 2.036 (1.10), 2.044 (1.18), 2.051 (1.10), 2.060 (0.95), 2.071 (0.85), 2.079 (0.97), 2.086 (0.81), 2.327 (0.64), 2.366 (0.85 ), 2.524 (2.40), 2.566 (2.56), 2.576 (1.78), 2.591 (2.40), 2.603 (3.14), 2.615 (1.76), 2.634 (0.68), 2.645 (1.07), 2.670 (0.79), 2.710 (0.91 ), 3.484 (2.25), 3.505 (1.69), 3.515 (1.65), 3.524 (1.36), 3.533 (1.30), 3.557 (0.83), 3.566 (1.01), 3.610 (0.97), 3.623 (1.05), 3.643 (0.70 ), 3.656 (0.76), 3.666 (0.99), 3.679 (1.80), 3.690 (1.16), 3.699 (1.10), 3.712 (1.51), 3.724 (1.36), 3.743 (1.07), 3.755 (1.10), 3.775 (0.89 ), 3.789 (0.60), 3.865 (0.79), 3.902 (0.60), 3.928 (0.79), 3.941 (0.89), 3.956 (0.58), 3.977 (0.91), 3.991 (0.91), 4.005 (0.62), 4.020 (0.52 ), 4.128 (0.54), 4.143 (0.62), 4.156 (0.68), 4.169 (1.07), 4.185 (2.79), 4.204 (7.26), 4.222 (7.15), 4.240 (2.40), 4.751 (1.01), 4.767 (2.34 ), 4.791 (16.00), 4.798 (7.81), 4.838 (0.79), 5.254 (0.87), 5.265 (0.87), 5.274 (1.01), 5.284 (0.97), 5.296 (0.64), 5.311 (0.60), 5.329 (0.74 ), 5.337 (0.74), 5.351 (0.77), 5.364 (0.74), 5.374 (1.01), 5.387 (1.12), 5.398 (0.87), 5.406 (0.89), 5.427 (0.60), 5.440 (0.62), 5.458 (0.74 ), 5.472 (0.74), 5.480 (0.77), 5.494 (0.60), 6.619 (5.44), 6.624 (6.20). Example 362 (5S)-5-[(3,3-Difluoropyrrolidin-1-yl)carbonyl]-2-{[1-ethyl-3-(trifluoromethyl)-1H-pyrazol-5-yl]methyl}-5, 6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one

[01440] (5S)-2-{[1-Ethyl-3-(trifluoromethyl)-1H-pyrazol-5-yl]methyl}-3-oxo- 2,3,5,6,7,8-hexa- hydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylic acid (99.9 mg, 91% purity, 254 μmol) was initially loaded into THF (2.0 mL), and HBTU (125 mg, 330 μmol) and N,N-diisopropylethylamine (130 μl, 760 μmol) were subsequently added. After stirring at room temperature for 15 minutes, 3,3-difluoropyrrolidine hydrochloride (43.7 mg, 304 μmol) was added and the reaction mixture was stirred at room temperature overnight. The solvent was removed under reduced pressure, and the residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/water gradient). The fractions containing the product were concentrated under reduced pressure and 49.8 mg (43% possibility) of the title compound were obtained. LC-MS (Method 3): Rt = 1.53 min; MS (ESIpos): m /z = 449 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.008 (3.74), 0.008 (1.80), 1.350 (7.76), 1.368 ( 16.00), 1.386 (7.57), 1.685 (0.98), 1.701 (1.16), 1.714 (1.30), 1.722 (1.30), 1.971 (1.06), 1.984 (1.07), 1.995 (1.23), 2.020 (0.91), 2.030 ( 0.86), 2.039 (0.91), 2.046 (0.91), 2.056 (0.86), 2.066 (0.68), 2.074 (0.66), 2.082 (0.58), 2.327 (0.54), 2.366 (0.66), 2.379 (0.73), 2.408 ( 0.88), 2.429 (0.89), 2.563 (2.10), 2.572 (2.36), 2.587 (2.57), 2.604 (2.36), 2.615 (1.11), 2.646 (0.69), 2.670 (0.52), 2.710 (0.45), 3.368 ( 1.56), 3.527 (1.26), 3.546 (1.89), 3.562 (0.89), 3.568 (0.88), 3.666 (0.91), 3.700 (1.05), 3.731 (0.76), 3.762 (1.37), 3.782 (0.84), 3.793 ( 1.22), 3.808 (1.07), 3.826 (0.73), 3.889 (0.49), 3.907 (1.08), 3.926 (0.62), 3.934 (0.74), 3.992 (0.69), 4.021 (0.49), 4.034 (0.60), 4.141 ( 0.43), 4.186 (2.33), 4.204 (6.79), 4.222 (6.20), 4.240 (1.95), 4.731 (0.93), 4.746 (1.32), 4.791 (6.98), 4.797 (8.50), 4.815 (1.25), 4.820 ( 1.29), 4.830 (0.96), 4.836 (0.88), 6.622 (6.40). Example 363 (5S)-2-{[1-Ethyl-3-(trifluoromethyl)-1H-pyrazol-5-yl]methyl}-5-[(3-fluoroazetidin-1-yl)carbonyl]-5,6, 7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one

[01441] (5S)-2-{[1-Ethyl-3-(trifluoromethyl)-1H-pyrazol-5-yl]methyl}-3-oxo- 2,3,5,6,7,8-hexa- hydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylic acid (99.9 mg, 91% purity, 254 μmol) was initially loaded into THF (2.0 mL), and HBTU (125 mg, 330 μmol) and N,N-diisopropylethylamine (130 μl, 760 μmol) were subsequently added. After stirring at room temperature for 15 minutes, 3-fluoroazetidine hydrochloride (33.9 mg, 304 μmol) was added and the reaction mixture was stirred at room temperature overnight. The solvent was removed under reduced pressure, and the residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/water gradient). The fractions containing the product were concentrated under reduced pressure and 50.6 mg (48% possibility) of the title compound were obtained. LC-MS (Method 3): Rt = 1.36 min; MS (ESIpos): m /z = 417 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (0.83), -0.008 (6.74), 0.008 (7.66), 0.146 (0.87) (4.08) (1.93) (1.47) (0.60) (0.64), 6.632 (7.61). Example 364 (5S)-5-[(3,3-Difluoropyrrolidin-1-yl)carbonyl]-2-{[2-(trifluoromethyl)-1,3-thiazol-4-yl]methyl}-5,6, 7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one

[01442] (5S)-3-Oxo-2-{[2-(trifluoromethyl)-1,3-thiazol-4-yl]methyl}-2,3,5,6,7,8-hexahydro[ 1,2,4]triazolo[4,3-a]pyridine-5-carboxylic acid (50.0 mg, 144 μmol) was initially loaded into THF (2.0 mL), and HBTU (70.8 mg, 187 μmol) and N,N-diisopropylethylamine (75 μl, 430 μmol) were subsequently added. After stirring at room temperature for 15 minutes, 3,3-difluoropyrrolidine hydrochloride (24.7 mg, 172 μmol) was added and the reaction mixture was stirred at room temperature overnight. The solvent was removed under reduced pressure, and the residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/water gradient). The fractions containing the product were concentrated under reduced pressure and 12.0 mg (19% possibility) of the title compound were obtained. LC-MS (Method 3): Rt = 1.43 min; MS (ESIpos): m /z = 438 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (1.35), -0.008 (11.66), 0.008 (10.84), 0.146 (1.41), 1236 (0.59), 1684 (2.05), 1733 (2.64), 1986 (2.23), 2001 (2.23), 2012 (2.58), 2035 (1.99), 2045 (1.82), 2054 (1.93), 2061 (1.93) (1.11) (2.70) (1.99) (0.82) (2.11) (14.07). Example 365 (5S)-5-{[(3S)-3-Fluoropyrrolidin-1-yl]carbonyl}-2-{[2-(trifluoromethyl)-1,3-thiazol-4-yl]methyl}-5, 6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one

[01443] (5S)-3-Oxo-2-{[2-(trifluoromethyl)-1,3-thiazol-4-yl]methyl}-2,3,5,6,7,8-hexahydro[ 1,2,4]triazolo[4,3-a]pyridine-5-carboxylic acid (100 mg, 287 μmol) was initially loaded into THF (2.0 mL), and HBTU (142 mg, 373 μmol) and N N-diisopropylethylamine (150 μl, 860 μmol) was added subsequently. After stirring at room temperature for 15 minutes, (3S)-3-fluoropyrrolidine hydrochloride (43.3 mg, 345 μmol) was added and the reaction mixture was stirred at room temperature for 72 hours. The solvent was removed under reduced pressure, and the residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/water gradient). The fractions containing the product were concentrated under reduced pressure and 28.0 mg (23% possibility) of the title compound were obtained. LC-MS (Method 3): Rt = 1.29 min; MS (ESIpos): m /z = 420 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (0.75), -0.008 (6.39), 0.008 (6.48), 0.146 (0.77) (2.36) (0.84) (1.26) (3.94) (4.19) (16.00), 5,011 (10.53), 5,050 (1.98), 5,258 (2.01), 5,384 (2.73), 5,390 (2.80), 5,517 (1.48), 5,944 (0.64), 7,887 (12.65). Example 366 (5S)-5-{[(3R,4S)-3,4-Difluoropyrrolidin-1-yl]carbonyl}-2-{[2-(trifluoromethyl)-1,3-thiazol-4-yl]methyl }-5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one

[01444] (5S)-3-Oxo-2-{[2-(trifluoromethyl)-1,3-thiazol-4-yl]methyl}-2,3,5,6,7,8-hexahydro[ 1,2,4]triazolo[4,3-a]pyridine-5-carboxylic acid (100 mg, 287 μmol) was initially loaded into THF (2.0 mL), and HBTU (142 mg, 373 μmol) and N N-diisopropylethylamine (150 μl, 860 μmol) was added subsequently. After stirring at room temperature for 15 minutes, (3R,4S)-3,4-difluoropyrrolidine hydrochloride (49.5 mg, 345 μmol) was added and the reaction mixture was stirred at room temperature overnight. The solvent was removed under reduced pressure, and the residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/water gradient). The fractions containing the product were concentrated under reduced pressure and 25.0 mg (20% possibility) of the title compound were obtained. LC-MS (Method 3): Rt = 1.37 min; MS (ESIpos): m /z = 438 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (1.19), -0.008 (10.41), 0.008 (9.40), 0.146 (1.23) (1.49) (1.08) (1.75) (2.01), 3720 (2.09), 3735 (2.05), 3752 (1.60), 3765 (1.75), 3785 (1.34), 3799 (0.82), 3873 (1.27), 3909 (0.97), 3932 (1.31), 3946 (1.45) (1.12) (1.34) (1.49), 5.429 (0.97), 5.474 (1.16), 5.482 (1.23), 5.496 (0.97), 7.880 (8.13), 7.889 (9.14). Example 367 (2S)-1-{[(5S)-3-Oxo-2-{[2-(trifluoromethyl)-1,3-thiazol-4-yl]methyl}-2,3,5,6,7 ,8-hexahydro[1,2,4]triazolo[4,3-a]pyridin-5-yl]carbonyl}pyrrolidine-2-carbonitrile

[01445] (5S)-3-Oxo-2-{[2-(trifluoromethyl)-1,3-thiazol-4-yl]methyl}-2,3,5,6,7,8-hexahydro[ 1,2,4]triazolo[4,3-a]pyridine-5-carboxylic acid (50.0 mg, 144 μmol) was initially loaded into THF (2.0 mL), and HBTU (70.8 mg, 187 μmol) and N,N-diisopropylethylamine (75 μl, 430 μmol) were subsequently added. After stirring at room temperature for 15 minutes, (2S)-pyrrolidine-2-carbonitrile hydrochloride (22.8 mg, 172 μmol) was added and the reaction mixture was stirred at room temperature overnight. The solvent was removed under reduced pressure, and the residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/water gradient). The fractions containing the product were concentrated under reduced pressure and 20.0 mg (33% possibility) of the title compound were obtained. LC-MS (Method 3): Rt = 1.36 min; MS (ESIpos): m /z = 427 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (0.78), -0.008 (6.45), 0.008 (6.32), 0.146 (0.70), 1245 (0.52), 1260 (0.70), 1396 (0.83), 1665 (1.66), 1791 (2.18), 1805 (1.66), 2048 (6.84), 2061 (8.33), 2080 (8.28), 2096 (4.45), 2.107 (3.27), 2.117 (3.57), 2.138 (3.05), 2.152 (4.23), 2.163 (3.40), 2.178 (1.44), 2.187 (1.92), 2.207 (4.10), 2.219 (1.40), 2.226 (3.88) (3.36) (13.47) (16.00), 5,010 (15.83), 5,051 (1.35), 7,880 (13.34). Example 368 (5S)-5-[(3,3-Difluoropyrrolidin-1-yl)carbonyl]-2-{[6-(trifluoromethyl)pyridin-2-yl]methyl}-5,6,7,8-tetra -hydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one

[01446] (5S)-3-Oxo-2-{[6-(trifluoromethyl)pyridin-2-yl]methyl}-2,3,5,6,7,8-hexahydro[1,2,4 ]triazolo[4,3-a]pyridine-5-carboxylic acid (63.9 mg, 187 μmol) was initially loaded into THF (2.0 mL), and HBTU (92.0 mg, 243 μmol) and N, N-diisopropylethylamine (98 μl, 560 μmol) was subsequently added. After stirring at room temperature for 15 minutes, 3,3-difluoropyrrolidine hydrochloride (32.2 mg, 224 μmol) was added and the reaction mixture was stirred at room temperature overnight. The solvent was removed under reduced pressure, and the residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/water gradient). The fractions containing the product were concentrated under reduced pressure and 35.5 mg (44% possibility) of the title compound were obtained. LC-MS (Method 3): Rt = 1.43 min; MS (ESIpos): m /z = 432 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (0.90), -0.008 (8.08), 0.008 (7.97), 0.146 (0.87) (0.97) (1.72) (0.54) (1.00) (4.72), 8,081 (2.38), 8,101 (4.18), 8,121 (2.05). Example 369 (5S)-5-[(3-Fluoroazetidin-1-yl)carbonyl]-2-{[6-(trifluoromethyl)pyridin-2-yl]methyl}-5,6,7,8-tetrahydro [1,2,4]triazolo[4,3-a]pyridin-3(2H)-one

[01447] (5S)-3-Oxo-2-{[6-(trifluoromethyl)pyridin-2-yl]methyl}-2,3,5,6,7,8-hexahydro[1,2,4 ]triazolo[4,3-a]pyridine-5-carboxylic acid (63.9 mg, 187 μmol) was initially loaded into THF (2.0 mL), and HBTU (92.0 mg, 243 μmol) and N, N-diisopropylethylamine (98 μl, 560 μmol) was subsequently added. After stirring at room temperature for 15 minutes, 3-fluoroazetidine hydrochloride (25.0 mg, 224 μmol) was added and the reaction mixture was stirred at room temperature overnight. N,N-Diisopropylethylamine (30 μl, 171 μmol) and 3-fluoroazetidine hydrochloride (10.0 mg, 90 μmol) were added again and the mixture was stirred at room temperature for 2 hours. The solvent was removed under reduced pressure, and the residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/water gradient). The fractions containing the product were concentrated under reduced pressure and 48.0 mg (64% possibility) of the title compound were obtained. LC-MS (Method 4): Rt = 0.67 min; MS (ESIpos): m /z = 400 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) delta [ppm]: -0.149 (0.59), -0.008 (5.08), 0.146 (0.62), 1.689 (1.49) (2.89) (1.52) (1.53) (4.31) (0.96), 6957 (0.24), 7086 (0.29), 7213 (0.26), 7419 (6.28), 7439 (6.67), 7827 (6.31), 7847 (7.44), 8079 (3.43), 8099 (6.16), 8118 (2.92), 9.029 (0.16), 9.156 (0.19). Example 370 (5S)-5-{[(3S)-3-Fluoropyrrolidin-1-yl]carbonyl}-2-{[6-(trifluoromethyl)pyridin-2-yl]methyl}-5,6,7,8 -tetrahydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one

[01448] (5S)-3-Oxo-2-{[6-(trifluoromethyl)pyridin-2-yl]methyl}-2,3,5,6,7,8-hexahydro[1,2,4 ]triazolo[4,3-a]pyridine-5-carboxylic acid (63.9 mg, 187 μmol) was initially loaded into THF (2.0 mL), and HBTU (92.0 mg, 243 μmol) and N, N-diisopropylethylamine (98 μl, 560 μmol) was subsequently added. After stirring at room temperature for 15 minutes, (3S)-3-fluoropyrrolidine hydrochloride (28.1 mg, 224 μmol) was added and the reaction mixture was stirred at room temperature overnight. N,N-Diisopropylethylamine (30 μl, 171 μmol) and 3-fluoroazetidine hydrochloride (10.0 mg, 90 μmol) were added again and the mixture was stirred at room temperature for 2 hours. The solvent was removed under reduced pressure, and the residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/water gradient). The fractions containing the product were concentrated under reduced pressure and 45.8 mg (58% possibility) of the title compound were obtained. LC-MS (Method 4): Rt = 0.69 min; MS (ESIpos): m /z = 414 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (1.00), -0.008 (8.75), 0.008 (7.10), 0.146 (0.96), 1751 (2.34), 1901 (0.50), 1941 (0.73), 2006 (0.58), 2063 (1.27), 2073 (2.26), 2086 (1.61), 2106 (1.76), 2121 (1.61), 2271 (0.96) (1.42) (1.76) (1.34) (0.77), 7,405 (3.84), 7,425 (4.14), 7,828 (4.37), 7,848 (5.06), 8,081 (2.76), 8,101 (4.95), 8,121 (2.34). Example 371 (5S)-5-{[(3R,4S)-3,4-Difluoropyrrolidin-1-yl]carbonyl}-2-{[6-(trifluoromethyl)pyridin-2-yl]methyl}-5,6 ,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one

[01449] (5S)-3-Oxo-2-{[6-(trifluoromethyl)pyridin-2-yl]methyl}-2,3,5,6,7,8-hexahydro[1,2,4 ]triazolo[4,3-a]pyridine-5-carboxylic acid (63.9 mg, 187 μmol) was initially loaded into THF (2.0 mL), and HBTU (92.0 mg, 243 μmol) and N, N-diisopropylethylamine (98 μl, 560 μmol) was subsequently added. After stirring at room temperature for 15 minutes, (3R,4S)-3,4-difluoropyrrolidine hydrochloride (32.2 mg, 224 μmol) was added and the reaction mixture was stirred at room temperature overnight. The solvent was removed under reduced pressure, and the residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/water gradient). The fractions containing the product were concentrated under reduced pressure and 35.4 mg (44% possibility) of the title compound were obtained. LC-MS (Method 4): Rt = 0.72 min; MS (ESIpos): m /z = 432 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.151 (0.30), -0.010 (2.83), 0.006 (2.53), 0.144 (0.31) (0.99) (0.57) (0.69) (2.51) (1.33), 8,100 (2.38), 8,120 (1.12). Example 372 (5S)-2-{[5-Chloro-4-(trifluoromethyl)pyridin-2-yl]methyl}-5-{[(3R,4S)-3,4-difluoropyrrolidin-1-yl]carbonyl} -5,6,7,8-tetrahydro[1,2,4]triazolo[4,3- a]pyridin-3(2H)-one

[01450] (5S)-2-{[5-Chloro-4-(trifluoromethyl)pyridin-2-yl]methyl}-3-oxo-2,3,5,6,7,8-hexahydro[1 ,2,4]triazolo[4,3-a]pyridine-5-carboxylic acid (70.0 mg, 186 μmol) was initially loaded into THF (3.0 mL), and HBTU (91.6 mg, 242 μmol ) and N,N-diisopropylethylamine (97 μl, 560 μmol) were subsequently added. After stirring at room temperature for 15 minutes, (3R,4S)-3,4-difluoropyrrolidine hydrochloride (32.0 mg, 223 μmol) was added and the reaction mixture was stirred at room temperature for 6 days. The solvent was removed under reduced pressure, and the residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/water gradient). The fractions containing the product were concentrated under reduced pressure and 53.4 mg (62% possibility) of the title compound were obtained. LC-MS (Method 3): Rt = 1.51 min; MS (ESIpos): m /z = 466 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (0.41), -0.008 (3.04), 0.008 (3.60), 1.175 (0.45) (2.39) (0.86) (0.99), 3979 (0.97), 3993 (0.84), 4008 (0.60), 4021 (0.67), 4147 (0.67), 4173 (1.01), 4187 (0.75), 4200 (0.62), 4215 (0.65), 4810 (2.63), 4.825 (3.36), 4.835 (2.28), 5.040 (16.00), 5.274 (1.01), 5.351 (0.82), 5.388 (1.03), 5.455 (0.82), 7.718 (9.09), 8.901 (8.66). Example 373 (5S)-2-{[5-Chloro-4-(trifluoromethyl)pyridin-2-yl]methyl}-5-[(3-hydroxyazetidin-1-yl)carbonyl]-5,6,7,8 -tetrahydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one

[01451] (5S)-2-{[5-Chloro-4-(trifluoromethyl)pyridin-2-yl]methyl}-3-oxo-2,3,5,6,7,8-hexahydro[1 ,2,4]triazolo[4,3-a]pyridine-5-carboxylic acid (70.0 mg, 186 μmol) was initially loaded into THF (3.0 mL), and HBTU (91.6 mg, 242 μmol ) and N,N-diisopropylethylamine (97 μl, 560 μmol) were subsequently added. After stirring at room temperature for 15 minutes, azetidin-3-ol hydrochloride (24.4 mg, 223 μmol) was added and the reaction mixture was stirred at room temperature for 6 days. The solvent was removed under reduced pressure, and the residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/water gradient). The fractions containing the product were concentrated under reduced pressure and 46.0 mg (57% possibility) of the title compound were obtained. LC-MS (Method 3): Rt = 1.20 min; MS (ESIpos): m /z = 432 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (1.32), -0.008 (11.98), 0.008 (10.40), 0.146 (1.38) (2.57) (1.51) (2.04), 4,386 (1.51), 4,495 (4.08), 4,509 (4.48), 4,531 (4.67), 4,546 (4.41), 5,037 (16.00), 5,802 (4.94), 7,731 (14.22), 8,898 (5.99). Example 374 (5S)-2-{[5-Chloro-4-(trifluoromethyl)pyridin-2-yl]methyl}-5-{[(3S)-3-hydroxypyrrolidin-1-yl]carbonyl}-5.6 ,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one

[01452] (5S)-2-{[5-Chloro-4-(trifluoromethyl)pyridin-2-yl]methyl}-3-oxo-2,3,5,6,7,8-hexahydro[1 ,2,4]triazolo[4,3-a]pyridine-5-carboxylic acid (70.0 mg, 186 μmol) was initially loaded into THF (3.0 mL), and HBTU (91.6 mg, 242 μmol ) and N,N-diisopropylethylamine (97 μl, 560 μmol) were subsequently added. After stirring at room temperature for 15 minutes, (3S)-pyrrolidin-3-ol hydrochloride (27.6 mg, 223 μmol) was added and the reaction mixture was stirred at room temperature for 6 days. The solvent was removed under reduced pressure, and the residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/water gradient). The fractions containing the product were concentrated under reduced pressure and 47.2 mg (57% possibility) of the title compound were obtained. LC-MS (Method 3): Rt = 1.22 min; MS (ESIpos): m /z = 446 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (0.73), -0.008 (6.82), 0.008 (5.51), 0.146 (0.70) (2.69) (1.01) (2.17) (1.25) (5.38), 7,714 (6.70), 7,720 (8.08), 8,902 (11.96). Example 375 (5S)-2-{[5-Chloro-4-(trifluoromethyl)pyridin-2-yl]methyl}-5-[(3-fluoroazetidin-1-yl)carbonyl]-5,6,7,8 -tetrahydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one

[01453] (5S)-2-{[5-Chloro-4-(trifluoromethyl)pyridin-2-yl]methyl}-3-oxo-2,3,5,6,7,8-hexahydro[1 ,2,4]triazolo[4,3-a]pyridine-5-carboxylic acid (70.0 mg, 186 μmol) was initially loaded into THF (3.0 mL), and HBTU (91.6 mg, 242 μmol ) and N,N-diisopropylethylamine (97 μl, 560 μmol) were subsequently added. After stirring at room temperature for 15 minutes, 3-fluoroazetidine hydrochloride (24.9 mg, 223 μmol) was added and the reaction mixture was stirred at room temperature for 6 days. The solvent was removed under reduced pressure, and the residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/water gradient). The fractions containing the product were concentrated under reduced pressure and 42.0 mg (52% possibility) of the title compound were obtained. LC-MS (Method 3): Rt = 1.41 min; MS (ESIpos): m /z = 434 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (0.64), -0.008 (6.01) 0.008 (5.20), 0.146 ( 0.71), 1.691 (1.93), 1.715 (3.51), 1.970 (1.70), 2.038 (1.49), 2.327 (1.08), 2.366 (0.53), 2.560 (2.77), 2.585 (3.14), 2.598 (4.47), 2.612 ( 2.34), 2.628 (0.96), 2.641 (1.56), 2.669 (1.24), 2.710 (0.66), 3.908 (0.99), 3.937 (1.21), 3.999 (1.08), 4.174 (0.64), 4.211 (1.05), 4.226 ( 1.12), 4.259 (1.10), 4.278 (1.21), 4.305 (1.15), 4.335 (0.64), 4.365 (1.17), 4.392 (0.76), 4.431 (0.57), 4.455 (0.71), 4.522 (0.64), 4.557 ( 2.73), 4.569 (4.40), 4.581 (2.84), 4.639 (0.60), 4.677 (0.60), 5.044 (16.00), 5.355 (0.71), 5.402 (0.73), 5.498 (0.76), 5.546 (0.76), 7.737 ( 10.15), 8,891 (4.17), 8,902 (4.15). Example 376 (5S)-2-{[5-Chloro-4-(trifluoromethyl)pyridin-2-yl]methyl}-5-{[(3S)-3-fluoropyrrolidin-1-yl]carbonyl}-5.6 ,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one

[01454] (5S)-2-{[5-Chloro-4-(trifluoromethyl)pyridin-2-yl]methyl}-3-oxo-2,3,5,6,7,8-hexahydro[1 ,2,4]triazolo[4,3-a]pyridine-5-carboxylic acid (70.0 mg, 186 μmol) was initially loaded into THF (3.0 mL), and HBTU (91.6 mg, 242 μmol ) and N,N-diisopropylethylamine (97 μl, 560 μmol) were subsequently added. After stirring at room temperature for 15 minutes, (3S)-3-fluoropyrrolidine hydrochloride (28.0 mg, 223 μmol) was added and the reaction mixture was stirred at room temperature for 6 days. The solvent was removed under reduced pressure, and the residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/water gradient). The fractions containing the product were concentrated under reduced pressure and 50.3 mg (60% possibility) of the title compound were obtained. LC-MS (Method 3): Rt = 1.44 min; MS (ESIpos): m /z = 448 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (1.07), -0.008 (10.68), 0.008 (7.72), 0.146 (1.11), 1736 (2.73), 1929 (0.59), 2006 (2.25), 2017 (2.00), 2073 (4.25), 2087 (2.03), 2106 (2.07), 2137 (1.59), 2255 (1.15), 2327 (1.59) (1.92) (1.92) (0.52) (1.26) (0.63), 7,717 (8.46), 8,903 (7.94). Example 377 (5S)-2-[(5-Chloropyridin-2-yl)methyl]-5-[(3,3-difluoropyrrolidin-1-yl)carbonyl]-5,6,7,8-tetrahydro[ 1,2,4]triazolo[4,3-a]pyridin-3(2H)-one

[01455] (5S)-2-[(5-Chloropyridin-2-yl)methyl]-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[ 4,3-a]pyridine-5-carboxylic acid (100 mg, 324 μmol) was initially loaded into THF (2.0 mL), and HBTU (160 mg, 421 μmol) and N,N-diisopropylethylamine (170 μl, 970 μmol) were subsequently added. After stirring at room temperature for 15 minutes, 3,3-difluoropyrrolidine hydrochloride (55.8 mg, 389 μmol) was added and the reaction mixture was stirred at room temperature overnight. N,N-Diisopropylethylamine (170 μl, 970 μmol) was added again and the mixture was stirred at room temperature for 2 hours. The solvent was removed under reduced pressure, and the residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/water gradient). The fractions containing the product were concentrated under reduced pressure and 47.0 mg (36% possibility) of the title compound were obtained. LC-MS (Method 3): Rt = 1.24 min; MS (ESIpos): m /z = 398 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (0.69), -0.008 (5.97), 0.008 (5.29), 0.146 (0.69) (1.52) (1.27) (1.38) (2.28) (0.51), 4001 (1.09), 4030 (0.76), 4044 (1.01), 4072 (0.62), 4148 (0.65), 4180 (0.94), 4204 (0.94), 4234 (0.43), 4761 (1.41), 4776 (1.92) (4.38), 7,920 (4.52), 7,935 (4.24), 7,941 (4.34), 8,572 (5.39), 8,578 (5.29). Example 378 (5S)-2-[(5-Chloropyridin-2-yl)methyl]-5-{[(3R,4S)-3,4-difluoropyrrolidin-1-yl]carbonyl}-5,6,7, 8-tetrahydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one

[01456] (5S)-2-[(5-Chloropyridin-2-yl)methyl]-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[ 4,3-a]pyridine-5-carboxylic acid (100 mg, 324 μmol) was initially loaded into THF (2.0 mL), and HBTU (160 mg, 421 μmol) and N,N-diisopropylethylamine (170 μl, 970 μmol) were subsequently added. After stirring at room temperature for 15 minutes, (3R, 4S)-3,4-difluoropyrrolidine hydrochloride (55.8 mg, 389 μmol) was added and the reaction mixture was stirred at room temperature for 72 hours. The solvent was removed under reduced pressure, and the residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/water gradient). The fractions containing the product were concentrated under reduced pressure and 10.0 mg (8% possibility) of the title compound were obtained. LC-MS (Method 4): Rt = 0.64 min; MS (ESIpos): m /z = 398 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.008 (1.28), 0.008 (1.25), 1.656 (0.94), 1.669 ( 1.15), 1.682 (1.23), 1.692 (1.08), 1.707 (0.89), 1.718 (1.18), 1.729 (1.39), 1.740 (1.56), 1.753 (1.30), 1.936 (0.50), 1.943 (0.52), 1.978 ( 1.16), 1.986 (1.06), 2.000 (0.81), 2.021 (1.50), 2.045 (0.97), 2.055 (1.06), 2.063 (1.17), 2.073 (2.34), 2.090 (0.84), 2.098 (0.92), 2.106 ( 0.78), 2.582 (1.56), 2.596 (2.30), 2.608 (3.05), 2.620 (1.71), 2.639 (0.60), 2.650 (0.98), 2.663 (0.53), 3.322 (2.23), 3.449 (0.59), 3.459 ( 0.81), 3.468 (0.57), 3.483 (0.84), 3.493 (1.38), 3.502 (1.01), 3.514 (1.18), 3.524 (1.17), 3.535 (1.04), 3.547 (1.13), 3.555 (0.73), 3.568 ( 0.60), 3.578 (0.81), 3.588 (0.54), 3.619 (0.83), 3.633 (0.93), 3.652 (0.59), 3.666 (0.67), 3.674 (0.91), 3.688 (1.62), 3.701 (1.11), 3.707 ( 1.12), 3.722 (1.44), 3.736 (1.26), 3.753 (1.04), 3.765 (1.10), 3.786 (0.86), 3.799 (0.54), 3.852 (0.50), 3.864 (0.63), 3.871 (0.79), 3.900 ( 0.51), 3.907 (0.56), 3.912 (0.56), 3.919 (0.49), 3.934 (0.75), 3.947 (0.88), 3.962 (0.53), 3.977 (0.62), 3.984 (0.83), 3.997 (0.85), 4.012 ( 0.55), 4.026 (0.49), 4.133 (0.53), 4.148 (0.61), 4.162 (0.58), 4.175 (0.98), 4.189 (0.67), 4.202 (0.59), 4.217 (0.54), 4.798 (2.25), 4.811 ( 3.22), 4.821 (2.12), 4.870 (0.57), 4.911 (16.00), 4.958 (0.47), 5.256 (0.79), 5.265 (0.86), 5.276 (0.95), 5.287 (0.84), 5.299 (0.55), 5.314 ( 0.65), 5.322 (0.61), 5.329 (0.68), 5.338 (0.66), 5.344 (0.62), 5.353 (0.76), 5.366 (0.68), 5.381 (0.83), 5.388 (1.01), 5.398 (0.80), 5.408 ( 0.91), 5.418 (0.84), 5.429 (0.64), 5.443 (0.61), 5.451 (0.67), 5.457 (0.67), 5.465 (0.71), 5.475 (0.66), 5.482 (0.62), 5.495 (0.55), 7.197 ( 3.48), 7,200 (3.78), 7,218 (3.76), 7,220 (4.05), 7,912 (2.52), 7,915 (3.07), 7,918 (2.95), 7,921 (2.92), 7,933 (2.46), 7,935 (2.96), 7,939 ( 2.85), 7,941 (2.78), 8,215 (0.62), 8,571 (3.84), 8,573 (3.84), 8,577 (3.84). Example 379 (5S)-2-[(5-Chloropyridin-2-yl)methyl]-5-[(3-fluoroazetidin-1-yl)carbonyl]-5,6,7,8-tetrahydro[1, 2,4]triazolo[4,3-a]pyridin-3(2H)-one

[01457] (5S)-2-[(5-Chloropyridin-2-yl)methyl]-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[ 4,3-a]pyridine-5-carboxylic acid (100 mg, 324 μmol) was initially loaded into THF (2.0 mL), and HBTU (160 mg, 421 μmol) and N,N-diisopropylethylamine (170 μl, 970 μmol) were subsequently added. After stirring at room temperature for 15 minutes, 3-fluoroazetidine hydrochloride (43.4 mg, 389 μmol) was added and the reaction mixture was stirred at room temperature overnight. The solvent was removed under reduced pressure, and the residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/water gradient). The fractions containing the product were concentrated under reduced pressure and the residue was purified via preparatory HPLC (Method 11). The fractions containing the product were concentrated under reduced pressure and 1.00 mg (1% possibility) of the title compound were obtained. LC-MS (Method 3): Rt = 1.04 min; MS (ESIpos): m /z = 366 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (1.02), -0.008 (8.51), 0.008 (5.75), 0.146 (0.64) (2.35) (0.77) (0.89) (0.84), 5.546 (0.84), 7.212 (7.00), 7.234 (7.44), 7.912 (3.55), 7.918 (3.65), 7.933 (3.35), 7.938 (3.35), 8.571 (3.40). Example 380 (5S)-5-{[(3R,4S)-3,4-Difluoropyrrolidin-1-yl]carbonyl}-2-[(5-methoxypyridin-2-yl)methyl]-5,6,7, 8-tetrahydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one

[01458] (5S)-2-[(5-Methoxypyridin-2-yl)methyl]-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[ 4,3-a]pyridine-5-carboxylic acid (45.0 mg, 148 μmol) was initially loaded into THF (2.0 mL), and HBTU (72.9 mg, 192 μmol) and N,N-diisopropylethylamine (77 μl, 440 μmol) were subsequently added. After stirring at room temperature for 15 minutes, (3R,4S)-3,4-difluoropyrrolidine hydrochloride (25.5 mg, 177 μmol) was added and the reaction mixture was stirred at room temperature overnight. The solvent was removed under reduced pressure, and the residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/water gradient). The fractions containing the product were concentrated under reduced pressure and 11.0 mg (19% possibility) of the title compound were obtained. LC-MS (Method 3): Rt = 1.15 min; MS (ESIpos): m /z = 394 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: 0.008 (1.72), 1.679 (0.66), 1.720 (0.83), 1.732 (0.84 ), 1.742 (0.80), 1.968 (0.60), 2.011 (0.73), 2.037 (0.49), 2.047 (0.54), 2.055 (0.57), 2.062 (0.53), 2.071 (0.45), 2.089 (0.43), 2.559 (1.35 ), 2.569 (0.98), 2.583 (1.23), 2.595 (1.50), 2.607 (0.84), 2.637 (0.50), 3.491 (0.61), 3.501 (0.46), 3.514 (0.51), 3.523 (0.51), 3.535 (0.51 ), 3.546 (0.56), 3.619 (0.41), 3.632 (0.45), 3.674 (0.46), 3.688 (0.77), 3.704 (0.64), 3.721 (0.66), 3.736 (0.72), 3.754 (0.65), 3.766 (0.66 ), 3.787 (0.68), 3.810 (16.00), 3.871 (0.41), 3.947 (0.42), 3.983 (0.41), 4.178 (0.46), 4.787 (1.48), 4.797 (1.73), 4.827 (6.88), 5.256 (0.42 ), 5.267 (0.43), 5.277 (0.49), 5.287 (0.41), 5.378 (0.46), 5.388 (0.53), 5.409 (0.46), 5.418 (0.41), 7.102 (1.50), 7.106 (1.54), 7.124 (1.77 ), 7,128 (1.82), 7,353 (1.37), 7,357 (1.33), 7,375 (1.17), 7,379 (1.11), 8,209 (1.99), 8,216 (1.83). Example 381 (5S)-5-[(3,3-Difluoropyrrolidin-1-yl)carbonyl]-2-[(5-methoxypyridin-2-yl)methyl]-5,6,7,8-tetrahydro[ 1,2,4]triazolo[4,3-a]pyridin-3(2H)-one

[01459] (5S)-2-[(5-Methoxypyridin-2-yl)methyl]-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[ 4,3-a]pyridine-5-carboxylic acid (45.0 mg, 148 μmol) was initially loaded into THF (2.0 mL), and HBTU (72.9 mg, 192 μmol) and N,N-diisopropylethylamine (77 μl, 440 μmol) were subsequently added. After stirring at room temperature for 15 minutes, 3,3-difluoropyrrolidine hydrochloride (25.5 mg, 177 μmol) was added and the reaction mixture was stirred at room temperature overnight. The solvent was removed under reduced pressure, and the residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/water gradient). The fractions containing the product were concentrated under reduced pressure and 14.0 mg (23% possibility) of the title compound were obtained. LC-MS (Method 4): Rt = 0.57 min; MS (ESIpos): m /z = 394 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) delta [ppm]: -0.008 (0.99), 0.008 (0.92), 1.675 (0.28), 1.722 ( 0.51), 1.914 (0.21), 1.981 (0.48), 1.998 (0.36), 2.015 (0.40), 2.031 (0.33), 2.042 (0.30), 2.051 (0.30), 2.057 (0.31), 2.067 (0.31), 2.073 ( 0.49), 2.085 (0.24), 2.093 (0.21), 2.366 (0.24), 2.382 (0.26), 2.412 (0.29), 2.432 (0.29), 2.452 (0.21), 2.566 (0.80), 2.580 (0.84), 2.597 ( 0.86), 2.608 (0.55), 2.626 (0.19), 2.639 (0.26), 2.670 (0.19), 2.710 (0.18), 2.893 (0.51), 3.540 (0.40), 3.552 (0.54), 3.560 (0.59), 3.571 ( 0.34), 3.579 (0.31), 3.673 (0.37), 3.706 (0.40), 3.742 (0.32), 3.774 (0.51), 3.790 (0.33), 3.810 (16.00), 3.835 (0.26), 3.897 (0.20), 3.916 ( 0.41), 3.935 (0.23), 3.942 (0.29), 4.002 (0.25), 4.031 (0.18), 4.043 (0.23), 4.180 (0.24), 4.207 (0.23), 4.748 (0.34), 4.757 (0.39), 4.763 ( 0.47), 4.772 (0.33), 4.787 (0.21), 4.827 (3.23), 4.831 (3.75), 4.849 (0.40), 4.871 (0.23), 7.106 (1.41), 7.127 (1.69), 7.352 (1.06), 7.359 ( 1.08), 7.373 (0.91), 7.381 (0.93), 8.209 (1.75), 8.217 (1.73). Example 382 (5S)-5-[(3-Fluoroazetidin-1-yl)carbonyl]-2-[(5-methoxypyridin-2-yl)methyl]-5,6,7,8-tetrahydro[1, 2,4]triazolo[4,3-a]pyridin-3(2H)-one

[01460] (5S)-2-[(5-Methoxypyridin-2-yl)methyl]-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[ 4,3-a]pyridine-5-carboxylic acid (45.0 mg, 148 μmol) was initially loaded into THF (2.0 mL), and HBTU (72.9 mg, 192 μmol) and N,N-diisopropylethylamine (77 μl, 440 μmol) were subsequently added. After stirring at room temperature for 15 minutes, 3-fluoroazetidine hydrochloride (19.8 mg, 177 μmol) was added and the reaction mixture was stirred at room temperature for 72 hours. The solvent was removed under reduced pressure, and the residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/water gradient). The fractions containing the product were concentrated under reduced pressure and 14.0 mg (26% possibility) of the title compound were obtained. LC-MS (Method 4): Rt = 0.48 min; MS (ESIpos): m /z = 362 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) delta [ppm]: -0.149 (0.34), -0.008 (3.04), 0.008 (2.32), 0.146 (0.30), 1720 (1.27), 1960 (0.60), 2021 (0.51), 2032 (0.53), 2327 (0.48), 2366 (0.51), 2523 (1.43), 2572 (1.15), 2585 (1.45), 2598 (0.71), 2614 (0.27), 2627 (0.42), 2641 (0.18), 2670 (0.46), 2710 (0.44), 3809 (16.00), 3901 (0.21), 3928 (0.41), 3956 (0.41), 3988 (0.46) (0.39) (0.19) (0.97), 7,379 (0.99), 8,210 (1.66). Example 383 (5S)-2-[(6-Chloropyridin-2-yl)methyl]-5-[(3,3-difluoropyrrolidin-1-yl)carbonyl]-5,6,7,8-tetrahydro[ 1,2,4]triazolo[4,3-a]pyridin-3(2H)-one

[01461] (5S)-2-[(6-Chloropyridin-2-yl)methyl]-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[ 4,3-a]pyridine-5-carboxylic acid (62.9 mg, 204 μmol) was initially loaded into THF (2.0 mL), and HBTU (100 mg, 265 μmol) and N,N-diisopropylethylamine (110 μl, 610 μmol) were subsequently added. After stirring at room temperature for 15 minutes, 3,3-difluoropyrrolidine hydrochloride (35.1 mg, 244 μmol) was added and the reaction mixture was stirred at room temperature overnight. The solvent was removed under reduced pressure, and the residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/water gradient). The fractions containing the product were concentrated under reduced pressure and 52.6 mg (65% possibility) of the title compound were obtained. LC-MS (Method 3): Rt = 1.24 min; MS (ESIpos): m /z = 398 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (1.19), -0.008 (10.77), 0.008 (8.41), 0.146 (1.17) (1.07) (2.34) (1.12) (0.90) (1.37) (3.04), 7,860 (5.42), 7,879 (2.69). Example 384 (5S)-2-[(6-Chloropyridin-2-yl)methyl]-5-[(3-fluoroazetidin-1-yl)carbonyl]-5,6,7,8-tetrahydro[1, 2,4]triazolo[4,3-a]pyridin-3(2H)-one

[01462] (5S)-2-[(6-Chloropyridin-2-yl)methyl]-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[ 4,3-a]pyridine-5-carboxylic acid (62.9 mg, 204 μmol) was initially loaded into THF (2.0 mL), and HBTU (100 mg, 265 μmol) and N,N-diisopropylethylamine (110 μl, 610 μmol) were subsequently added. After stirring at room temperature for 15 minutes, 3-fluoroazetidine hydrochloride (27.3 mg, 244 μmol) was added and the reaction mixture was stirred at room temperature overnight. The solvent was removed under reduced pressure, and the residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/water gradient). The fractions containing the product were concentrated under reduced pressure and 45.5 mg (61% possibility) of the title compound were obtained. LC-MS (Method 3): Rt = 1.04 min; MS (ESIpos): m /z = 366 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (1.89), -0.008 (16.00), 0.008 (15.16), 0.146 (1.89) (1.68) (1.40) (15.02) (3.42), 7,858 (6.50), 7,877 (3.14). Example 385(5S)-2-[(6-Chloropyridin-2-yl)methyl]-5-{[(3R,4S)-3,4-difluoropyrrolidin-1-yl]carbonyl}-5,6,7, 8-tetrahydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one

[01463] (5S)-2-[(6-Chloropyridin-2-yl)methyl]-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[ 4,3-a]pyridine-5-carboxylic acid (62.9 mg, 204 μmol) was initially loaded into THF (2.0 mL), and HBTU (100 mg, 265 μmol) and N,N-diisopropylethylamine (110 μl, 610 μmol) were subsequently added. After stirring at room temperature for 15 minutes, (3R,4S)-3,4-difluoropyrrolidine hydrochloride (35.1 mg, 244 μmol) was added and the reaction mixture was stirred at room temperature overnight. The solvent was removed under reduced pressure, and the residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/water gradient). The fractions containing the product were concentrated under reduced pressure and 60.4 mg (75% possibility) of the title compound were obtained. LC-MS (Method 3): Rt = 1.17 min; MS (ESIpos): m /z = 398 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (0.90), -0.008 (7.33), 0.008 (6.93), 0.146 (0.97) (1.87) (1.23) (0.90) (0.57) (0.67) (0.53) (4.50), 7,453 (5.13), 7,838 (2.67), 7,842 (2.93), 7,858 (4.63), 7,861 (5.10), 7,878 (2.37), 7,881 (2.57). Example 386 (5S)-2-[(6-Chloropyridin-2-yl)methyl]-5-{[(3S)-3-fluoropyrrolidin-1-yl]carbonyl}-5,6,7,8-tetra- hydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one

[01464] (5S)-2-[(6-Chloropyridin-2-yl)methyl]-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[ 4,3-a]pyridine-5-carboxylic acid (62.9 mg, 204 μmol) was initially loaded into THF (2.0 mL), and HBTU (100 mg, 265 μmol) and N,N-diisopropylethylamine (110 μl, 610 μmol) were subsequently added. After stirring at room temperature for 15 minutes, (3S)-3-fluoropyrrolidine hydrochloride (30.7 mg, 244 μmol) was added and the reaction mixture was stirred at room temperature overnight. HBTU (38 mg, 102 μmol) and N,N-diisopropylethylamine (18 μl, 102 μmol) were added again and the mixture was stirred overnight. The solvent was removed under reduced pressure, and the residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/water gradient). The fractions containing the product were concentrated under reduced pressure and 53.3 mg (69% possibility) of the title compound were obtained. LC-MS (Method 3): Rt = 1.09 min; MS (ESIpos): m /z = 380 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (0.48), -0.008 (4.53), 0.008 (3.45), 0.146 (0.46), 1747 (2.81), 1890 (0.58), 1932 (0.79), 1968 (0.40), 2005 (0.79), 2041 (1.27), 2073 (2.00), 2090 (1.79), 2108 (2.12), 2139 (1.47) (1.25) (0.58) (1.45) (1.37) (5.32), 7,841 (3.97), 7,860 (7.07), 7,879 (3.45). Example 387 (5S)-2-{[3-Chloro-4-(trifluoromethyl)pyridin-2-yl]methyl}-5-[(3,3-difluoropyrrolidin-1-yl)carbonyl]-5,6,7 ,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one

[01465] (5S)-2-{[3-Chloro-4-(trifluoromethyl)pyridin-2-yl]methyl}-3-oxo-2,3,5,6,7,8-hexahydro[1 ,2,4]triazolo[4,3-a]pyridine-5-carboxylic acid (47.0 mg, 125 μmol) was initially loaded into THF (2.0 mL) at room temperature. Subsequently, HBTU (61.5 mg, 162 μmol) and N,N-diisopropylethylamine (65 μl, 370 μmol) were added. After stirring for 15 minutes, 3,3-difluoropyrrolidine hydrochloride (21.5 mg, 150 μmol) was added and the reaction mixture was stirred at room temperature overnight. The reaction mixture was mixed with water and ethyl acetate. The organic phase was removed and the aqueous phase was extracted three times with ethyl acetate. The combined organic phases were washed with saturated aqueous sodium chloride solution, dried over sodium sulfate and filtered, and the filtrate was concentrated. The residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/gradient water). The fractions containing the product were concentrated under reduced pressure and 18.5 mg (32% possibility) of the title compound were obtained. LC-MS (Method 3): Rt = 1.47 min; MS (ESIpos): m /z = 466 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (1.17), 0.008 (8.40), 0.146 (1.07), 1.711 ( 4.48), 1978 (2.57), 2328 (2.38), 2366 (2.47), 2576 (5.46), 2589 (6.16), 2603 (3.31), 2631 (1.54), 2670 (2.05), 2710 (1.91), 3533 ( 3.17), 3.552 (5.22), 3.573 (2.47), 3.671 (2.33), 3.705 (2.61), 3.736 (2.01), 3.769 (3.27), 3.802 (2.61), 3.813 (2.57), 3.832 (1.73), 3.911 ( 2.47), 3.939 (1.77), 3.997 (1.73), 4.039 (1.45), 4.143 (1.03), 4.176 (1.45), 4.201 (1.59), 4.769 (2.89), 4.847 (2.71), 4.858 (2.15), 5.104 ( 3.50), 5.144 (13.62), 5.166 (16.00), 5.207 (3.64), 7.844 (10.78), 7.856 (10.87), 8.735 (9.19), 8.748 (9.00). Example 388 (5S)-2-{[3-Chloro-4-(trifluoromethyl)pyridin-2-yl]methyl}-5-{[(3R,4S)-3,4-difluoropyrrolidin-1-yl]carbonyl} -5,6,7,8-tetrahydro[1,2,4]triazolo[4,3- a]pyridin-3(2H)-one

[01466] (5S)-2-{[3-Chloro-4-(trifluoromethyl)pyridin-2-yl]methyl}-3-oxo-2,3,5,6,7,8-hexahydro[1 ,2,4]triazolo[4,3-a]pyridine-5-carboxylic acid (50.0 mg, 133 μmol) was initially loaded into THF (3.1 mL), and HBTU (65.4 mg, 173 μmol ) and N,N-diisopropylethylamine (69 μl, 400 μmol) were subsequently added. After stirring at room temperature for 15 minutes, (3R,4S)-3,4-difluoropyrrolidine hydrochloride (22.9 mg, 159 μmol) was added and the reaction mixture was stirred at room temperature overnight. The solvent was removed under reduced pressure, and the residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/water gradient). The fractions containing the product were concentrated under reduced pressure and 37.0 mg (60% possibility) of the title compound were obtained. LC-MS (Method 3): Rt = 1.40 min; MS (ESIpos): m /z = 466 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (1.23), -0.008 (15.35), 0.008 (9.72), 0.146 (1.36) (2.91) (12.89) (2.46) (1.30) (2.59) (2.20) (1.36) 8 (2.01) (2.07) (1.43), 7,844 (15.74), 7,856 (16.00), 8,735 (10.62), 8,748 (10.11). Example 389 (5S)-2-{[3-Chloro-4-(trifluoromethyl)pyridin-2-yl]methyl}-5-[(3-fluoroazetidin-1-yl)carbonyl]-5,6,7,8 -tetrahydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one

[01467] (5S)-2-{[3-Chloro-4-(trifluoromethyl)pyridin-2-yl]methyl}-3-oxo-2,3,5,6,7,8-hexahydro[1 ,2,4]triazolo[4,3-a]pyridine-5-carboxylic acid (50.0 mg, 133 μmol) was initially loaded into THF (3.1 mL), and HBTU (65.4 mg, 173 μmol ) and N,N-diisopropylethylamine (69 μl, 400 μmol) were subsequently added. After stirring at room temperature for 15 minutes, 3-fluoroazetidine hydrochloride (17.8 mg, 159 μmol) was added and the reaction mixture was stirred at room temperature overnight. The solvent was removed under reduced pressure, and the residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/water gradient). The fractions containing the product were concentrated under reduced pressure and 30.0 mg (52% possibility) of the title compound were obtained. LC-MS (Method 3): Rt = 1.30 min; MS (ESIpos): m /z = 434 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.008 (1.41), 0.008 (1.30), 1.721 (4.73), 1.934 ( 1.28), 1.946 (1.80), 1.957 (1.88), 1.967 (1.75), 1.979 (1.27), 1.991 (0.90), 2.008 (1.32), 2.026 (1.85), 2.044 (1.66), 2.063 (1.20), 2.073 ( 0.76), 2.080 (0.64), 2.524 (1.40), 2.572 (3.52), 2.586 (5.17), 2.599 (2.48), 2.614 (0.89), 2.628 (1.52), 2.642 (0.62), 3.895 (0.63), 3.923 ( 1.28), 3.953 (1.26), 3.985 (1.30), 4.012 (0.73), 4.155 (0.55), 4.169 (0.62), 4.184 (0.51), 4.234 (0.97), 4.286 (1.22), 4.314 (1.22), 4.348 ( 0.73), 4.368 (1.16), 4.389 (0.84), 4.426 (0.57), 4.453 (0.76), 4.509 (0.60), 4.526 (2.15), 4.537 (3.77), 4.551 (3.73), 4.561 (2.07), 4.576 ( 0.70), 4.604 (0.47), 4.620 (0.56), 4.635 (0.63), 4.646 (0.55), 4.662 (0.58), 4.671 (0.59), 4.686 (0.62), 4.699 (0.55), 4.713 (0.49), 5.118 ( 1.66), 5.159 (16.00), 5.171 (5.56), 5.213 (0.81), 5.355 (0.81), 5.370 (0.60), 5.381 (0.64), 5.389 (0.73), 5.396 (0.82), 5.497 (0.78), 5.505 ( 0.70), 5.512 (0.62), 5.532 (0.71), 5.539 (0.81), 7.845 (8.15), 7.857 (8.51), 8.722 (2.50), 8.734 (4.62), 8.747 (2.37). Example 390 (5S)-2-{[3-Chloro-4-(trifluoromethyl)pyridin-2-yl]methyl}-5-[(3-hydroxyazetidin-1-yl)carbonyl]-5,6,7,8 -tetrahydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one

[01468] (5S)-2-{[3-Chloro-4-(trifluoromethyl)pyridin-2-yl]methyl}-3-oxo-2,3,5,6,7,8-hexahydro[1 ,2,4]triazolo[4,3-a]pyridine-5-carboxylic acid (50.0 mg, 133 μmol) was initially loaded into THF (3.1 mL), and HBTU (65.4 mg, 173 μmol ) and N,N-diisopropylethylamine (69 μl, 400 μmol) were subsequently added. After stirring at room temperature for 15 minutes, azetidin-3-ol hydrochloride (17.4 mg, 159 μmol) was added and the reaction mixture was stirred at room temperature overnight. The solvent was removed under reduced pressure, and the residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/water gradient). The fractions containing the product were concentrated under reduced pressure and 26.0 mg (45% possibility) of the title compound were obtained. LC-MS (Method 3): Rt = 1.11 min; MS (ESIpos): m /z = 432 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (1.15), 0.008 (8.71), 0.146 (1.10), 1.706 ( 7.23), 1.719 (7.18), 1.903 (2.41), 1.915 (2.47), 1.938 (4.55), 1.989 (2.30), 2.001 (3.23), 2.014 (3.01), 2.023 (3.01), 2.038 (2.30), 2.328 ( 2.30), 2.366 (1.81), 2.523 (9.81), 2.564 (5.48), 2.579 (7.07), 2.592 (3.45), 2.607 (1.48), 2.621 (2.25), 2.670 (2.19), 2.710 (1.75), 3.593 ( 2.47), 3.601 (2.79), 3.627 (3.78), 3.643 (2.58), 3.658 (2.52), 3.668 (2.47), 3.943 (2.74), 3.954 (3.18), 4.020 (4.82), 4.043 (4.93), 4.061 ( 2,52), 4,097 (1.97), 4,113 (2.68), 4,137 (1.86), 4,347 (1.92), 4,366 (3.23), 4,387 (2.41), 4,508 (13,21), 5,111 (1.97), 5,152 (16.00), 5.157 ( 13.97), 5,164 (12.00), 5,204 (1.64), 5,803 (5.42), 7,844 (13.70), 7,857 (14.19), 8,733 (11.29), 8,745 (11.01). Example 391 (5S)-2-{[3-Chloro-4-(trifluoromethyl)pyridin-2-yl]methyl}-5-{[(3S)-3-hydroxypyrrolidin-1-yl]carbonyl}-5.6 ,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one

[01469] (5S)-2-{[3-Chloro-4-(trifluoromethyl)pyridin-2-yl]methyl}-3-oxo-2,3,5,6,7,8-hexahydro[1 ,2,4]triazolo[4,3-a]pyridine-5-carboxylic acid (50.0 mg, 133 μmol) was initially loaded into THF (2.0 mL), and HBTU (65.4 mg, 173 μmol ) and N,N-diisopropylethylamine (69 μl, 400 μmol) were subsequently added. After stirring at room temperature for 15 minutes, (3S)-pyrrolidin-3-ol hydrochloride (19.7 mg, 159 μmol) was added and the reaction mixture was stirred at room temperature overnight. The solvent was removed under reduced pressure, and the residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/water gradient). The fractions containing the product were concentrated under reduced pressure and 11.0 mg (19% possibility) of the title compound were obtained. LC-MS (Method 3): Rt = 1.12 min; MS (ESIpos): m /z = 446 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.150 (1.86), -0.008 (16.00), 0.008 (12.93), 0.146 (1.86), 1243 (2.08), 1257 (2.30), 1728 (6.03), 1846 (2.63), 1855 (2.74), 1877 (3.07), 1959 (2.85), 2004 (3.07), 2044 (3.07), 2327 (4.60) (1.75) (1.75), 5,091 (3.95), 5,132 (12.05), 5,159 (10.52), 5,199 (3.07), 7,842 (10.85), 7,855 (11.18), 7,910 (2.30), 8,738 (8.44), 8,750 (8.00). Example 392 (5S)-2-{[3-Chloro-4-(trifluoromethyl)pyridin-2-yl]methyl}-5-{[(3S)-3-fluoropyrrolidin-1-yl]carbonyl}-5.6 ,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one

[01470] (5S)-2-{[3-Chloro-4-(trifluoromethyl)pyridin-2-yl]methyl}-3-oxo-2,3,5,6,7,8-hexahydro[1 ,2,4]triazolo[4,3-a]pyridine-5-carboxylic acid (53.0 mg, 141 μmol) was initially loaded into THF (2.0 mL) at room temperature. Subsequently, HBTU (69.4 mg, 183 μmol) and N,N-diisopropylethylamine (74 μl, 420 μmol) were added. After stirring for 15 minutes, (3S)-3-fluoropyrrolidine (15.0 mg, 169 μmol) was added and the reaction mixture was stirred at room temperature overnight. The reaction mixture was mixed with water and ethyl acetate. The organic phase was removed and the aqueous phase was extracted three times with ethyl acetate. The combined organic phases were washed with saturated aqueous sodium chloride solution, dried over sodium sulfate and filtered, and the filtrate was concentrated. The residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/gradient water). The fractions containing the product were concentrated under reduced pressure and the residue was purified via preparatory HPLC (Method 10). The fractions containing the product were concentrated under reduced pressure and 11.0 mg (17% possibility) of the title compound were obtained. LC-MS (Method 3): Rt = 1.33 min; MS (ESIpos): m /z = 448 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (1.89), -0.008 (16.00), 0.008 (13.03), 0.146 (1.80) (3.96) (1.08) (4.67) (12.85), 5,160 (8.54), 5.170 (9.62), 5,200 (2.07), 5,211 (3.24), 5,257 (2.25), 5,388 (2.97), 5,508 (1.62), 7,844 (11,51), 7,856 (12,04), 8,738 (9.17), 8.751 (8.90). Example 393 (5S)-2-[(3-Chloropyridin-2-yl)methyl]-5-{[(3S)-3-fluoropyrrolidin-1-yl]carbonyl}-5,6,7,8-tetra- hydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one

[01471] (5S)-2-[(3-Chloropyridin-2-yl)methyl]-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[ 4,3-a]pyridine-5-carboxylic acid (102 mg, 330 μmol) was initially loaded into THF (4.0 mL), and HBTU (163 mg, 430 μmol) and N,N-diisopropylethylamine (170 μl, 990 μmol) were subsequently added. After stirring at room temperature for 15 minutes, (3S)-3-fluoropyrrolidine hydrochloride (49.8 mg, 396 μmol) was added and the reaction mixture was stirred at room temperature overnight. The solvent was removed under reduced pressure, and the residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/water gradient). The fractions containing the product were concentrated under reduced pressure and 58.1 mg (46% possibility) of the title compound were obtained. LC-MS (Method 3): Rt = 0.95 min; MS (ESIpos): m /z = 380 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (1.01), -0.008 (8.13), 0.008 (8.46), 0.146 (1.01) (4.10) (7.20) (2.18) (4.69) (4.19) 3 (6.20) 3 (11.23), 7,926 (11.39), 7,943 (10.72), 7,946 (10.47), 8,468 (11.39), 8,479 (11.39). Example 394 (5S)-2-[(3-Chloropyridin-2-yl)methyl]-5-[(3,3-difluoroazetidin-1-yl)carbonyl]-5,6,7,8-tetrahydro[ 1,2,4]triazolo[4,3-a]pyridin-3(2H)-one

[01472] (5S)-2-[(3-Chloropyridin-2-yl)methyl]-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[ 4,3-a]pyridine-5-carboxylic acid (102 mg, 330 μmol) was initially loaded into THF (4.0 mL), and HBTU (163 mg, 430 μmol) and N,N-diisopropylethylamine (170 μl, 990 μmol) were subsequently added. After stirring at room temperature for 15 minutes, 3,3-difluoroazetidine hydrochloride (51.4 mg, 396 μmol) was added and the reaction mixture was stirred at room temperature overnight. The solvent was removed under reduced pressure, and the residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/water gradient). The fractions containing the product were concentrated under reduced pressure and 75.6 mg (60% possibility) of the title compound were obtained. LC-MS (Method 3): Rt = 1.07 min; MS (ESIpos): m /z = 384 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (0.48), -0.008 (4.34), 0.008 (4.02), 0.146 (0.48) (1.09), 2.030 (1.25), 2.046 (1.83), 2.057 (1.93), 2.066 (2.25), 2.079 (1.83), 2.089 (1.25) (0.71) (1.73) (1.12) (6.23), 7,929 (6.71), 7,933 (7.07), 7,949 (6.43), 7,953 (6.43), 8,451 (6.52), 8,455 (6.81), 8,463 (6.68), 8,466 (6.52). Example 395 (5S)-2-[(3-Chloropyridin-2-yl)methyl]-5-{[(3R,4S)-3,4-difluoropyrrolidin-1-yl]carbonyl}-5,6,7, 8-tetrahydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one

[01473] (5S)-2-[(3-Chloropyridin-2-yl)methyl]-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[ 4,3-a]pyridine-5-carboxylic acid (102 mg, 330 μmol) was initially loaded into THF (4.0 mL), and HBTU (163 mg, 430 μmol) and N,N-diisopropylethylamine (170 μl, 990 μmol) were subsequently added. After stirring at room temperature for 15 minutes, (3R,4S)-3,4-difluoropyrrolidine hydrochloride (56.9 mg, 396 μmol) was added and the reaction mixture was stirred at room temperature overnight. The solvent was removed under reduced pressure, and the residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/water gradient). The fractions containing the product were concentrated under reduced pressure and 61.2 mg (47% possibility) of the title compound were obtained. LC-MS (Method 3): Rt = 1.05 min; MS (ESIpos): m /z = 398 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.150 (1.35), -0.008 (11.87), 0.008 (10.29), 0.146 (1.35) (3.15) (9.84) (1.95) (1.50) (2.78) (1.65) (1.80), 4,216 (1.65), 4,781 (7.96), 4,791 (9,31), 4,797 (10,37), 4,806 (7,51), 4,952 (6,84), 4,959 (4,88), 4,992 (16.00), 4,998 (15,47), 5,029 (14.50) (1.73) (2.10) (11.42), 7,406 (11.72), 7,924 (13.00), 7,944 (12.24), 8,465 (12.85), 8,476 (12.85). Example 396 (5S)-2-[(3-Chloropyridin-2-yl)methyl]-5-[(3-fluoroazetidin-1-yl)carbonyl]-5,6,7,8-tetrahydro[1, 2,4]triazolo[4,3-a]pyridin-3(2H)-one

[01474] 5S)-2-[(3-Chloropyridin-2-yl)methyl]-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4 ,3-a]pyridine-5-carboxylic acid (102 mg, 330 μmol) was initially loaded into THF (4.0 mL), and HBTU (163 mg, 430 μmol) and N,N-diisopropylethylamine (170 μl, 990 μmol) were subsequently added. After stirring at room temperature for 15 minutes, 3-fluoroazetidine hydrochloride (44.2 mg, 396 μmol) was added and the reaction mixture was stirred at room temperature overnight. The solvent was removed under reduced pressure, and the residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/water gradient). The fractions containing the product were concentrated under reduced pressure and 44.7 mg (37% possibility) of the title compound were obtained. LC-MS (Method 3): Rt = 0.95 min; MS (ESIpos): m /z = 366 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.008 (1.57), 0.008 (1.11), 1.718 (5.92), 1.928 ( 1.66), 1939 (2.29), 1951 (2.40), 1961 (2.25), 1972 (1.69), 1985 (1.20), 2002 (1.67), 2021 (2.41), 2039 (2.28), 2056 (1.75), 2073 ( 16.00), 2.524 (3.36), 2.561 (4.73), 2.575 (6.55), 2.588 (3.16), 2.603 (1.16), 2.617 (1.86), 2.631 (0.77), 3.894 (0.84), 3.923 (1.64), 3.953 ( 1.64), 3.984 (1.63), 4.013 (0.91), 4.154 (0.71), 4.168 (0.80), 4.183 (0.68), 4.219 (1.26), 4.233 (1.28), 4.248 (1.10), 4.262 (1.00), 4.286 ( 1.40), 4.296 (1.38), 4.315 (1.43), 4.359 (1.19), 4.385 (1.41), 4.429 (0.76), 4.454 (0.96), 4.513 (2.81), 4.525 (5.12), 4.538 (4.60), 4.549 ( 2.31), 4.563 (0.89), 4.579 (0.85), 4.590 (0.66), 4.607 (0.64), 4.618 (0.74), 4.635 (0.82), 4.644 (0.71), 4.662 (0.76), 4.671 (0.81), 4.686 ( 0.85), 4.697 (0.74), 4.713 (0.61), 4.975 (3.42), 5.015 (15.16), 5.031 (6.48), 5.041 (5.56), 5.071 (1.15), 5.081 (1.50), 5.355 (1.02), 5.362 ( 0.91), 5.370 (0.85), 5.380 (0.89), 5.388 (0.96), 5.395 (1.04), 5.498 (1.07), 5.513 (0.91), 5.522 (0.87), 5.531 (0.96), 5.539 (1.02), 7.375 ( 5.78), 7.386 (5.99), 7.395 (6.11), 7.407 (6.15), 7.925 (6.95), 7.929 (6.74), 7.945 (6.47), 7.949 (6.04), 8.453 (3.20), 8.463 (5.44), 8.474 ( 2.85). Example 397 (5S)-2-[(3,5-Dichloropyridin-2-yl)methyl]-5-[(3,3-difluoroazetidin-1-yl)carbonyl]-5,6,7,8-tetra- hydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one

[01475] (5S)-2-[(3,5-Dichloropyridin-2-yl)methyl]-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4] triazolo[4,3-a]pyridine-5-carboxylic acid (42.1 mg, 123 μmol) was initially loaded into THF (1.0 mL), and HBTU (93.1 mg, 245 μmol) and N,N -diisopropylethylamine (85 μl, 490 μmol) were subsequently added. After stirring at room temperature for 15 minutes, 3,3-difluoroazetidine hydrochloride (23.8 mg, 184 μmol) was added and the reaction mixture was stirred at room temperature overnight. The solvent was removed under reduced pressure, and the residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/water gradient). The fractions containing the product were concentrated under reduced pressure and 43.8 mg (85% possibility) of the title compound were obtained. LC-MS (Method 3): Rt = 1.32 min; MS (ESIpos): m /z = 418 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (1.71), -0.008 (16.00), 0.008 (14.02), 0.146 (1.78) (2.57) (2.04) (4.81), 8.552 (5.33), 8.557 (5.20). Example 398 (5S)-2-[(3,5-Dichloropyridin-2-yl)methyl]-5-[(3-fluoroazetidin-1-yl)carbonyl]-5,6,7,8-tetrahydro[ 1,2,4]triazolo[4,3-a]pyridin-3(2H)-one

[01476] (5S)-2-[(3,5-Dichloropyridin-2-yl)methyl]-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4] triazolo[4,3-a]pyridine-5-carboxylic acid (42.1 mg, 123 μmol) was initially loaded into THF (1.0 mL), and HBTU (93.1 mg, 245 μmol) and N,N -diisopropylethylamine (85 μl, 490 μmol) were subsequently added. After stirring at room temperature for 15 minutes, 3-fluoroazetidine hydrochloride (20.5 mg, 184 μmol) was added and the reaction mixture was stirred at room temperature for 72 hours. The solvent was removed under reduced pressure, and the residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/water gradient). The fractions containing the product were concentrated under reduced pressure and 37.5 mg (76% possibility) of the title compound were obtained. LC-MS (Method 3): Rt = 1.20 min; MS (ESIpos): m /z = 400 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: 1.713 (6.00), 1.937 (2.24), 1.948 (2.38), 1.957 (2.23 ), 1,997 (1.64), 2,016 (2.36), 2,034 (2.18), 2,052 (1.51), 2,069 (0.81), 2,328 (0.45), 2,366 (0.45), 2,558 (4.75), 2,572 (5.93), 2,586 (2.94 ), 2.601 (1.13), 2.614 (1.73), 2.628 (0.76), 2.670 (0.50), 2.710 (0.47), 3.892 (0.81), 3.920 (1.61), 3.950 (1.58), 3.982 (1.66), 4.009 (0.93 ), 4.152 (0.66), 4.167 (0.78), 4.181 (0.66), 4.224 (1.23), 4.279 (1.56), 4.308 (1.43), 4.338 (0.95), 4.362 (1.56), 4.385 (1.03), 4.423 (0.73 ), 4.449 (0.98), 4.527 (4.92), 4.571 (0.86), 4.597 (0.58), 4.617 (0.68), 4.633 (0.80), 4.669 (0.76), 4.686 (0.76), 4.710 (0.60), 4.971 (2.86 ), 5.011 (16.00), 5.021 (6.85), 5.031 (5.96), 5.061 (0.91), 5.071 (1.28), 5.355 (0.98), 5.396 (1.03), 5.498 (0.98), 5.539 (1.00), 8.253 (7.23 ), 8,258 (7.31), 8,553 (3.19), 8,564 (3.14). Example 399 (5S)-2-[(3,5-Dichloropyridin-2-yl)methyl]-5-[(3,3-difluoropyrrolidin-1-yl)carbonyl]-5,6,7,8-tetra- hydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one

[01477] (5S)-2-[(3,5-Dichloropyridin-2-yl)methyl]-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4] triazolo[4,3-a]pyridine-5-carboxylic acid (42.1 mg, 123 μmol) was initially loaded into THF (1.0 mL), and HBTU (93.1 mg, 245 μmol) and N,N -diisopropylethylamine (85 μl, 490 μmol) were subsequently added. After stirring at room temperature for 15 minutes, 3,3-difluoropyrrolidine hydrochloride (26.4 mg, 184 μmol) was added and the reaction mixture was stirred at room temperature for 72 hours. The solvent was removed under reduced pressure, and the residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/water gradient). The fractions containing the product were concentrated under reduced pressure and 34.3 mg (65% possibility) of the title compound were obtained. LC-MS (Method 4): Rt = 0.73 min; MS (ESIpos): m /z = 432 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (1.92), -0.008 (16.00), 0.008 (15.60), 0.146 (1.84) (5.68) (2.32) (1.28) (1.92), 4,955 (4.56), 4,995 (13.92), 5,027 (15.92), 5,067 (5.28), 8,250 (10.96), 8,255 (11.12), 8,563 (11.76), 8,568 (11.36). Example 400 (5S)-2-[(3,5-Dichloropyridin-2-yl)methyl]-5-{[(3R,4S)-3,4-difluoropyrrolidin-1-yl]carbonyl}-5,6, 7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one

[01478] (5S)-2-[(3,5-Dichloropyridin-2-yl)methyl]-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4] triazolo[4,3-a]pyridine-5-carboxylic acid (42.1 mg, 123 μmol) was initially loaded into THF (1.0 mL), and HBTU (93.1 mg, 245 μmol) and N,N -diisopropylethylamine (85 μl, 490 μmol) were subsequently added. After stirring at room temperature for 15 minutes, (3R, 4S)-3,4-difluoropyrrolidine hydrochloride (26.4 mg, 184 μmol) was added and the reaction mixture was stirred at room temperature for 72 hours. The solvent was removed under reduced pressure, and the residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/water gradient). The fractions containing the product were concentrated under reduced pressure and 46.2 mg (87% possibility) of the title compound were obtained. LC-MS (Method 4): Rt = 0.70 min; MS (ESIpos): m /z = 432 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (1.86), -0.008 (16.00), 0.008 (12.91), 0.146 (1.78) (2.16) (2.78) (1.70) (2.01) (1.70) (5.18) 8 (2.55) (1.86) (8.97), 8.570 (7.42). Example 401 (5S)-2-{[3-Chloro-5-(trifluoromethyl)pyridin-2-yl]methyl}-5-{[(3R)-3-fluoropyrrolidin-1-yl]carbonyl}-5.6 ,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one

[01479] (5S)-2-{[3-Chloro-5-(trifluoromethyl)pyridin-2-yl]methyl}-3-oxo-2,3,5,6,7,8-hexahydro[1 ,2,4]triazolo[4,3-a]pyridine-5-carboxylic acid (45.0 mg, 119 μmol) was initially loaded into THF (2.0 mL) at room temperature. Subsequently, HATU (59.0 mg, 155 μmol) and triethylamine (50 μl, 360 μmol) were added. After stirring for 15 minutes, (3R)-3-fluoropyrrolidine hydrochloride (18.0 mg, 143 μmol) was added and the reaction mixture was stirred at room temperature for 72 hours. The reaction mixture was mixed with water and ethyl acetate. The organic phase was removed and the aqueous phase was extracted three times with ethyl acetate. The combined organic phases were washed with saturated aqueous sodium chloride solution, dried over sodium sulfate and filtered, and the filtrate was concentrated. The residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/gradient water). The fractions containing the product were concentrated under reduced pressure and 27.0 mg (50% possibility) of the title compound were obtained. LC-MS (Method 3): Rt = 1.35 min; MS (ESIpos): m /z = 448 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (1.64), -0.008 (16.00), 0.008 (12.00), 0.146 (1.33) (2.73) (1.76) (8.67), 5,183 (2.67), 5,268 (2.24), 5,349 (2.18), 5,401 (2.36), 5,482 (2.18), 8,487 (14.30), 8,905 (13.88). Example 402 (5S)-2-{[3-Chloro-5-(trifluoromethyl)pyridin-2-yl]methyl}-5-[(3-fluoroazetidin-1-yl)carbonyl]-5,6,7,8 -tetrahydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one

[01480] (5S)-2-{[3-Chloro-5-(trifluoromethyl)pyridin-2-yl]methyl}-3-oxo-2,3,5,6,7,8-hexahydro[1 ,2,4]triazolo[4,3-a]pyridine-5-carboxylic acid (45.0 mg, 119 μmol) was initially loaded into THF (2.0 mL) at room temperature. Subsequently, HATU (59.0 mg, 155 μmol) and triethylamine (50 μl, 360 μmol) were added. After stirring for 15 minutes, 3-fluoroazetidine hydrochloride (16.0 mg, 143 μmol) was added and the reaction mixture was stirred at room temperature overnight. The reaction mixture was mixed with water and ethyl acetate. The organic phase was removed and the aqueous phase was extracted three times with ethyl acetate. The combined organic phases were washed with saturated aqueous sodium chloride solution, dried over sodium sulfate and filtered, and the filtrate was concentrated. The residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/gradient water). The fractions containing the product were concentrated under reduced pressure and 14.0 mg (27% possibility) of the title compound were obtained. LC-MS (Method 4): Rt = 0.72 min; MS (ESIpos): m /z = 434 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (1.02), -0.008 (10.73), 0.008 (8.00), 0.146 (1.02) (1.55) (5.23), 2595 (3.00), 2624 (1.59), 2665 (1.29), 2670 (1.71), 2674 (1.21), 2689 (0.87), 2710 (1.36), 2731 (1.18), 2866 (0.87), 2890 (1.67) (0.87) (0.53) (5.80), 8,494 (5.76), 8,884 (2.62), 8,901 (2.46). Example 403 (5RS)-2-{[3-Chloro-5-(trifluoromethyl)pyridin-2-yl]methyl}-5-[(3-hydroxyazetidin-1-yl)carbonyl]-5,6,7,8 -tetrahydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one (racemate)

[01481] (5RS)-2-{[3-Chloro-5-(trifluoromethyl)pyridin-2-yl]methyl}-3-oxo-2,3,5,6,7,8-hexahydro[1 ,2,4]triazolo[4,3-a]pyridine-5-carboxylic acid (racemate) (45.0 mg, 119 μmol) was initially loaded into THF (2.0 mL) at room temperature. Subsequently, HATU (59.0 mg, 155 μmol) and triethylamine (50 μl, 360 μmol) were added. After stirring for 15 minutes, azetidin-3-ol hydrochloride (15.7 mg, 143 μmol) was added and the reaction mixture was stirred at room temperature for 72 hours. HATU (59.0 mg, 155 μmol) and triethylamine (50 μl, 360 μmol) were added again and the mixture was stirred at room temperature for 3 hours. The reaction mixture was mixed with water and ethyl acetate. The organic phase was removed and the aqueous phase was extracted three times with ethyl acetate. The combined organic phases were washed with saturated aqueous sodium chloride solution, dried over sodium sulfate and filtered, and the filtrate was concentrated. The residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/gradient water). The fractions containing the product were concentrated under reduced pressure and the residue was purified via preparatory HPLC (Method 10). The fractions containing the product were concentrated under reduced pressure and 800 μg (2% possibility) of the title compound were obtained. LC-MS (Method 3): Rt = 1.12 min; MS (ESIpos): m /z = 432 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.150 (1.80), -0.009 (16.00), 0.007 (12.68), 0.146 (1.63) (0.87), 4.365 (0.64), 4.505 (1.75), 5.081 (0.70), 5.121 (2.44), 5.802 (1.57), 8.487 (2.21), 8.896 (2.44). Example 404 (5S)-2-{[3-Chloro-5-(trifluoromethyl)pyridin-2-yl]methyl}-5-[(3,3-difluoropyrrolidin-1-yl)carbonyl]-5,6,7 ,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one

[01482] (5S)-2-{[3-Chloro-5-(trifluoromethyl)pyridin-2-yl]methyl}-3-oxo-2,3,5,6,7,8-hexahydro[1 ,2,4]triazolo[4,3-a]pyridine-5-carboxylic acid (35.0 mg, 92.9 μmol) was initially loaded into THF (1.0 mL), and HBTU (45.8 mg, 121 μmol) and N,N-diisopropylethylamine (49 μl, 280 μmol) were subsequently added. After stirring at room temperature for 15 minutes, 3,3-difluoropyrrolidine hydrochloride (16.0 mg, 111 μmol) was added and the reaction mixture was stirred at room temperature overnight. The solvent was removed under reduced pressure, and the residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/water gradient). The fractions containing the product were concentrated under reduced pressure and 33.8 mg (78% possibility) of the title compound were obtained. LC-MS (Method 3): Rt = 1.50 min; MS (ESIpos): m /z = 466 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (0.47), -0.008 (4.42), 0.008 (2.91), 1.252 (14.54) 2 (2.71) (0.83), 2328 (1.12), 2366 (1.53), 2379 (1.77), 2408 (2.13), 2429 (2.08), 2453 (1.85), 2471 (1.93), 2524 (6.48), 2571 (6.61), 2587 (7.49) (1.61) (1.82) (1.90) (1.20) (2.26) (9.52), 8.902 (9.42), 8.987 (0.62). Example 405 (5S)-2-{[3-Chloro-5-(trifluoromethyl)pyridin-2-yl]methyl}-5-{[(3S)-3-fluoropyrrolidin-1-yl]carbonyl}-5.6 ,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one

[01483] (5S)-2-{[3-Chloro-5-(trifluoromethyl)pyridin-2-yl]methyl}-3-oxo-2,3,5,6,7,8-hexahydro[1 ,2,4]triazolo[4,3-a]pyridine-5-carboxylic acid (35.0 mg, 92.9 μmol) was initially loaded into THF (1.0 mL), and HBTU (45.8 mg, 121 μmol) and N,N-diisopropylethylamine (49 μl, 280 μmol) were subsequently added. After stirring at room temperature for 15 minutes, (3S)-3-fluoropyrrolidine hydrochloride (14.0 mg, 111 μmol) was added and the reaction mixture was stirred at room temperature overnight. The solvent was removed under reduced pressure, and the residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/water gradient). The fractions containing the product were concentrated under reduced pressure and 25.0 mg (61% possibility) of the title compound were obtained. LC-MS (Method 3): Rt = 1.36 min; MS (ESIpos): m /z = 448 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (1.09), -0.008 (13.31), 0.008 (8.11), 0.146 (1.09) (5.26) (2.63) (5.26) (2.80) (9.49), 5.143 (10.46), 5.174 (2.46), 5.184 (3.43), 5.258 (2.74), 5.388 (3.66), 5.511 (2.06), 5.944 (0.86), 8.491 (12.97), 8.904 (13.03). Example 406 (5S)-2-[(5-Chloro-3-fluoropyridin-2-yl)methyl]-5-[(3,3-difluoropyrrolidin-1-yl)carbonyl]-5,6,7,8- tetrahydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one

[01484] (5S)-2-[(5-Chloro-3-fluoropyridin-2-yl)methyl]-3-oxo-2,3,5,6,7,8-hexahydro[1,2, 4]triazolo[4,3-a]pyridine-5-carboxylic acid (79.3 mg, 243 μmol) was initially loaded into THF (2.0 mL), and HBTU (120 mg, 316 μmol) and N,N -diisopropylethylamine (130 μl, 730 μmol) were subsequently added. After stirring at room temperature for 15 minutes, 3,3-difluoropyrrolidine hydrochloride (41.8 mg, 291 μmol) was added and the reaction mixture was stirred at room temperature overnight. HBTU (120 mg, 316 μmol), 3,3-difluoropyrrolidine hydrochloride (41.8 mg, 291 μmol) and N,N-diisopropylethylamine (130 μl, 730 μmol) were added again and the mixture was stirred at room temperature during the night. The solvent was removed under reduced pressure, and the residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/water gradient). The fractions containing the product were concentrated under reduced pressure and 71.0 mg (70% possibility) of the title compound were obtained. LC-MS (Method 3): Rt = 1.32 min; MS (ESIpos): m /z = 416 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.150 (1.61), -0.008 (16.00), 0.008 (12.15), 0.146 (1.57) (1.81) (6.96) (2.20), 3.733 (1.93), 3.765 (2.79), 3.779 (1.69), 3.788 (1.57), 3.798 (2.95), 3.805 (2.44), 3.824 (1.14), 3.888 (0.98), 3.906 (2.32), 3.931 (1.53) (0.59) (7.90), 4,988 (7.98), 5,023 (3.07), 5,027 (3.07), 8,089 (5.07), 8,094 (5.27), 8,113 (5.31), 8,118 (5.35), 8,476 (6.64), 8,480 (6.41). Example 407 (5S)-2-[(5-Chloro-3-fluoropyridin-2-yl)methyl]-5-[(3-fluoroazetidin-1-yl)carbonyl]-5,6,7,8-tetra- hydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one

[01485] (5S)-2-[(5-Chloro-3-fluoropyridin-2-yl)methyl]-3-oxo-2,3,5,6,7,8-hexahydro[1,2, 4]triazolo[4,3-a]pyridine-5-carboxylic acid (79.3 mg, 243 μmol) was initially loaded into THF (2.0 mL), and HBTU (120 mg, 316 μmol) and N,N -diisopropylethylamine (130 μl, 730 μmol) were subsequently added. After stirring at room temperature for 15 minutes, 3-fluoroazetidine hydrochloride (32.5 mg, 291 μmol) was added and the reaction mixture was stirred at room temperature overnight. HBTU (120 mg, 316 μmol), 3-fluoroazetidine hydrochloride (32.5 mg, 291 μmol) and N,N-diisopropylethylamine (130 μl, 730 μmol) were added again and the mixture was stirred at room temperature overnight. The solvent was removed under reduced pressure, and the residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/water gradient). The fractions containing the product were concentrated under reduced pressure and 64.1 mg (69% possibility) of the title compound were obtained. LC-MS (Method 3): Rt = 1.13 min; MS (ESIpos): m /z = 384 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (0.90), -0.008 (8.03), 0.008 (7.55), 0.146 (0.90) (3.59) (1.38) (1.28) (1.67) (1.36) (1.67), 5,398 (1.70), 5,496 (1.65), 5,541 (1.67), 8,091 (8.53), 8,095 (8.96), 8,115 (8.77), 8,119 (9.09), 8,469 (5.93), 8,478 (5.95). Example 408 (5S)-2-[(5-Chloro-3-fluoropyridin-2-yl)methyl]-5-{[(3R,4S)-3,4-difluoropyrrolidin-1-yl]carbonyl}-5, 6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one

[01486] (5S)-2-[(5-Chloro-3-fluoropyridin-2-yl)methyl]-3-oxo-2,3,5,6,7,8-hexahydro[1,2, 4]triazolo[4,3-a]pyridine-5-carboxylic acid (79.3 mg, 243 μmol) was initially loaded into THF (2.0 mL), and HBTU (120 mg, 316 μmol) and N,N -diisopropylethylamine (130 μl, 730 μmol) were subsequently added. After stirring at room temperature for 15 minutes, (3R,4S)-3,4-difluoropyrrolidine hydrochloride (41.8 mg, 291 μmol) was added and the reaction mixture was stirred at room temperature overnight. HBTU (120 mg, 316 μmol), (3R,4S)-3,4-difluoropyrrolidine hydrochloride (41.8 mg, 291 μmol) and N,N-diisopropylethylamine (130 μl, 730 μmol) were added again and the mixture was stirred at room temperature overnight. The solvent was removed under reduced pressure, and the residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/water gradient). The fractions containing the product were concentrated under reduced pressure and 61.7 mg (61% possibility) of the title compound were obtained. LC-MS (Method 3): Rt = 1.25 min; MS (ESIpos): m /z = 416 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.150 (0.54), -0.008 (5.15), 0.008 (5.00), 0.146 (0.58), 1405 (0.52), 1650 (1.84), 1660 (2.36), 1675 (3.11), 1685 (4.35), 1697 (5.00), 1708 (4.91), 1911 (1.80), 1922 (1.29), 1939 (2.40) (1.95) (0.97) (1.95) (1.84) (1.70) (1.72) (5.23) (2.08) (1.50) (1.20), 5.457 (1.56), 5.470 (1.50), 5.479 (1.56), 5.492 (1.18), 5.502 (0.75), 8.090 (6.39), 8.114 (6.56), 8.478 (9.27). Example 409 (5S)-2-[(5-Chloro-3-fluoropyridin-2-yl)methyl]-5-[(3,3-difluoroazetidin-1-yl)carbonyl]-5,6,7,8- tetrahydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one

[01487] (5S)-2-[(5-Chloro-3-fluoropyridin-2-yl)methyl]-3-oxo-2,3,5,6,7,8-hexahydro[1,2, 4]triazolo[4,3-a]pyridine-5-carboxylic acid (79.3 mg, 243 μmol) was initially loaded into THF (2.0 mL), and HBTU (120 mg, 316 μmol) and N,N -diisopropylethylamine (130 μl, 730 μmol) were subsequently added. After stirring at room temperature for 15 minutes, 3,3-difluoroazetidine hydrochloride (37.7 mg, 291 μmol) was added and the reaction mixture was stirred at room temperature overnight. HBTU (120 mg, 316 μmol), 3,3-difluoroazetidine hydrochloride (37.7 mg, 291 μmol) and N,N-diisopropylethylamine (130 μl, 730 μmol) were added again and the mixture was stirred at room temperature during the night. The solvent was removed under reduced pressure, and the residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/water gradient). The fractions containing the product were concentrated under reduced pressure and 78.3 mg (80% possibility) of the title compound were obtained. LC-MS (Method 3): Rt = 1.19 min; MS (ESIpos): m /z = 402 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (1.72), -0.008 (16.00), 0.008 (14.28), 0.146 (1.61) (4.10) (2.44) (3.03) (14.22), 4,991 (14.28), 5,026 (3.33), 5,030 (3.39), 8,094 (9.16), 8,099 (9.52), 8,118 (9.40), 8,123 (9.64), 8,469 (12.61), 8,473 (12.97). Example 410 (5S)-2-[(3,5-Difluoropyridin-2-yl)methyl]-5-[(3-fluoroazetidin-1-yl)carbonyl]-5,6,7,8-tetrahydro[ 1,2,4]triazolo[4,3-a]pyridin-3(2H)-one

[01488] (5S)-2-[(3,5-Difluoropyridin-2-yl)methyl]-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4] triazolo[4,3-a]pyridine-5-carboxylic acid (34.2 mg, 90% purity, 99.2 μmol) was initially loaded into THF (1.0 mL), and HBTU (48.9 mg, 129 μmol) and N,N-diisopropylethylamine (52 μl, 300 μmol) were subsequently added. After stirring at room temperature for 15 minutes, 3-fluoroazetidine hydrochloride (13.3 mg, 119 μmol) was added and the reaction mixture was stirred at room temperature overnight. The solvent was removed under reduced pressure, and the residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/water gradient). The fractions containing the product were concentrated under reduced pressure and 25.9 mg (71% possibility) of the title compound were obtained. LC-MS (Method 3): Rt = 0.95 min; MS (ESIpos): m /z = 368 [M+H]+ [ppm]: -0.149 (2.23), 0.146 (2.23), (4.62), 2.021 (4.46), 2.327 (4.54), (5.54), 2.586 (2.08), 2.602 (3.00), (1.15), 3.844 (1.69), 3.892 (1.85), (3.15), 4.009 (2.08), 4.262 (3.46) , (4.54), 4.945 (16.00), 4.971 (9.31), (2.08), 6.950 (6.23), 7.078 (6.69), (4.69), 7.952 (8.23), 7.974 (4.69), 8.458 (9.00). Example 411 (5S)-2-[(3,5-Difluoropyridin-2-yl)methyl]-5-{[(3R,4S)-3,4-difluoropyrrolidin-1-yl]carbonyl}-5,6, 7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one

[01489] (5S)-2-[(3,5-Difluoropyridin-2-yl)methyl]-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4] triazolo[4,3-a]pyridine-5-carboxylic acid (34.2 mg, 90% purity, 99.2 μmol) was initially loaded into THF (1.0 mL), and HBTU (48.9 mg, 129 μmol) and N,N-diisopropylethylamine (52 μl, 300 μmol) were subsequently added. After stirring at room temperature for 15 minutes, (3R,4S)-3,4-difluoropyrrolidine hydrochloride (17.1 mg, 119 μmol) was added and the reaction mixture was stirred at room temperature overnight. The solvent was removed under reduced pressure, and the residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/water gradient). The fractions containing the product were concentrated under reduced pressure and 19.7 mg (50% possibility) of the title compound were obtained. LC-MS (Method 3): Rt = 1.06 min; MS (ESIpos): m /z = 400 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (1.87), -0.008 (16.00), 0.008 (14.04), 0.146 (1.77) (1.57) (1.18) (1.18) (3.93) (0.98), 7,928 (1.67), 7,950 (3.14), 7,973 (1.57), 8,465 (5.60). Example 412 (5S)-2-[(3,5-Difluoropyridin-2-yl)methyl]-5-[(3,3-difluoropyrrolidin-1-yl)carbonyl]-5,6,7,8-tetra- hydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one

[01490] (5S)-2-[(3,5-Difluoropyridin-2-yl)methyl]-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4] triazolo[4,3-a]pyridine-5-carboxylic acid (34.2 mg, 90% purity, 99.2 μmol) was initially loaded into THF (1.0 mL), and HBTU (48.9 mg, 129 μmol) and N,N-diisopropylethylamine (52 μl, 300 μmol) were subsequently added. After stirring at room temperature for 15 minutes, 3,3-difluoropyrrolidine hydrochloride (17.1 mg, 119 μmol) was added and the reaction mixture was stirred at room temperature overnight. The solvent was removed under reduced pressure, and the residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/water gradient). The fractions containing the product were concentrated under reduced pressure and 19.9 mg (50% possibility) of the title compound were obtained. Specific rotation: -19.10 (589 nm, 0.5200 g/100 cm3 chloroform)

[01491] Analytical chiral HPLC: Rt = 3.77 min, ee = 98.5% [column: Daicel Chiralpak® AZ-3 3 ym, 50 x 4.6 mm; eluent: i-hexane/i-propanol 50:50; flow rate: 1 ml/min; UV detection: 220 nm]. LC-MS (Method 3): Rt = 1.14 min; MS (ESIpos): m /z = 400 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (1.80), 0.008 (16.00), 0.146 (1.69), 1.693 ( 3.83), 1.957 (2.03), 2.086 (3.61), 2.328 (3.27), 2.366 (4.06), 2.566 (6.20), 2.670 (3.27), 2.710 (3.49), 3.530 (2.25), 3.550 (3.27), 3.666 ( 1.69), 3.700 (1.92), 3.734 (1.69), 3.765 (2.37), 3.800 (2.48), 3.845 (1.46), 3.890 (0.90), 3.907 (1.92), 3.933 (1.46), 3.991 (1.24), 4.033 ( 1.13), 4.168 (1.24), 4.198 (1.13), 4.739 (2.37), 4.749 (1.58), 4.819 (2.14), 4.895 (2.59), 4.933 (6.42), 4.978 (6.31), 5.015 (2.48), 7.925 ( 2.37), 7.930 (2.37), 7.949 (3.72), 7.972 (2.25), 7.978 (2.25), 8.463 (7.89), 8.469 (7.66). Example 413 (5S)-5-[(3,3-Difluoropyrrolidin-1-yl)carbonyl]-2-[(1-methyl-1H-pyrazol[3,4-b]pyridin-3-yl)methyl]- 5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one

[01492] (5S)-2-[(1-Methyl-1H-pyrazol[3,4-b]pyridin-3-yl)methyl]-3-oxo- 2,3,5,6,7,8- hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylic acid (38.0 mg, 116 μmol) was initially loaded into THF (2.0 mL), and HBTU (57. 1 mg, 150 μmol) and N,N-diisopropylethylamine (60 μl, 350 μmol) were subsequently added. After stirring at room temperature for 15 minutes, 3,3-difluoropyrrolidine hydrochloride (19.9 mg, 139 μmol) was added and the reaction mixture was stirred at room temperature overnight. HBTU (57.1 mg, 150 μmol) and 3,3-difluoropyrrolidine hydrochloride (19.9 mg, 139 μmol) were added again. After stirring for 6 hours, N,N-diisopropylethylamine (60 μl, 350 μmol) was added and the mixture was stirred at room temperature overnight. The solvent was removed under reduced pressure, and the residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/water gradient). The fractions containing the product were concentrated under reduced pressure and 38.9 mg (93% purity, 75% chance) of the title compound were obtained. LC-MS (Method 4): Rt = 0.61 min; MS (ESIpos): m /z = 418 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (0.81), -0.008 (6.99), 0.008 (5.93), 0.146 (0.77) (1.32) (0.48) (1.61), 7,197 (1.68), 7,206 (1.79), 7,217 (1.76), 8,151 (1.50), 8,170 (1.46), 8,544 (1.72), 8,548 (1.76), 8,555 (1.83), 8,559 (1.68). Example 414 (5S)-5-{[(3R,4S)-3,4-Difluoropyrrolidin-1-yl]carbonyl}-2-[(1-methyl-1H-pyrazol[3,4-b]pyridin-3 -yl)methyl]-5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one

[01493] (5S)-2-[(1-Methyl-1H-pyrazol[3,4-b]pyridin-3-yl)methyl]-3-oxo- 2,3,5,6,7,8- hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylic acid (38.0 mg, 116 μmol) was initially loaded into THF (2.0 mL), and HBTU (57. 1 mg, 150 μmol) and N,N-diisopropylethylamine (60 μl, 350 μmol) were subsequently added. After stirring at room temperature for 15 minutes, (3R,4S)-3,4-difluoropyrrolidine hydrochloride (19.9 mg, 139 μmol) was added and the reaction mixture was stirred at room temperature overnight. HBTU (57.1 mg, 150 μmol) and 3,3-difluoropyrrolidine hydrochloride (19.9 mg, 139 μmol) were added again. After stirring for 6 hours, N,N-diisopropylethylamine (60 μl, 350 μmol) was added and the mixture was stirred at room temperature overnight. The solvent was removed under reduced pressure, and the residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/water gradient). The fractions containing the product were concentrated under reduced pressure and 33.6 mg (70% possibility) of the title compound were obtained. LC-MS (Method 4): Rt = 0.58 min; MS (ESIpos): m /z = 418 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (1.77), -0.008 (16.00), 0.008 (9.91), 0.146 (1.20) (0.74) (1.37), 7.213 (1.08), 7.219 (1.14), 8.147 (1.08), 8.153 (1.20), 8.167 (1.08), 8.173 (1.14), 8.548 (1.94), 8.555 (1.99), 8.559 (1.94). Example 415 (5S)-5-[(3,3-Difluoroazetidin-1-yl)carbonyl]-2-[(1-methyl-1H-pyrazol[3,4-b]pyridin-3-yl)methyl]- 5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one

[01494] (5S)-2-[(1-Methyl-1H-pyrazol[3,4-b]pyridin-3-yl)methyl]-3-oxo- 2,3,5,6,7,8- hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylic acid (38.0 mg, 116 μmol) was initially loaded into THF (2.0 mL), and HBTU (57. 1 mg, 150 μmol) and N,N-diisopropylethylamine (60 μl, 350 μmol) were subsequently added. After stirring at room temperature for 15 minutes, 3,3-difluoroazetidine hydrochloride (18.0 mg, 139 μmol) was added and the reaction mixture was stirred at room temperature overnight. The solvent was removed under reduced pressure, and the residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/water gradient). The fractions containing the product were concentrated under reduced pressure and 11.8 mg (25% possibility) of the title compound were obtained. LC-MS (Method 3): Rt = 1.05 min; MS (ESIpos): m /z = 404 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (0.90), 0.008 (6.58), 0.146 (0.85), 1.689 ( 1.45), 1.968 (0.80), 2.033 (0.65), 2.366 (1.55), 2.523 (4.93), 2.559 (2.04), 2.602 (0.45), 2.710 (1.50), 4.026 (16.00), 4.368 (0.80), 4.395 ( 0.75), 4.595 (1.00), 4.609 (1.50), 4.621 (1.05), 4.717 (0.50), 4.744 (0.55), 4.861 (0.60), 5.122 (7.13), 7.191 (1.60), 7.202 (1.74), 7.211 ( 1.69), 7.222 (1.64), 8.153 (1.74), 8.157 (1.79), 8.173 (1.74), 8.177 (1.60), 8.545 (1.79), 8.549 (1.79), 8.556 (1.74), 8.560 (1.64). Example 416 (5RS)-5-{[(3S)-3-Fluoropyrrolidin-1-yl]carbonyl}-2-[(3-methyl-1,2-oxazol-5-yl)methyl]-5,6, 7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one (racemate)

[01495] (5RS)-2-[(3-Methyl-1,2-oxazol-5-yl)methyl]-3-oxo-2,3,5,6,7,8-hexahydro[1, 2,4]triazolo[4,3-a]pyridine-5-carboxylic acid (racemate) (60.0 mg, 216 μmol) was initially loaded into THF (3.0 mL) at room temperature. Subsequently, HBTU (123 mg, 323 μmol) and triethylamine (90 μL, 650 μmol) were added. After stirring for 15 minutes, (3S)-3-fluoropyrrolidine (28.8 mg, 323 μmol) was added and the mixture of the reaction was stirred at room temperature for 48 hours. The reaction mixture was mixed with water and ethyl acetate. The organic phase was removed and the aqueous phase was extracted three times with ethyl acetate. saturated aqueous sodium chloride solution, dried over sodium sulfate and filtered, and the filtrate was concentrated. The residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/gradient water). the product were concentrated under reduced pressure and 24.3 mg (32% possibility) of the title compound were obtained. LC-MS (Method 3): Rt = 0.88 min MS (ESIpos): m / z = 350 [ M+H]+ ¹H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.008 (1.93), 0.008 (1.11), 1.721 (0.98), 1.733 (1.10), 1.988 (1.00), 2.040 (0.46 ), 2.073 (1.80), 2.104 (0.82), 2.136 (0.64), 2.203 (16.00), 2.238 (0.46), 2.268 (0.50), 2.300 (0.64), 2.303 (0.68), 2.327 (0.41), 2.523 (1.89 ), 2.571 (1.07), 2.595 (1.09), 2.608 (1.43), 2.620 (0.83), 2.650 (0.49), 2.665 (0.50), 2.669 (0.49), 3.345 (0.40), 3.357 (0.54), 3.501 (0.52 ), 3.508 (0.55), 3.522 (0.69), 3.550 (0.56), 3.569 (0.49), 3.595 (0.91), 3.632 (0.66), 3.653 (0.72), 3.677 (0.52), 3.743 (0.66), 3.775 (0.51 ), 3.783 (0.46), 3.854 (0.61), 3.940 (0.52), 4.739 (0.43), 4.745 (0.46), 4.812 (0.49), 4.845 (0.42), 4.851 (0.45), 4.946 (5.75), 5.259 (0.41 ), 5,389 (0.47), 6,226 (2.65). Example 417(5RS)-5-[(3-Fluoroazetidin-1-yl)carbonyl]-2-[(3-methyl-1,2-oxazol-5-yl)methyl]-5,6,7,8- tetrahydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one (racemate)

[01496] (5RS)-2-[(3-Methyl-1,2-oxazol-5-yl)methyl]-3-oxo-2,3,5,6,7,8-hexahydro[1, 2,4]triazolo[4,3-a]pyridine-5-carboxylic acid (racemate) (60.0 mg, 216 μmol) was initially loaded into THF (3.0 mL) at room temperature. Subsequently, HBTU (123 mg, 323 μmol) and triethylamine (90 μL, 650 μmol) were added. After stirring for 15 minutes, 3-fluoroazetidine hydrochloride (36.1 mg, 323 μmol) was added and the reaction mixture was stirred at room temperature for 48 hours. The reaction mixture was mixed with water and ethyl acetate. The organic phase was removed and the aqueous phase was extracted three times with ethyl acetate. sodium chloride, dried over sodium sulfate and filtered, and the filtrate was concentrated. The residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/gradient water). concentrated under reduced pressure and 19.2 mg (27% possibility) of the title compound were obtained LC-MS (Method 3): Rt = 0.83 min (ESIpos): m / z = 336 [M+H; ]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: 1.714 (1.68), 1.949 (0.76), 2.029 (0.69), 2.072 (0.96), 2.201 (16.00), 2.293 (1.37), 2.585 ( 1.67), 2.598 (2.00), 2.612 (1.02), 2.639 (0.61), 2.670 (0.45), 3.928 (0.55), 3.954 (0.54), 3.988 (0.53), 4.269 (0.58), 4.300 (0.50), 4.364 ( 0.45), 4.528 (1.44), 4.541 (2.10), 4.554 (1.49), 4.950 (5.39), 6.234 (3.50), 6.924 (0.44). Example 418 (5S)-5-[(3,3-Difluoropyrrolidin-1-yl)carbonyl]-2-{[2-(trifluoromethyl)-1,8-naphthyridin-3-yl]methyl}-5,6, 7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one

[01497] (5S)-3-Oxo-2-{[2-(trifluoromethyl)-1,8-naphthyridin-3-yl]methyl}- 2,3,5,6,7,8-hexahydro[ 1,2,4]triazolo[4,3-a]pyridine-5-carboxylic acid (50.0 mg, 127 μmol) was initially loaded into THF (3.0 mL), and HBTU (62.7 mg, 165 μmol) and N,N-diisopropylethylamine (66 μl, 380 μmol) were subsequently added. After stirring at room temperature for 15 minutes, 3,3-difluoropyrrolidine hydrochloride (21.9 mg, 153 μmol) was added and the reaction mixture was stirred at room temperature overnight. The solvent was removed under reduced pressure, and the residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/water gradient). The fractions containing the product were concentrated under reduced pressure and 23.1 mg (38% possibility) of the title compound were obtained. LC-MS (Method 3): Rt = 1.28 min; MS (ESIpos): m /z = 483 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (1.63), -0.008 (16.00), 0.008 (12.96), 0.146 (1.63) (2.39) (1.85) (0.87) (1.01) (4.02), 8,560 (3.40), 8,564 (3.44), 8,580 (3.29), 8,585 (3.11), 9,242 (3.73), 9,247 (3.95), 9,252 (3.87), 9,257 (3.55). Example 419 (5S)-5-{[(3S)-3-Fluoropyrrolidin-1-yl]carbonyl}-2-{[2-(trifluoromethyl)-1,8-naphthyridin-3-yl]methyl}-5, 6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one

[01498] (5S)-3-Oxo-2-{[2-(trifluoromethyl)-1,8-naphthyridin-3-yl]methyl}- 2,3,5,6,7,8-hexahydro[ 1,2,4]triazolo[4,3-a]pyridine-5-carboxylic acid (50.0 mg, 127 μmol) was initially loaded into THF (3.0 mL), and HBTU (62.7 mg, 165 μmol) and N,N-diisopropylethylamine (66 μl, 380 μmol) were subsequently added. After stirring at room temperature for 15 minutes, (3S)-3-fluoropyrrolidine hydrochloride (1:1) (19.2 mg, 153 μmol) was added and the reaction mixture was stirred at room temperature overnight. The solvent was removed under reduced pressure, and the residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/water gradient). The fractions containing the product were concentrated under reduced pressure and 36.2 mg (61% possibility) of the title compound were obtained. LC-MS (Method 3): Rt = 1.14 min; MS (ESIpos): m /z = 465 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (1.73), -0.008 (16.00), 0.008 (12.57), 0.146 (1.73) (1.24) (0.90), 8,368 (1.69), 8,570 (0.79), 8,590 (0.72), 9,242 (0.87), 9,246 (0.90), 9,252 (0.87), 9,257 (0.79). Example 420 (5S)-5-[(3-Fluoroazetidin-1-yl)carbonyl]-2-{[2-(trifluoromethyl)-1,8-naphthyridin-3-yl]methyl}-5,6,7, 8-tetrahydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one

[01499] (5S)-3-Oxo-2-{[2-(trifluoromethyl)-1,8-naphthyridin-3-yl]methyl}- 2,3,5,6,7,8-hexahydro[ 1,2,4]triazolo[4,3-a]pyridine-5-carboxylic acid (50.0 mg, 127 μmol) was initially loaded into THF (3.0 mL), and HBTU (62.7 mg, 165 μmol) and N,N-diisopropylethylamine (66 μl, 380 μmol) were subsequently added. After stirring at room temperature for 15 minutes, 3-fluoroazetidine hydrochloride (17.0 mg, 153 μmol) was added and the reaction mixture was stirred at room temperature overnight. The solvent was removed under reduced pressure, and the residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/water gradient). The fractions containing the product were concentrated under reduced pressure and 20.0 mg (35% possibility) of the title compound were obtained. LC-MS (Method 3): Rt = 1.09 min; MS (ESIpos): m /z = 451 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (1.80), -0.008 (16.00), 0.008 (14.79), 0.146 (1.84) (0.88) (3.31), 8,384 (3.77), 8,558 (2.35), 8,579 (2.30), 9,241 (3.39), 9,246 (3.64), 9,252 (3.73), 9,257 (3.35). Example 421 (5S)-2-[(6-Chloropyridin-3-yl)methyl]-5-[(3-fluoroazetidin-1-yl)carbonyl]-5,6,7,8-tetrahydro[1, 2,4]triazolo[4,3-a]pyridin-3(2H)-one

[01500] (5S)-2-[(6-Chloropyridin-3-yl)methyl]-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[ 4,3-a]pyridine-5-carboxylic acid (50.0 mg, 162 μmol) was initially loaded into THF (3.0 mL), and HBTU (79.8 mg, 211 μmol) and N,N-diisopropylethylamine (85 μl, 490 μmol) were subsequently added. After stirring at room temperature for 15 minutes, 3-fluoroazetidine hydrochloride (21.7 mg, 194 μmol) was added and the reaction mixture was stirred at room temperature overnight. The solvent was removed under reduced pressure, and the residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/water gradient). The fractions containing the product were concentrated under reduced pressure and 21.0 mg (35% possibility) of the title compound were obtained. LC-MS (Method 3): Rt = 0.99 min; MS (ESIpos): m /z = 366 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (0.64), -0.008 (6.53), 0.008 (4.72), 0.146 (0.64) (1.71) (0.52) (1.29) (0.67) (0.72) (6.98), 7,694 (4.39), 7,714 (3.70), 8,305 (5.65). Example 422 (5S)-2-[(6-Chloropyridin-3-yl)methyl]-5-{[(3S)-3-fluoropyrrolidin-1-yl]carbonyl}-5,6,7,8-tetra- hydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one

[01501] (5S)-2-[(6-Chloropyridin-3-yl)methyl]-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[ 4,3-a]pyridine-5-carboxylic acid (50.0 mg, 162 μmol) was initially loaded into THF (3.0 mL), and HBTU (79.8 mg, 211 μmol) and N,N-diisopropylethylamine (85 μl, 490 μmol) were subsequently added. After stirring at room temperature for 15 minutes, (3S)-3-fluoropyrrolidine hydrochloride (24.4 mg, 194 μmol) was added and the reaction mixture was stirred at room temperature overnight. The solvent was removed under reduced pressure, and the residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/water gradient). The fractions containing the product were concentrated under reduced pressure and 32.1 mg (52% possibility) of the title compound were obtained. LC-MS (Method 3): Rt = 1.05 min; MS (ESIpos): m /z = 380 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: 0.008 (1.05), 1.720 (2.57), 1.727 (2.64), 1.870 (0.64 ), 1.894 (0.61), 1.904 (0.81), 1.968 (0.58), 1.993 (1.05), 2.020 (1.59), 2.042 (1.32), 2.058 (1.52), 2.074 (1.86), 2.085 (2.16), 2.094 (2.00 ), 2.101 (2.00), 2.121 (1.39), 2.135 (1.42), 2.217 (0.95), 2.237 (0.88), 2.266 (1.15), 2.519 (3.96), 2.524 (4.19), 2.563 (1.96), 2.578 (1.66 ), 2.602 (2.47), 2.646 (0.91), 2.670 (0.41), 3.344 (1.01), 3.357 (0.85), 3.365 (0.81), 3.393 (0.81), 3.401 (0.78), 3.454 (0.64), 3.464 (0.64 ), 3.490 (0.85), 3.499 (0.74), 3.606 (0.74), 3.632 (2.77), 3.649 (2.27), 3.655 (2.06), 3.675 (1.76), 3.697 (1.22), 3.721 (1.32), 3.740 (2.10 ), 3,764 (1.69), 3,783 (1.22), 3,850 (2.40), 4,678 (1.32), 4,687 (1.52), 4,694 (1.56), 4,703 (1.25), 4,736 (1.69), 4,745 (1.83), 4,751 (1.89 ), 4,760 (1.35), 4,880 (16.00), 5,257 (1.18), 5,380 (1.52), 5,388 (1.49), 5,509 (0.88), 7,504 (4.87), 7,524 (5.92), 7,683 (2.23), 7,690 (3.92 ), 7,696 (2.44), 7,704 (1.83), 7,710 (3.11), 7,717 (1.76), 8,296 (4.06), 8,302 (3.55). Example 423 (5S)-2-[(6-Chloropyridin-3-yl)methyl]-5-[(3,3-difluoropyrrolidin-1-yl)carbonyl]-5,6,7,8-tetrahydro[ 1,2,4]triazolo[4,3-a]pyridin-3(2H)-one

[01502] (5S)-2-[(6-Chloropyridin-3-yl)methyl]-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[ 4,3-a]pyridine-5-carboxylic acid (50.0 mg, 162 μmol) was initially loaded into THF (3.0 mL), and HBTU (79.8 mg, 211 μmol) and N,N-diisopropylethylamine (85 μl, 490 μmol) were subsequently added. After stirring at room temperature for 15 minutes, 3,3-difluoropyrrolidine hydrochloride (27.9 mg, 194 μmol) was added and the reaction mixture was stirred at room temperature overnight. The solvent was removed under reduced pressure, and the residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/water gradient). The fractions containing the product were concentrated under reduced pressure and 32.2 mg (50% possibility) of the title compound were obtained. LC-MS (Method 4): Rt = 0.66 min; MS (ESIpos): m /z = 398 [M+H]+ ¹H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (0.50), -0.008 (4.74), 0.008 (4.04), 0.146 (0.47) (0.64) (0.69) (0.62) (0.72) (1.19), 4,884 (16.00), 7,505 (4.99), 7,525 (6.28), 7,686 (3.32), 7,692 (3.40), 7,707 (2.70), 7,713 (2.73), 8,296 (4.94), 8,302 (4.79). Example 424 (5S)-2-[(6-Chloropyridin-3-yl)methyl]-5-{[(3R,4S)-3,4-difluoropyrrolidin-1-yl]carbonyl}-5,6,7, 8-tetrahydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one

[01503] (5S)-2-[(6-Chloropyridin-3-yl)methyl]-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[ 4,3-a]pyridine-5-carboxylic acid (70.0 mg, 227 μmol) was initially loaded into THF (4.0 mL), and HBTU (112 mg, 295 μmol) and N,N-diisopropylethylamine (120 μl, 680 μmol) were subsequently added. After stirring at room temperature for 15 minutes, (3R,4S)-3,4-difluoropyrrolidine hydrochloride (39.1 mg, 272 μmol) was added and the reaction mixture was stirred at room temperature overnight. The solvent was removed under reduced pressure, and the residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/water gradient). The fractions containing the product were concentrated under reduced pressure and 66.6 mg (74% possibility) of the title compound were obtained. LC-MS (Method 3): Rt = 1.10 min; MS (ESIpos): m /z = 398 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (1.29), -0.008 (12.08), 0.008 (10.65), 0.146 (1.38) (2.93), 2644 (1.08), 2669 (1.73), 2710 (1.25), 3532 (1.25), 3577 (0.82), 3626 (0.99), 3683 (1.51), 3700 (1.51), 3731 (1.29), 3752 (1.21) (1.16), 7,506 (4.27), 7,526 (5.13), 7,680 (1.94), 7,688 (3.15), 7,695 (2.42), 7,709 (2.59), 7,716 (1.90), 8,297 (5.65). Example 425 (5S)-5-{[(3S)-3-Hydroxypyrrolidin-1-yl]carbonyl}-2-{[6-(trifluoromethyl)pyridin-3-yl]methyl}-5,6,7,8 -tetrahydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one

[01504] (5S)-3-Oxo-2-{[6-(trifluoromethyl)pyridin-3-yl]methyl}-2,3,5,6,7,8-hexahydro[1,2,4 ]triazolo[4,3-a]pyridine-5-carboxylic acid (60.0 mg, 175 μmol) was initially loaded into THF (2.0 mL), and HATU (86.6 mg, 228 μmol) and triethylamine ( 73 μl, 530 μmol) were subsequently added. After stirring at room temperature for 15 minutes, (3S)-pyrrolidin-3-ol hydrochloride (26.0 mg, 210 μmol) was added and the reaction mixture was stirred at room temperature overnight. The solvent was removed under reduced pressure, and the residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/water gradient). The fractions containing the product were concentrated under reduced pressure and the residue was purified via preparatory HPLC (Method 10). The product-containing fractions were concentrated under reduced pressure and 1.00 mg (92% purity, 1% chance) of the title compound were obtained. LC-MS (Method 3): Rt = 0.99 min; MS (ESIpos): m /z = 412 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.008 (0.69), 0.008 (0.58), 1.637 (0.77), 1.644 ( 0.75), 1.650 (0.83), 1.663 (1.03), 1.677 (0.98), 1.689 (0.86), 1.736 (2.05), 1.751 (1.94), 1.774 (1.47), 1.783 (1.06), 1.828 (0.46), 1.840 ( 0.61), 1.851 (1.28), 1.862 (1.57), 1.873 (1.33), 1.883 (1.65), 1.894 (1.33), 1.905 (0.93), 1.939 (0.53), 1.973 (1.71), 1.985 (1.87), 1.997 ( 2.24), 2.007 (2.18), 2.019 (2.06), 2.029 (1.92), 2.036 (1.50), 2.045 (1.31), 2.057 (1.10), 2.065 (1.19), 2.073 (1.20), 2.523 (1.16), 2.561 ( 1.75), 2.575 (1.29), 2.597 (1.55), 2.608 (2.72), 2.619 (1.46), 2.638 (0.72), 2.650 (1.08), 2.661 (0.60), 3.204 (0.72), 3.236 (1.03), 3.343 ( 1.75), 3.369 (1.82), 3.379 (2.23), 3.397 (1.40), 3.419 (0.57), 3.434 (0.59), 3.443 (0.61), 3.457 (1.07), 3.464 (1.17), 3.473 (0.55), 3.485 ( 1.17), 3.550 (0.84), 3.567 (1.42), 3.573 (1.63), 3.589 (1.08), 3.599 (0.79), 3.640 (0.94), 3.651 (1.41), 3.667 (0.92), 3.678 (1.09), 3.756 ( 0.58), 4.270 (1.41), 4.363 (1.43), 4.696 (0.83), 4.705 (0.97), 4.712 (1.06), 4.720 (0.84), 4.739 (1.24), 4.752 (1.60), 4.761 (1.16), 4.806 ( 0.64), 4.815 (0.73), 4.821 (0.85), 4.830 (0.66), 4.964 (2.61), 5.005 (10.49), 5.078 (2.55), 5.087 (2.46), 7.909 (16.00), 8.640 (4.92). Example 426 (5S)-5-[(3,3-Difluoropyrrolidin-1-yl)carbonyl]-2-{[6-(trifluoromethyl)pyridin-3-yl]methyl}-5,6,7,8-tetra -hydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one

[01505] (5S)-3-Oxo-2-{[6-(trifluoromethyl)pyridin-3-yl]methyl}-2,3,5,6,7,8-hexahydro[1,2,4 ]triazolo[4,3-a]pyridine-5-carboxylic acid (100 mg, 85% purity, 248 μmol) was initially loaded into THF (2.0 mL), and HBTU (122 mg, 323 μmol) and N N-diisopropylethylamine (130 μl, 750 μmol) was added subsequently. After stirring at room temperature for 15 minutes, 3,3-difluoropyrrolidine hydrochloride (42.8 mg, 298 μmol) was added and the reaction mixture was stirred at room temperature overnight. HBTU (122 mg, 323 μmol) and 3,3-difluoropyrrolidine hydrochloride (42.8 mg, 298 μmol) were added again. After stirring at room temperature for 48 hours, N,N-diisopropylethylamine (130 μl, 750 μmol) was added and the mixture was stirred overnight. The solvent was removed under reduced pressure, and the residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/water gradient). The fractions containing the product were concentrated under reduced pressure and 79.6 mg (72% possibility) of the title compound were obtained. LC-MS (Method 1): Rt = 1.01 min; MS (ESIpos): m /z = 432 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.150 (0.48), -0.008 (6.41), 0.008 (3.51), 0.146 (0.45), 1375 (0.48), 1405 (1.49), 1663 (1.24), 1673 (1.15), 1736 (1.52), 1753 (1.60), 1879 (0.96), 1973 (1.38), 2008 (1.88), 2018 (1.83) (1.77) (0.96), 2710 (0.53), 3534 (1.38), 3541 (1.55), 3551 (2.11), 3561 (2.17), 3570 (1.29), 3580 (1.07), 3637 (0.45), 3670 (1.32), 3704 (1.52) (1.04) (0.87) (16.00), 7,912 (15.38), 8,641 (5.34). Example 427 (5S)-5-{[(3S)-3-Fluoropyrrolidin-1-yl]carbonyl}-2-{[6-(trifluoromethyl)pyridin-3-yl]methyl}-5,6,7,8 -tetrahydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one

[01506] (5S)-3-Oxo-2-{[6-(trifluoromethyl)pyridin-3-yl]methyl}-2,3,5,6,7,8-hexahydro[1,2,4 ]triazolo[4,3-a]pyridine-5-carboxylic acid (1000 mg, 2.92 mmol) was initially loaded into THF (18 mL) at room temperature. Subsequently, HBTU (1.44 g, 3.80 mmol) and N,N-diisopropylethylamine (1.5 mL, 8.8 mmol) were added. After stirring for 15 minutes, (3S)-3-fluoropyrrolidine hydrochloride (404 mg, 3.21 mmol) was added and the reaction mixture was stirred at room temperature overnight. N,N-Diisopropylethylamine (1.5 mL, 8.8 mmol) was added again, and the mixture was stirred again at room temperature overnight. The reaction mixture was mixed with water and ethyl acetate. The organic phase was removed and the aqueous phase was extracted three times with ethyl acetate. The combined organic phases were washed with saturated aqueous sodium chloride solution, dried over sodium sulfate and filtered, and the filtrate was concentrated. The residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/gradient water). The fractions containing the product were concentrated under reduced pressure and 797 mg (66% possibility) of the title compound were obtained. LC-MS (Method 3): Rt = 1.23 min; MS (ESIpos): m /z = 414 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.008 (1.38), 0.008 (1.26), 1.701 (1.17), 1.712 ( 1.38), 1.726 (2.00), 1.736 (2.23), 1.883 (0.48), 1.906 (0.51), 1.923 (0.69), 1.997 (0.78), 2.005 (0.71), 2.022 (0.83), 2.032 (1.29), 2.053 ( 1.08), 2.073 (2.09), 2.088 (1.68), 2.104 (2.05), 2.124 (1.15), 2.139 (1.40), 2.173 (0.41), 2.221 (0.76), 2.243 (0.69), 2.256 (0.74), 2.270 ( 1.03), 2.327 (0.53), 2.366 (0.55), 2.519 (2.48), 2.523 (2.09), 2.562 (1.54), 2.566 (1.52), 2.572 (1.59), 2.588 (1.33), 2.614 (2.30), 2.657 ( 0.90), 2.670 (0.87), 2.710 (0.53), 3.275 (0.69), 3.350 (0.62), 3.362 (0.60), 3.371 (0.64), 3.398 (0.74), 3.407 (0.74), 3.459 (0.55), 3.468 ( 0.57), 3.495 (0.78), 3.504 (0.74), 3.610 (0.51), 3.637 (2.16), 3.654 (1.86), 3.661 (1.86), 3.681 (1.54), 3.703 (0.97), 3.727 (1.06), 3.746 ( 1.89), 3.769 (1.36), 3.775 (1.40), 3.789 (1.15), 3.857 (2.28), 4.694 (1.10), 4.703 (1.33), 4.710 (1.38), 4.719 (1.10), 4.752 (1.43), 4.761 ( 1.56) ( 4.76). Example 428 (5S)-5-[(3-Hydroxyazetidin-1-yl)carbonyl]-2-{[6-(trifluoromethyl)pyridin-3-yl]methyl}-5,6,7,8-tetrahydro [1,2,4]triazolo[4,3-a]pyridin-3(2H)-one

[01507] (5S)-3-Oxo-2-{[6-(trifluoromethyl)pyridin-3-yl]methyl}-2,3,5,6,7,8-hexahydro[1,2,4 ]triazolo[4,3-a]pyridine-5-carboxylic acid (65.0 mg, 190 μmol) was initially loaded into THF at room temperature. Subsequently, HATU (93.9 mg, 247 μmol) and triethylamine (79 μl, 570 μmol) were added. After stirring for 15 minutes, azetidin-3-ol hydrochloride (25.0 mg, 228 μmol) was added and the reaction mixture was stirred at room temperature overnight. The reaction mixture was mixed with water and ethyl acetate. The organic phase was removed and the aqueous phase was extracted three times with ethyl acetate. The combined organic phases were washed with saturated aqueous sodium chloride solution, dried over sodium sulfate and filtered, and the filtrate was concentrated. The residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/gradient water). The fractions containing the product were concentrated under reduced pressure and the residue was purified via preparatory HPLC (Method 10). The fractions containing the product were concentrated under reduced pressure and 1.00 mg (1% possibility) of the title compound were obtained. LC-MS (Method 3): Rt = 0.98 min; MS (ESIpos): m /z = 398 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (2.09), -0.008 (15.61), 0.008 ( 16.00), 0.146 (2.16), 2.327 (4.71), 2.366 (2.16), 2.669 (4.41), 2.709 (2.40), 4.534 (2.09), 5.010 (4 .48), 5.803 (1.93), 7.908 (5.87), 8.644 (3.25). Example 429 (5S)-5-[(3-Fluoroazetidin-1-yl)carbonyl]-2-{[6-(trifluoromethyl)pyridin-3-yl]methyl}-5,6,7,8-tetrahydro [1,2,4]triazolo[4,3-a]pyridin-3(2H)-one

[01508] (5S)-3-Oxo-2-{[6-(trifluoromethyl)pyridin-3-yl]methyl}-2,3,5,6,7,8-hexahydro[1,2,4 ]triazolo[4,3-a]pyridine-5-carboxylic acid (100 mg, 292 μmol) was initially loaded into THF (2.0 mL), and HBTU (144 mg, 380 μmol) and N,N-diisopropylethylamine ( 150 μl, 880 μmol) were subsequently added. After stirring at room temperature for 15 minutes, 3-fluoroazetidine hydrochloride (39.1 mg, 351 μmol) was added and the reaction mixture was stirred at room temperature for 72 hours. The solvent was removed under reduced pressure, and the residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/water gradient). The fractions containing the product were concentrated under reduced pressure and 74.0 mg (63% possibility) of the title compound were obtained. LC-MS (Method 1): Rt = 0.90 min; MS (ESIpos): m /z = 400 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: 1.658 (1.45), 1.670 (1.85), 1.683 (2.02), 1.694 (2.48 ), 1.708 (2.77), 1.961 (1.98), 1.975 (1.90), 2.004 (1.65), 2.025 (1.68), 2.359 (0.41), 2.579 (3.40), 2.593 (4.36), 2.606 (2.24), 2.622 (0.89 ), 2.635 (1.39), 2.648 (0.64), 2.662 (0.41), 3.898 (0.65), 3.925 (1.33), 3.956 (1.38), 3.986 (1.29), 4.017 (0.76), 4.153 (0.58), 4.168 (0.66 ), 4.181 (0.58), 4.206 (0.78), 4.222 (1.20), 4.236 (1.17), 4.250 (1.09), 4.269 (1.43), 4.290 (1.27), 4.321 (0.95), 4.359 (1.03), 4.393 (0.82 ), 4.429 (0.61), 4.455 (0.79), 4.505 (0.69), 4.518 (0.83), 4.550 (3.29), 4.562 (4.78), 4.575 (3.11), 4.597 (0.48), 4.630 (0.56), 4.646 (0.65 ), 4.681 (0.63), 4.699 (0.62), 4.724 (0.46), 5.004 (12.79), 5.347 (0.79), 5.401 (0.77), 5.489 (0.79), 5.543 (0.75), 7.905 (16.00), 8.642 (6.38 ). Example 430 (5S)-5-{[(3S)-3-Fluoropyrrolidin-1-yl]carbonyl}-2-[(6-methoxypyridin-3-yl)methyl]-5,6,7,8-tetra- hydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one

[01509] (5S)-2-[(6-Methoxypyridin-3-yl)methyl]-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[ 4,3-a]pyridine-5-carboxylic acid (390 mg, 1.28 mmol) was initially loaded into THF (5.0 mL), and HBTU (632 mg, 1.67 mmol) and N,N-diisopropylethylamine (670 μl, 3.8 mmol) were subsequently added. After stirring at room temperature for 15 minutes, (3S)-3-fluoropyrrolidine hydrochloride (193 mg, 1.54 mmol) was added and the reaction mixture was stirred at room temperature overnight. The solvent was removed under reduced pressure, and the residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/water gradient). The fractions containing the product were concentrated under reduced pressure and 98.9 mg (20% possibility) of the title compound were obtained. LC-MS (Method 4): Rt = 0.57 min; MS (ESIpos): m /z = 376 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.008 (1.34), 0.008 (1.26), 1.706 (0.98), 1.718 ( 1.14), 2.003 (0.53), 2.048 (0.45), 2.073 (0.60), 2.083 (0.66), 2.108 (0.58), 2.134 (0.43), 2.524 (1.18), 2.565 (0.60), 2.593 (0.91), 3.632 ( 1.01), 3.650 (0.75), 3.677 (0.48), 3.718 (0.42), 3.736 (0.77), 3.765 (0.54), 3.781 (0.53), 3.827 (16.00), 3.851 (0.91), 4.661 (0.43), 4.671 ( 0.50), 4.677 (0.55), 4.686 (0.45), 4.719 (0.57), 4.727 (0.67), 4.734 (0.76), 4.743 (0.60), 4.762 (5.88), 5.258 (0.42), 5.389 (0.56), 6.784 ( 2.23), 6.806 (2.39), 7.551 (0.72), 7.557 (1.53), 7.563 (0.93), 7.572 (0.71), 7.578 (1.46), 7.584 (0.86), 8.054 (1.92). Example 431 (5S)-5-{[(3R,4S)-3,4-Difluoropyrrolidin-1-yl]carbonyl}-2-[(6-methoxypyridin-3-yl)methyl]-5,6,7, 8-tetrahydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one

[01510] (5S)-2-[(6-Methoxypyridin-3-yl)methyl]-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[ 4,3-a]pyridine-5-carboxylic acid (390 mg, 1.28 mmol) was initially loaded into THF (5.0 mL), and HBTU (632 mg, 1.67 mmol) and N,N-diisopropylethylamine (670 μl, 3.8 mmol) were subsequently added. After stirring at room temperature for 15 minutes, (3R,4S)-3,4-difluoropyrrolidine hydrochloride (221 mg, 1.54 mmol) was added and the reaction mixture was stirred at room temperature overnight. The solvent was removed under reduced pressure, and the residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/water gradient). The fractions containing the product were concentrated under reduced pressure and 111 mg (22% possibility) of the title compound were obtained. LC-MS (Method 4): Rt = 0.61 min; MS (ESIpos): m /z = 394 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.008 (0.88), 0.008 (0.85), 1.657 (0.55), 1.695 ( 0.52), 1.707 (0.63), 1.716 (0.71), 1.730 (0.60), 1.948 (0.53), 1.956 (0.47), 1.994 (0.68), 2.003 (0.53), 2.018 (0.42), 2.029 (0.48), 2.037 ( 0.53), 2.045 (0.50), 2.052 (0.41), 2.073 (0.81), 2.525 (0.94), 2.575 (0.99), 2.588 (1.28), 2.599 (0.72), 2.630 (0.43), 3.482 (0.43), 3.491 ( 0.41), 3.532 (0.52), 3.539 (0.47), 3.625 (0.42), 3.666 (0.41), 3.679 (0.56), 3.686 (0.47), 3.699 (0.72), 3.713 (0.46), 3.722 (0.55), 3.752 ( 0.47), 3,764 (0.45), 3,825 (14.71), 3,828 (16.00), 3,935 (0.40), 4,169 (0.44), 4,766 (8.26), 5,275 (0.42), 5,376 (0.42), 5,386 (0.47), 5,398 (5,398 ( 0.40), 6.785 (1.86), 6.806 (2.01), 7.547 (0.88), 7.555 (1.43), 7.562 (1.08), 7.569 (0.92), 7.576 (1.40), 7.583 (1.01), 8.054 (2.30). Example 432 (2S)-1-({(5S)-2-[(6-Methoxypyridin-3-yl)methyl]-3-oxo-2,3,5,6,7,8-hexahydro[1 ,2,4]triazolo[4,3-a]pyridin-5-yl}carbonyl)pyrrolidine-2-carbonitrile

[01511] (5S)-2-[(6-Methoxypyridin-3-yl)methyl]-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[ 4,3-a]pyridine-5-carboxylic acid (390 mg, 1.28 mmol) was initially loaded into THF (5.0 mL), and HBTU (632 mg, 1.67 mmol) and N,N-diisopropylethylamine (670 μl, 3.8 mmol) were subsequently added. After stirring at room temperature for 15 minutes, (2S)-pyrrolidine-2-carbonitrile hydrochloride (204 mg, 1.54 mmol) was added and the reaction mixture was stirred at room temperature overnight. The solvent was removed under reduced pressure, and the residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/water gradient). The fractions containing the product were concentrated under reduced pressure and 109 mg (18% possibility) of the title compound were obtained. LC-MS (Method 4): Rt = 0.60 min; MS (ESIpos): m /z = 383 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.008 (0.93), 0.008 (0.87), 1.988 (0.50), 2.027 ( 0.70), 2.045 (0.98), 2.059 (1.43), 2.076 (1.42), 2.093 (0.73), 2.104 (0.58), 2.115 (0.48), 2.135 (0.50), 2.148 (0.61), 2.159 (0.53), 2.206 ( 0.71), 2.225 (0.67), 2.237 (0.42), 2.562 (0.56), 2.573 (0.59), 2.587 (0.46), 2.608 (0.41), 2.620 (0.75), 2.632 (0.43), 2.899 (0.83), 3.670 ( 1.14), 3.686 (2.31), 3.703 (1.10), 3.828 (16.00), 4.767 (3.05), 4.772 (2.80), 4.786 (0.78), 4.793 (1.36), 4.803 (1.54), 4.813 (1.53), 4.823 ( 0.80), 6.788 (1.71), 6.810 (1.83), 7.550 (1.02), 7.556 (1.09), 7.571 (1.03), 7.577 (1.07), 8.051 (1.46), 8.056 (1.52). Example 433 (5S)-5-[(3-Fluoroazetidin-1-yl)carbonyl]-2-[(6-methoxypyridin-3-yl)methyl]-5,6,7,8-tetrahydro[1, 2,4]triazolo[4,3-a]pyridin-3(2H)-one

[01512] (5S)-2-[(6-Methoxypyridin-3-yl)methyl]-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[ 4,3-a]pyridine-5-carboxylic acid (390 mg, 1.28 mmol) was initially loaded into THF (5.0 mL), and HBTU (632 mg, 1.67 mmol) and N,N-diisopropylethylamine (670 μl, 3.8 mmol) were subsequently added. After stirring at room temperature for 15 minutes, 3-fluoroazetidine hydrochloride (172 mg, 1.54 mmol) was added and the reaction mixture was stirred at room temperature overnight. The solvent was removed under reduced pressure, and the residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/water gradient). The fractions containing the product were concentrated under reduced pressure and 82.9 mg (18% possibility) of the title compound were obtained. LC-MS (Method 4): Rt = 0.55 min; MS (ESIpos): m /z = 362 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.008 (0.77), 0.008 (0.79), 1.697 (1.16), 1.940 ( 0.55), 2.002 (0.46), 2.013 (0.50), 2.524 (1.06), 2.564 (1.20), 2.578 (1.49), 2.591 (0.77), 2.620 (0.48), 3.825 (16.00), 3.955 (0.41), 4.252 ( 0.44), 4.517 (0.94), 4.529 (1.44), 4.542 (0.94), 4.769 (4.35), 6.783 (1.53), 6.804 (1.66), 7.561 (1.13), 7.582 (1.11), 8.061 (1.73). Example 434 (5S)-5-[(3,3-Difluoropyrrolidin-1-yl)carbonyl]-2-[(6-methoxypyridin-3-yl)methyl]-5,6,7,8-tetrahydro[ 1,2,4]triazolo[4,3-a]pyridin-3(2H)-one

[01513] (5S)-2-[(6-Methoxypyridin-3-yl)methyl]-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[ 4,3-a]pyridine-5-carboxylic acid (390 mg, 1.28 mmol) was initially loaded into THF (5.0 mL), and HBTU (632 mg, 1.67 mmol) and N,N-diisopropylethylamine (670 μl, 3.8 mmol) were subsequently added. After stirring at room temperature for 15 minutes, 3,3-difluoropyrrolidine hydrochloride (221 mg, 1.54 mmol) was added and the reaction mixture was stirred at room temperature overnight. The solvent was removed under reduced pressure, and the residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/water gradient). The fractions containing the product were concentrated under reduced pressure and 113 mg (22% possibility) of the title compound were obtained. LC-MS (Method 4): Rt = 0.64 min; MS (ESIpos): m /z = 394 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.008 (0.54), 0.008 (0.53), 1.688 (0.41), 1.711 ( 0.48), 1.970 (0.42), 1.978 (0.42), 1.988 (0.48), 1.996 (0.44), 2.003 (0.43), 2.571 (1.03), 2.587 (1.08), 2.602 (0.57), 3.535 (0.42), 3.544 ( 0.64), 3.555 (0.70), 3.663 (0.41), 3.697 (0.46), 3.776 (0.65), 3.805 (0.80), 3.826 (16.00), 3.906 (0.47), 4.728 (0.41), 4.737 (0.47), 4.743 ( 0.54), 4.752 (0.49), 4.766 (6.00), 4.802 (0.43), 4.812 (0.47), 4.817 (0.53), 6.784 (1.80), 6.806 (1.94), 7.553 (1.14), 7.559 (1.17), 7.574 ( 1.11), 7,580 (1.14), 8,052 (1.50), 8,058 (1.50). Example 435 (5S)-2-[(5-Chloropyridin-3-yl)methyl]-5-[(3,3-difluoropyrrolidin-1-yl)carbonyl]-5,6,7,8-tetrahydro[ 1,2,4]triazolo[4,3-a]pyridin-3(2H)-one

[01514] (5S)-2-[(5-Chloropyridin-3-yl)methyl]-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[ 4,3-a]pyridine-5-carboxylic acid (80.3 mg, 260 μmol) was initially loaded into THF (2.0 mL), and HBTU (128 mg, 338 μmol) and N,N-diisopropylethylamine (140 μl, 780 μmol) were subsequently added. After stirring at room temperature for 15 minutes, 3,3-difluoropyrrolidine hydrochloride (44.8 mg, 312 μmol) was added and the reaction mixture was stirred at room temperature overnight. The solvent was removed under reduced pressure, and the residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/water gradient). The fractions containing the product were concentrated under reduced pressure and 32.0 mg (31% possibility) of the title compound were obtained. LC-MS (Method 4): Rt = 0.64 min; MS (ESIpos): m /z = 398 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (1.81), -0.008 (16.00), 0.008 (13.78), 0.146 (1.81) (2.01), 2616 (2.22), 2669 (2.43), 2709 (1.91), 3550 (1.55), 3561 (1.65), 3670 (0.98), 3704 (1.19), 3744 (0.72), 3777 (1.34), 3809 (2.01) (1.29), 4,917 (13.42), 7,757 (4.34), 8,421 (4.44), 8,562 (4.03), 8,568 (3.77). Example 436 (5S)-2-[(5-Chloropyridin-3-yl)methyl]-5-[(3-fluoroazetidin-1-yl)carbonyl]-5,6,7,8-tetrahydro[1, 2,4]triazolo[4,3-a]pyridin-3(2H)-one

[01515] (5S)-2-[(5-Chloropyridin-3-yl)methyl]-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[ 4,3-a]pyridine-5-carboxylic acid (80.3 mg, 260 μmol) was initially loaded into THF (2.0 mL), and HBTU (128 mg, 338 μmol) and N,N-diisopropylethylamine (140 μl, 780 μmol) were subsequently added. After stirring at room temperature for 15 minutes, 3-fluoroazetidine hydrochloride (34.8 mg, 312 μmol) was added and the reaction mixture was stirred at room temperature overnight. HBTU (49 mg, 130 μmol) and N,N-diisopropylethylamine (23 μl, 125 μmol) were added again and the mixture was stirred at room temperature overnight. The solvent was removed under reduced pressure, and the residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/water gradient). The fractions containing the product were concentrated under reduced pressure and 49.1 mg (52% possibility) of the title compound were obtained. LC-MS (Method 4): Rt = 0.57 min; MS (ESIpos): m /z = 366 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.008 (0.83), 0.008 (0.80), 1.651 (0.61), 1.665 ( 0.79), 1.675 (1.03), 1.690 (1.16), 1.700 (1.51), 1.714 (1.68), 1.723 (1.58), 1.909 (0.49), 1.953 (0.99), 1.963 (1.10), 1.972 (1.01), 1.986 ( 0.90), 1.995 (0.74), 2.012 (0.88), 2.022 (0.90), 2.032 (0.99), 2.057 (0.66), 2.074 (16.00), 2.520 (1.07), 2.524 (0.97), 2.566 (1.41), 2.573 ( 1.38), 2.591 (2.03), 2.605 (2.84), 2.618 (1.45), 2.634 (0.55), 2.646 (0.92), 2.660 (0.43), 2.690 (0.60), 3.932 (0.79), 3.962 (0.80), 3.994 ( 0.79), 4.023 (0.46), 4.215 (0.43), 4.228 (0.70), 4.243 (0.67), 4.257 (0.64), 4.274 (0.83), 4.297 (0.77), 4.327 (0.60), 4.366 (0.55), 4.400 ( 0.50), 4.461 (0.51), 4.524 (0.43), 4.556 (2.02), 4.568 (2.95), 4.581 (2.13), 4.921 (8.65), 5.192 (0.68), 5.347 (0.77), 5.354 (0.83), 5.402 ( 0.67), 5.410 (0.72), 5.490 (0.53), 5.497 (0.60), 5.545 (0.50), 5.552 (0.56), 7.775 (2.69), 8.432 (4.55), 8.572 (3.67), 8.577 (3.79). Example 437 (5S)-2-[(5-Chloropyridin-3-yl)methyl]-5-[(3,3-difluoroazetidin-1-yl)carbonyl]-5,6,7,8-tetrahydro[ 1,2,4]triazolo[4,3-a]pyridin-3(2H)-one

[01516] (5S)-2-[(5-Chloropyridin-3-yl)methyl]-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[ 4,3-a]pyridine-5-carboxylic acid (80.3 mg, 260 μmol) was initially loaded into THF (2.0 mL), and HBTU (128 mg, 338 μmol) and N,N-diisopropylethylamine (140 μl, 780 μmol) were subsequently added. After stirring at room temperature for 15 minutes, 3,3-difluoroazetidine hydrochloride (40.4 mg, 312 μmol) was added and the reaction mixture was stirred at room temperature for 72 hours. HBTU (49 mg, 130 μmol) and N,N-diisopropylethylamine (23 μl, 125 μmol) were added again and the mixture was stirred at room temperature overnight. The solvent was removed under reduced pressure, and the residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/water gradient). The fractions containing the product were concentrated under reduced pressure and 46.8 mg (47% possibility) of the title compound were obtained. LC-MS (Method 3): Rt = 1.31 min; MS (ESIpos): m /z = 384 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (0.59), -0.008 (5.47), 0.008 (4.69), 0.146 (0.60) (1.05), 2.051 (1.54), 2.061 (1.18), 2.073 (1.96), 2.087 (0.63), 2.327 (0.67), 2.366 (0.54), 2.523 (2.30) (2.00) (1.76) (1.12), 4,924 (16.00), 7,768 (5.18), 7,773 (3.13), 8,428 (5.44), 8,432 (5.42), 8,565 (4.90), 8,571 (4.84). Example 438 (5S)-2-[(5-Chloropyridin-3-yl)methyl]-5-{[(3S)-3-fluoropyrrolidin-1-yl]carbonyl}-5,6,7,8-tetra- hydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one

[01517] (5S)-2-[(5-Chloropyridin-3-yl)methyl]-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[ 4,3-a]pyridine-5-carboxylic acid (80.3 mg, 260 μmol) was initially loaded into THF (2.0 mL), and HBTU (128 mg, 338 μmol) and N,N-diisopropylethylamine (140 μl, 780 μmol) were subsequently added. After stirring at room temperature for 15 minutes, (3S)-3-fluoropyrrolidine hydrochloride (39.2 mg, 312 μmol) was added and the reaction mixture was stirred at room temperature overnight. HBTU (49 mg, 130 μmol) and N,N-diisopropylethylamine (23 μl, 125 μmol) were added again and the mixture was stirred at room temperature for 72 hours. The solvent was removed under reduced pressure, and the residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/water gradient). The fractions containing the product were concentrated under reduced pressure and 45.6 mg (46% possibility) of the title compound were obtained. LC-MS (Method 3): Rt = 1.16 min; MS (ESIpos): m /z = 380 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.008 (1.20), 0.008 (0.99), 1.177 (0.44), 1.410 ( 0.46), 1.700 (1.25), 1.711 (1.50), 1.725 (2.19), 1.734 (2.40), 1.877 (0.52), 1.911 (0.70), 1.997 (0.86), 2.029 (1.30), 2.051 (0.98), 2.067 ( 1.28), 2.078 (1.62), 2.088 (1.79), 2.103 (2.22), 2.138 (1.51), 2.221 (0.81), 2.242 (0.75), 2.270 (1.07), 2.524 (1.52), 2.566 (1.62), 2.570 ( 1.54), 2.576 (1.72), 2.592 (1.47), 2.619 (2.43), 2.661 (1.02), 2.670 (0.75), 2.891 (0.42), 3.274 (0.51), 3.293 (0.65), 3.303 (0.97), 3.321 ( 1.00), 3.331 (0.68), 3.349 (0.59), 3.362 (0.61), 3.371 (0.69), 3.398 (0.80), 3.406 (0.81), 3.460 (0.67), 3.468 (0.69), 3.495 (0.93), 3.504 ( 0.91), 3.613 (0.95), 3.637 (3.39), 3.655 (3.06), 3.660 (3.02), 3.681 (3.39), 3.705 (3.85), 3.723 (4.42), 3.743 (5.52), 3.770 (4.46), 3.778 ( 4.07) 1.44), 4.915 (16.00), 5.260 (1.18), 5.384 (1.48), 5.391 (1.55), 5.512 (0.86), 7.756 (4.66), 7.761 (5.11), 8.422 (6.31), 8.564 (5.64), 8.569 ( 5.61). Example 439 (5S)-2-[(5-Chloropyridin-3-yl)methyl]-5-{[(3R,4S)-3,4-difluoropyrrolidin-1-yl]carbonyl}-5,6,7, 8-tetrahydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one

[01518] (5S)-2-[(5-Chloropyridin-3-yl)methyl]-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[ 4,3-a]pyridine-5-carboxylic acid (80.3 mg, 260 μmol) was initially loaded into THF (2.0 mL), and HBTU (128 mg, 338 μmol) and N,N-diisopropylethylamine (140 μl, 780 μmol) were subsequently added. After stirring at room temperature for 15 minutes, (3R,4S)-3,4-difluoropyrrolidine hydrochloride (44.8 mg, 312 μmol) was added and the reaction mixture was stirred at room temperature overnight. HBTU (49 mg, 130 μmol) and N,N-diisopropylethylamine (23 μl, 125 μmol) were added again and the mixture was stirred at room temperature for 72 hours. 1-[Bis(dimethylamino)methylene]-1H-benzotriazol-1-ium 3-oxide hexafluorophosphate (49 mg, 130 μmol), N,N-diisopropylethylamine (23 μl, 125 μmol) and (3R,4S)-3, 4-Difluoropyrrolidine hydrochloride (19 mg, 130 μmol) was added again, and the mixture was stirred at room temperature overnight. The solvent was removed under reduced pressure, and the residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/water gradient). The fractions containing the product were concentrated under reduced pressure and 15.1 mg (15% possibility) of the title compound were obtained. LC-MS (Method 3): Rt = 1.18 min; MS (ESIpos): m /z = 398 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (0.42), -0.008 (4.20), 0.008 (3.95), 0.146 (0.45), 1659 (1.27), 1685 (0.73), 1732 (1.72), 1938 (0.60), 1972 (1.30), 1994 (1.06), 2014 (1.71), 2038 (1.11), 2049 (1.17), 2056 (1.27) (1.88) (0.60) (1.36) (1.51) (0.49) (0.71) (0.84) (0.91) (0.75), 5.495 (0.62), 6.826 (1.08), 6.847 (1.30), 7.099 (1.17), 7.121 (1.00), 7.753 (3.97), 7.758 (4.19), 8.419 (5.98), 8.564 (4.00). Example 440 (5S)-2-{[5-Chloro-6-(trifluoromethyl)pyridin-3-yl]methyl}-5-{[(3R,4S)-3,4-difluoropyrrolidin-1-yl]carbonyl} -5,6,7,8-tetrahydro[1,2,4]triazolo[4,3- a]pyridin-3(2H)-one

[01519] (5S)-2-{[5-Chloro-6-(trifluoromethyl)pyridin-3-yl]methyl}-3-oxo-2,3,5,6,7,8-hexahydro[1 ,2,4]triazolo[4,3-a]pyridine-5-carboxylic acid (35.0 mg, 92.9 μmol) was initially loaded into THF (2.0 mL), and HBTU (45.8 mg, 121 μmol) and N,N-diisopropylethylamine (49 μl, 280 μmol) were subsequently added. After stirring at room temperature for 15 minutes, (3R, 4S)-3,4-difluoropyrrolidine hydrochloride (16.0 mg, 111 μmol) was added and the reaction mixture was stirred at room temperature for 72 hours. The solvent was removed under reduced pressure, and the residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/water gradient). The fractions containing the product were concentrated under reduced pressure and 25.0 mg (58% possibility) of the title compound were obtained. LC-MS (Method 3): Rt = 1.53 min; MS (ESIpos): m /z = 466 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.150 (1.49), -0.008 (13.42), 0.008 (10.58), 0.146 (1.49) (4.88) (1.36), 7,035 (9.63), 8,066 (6.10), 8,538 (8.14). Example 441 (5S)-2-{[5-Chloro-6-(trifluoromethyl)pyridin-3-yl]methyl}-5-[(3,3-difluoropyrrolidin-1-yl)carbonyl]-5,6,7 ,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one

[01520] (5S)-2-{[5-Chloro-6-(trifluoromethyl)pyridin-3-yl]methyl}-3-oxo-2,3,5,6,7,8-hexahydro[1 ,2,4]triazolo[4,3-a]pyridine-5-carboxylic acid (35.0 mg, 92.9 μmol) was initially loaded into THF (2.0 mL), and HBTU (45.8 mg, 121 μmol) and N,N-diisopropylethylamine (49 μl, 280 μmol) were subsequently added. After stirring at room temperature for 15 minutes, 3,3-difluoropyrrolidine hydrochloride (16.0 mg, 111 μmol) was added and the reaction mixture was stirred at room temperature for 72 hours. The solvent was removed under reduced pressure, and the residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/water gradient). The fractions containing the product were concentrated under reduced pressure and 27.0 mg (62% possibility) of the title compound were obtained. LC-MS (Method 3): Rt = 1.60 min; MS (ESIpos): m /z = 466 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (1.15), -0.008 (10.01), 0.008 (8.29), 0.146 (1.04) (11.28) (2.65) (1.73) (1.96), 4,805 (1.38), 4,849 (1.50), 4,864 (1.96), 4,873 (1.38), 5,040 (16.00), 8,068 (5.99), 8,538 (5.87). Example 442 (5S)-2-[(5-Chloro-6-methoxypyridin-3-yl)methyl]-5-{[(3R,4S)-3,4-difluoropyrrolidin-1-yl]carbonyl}-5, 6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one

[01521] (5S)-2-[(5-Chloro-6-methoxypyridin-3-yl)methyl]-3-oxo-2,3,5,6,7,8-hexahydro[1,2, 4]triazolo[4,3-a]pyridine-5-carboxylic acid (80.0 mg, 236 μmol) was initially loaded into THF (2.0 mL), and HBTU (116 mg, 307 μmol) and N,N -diisopropylethylamine (120 μl, 710 μmol) were subsequently added. After stirring at room temperature for 15 minutes, (3R, 4S)-3,4-difluoropyrrolidine hydrochloride (40.7 mg, 283 μmol) was added and the reaction mixture was stirred at room temperature for 72 hours. The solvent was removed under reduced pressure, and the residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/water gradient). The fractions containing the product were concentrated under reduced pressure and 37.0 mg (37% possibility) of the title compound were obtained. LC-MS (Method 4): Rt = 0.72 min; MS (ESIpos): m /z = 428 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.008 (2.46), 0.008 (2.19), 1.654 (0.57), 1.723 ( 0.70), 1.956 (0.53), 2.001 (0.70), 2.024 (0.45), 2.035 (0.49), 2.043 (0.55), 2.051 (0.51), 2.060 (0.43), 2.073 (2.65), 2.562 (1.13), 2.572 ( 0.79), 2.586 (1.04), 2.599 (1.36), 2.611 (0.79), 2.642 (0.49), 2.670 (0.45), 3.486 (0.49), 3.523 (0.43), 3.532 (0.57), 3.541 (0.57), 3.626 ( 0.43), 3,668 (0.43), 3,682 (0.62), 3,700 (0.74), 3,721 (0.62), 3,734 (0.42), 3,751 (0.49), 3,765 (0.51), 3,924 (14,47), 3,926 (16.00), 3.972 ( 0.42), 3.985 (0.43), 4.171 (0.45), 4.792 (1.87), 4.804 (8.38), 5.254 (0.42), 5.266 (0.43), 5.276 (0.47), 5.375 (0.45), 5.388 (0.51), 5.399 ( 0.42), 5.407 (0.40), 7.739 (1.63), 7.745 (2.99), 7.750 (1.89), 8.015 (1.65), 8.021 (3.08), 8.026 (1.76). Example 443 (5S)-2-[(5-Chloro-6-methoxypyridin-3-yl)methyl]-5-[(3,3-difluoropyrrolidin-1-yl)carbonyl]-5,6,7,8- tetrahydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one

[01522] (5S)-2-[(5-Chloro-6-methoxypyridin-3-yl)methyl]-3-oxo-2,3,5,6,7,8-hexahydro[1,2, 4]triazolo[4,3-a]pyridine-5-carboxylic acid (80.0 mg, 236 μmol) was initially loaded into THF (2.0 mL), and HBTU (116 mg, 307 μmol) and N,N -diisopropylethylamine (120 μl, 710 μmol) were subsequently added. After stirring at room temperature for 15 minutes, 3,3-difluoropyrrolidine hydrochloride (40.7 mg, 283 μmol) was added and the reaction mixture was stirred at room temperature for 72 hours. The solvent was removed under reduced pressure, and the residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/water gradient). The fractions containing the product were concentrated under reduced pressure and 35.0 mg (35% possibility) of the title compound were obtained. LC-MS (Method 3): Rt = 1.41 min; MS (ESIpos): m /z = 428 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.008 (2.15), 0.008 (1.91), 1.722 (0.45), 1.972 ( 0.71), 1.996 (0.50), 2.073 (0.45), 2.328 (0.43), 2.524 (1.63), 2.569 (1.20), 2.586 (1.03), 2.601 (1.03), 2.670 (0.49), 3.528 (0.41), 3.537 ( 0.45), 3.546 (0.65), 3.557 (0.73), 3.667 (0.43), 3.700 (0.49), 3.775 (0.64), 3.805 (0.84), 3.909 (0.58), 3.925 (16.00), 4.759 (0.54), 4.769 ( 0.41), 4.805 (6.06), 4.832 (0.60), 4.842 (0.49), 7.744 (2.13), 7.749 (2.24), 8.020 (1.96), 8.025 (1.94). Example 444 (5S)-5-{[(3S)-3-Fluoropyrrolidin-1-yl]carbonyl}-2-[3-(trifluoromethyl)benzyl]-5,6,7,8-tetrahydro[1, 2,4]triazolo[4,3-a]pyridin-3(2H)-one

[01523] (5S)-3-Oxo-2-[3-(trifluoromethyl)benzyl]-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3- a]pyridine-5-carboxylic acid (70.0 mg, 205 μmol) was initially loaded into THF (3.0 mL), and HATU (101 mg, 267 μmol) and triethylamine (86 μl, 620 μmol) were subsequently added . After stirring at room temperature for 15 minutes, (3S)-3-fluoropyrrolidine hydrochloride (30.9 mg, 246 μmol) was added and the reaction mixture was stirred at room temperature overnight. The solvent was removed under reduced pressure, and the residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/water gradient). The fractions containing the product were concentrated under reduced pressure and 36.9 mg (44% possibility) of the title compound were obtained. LC-MS (Method 3): Rt = 1.49 min; MS (ESIpos): m /z = 413 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.008 (1.84), 0.008 (1.64), 1.163 (0.63), 1.633 ( 0.62), 1.642 (0.77), 1.655 (0.92), 1.667 (1.04), 1.681 (0.99), 1.707 (1.53), 1.719 (2.14), 1.731 (2.70), 1.741 (2.21), 1.909 (0.49), 1.968 ( 0.74), 1.997 (2.63), 2.027 (1.41), 2.037 (1.44), 2.049 (1.05), 2.065 (1.42), 2.072 (3.24), 2.080 (1.67), 2.089 (1.84), 2.101 (2.01), 2.137 ( 1.51), 2.174 (0.50), 2.220 (0.91), 2.257 (1.10), 2.269 (1.15), 2.327 (0.55), 2.366 (0.43), 2.523 (2.43), 2.567 (2.31), 2.584 (1.52), 2.597 ( 1.92), 2.609 (3.44), 2.621 (2.07), 2.639 (0.82), 2.650 (1.26), 2.665 (0.98), 2.710 (0.48), 3.274 (0.47), 3.352 (0.69), 3.363 (1.15), 3.381 ( 0.87), 3.393 (0.71), 3.407 (0.80), 3.468 (0.52), 3.494 (0.59), 3.505 (1.14), 3.524 (1.79), 3.552 (1.39), 3.570 (1.09), 3.596 (2.27), 3.613 ( 0.45), 3.638 (1.50), 3.655 (1.92), 3.681 (1.22), 3.696 (0.75), 3.724 (0.78), 3.744 (1.50), 3.772 (1.20), 3.784 (1.18), 3.855 (1.53), 3.922 ( 0.58), 3.946 (1.15), 3.969 (0.53), 3.983 (0.47), 4.011 (0.55), 4.043 (0.44), 4.698 (0.75), 4.706 (0.90), 4.713 (0.96), 4.722 (0.74), 4.754 ( 0.99), 4.763 (1.08), 4.770 (1.21), 4.779 (0.91), 4.824 (0.79), 4.838 (1.28), 4.848 (0.82), 4.861 (0.92), 4.869 (1.02), 4.876 (1.13), 4.885 ( 1.03), 4930 (16.00), 5261 (1.04), 5270 (1.03), 5348 (0.69), 5393 (1.16), 5481 (0.68), 5512 (0.56), 7508 (2.41), 7527 (4.04), 7572 ( 2.77), 7,591 (5.41), 7,620 (5.71), 7,648 (4.73), 7,667 (2.61). Example 445 (5S)-5-{[(3R,4S)-3,4-Difluoropyrrolidin-1-yl]carbonyl}-2-[3-(trifluoromethyl)benzyl]-5,6,7,8-tetra- hydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one

[01524] (5S)-3-Oxo-2-[3-(trifluoromethyl)benzyl]-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3- a]pyridine-5-carboxylic acid (60.0 mg, 176 μmol) was initially loaded into THF (3.0 mL), and HBTU (86.7 mg, 229 μmol) and N,N-diisopropylethylamine (92 μl, 530 μmol) were subsequently added. After stirring at room temperature for 15 minutes, (3R,4S)-3,4-difluoropyrrolidine hydrochloride (30.3 mg, 211 μmol) was added and the reaction mixture was stirred at room temperature overnight. The solvent was removed under reduced pressure, and the residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/water gradient). The fractions containing the product were concentrated under reduced pressure and 41.9 mg (55% possibility) of the title compound were obtained. LC-MS (Method 4): Rt = 0.85 min; MS (ESIpos): m /z = 431 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (0.53), -0.008 (5.75), 0.008 (4.69), 0.146 (0.53), 1244 (0.79), 1259 (0.86), 1274 (0.53), 1667 (1.25), 1731 (1.52), 1937 (0.51), 1971 (1.17), 2012 (1.57), 2036 (1.01), 2054 (1.16) (3.14), 2.620 (1.85), 2.651 (1.14), 2.665 (1.16), 2.669 (1.07), 2.710 (0.78), 3.033 (0.43), 3.403 (0.58), 3.455 (0.63) (0.92) (0.94) (0.79) (0.99) (0.64) (0.73), 5.482 (0.76), 5.495 (0.59), 7.505 (1.73), 7.524 (2.86), 7.572 (1.90), 7.591 (3.72), 7.614 (6.46), 7.648 (3.85), 7.668 (2.18). Example 446 (5S)-5-[(3,3-Difluoropyrrolidin-1-yl)carbonyl]-2-[3-(trifluoromethyl)benzyl]-5,6,7,8-tetrahydro[1,2, 4]triazolo[4,3-a]pyridin-3(2H)-one

[01525] (5S)-3-Oxo-2-[3-(trifluoromethyl)benzyl]-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3- a]pyridine-5-carboxylic acid (60.0 mg, 176 μmol) was initially loaded into THF (3.0 mL), and HBTU (86.7 mg, 229 μmol) and N,N-diisopropylethylamine (92 μl, 530 μmol) were subsequently added. After stirring at room temperature for 15 minutes, 3,3-difluoropyrrolidine hydrochloride (30.3 mg, 211 μmol) was added and the reaction mixture was stirred at room temperature overnight. The solvent was removed under reduced pressure, and the residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/water gradient). The fractions containing the product were concentrated under reduced pressure and 38.0 mg (50% possibility) of the title compound were obtained. LC-MS (Method 3): Rt = 1.62 min; MS (ESIpos): m /z = 431 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.008 (3.35), 0.008 (3.36), 0.146 (0.40), 1.672 ( 1.05), 1.681 (0.96), 1.695 (0.89), 1.720 (1.32), 1.731 (1.28), 1.872 (0.59), 1.972 (1.05), 1.986 (1.17), 2.001 (1.31), 2.013 (1.47), 2.041 ( 1.03), 2.049 (1.03), 2.057 (1.00), 2.066 (0.92), 2.072 (0.98), 2.085 (0.76), 2.092 (0.66), 2.327 (0.56), 2.366 (0.78), 2.381 (0.85), 2.410 ( 1.01), 2.430 (0.96), 2.452 (0.79), 2.523 (2.83), 2.576 (2.41), 2.591 (2.53), 2.608 (2.78), 2.620 (1.36), 2.640 (0.54), 2.652 (0.84), 2.665 ( 0.79) 3,738 (1.12), 3,772 (1.54), 3,783 (1.03), 3,791 (0.84), 3,808 (1.83), 3,828 (0.65), 3,839 (0.48), 3,894 (0.62), 3,913 (1.56), 3,932 (0.75), 3,939 (0.96), 3,958 (0.61), 3,991 (0.82), 4,005 (0.42), 4,019 (0.56), 4,033 (0.75), 4,061 (0.45), 4,149 (0.46), 4,181 (0.73), 4,208 (0.71), 4,767 (1.12), 4,776 (1.31), 4,782 (1.45), 4,792 (1.06), 4,840 (1.14), 4,850 (1.29), 4,855 (1.47), 4,865 (1.09), 4,931 (16.00), 7,506 (2.20), 7,525 (3.60), 7,572 (2.11), 7,591 (4.15), 7,616 (5.26), 7,648 (3.33), 7,668 (1.87). Example 447 (5S)-5-[(3-Fluoroazetidin-1-yl)carbonyl]-2-[3-(trifluoromethyl)benzyl]-5,6,7,8-tetrahydro[1,2,4] triazolo[4,3-a]pyridin-3(2H)-one

[01526] (5S)-3-Oxo-2-[3-(trifluoromethyl)benzyl]-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3- a]pyridine-5-carboxylic acid (60.0 mg, 176 μmol) was initially loaded into THF (3.0 mL), and HBTU (86.7 mg, 229 μmol) and N,N-diisopropylethylamine (92 μl, 530 μmol) were subsequently added. After stirring at room temperature for 15 minutes, 3-fluoroazetidine hydrochloride (23.5 mg, 211 μmol) was added and the reaction mixture was stirred at room temperature overnight. The solvent was removed under reduced pressure, and the residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/water gradient). The fractions containing the product were concentrated under reduced pressure and 30.5 mg (44% possibility) of the title compound were obtained. LC-MS (Method 4): Rt = 0.80 min; MS (ESIpos): m /z = 399 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (1.79), -0.008 (16.00), 0.008 (13.70), 0.146 (1.87) (3.16) (12.77), 5.353 (0.79), 5.495 (0.79), 7.511 (2.44), 7.529 (4.23), 7.572 (2.22), 7.590 (4.30), 7.621 (5.88), 7.649 (4.66), 7.669 (2.65). Example 448 (5S)-5-{[(3S)-3-Fluoropyrrolidin-1-yl]carbonyl}-2-[4-fluoro-3-(trifluoromethyl)benzyl]-5,6,7,8-tetra- hydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one

[01527] (5S)-2-[4-Fluoro-3-(trifluoromethyl)benzyl]-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[ 4,3-a]pyridine-5-carboxylic acid (61.0 mg, 170 μmol) was initially loaded into THF (2.1 mL) at room temperature. Subsequently, HATU (83.9 mg, 221 μmol) and triethylamine (71 μl, 510 μmol) were added. After stirring for 15 minutes, (3S)-3-fluoropyrrolidine hydrochloride (25.6 mg, 204 μmol) was added and the reaction mixture was stirred at room temperature for 72 hours. The reaction mixture was mixed with water and ethyl acetate. The organic phase was removed and the aqueous phase was extracted three times with ethyl acetate. The combined organic phases were washed with saturated aqueous sodium chloride solution, dried over sodium sulfate and filtered, and the filtrate was concentrated. The residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/gradient water). The fractions containing the product were concentrated under reduced pressure and 38.0 mg (52% possibility) of the title compound were obtained. LC-MS (Method 3): Rt = 1.53 min; MS (ESIpos): m /z = 431 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.150 (1.93), -0.008 (16.00), 0.008 (15.16), 0.146 (2.01) (0.84), 4,908 (7.71), 5,400 (0.84), 7,481 (1.26), 7,502 (2.18), 7,528 (1.93), 7,577 (1.42), 7,685 (1.68). Example 449 (5S)-2-[4-Fluoro-3-(trifluoromethyl)benzyl]-5-[(3-hydroxyazetidin-1-yl)carbonyl]-5,6,7,8-tetrahydro[1, 2,4]triazolo[4,3-a]pyridin-3(2H)-one

[01528] (5S)-2-[4-Fluoro-3-(trifluoromethyl)benzyl]-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[ 4,3-a]pyridine-5-carboxylic acid (60.0 mg, 167 μmol) was initially loaded into THF at room temperature. Subsequently, HBTU (82.3 mg, 217 μmol) and N,N-diisopropylethylamine (87 μl, 500 μmol) were added. After stirring for 15 minutes, azetidin-3-ol hydrochloride (22.0 mg, 200 μmol) was added and the reaction mixture was stirred at room temperature overnight. The reaction mixture was mixed with water and ethyl acetate. The organic phase was removed and the aqueous phase was extracted three times with ethyl acetate. The combined organic phases were washed with saturated aqueous sodium chloride solution, dried over sodium sulfate and filtered, and the filtrate was concentrated. The residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/gradient water). The fractions containing the product were concentrated under reduced pressure and 32.0 mg (46% possibility) of the title compound were obtained. LC-MS (Method 3): Rt = 1.29 min; MS (ESIpos): m /z = 415 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.008 (2.18), 0.008 (1.77), 1.662 (1.86), 1.710 ( 2.59), 1719 (2.65), 1732 (2.18), 1906 (1.39), 1919 (1.36), 1931 (2.08), 1942 (3.09), 1954 (2.81), 1964 (1.67), 1993 (1.96), 2003 ( 2.15), 2012 (1.89), 2029 (1.51), 2328 (0.66), 2367 (0.50), 2519 (3.50), 2524 (3.94), 2566 (2.08), 2580 (2.81), 2592 (5.24), 2.605 ( 2.75), 2.621 (1.23), 2.634 (1.93), 2.646 (0.85), 2.670 (0.73), 2.675 (0.57), 2.710 (0.54), 3.596 (1.61), 3.603 (1.89), 3.621 (2.05), 3.630 ( 2.65), 3.646 (1.86), 3.660 (1.74), 3.671 (1.74), 3.920 (2.05), 3.932 (2.34), 3.952 (0.57), 4.021 (3.63), 4.045 (3.85), 4.054 (2.08), 4.062 ( 1.93), 4.101 (1.39), 4.116 (1.74), 4.127 (1.45), 4.142 (1.33), 4.339 (1.45), 4.357 (2.43), 4.378 (1.67), 4.485 (2.62), 4.502 (5.08), 4.515 ( 6.28), 4,526 (6.94), 4,537 (5.24), 4,551 (2.21), 4,905 (16.00), 4,910 (15.78), 5,791 (2.78), 5,803 (6,75), 5,817 (3.47), 7,476 (1.86), 7,501 ( 4.51), 7.525 (3.22), 7.565 (2.97), 7.570 (3.16), 7.577 (3.50), 7.598 (1.80), 7.674 (4.45), 7.691 (4.45). Example 450 (5S)-5-{[(3S)-3-Fluoropyrrolidin-1-yl]carbonyl}-2-{[2-(trifluoromethyl)pyridin-4-yl]methyl}-5,6,7,8 -tetrahydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one

[01529] (5S)-3-Oxo-2-{[2-(trifluoromethyl)pyridin-4-yl]methyl}-2,3,5,6,7,8-hexahydro[1,2,4 ]triazolo[4,3-a]pyridine-5-carboxylic acid (100 mg, 292 μmol) was initially loaded into DMF (3.3 mL) at room temperature. Subsequently, HBTU (144 mg, 380 μmol) and N,N-diisopropylethylamine (150 μl, 880 μmol) were added. After stirring for 15 minutes, (3S)-3-fluoropyrrolidine hydrochloride (44.0 mg, 351 μmol) was added and the reaction mixture was stirred at room temperature overnight. The reaction mixture was mixed with water and ethyl acetate. The organic phase was removed and the aqueous phase was extracted three times with ethyl acetate. The combined organic phases were washed with saturated aqueous sodium chloride solution, dried over sodium sulfate and filtered, and the filtrate was concentrated. The residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/gradient water). The fractions containing the product were concentrated under reduced pressure and 65.8 mg (54% possibility) of the title compound were obtained. LC-MS (Method 3): Rt = 1.18 min; MS (ESIpos): m /z = 414 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (1.51), -0.008 (16.00), 0.008 (10.48), 0.146 (1.36) (1.79) (1.72) (1.51), 5.027 (12.27), 5.261 (1.00), 5.383 (1.15), 5.512 (0.72), 7.486 (2.44), 7.752 (5.31), 8.729 (3.87), 8.741 (3.95). Example 451 (5S)-5-[(3,3-Difluoropyrrolidin-1-yl)carbonyl]-2-(4-fluorobenzyl)-5,6,7,8-tetrahydro[1,2,4]triazole [4,3-a]pyridin-3(2H)-one

[01530] (5S)2-(4-Fluorobenzyl)-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine- 5-carboxylic acid (62.8 mg, 215 μmol) was initially loaded into THF (2.0 mL, 25 mmol), and HBTU (106 mg, 280 μmol) and N,N-diisopropylethylamine (110 μl, 650 μmol) were added subsequently. After stirring at room temperature for 15 minutes, 3,3-difluoropyrrolidine hydrochloride (37.1 mg, 259 μmol) was added and the reaction mixture was stirred at room temperature overnight. The solvent was removed under reduced pressure, and the residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/water gradient). The fractions containing the product were concentrated under reduced pressure and 34.6 mg (42% possibility) of the title compound were obtained. LC-MS (Method 3): Rt = 1.38 min; MS (ESIpos): m /z = 381 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (1.79), -0.008 (16.00), 0.008 (12.60), 0.146 (1.70) (2.86) (0.72) (0.80) (5.90), 7,277 (4.38), 7,291 (3.66). Example 452 (5S)-5-{[(3R,4S)-3,4-Difluoropyrrolidin-1-yl]carbonyl}-2-(4-fluorobenzyl)-5,6,7,8-tetrahydro[1 ,2,4]triazolo[4,3-a]pyridin-3(2H)-one

[01531] (5S)2-(4-Fluorobenzyl)-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine- 5-carboxylic acid (62.8 mg, 215 μmol) was initially loaded into THF (2.0 mL), and HBTU (106 mg, 280 μmol) and N,N-diisopropylethylamine (110 μl, 650 μmol) were subsequently added . After stirring at room temperature for 15 minutes, (3R,4S)-3,4-difluoropyrrolidine hydrochloride (37.1 mg, 259 μmol) was added and the reaction mixture was stirred at room temperature overnight. The solvent was removed under reduced pressure, and the residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/water gradient). The fractions containing the product were concentrated under reduced pressure and 63.3 mg (77% possibility) of the title compound were obtained. LC-MS (Method 3): Rt = 1.30 min; MS (ESIpos): m /z = 381 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) delta [ppm]: -0.149 (1.91), -0.008 (16.00), 0.008 (12.70), 0.146 (1.74) (2.78) (0.70) (2.26), 7,258 (2.96), 7,264 (3.30), 7,272 (4.35), 7,279 (2.43), 7,287 (1.91), 7,293 (1.74). Example 453 (5S)-5-{[(3R,4S)-3,4-Difluoropyrrolidin-1-yl]carbonyl}-2-(4-methoxybenzyl)-5,6,7,8-tetrahydro[1 ,2,4]triazolo[4,3-a]pyridin-3(2H)-one

[01532] (5S)-2-(4-Methoxybenzyl)-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine -5-carboxylic acid (258 mg, 50% purity, 425 μmol) was initially loaded into THF (5.0 mL), and HBTU (210 mg, 553 μmol) and N,N-diisopropylethylamine (220 μl, 1. 3 mmol) were subsequently added. After stirring at room temperature for 15 minutes, (3R, 4S)-3,4-difluoropyrrolidine hydrochloride (73.3 mg, 510 μmol) was added and the reaction mixture was stirred at room temperature for 72 hours. The solvent was removed under reduced pressure, and the residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/water gradient). The fractions containing the product were concentrated under reduced pressure and 45.0 mg (27% possibility) of the title compound were obtained. LC-MS (Method 4): Rt = 0.70 min; MS (ESIpos): m /z = 393 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.008 (1.34), 0.008 (1.31), 1.251 (0.81), 1.261 ( 0.45), 1.268 (0.91), 1.274 (0.75), 1.291 (0.69), 1.642 (1.22), 1.666 (1.72), 1.676 (1.72), 1.692 (1.93), 1.704 (2.38), 1.714 (2.23), 1.728 ( 1.80), 1909 (1.09), 1927 (0.81), 1944 (1.55), 1970 (0.99), 1980 (1.58), 1993 (1.98), 2001 (1.45), 2018 (1.24), 2028 (1.43), 2036 ( 1.54), 2.043 (1.48), 2.052 (1.30), 2.063 (1.13), 2.071 (1.21), 2.079 (1.07), 2.088 (0.60), 2.519 (2.90), 2.570 (2.85), 2.583 (3.73), 2.595 ( 2.10), 2.615 (0.77), 2.626 (1.27), 2.637 (0.61), 2.689 (1.56), 3.441 (0.48), 3.450 (0.85), 3.459 (0.56), 3.483 (1.47), 3.493 (1.43), 3.505 ( 1.30), 3.514 (1.58), 3.567 (7.32), 3.576 (7.76), 3.586 (7.42), 3.612 (8.16), 3.625 (7.94), 3.644 (6.37), 3.666 (4.04), 3.681 (3.25), 3.688 ( 2.58), 3.701 (2.92), 3.714 (2.10), 3.754 (1.71), 3.766 (1.50), 3.787 (0.85), 3.800 (0.81), 3.816 (0.49), 3.829 (0.56), 3.835 (0.54), 3.845 ( 0.73), 3.858 (0.89), 3.864 (1.10), 3.883 (0.53), 3.893 (0.71), 3.906 (1.04), 3.925 (1.06), 3.938 (1.20), 3.953 (0.74), 3.967 (0.87), 3.974 ( 1.15), 3.988 (1.16), 4.002 (0.75), 4.017 (0.68), 4.130 (0.73), 4.144 (0.83), 4.158 (0.79), 4.171 (1.38), 4.186 (0.90), 4.198 (0.79), 4.214 ( 0.73), 4.679 (1.11), 4.719 (16.00), 4.727 (8.38), 4.766 (3.94), 4.772 (4.71), 4.777 (3.27), 5.244 (0.73), 5.254 (1.15), 5.266 (1.15), 5.276 ( 1.25), 5.285 (1.01), 5.296 (0.78), 5.309 (0.68), 5.318 (0.74), 5.329 (0.93), 5.338 (0.94), 5.350 (0.98), 5.365 (0.88), 5.377 (1.23), 5.387 ( 1.39), 5.399 (1.14), 5.408 (1.13), 5.414 (1.01), 5.427 (0.75), 5.439 (0.71), 5.448 (0.78), 5.458 (0.98), 5.467 (0.94), 5.471 (0.95), 5.480 ( 1,00), 5,494 (0.74), 5,503 (0.49), 6,871 (7.75), 6,875 (9,87), 6,893 (10,64), 6,896 (10,38), 7,023 (0.51), 7,150 (8.24), 7,158 (9,24), 7.172 (7.172 (7.172 (9,24) 7.28), 7.179 (7.47), 7.278 (0.53). Example 454 (5S)-2-(3-Chloro-4-fluorobenzyl)-5-{[(3S)-3-fluoropyrrolidin-1-yl]carbonyl}-5,6,7,8-tetrahydro[1 ,2,4]triazolo[4,3-a]pyridin-3(2H)-one

[01533] (5S)-2-(3-Chloro-4-fluorobenzyl)-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3 -a]pyridine-5-carboxylic acid (60.0 mg, 184 μmol) was initially loaded into THF (2.0 mL), and HBTU (90.8 mg, 239 μmol) and N,N-diisopropylethylamine (96 μl , 550 μmol) were subsequently added. After stirring at room temperature for 15 minutes, (3S)-3-fluoropyrrolidine hydrochloride (27.8 mg, 221 μmol) was added and the reaction mixture was stirred at room temperature overnight. The solvent was removed under reduced pressure, and the residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/water gradient). The fractions containing the product were concentrated under reduced pressure and 39.0 mg (53% possibility) of the title compound were obtained. LC-MS (Method 3): Rt = 1.44 min; MS (ESIpos): m /z = 397 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (1.96), -0.008 (16.00), 0.008 (13.73), 0.146 (1.86) (1.96) (1.50) (2.48), 7.449 (2.43). Example 455 (5S)-2-(3-Chloro-4-fluorobenzyl)-5-[(3,3-difluoropyrrolidin-1-yl)carbonyl]-5,6,7,8-tetrahydro[1,2 ,4]triazolo[4,3-a]pyridin-3(2H)-one

[01534] (5S)-2-(3-Chloro-4-fluorobenzyl)-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3 -a]pyridine-5-carboxylic acid (60.0 mg, 184 μmol) was initially loaded into THF (2.0 mL), and HBTU (90.8 mg, 239 μmol) and N,N-diisopropylethylamine (96 μl , 550 μmol) were subsequently added. After stirring at room temperature for 15 minutes, 3,3-difluoropyrrolidine hydrochloride (31.7 mg, 221 μmol) was added and the reaction mixture was stirred at room temperature for 72 hours. The solvent was removed under reduced pressure, and the residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/water gradient). The fractions containing the product were concentrated under reduced pressure and 58.0 mg (76% possibility) of the title compound were obtained. LC-MS (Method 3): Rt = 1.58 min; MS (ESIpos): m /z = 415 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.008 (2.55), 0.008 (1.32), 1.670 (1.23), 1.680 ( 1.17), 1692 (1.09), 1718 (1.53), 1728 (1.49), 1980 (1.43), 1995 (1.50), 2005 (1.65), 2011 (1.56), 2028 (1.19), 2039 (1.16), 2047 ( 1.23), 2.054 (1.17), 2.064 (1.10), 2.073 (2.24), 2.082 (0.88), 2.090 (0.75), 2.366 (0.60), 2.381 (1.02), 2.392 (0.77), 2.410 (1.20), 2.430 ( 1.27), 2.453 (1.50), 2.524 (3.13), 2.576 (2.70), 2.591 (2.97), 2.607 (3.10), 2.620 (1.50), 2.637 (0.64), 2.650 (0.89), 2.664 (0.57), 3.519 ( 0.50), 3.531 (1.37), 3.538 (1.52), 3.549 (2.11), 3.559 (2.19), 3.567 (1.25), 3.578 (1.06), 3.669 (1.29), 3.702 (1.46), 3.742 (0.87), 3.764 ( 0.74), 3.775 (1.80), 3.790 (1.00), 3.808 (2.63), 3.826 (0.68), 3.891 (0.72), 3.910 (1.44), 3.928 (0.83), 3.936 (1.00), 3.954 (0.54), 3.961 ( 0.49), 3.990 (0.91), 4.005 (0.49), 4.019 (0.64), 4.033 (0.81), 4.061 (0.48), 4.145 (0.56), 4.177 (0.81), 4.202 (0.81), 4.756 (1.32), 4.765 ( 1.56), 4.771 (1.70), 4.780 (1.35), 4.824 (16.00), 4.838 (1.92), 4.844 (1.80), 4.853 (1.29), 7.220 (1.53), 7.226 (1.67), 7.232 (1.69), 7.241 ( 2.18), 7.247 (2.07), 7.253 (1.88), 7.258 (1.76), 7.373 (3.79), 7.396 (5.05), 7.418 (3.12), 7.429 (3.04), 7.434 (2.80), 7.447 (2.95), 7.452 ( 2.59). Example 456 (5S)-2-(3-Chloro-4-fluorobenzyl)-5-{[(3R,4S)-3,4-difluoropyrrolidin-1-yl]carbonyl}-5,6,7,8-tetra -hydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one

[01535] (5S)-2-(3-Chloro-4-fluorobenzyl)-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3 -a]pyridine-5-carboxylic acid (60.0 mg, 184 μmol) was initially loaded into THF (2.0 mL), and HBTU (90.8 mg, 239 μmol) and N,N-diisopropylethylamine (96 μl , 550 μmol) were subsequently added. After stirring at room temperature for 15 minutes, (3R,4S)-3,4-difluoropyrrolidine hydrochloride (31.7 mg, 221 μmol) was added and the reaction mixture was stirred at room temperature overnight. The solvent was removed under reduced pressure, and the residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/water gradient). The fractions containing the product were concentrated under reduced pressure and 53.0 mg (69% possibility) of the title compound were obtained. LC-MS (Method 3): Rt = 1.47 min; MS (ESIpos): m /z = 415 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.150 (0.55), -0.008 (5.05), 0.008 (4.28), 0.146 (0.63), 1665 (1.23), 1729 (1.60), 1971 (1.16), 2008 (1.55), 2051 (1.26), 2073 (4.71), 2327 (0.99), 2366 (0.67), 2569 (2.20), 2594 (2.20) (0.89), 3684 (1.33), 3702 (1.48), 3723 (1.28), 3755 (1.01), 3868 (0.84), 3926 (0.78), 3939 (0.87), 3974 (0.78), 3989 (0.85), 4172 (0.92) (4.42), 7,419 (2.37), 7,430 (3.75), 7,448 (3.63). Example 457 (5S)-2-(3-Chloro-4-fluorobenzyl)-5-[(3-fluoroazetidin-1-yl)carbonyl]-5,6,7,8-tetrahydro[1,2,4 ]triazolo[4,3-a]pyridin-3(2H)-one

[01536] (5S)-2-(3-Chloro-4-fluorobenzyl)-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3 -a]pyridine-5-carboxylic acid (60.0 mg, 184 μmol) was initially loaded into THF (2.0 mL), and HBTU (90.8 mg, 239 μmol) and N,N-diisopropylethylamine (96 μl , 550 μmol) were subsequently added. After stirring at room temperature for 15 minutes, 3-fluoroazetidine hydrochloride (24.7 mg, 221 μmol) was added and the reaction mixture was stirred at room temperature overnight. The solvent was removed under reduced pressure, and the residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/water gradient). The fractions containing the product were concentrated under reduced pressure and 38.0 mg (54% possibility) of the title compound were obtained. LC-MS (Method 3): Rt = 1.37 min; MS (ESIpos): m /z = 383 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (0.57), 0.008 (3.84), 0.146 (0.49), 1.258 ( 0.93), 1.681 (2.36), 1.704 (3.76), 1.957 (2.08), 2.028 (1.83), 2.327 (0.80), 2.366 (0.82), 2.523 (4.91), 2.558 (3.01), 2.583 (3.84), 2.597 ( 5.04), 2.610 (2.50), 2.626 (0.97), 2.639 (1.59), 2.653 (0.69), 2.670 (0.82), 2.710 (0.77), 3.901 (0.73), 3.928 (1.44), 3.958 (1.46), 3.990 ( 1.41), 4.018 (0.80), 4.158 (0.62), 4.172 (0.71), 4.185 (0.60), 4.225 (1.30), 4.239 (1.30), 4.257 (1.41), 4.267 (1.53), 4.290 (1.46), 4.323 ( 1.22), 4.352 (0.88), 4.395 (0.88), 4.433 (0.66), 4.457 (0.86), 4.504 (0.75), 4.519 (0.91), 4.544 (3.87), 4.557 (5.50), 4.570 (3.62), 4.597 ( 0.49), 4.634 (0.62), 4.647 (0.75), 4.684 (0.71), 4.701 (0.64), 4.727 (0.51), 4.824 (16.00), 5.353 (0.88), 5.406 (0.88), 5.496 (0.86), 5.550 ( 0.82), 7,248 (2.87), 7,372 (3.29), 7,394 (5.26), 7,417 (2.67), 7,437 (3.31), 7,455 (3.12). Example 458 (5S)-2-[3-Chloro-4-(trifluoromethyl)benzyl]-5-{[(3R,4S)-3,4-difluoropyrrolidin-1-yl]carbonyl}-5,6,7, 8-tetrahydro[1,2,4]triazolo[4,3- a]pyridin-3(2H)-one

[01537] (5S)-2-[3-Chloro-4-(trifluoromethyl)benzyl]-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[ 4,3-a]pyridine-5-carboxylic acid (43.8 mg, 117 μmol) was initially loaded into THF (2.0 mL), and HBTU (57.5 mg, 152 μmol) and N,N-diisopropylethylamine (61 μl, 350 μmol) were subsequently added. After stirring at room temperature for 15 minutes, (3R,4S)-3,4-difluoropyrrolidine hydrochloride (20.1 mg, 140 μmol) was added and the reaction mixture was stirred at room temperature overnight. The solvent was removed under reduced pressure, and the residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/water gradient). The fractions containing the product were concentrated under reduced pressure and 34.5 mg (64% possibility) of the title compound were obtained. LC-MS (Method 4): Rt = 0.93 min; MS (ESIpos): m /z = 465 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (0.42), -0.008 (3.58), 0.008 (3.09), 1.226 (0.51) (1.26) (0.72), 2366 (0.69), 2523 (2.61), 2570 (1.65), 2581 (2.21), 2591 (1.59), 2605 (2.33), 2618 (3.14), 2630 (1.74), 2649 (0.63), 2661 (1.28) (2.52) (5.20) (1.08) (1.07) (0.89) (0.92), 5.430 (0.71), 5.443 (0.68), 5.452 (0.72), 5.466 (0.74), 5.475 (0.72) (5.75), 7,841 (4.19), 7,861 (3.82). Example 459 (5S)-2-[3-Chloro-4-(trifluoromethyl)benzyl]-5-[(3-fluoroazetidin-1-yl)carbonyl]-5,6,7,8-tetrahydro[1, 2,4]triazolo[4,3-a]pyridin-3(2H)-one

[01538] (5S)-2-[3-Chloro-4-(trifluoromethyl)benzyl]-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[ 4,3-a]pyridine-5-carboxylic acid (43.8 mg, 117 μmol) was initially loaded into THF (2.0 mL), and HBTU (57.5 mg, 152 μmol) and N,N-diisopropylethylamine (61 μl, 350 μmol) were subsequently added. After stirring at room temperature for 15 minutes, 3-fluoroazetidine hydrochloride (15.6 mg, 140 μmol) was added and the reaction mixture was stirred at room temperature overnight. The solvent was removed under reduced pressure, and the residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/water gradient). The fractions containing the product were concentrated under reduced pressure and 30.2 mg (58% possibility) of the title compound were obtained. LC-MS (Method 4): Rt = 0.89 min; MS (ESIpos): m /z = 433 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (0.53), 0.146 (0.51), 1.708 (3.04), 1.722 ( 3.28), 1.971 (2.07), 2.038 (1.83), 2.073 (2.00), 2.327 (0.95), 2.366 (0.68), 2.576 (2.89), 2.594 (3.71), 2.608 (5.08), 2.621 (2.63), 2.637 ( 1.10), 2.650 (1.74), 2.665 (1.38), 2.710 (0.77), 3.907 (0.79), 3.933 (1.42), 3.963 (1.48), 3.995 (1.47), 4.020 (0.91), 4.175 (0.70), 4.228 ( 1.29), 4.275 (1.60), 4.295 (1.38), 4.324 (0.95), 4.366 (1.12), 4.400 (0.97), 4.437 (0.73), 4.462 (0.95), 4.524 (0.79), 4.563 (3.93), 4.577 ( 5.79), 4.589 (3.84), 4.651 (0.74), 4.704 (0.74), 4.945 (16.00), 5.354 (0.91), 5.409 (0.92), 5.497 (0.91), 5.550 (0.92), 7.376 (4.42), 7.396 ( 4.84), 7,569 (8.14), 7,838 (5.78), 7,859 (5.38). Example 460 (5S)-2-[3-Chloro-4-(trifluoromethyl)benzyl]-5-[(3,3-difluoropyrrolidin-1-yl)carbonyl]-5,6,7,8-tetrahydro[ 1,2,4]triazolo[4,3-a]pyridin-3(2H)-one

[01539] (5S)-2-[3-Chloro-4-(trifluoromethyl)benzyl]-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[ 4,3-a]pyridine-5-carboxylic acid (43.8 mg, 117 μmol) was initially loaded into THF (2.0 mL), and HBTU (57.5 mg, 152 μmol) and N,N-diisopropylethylamine (61 μl, 350 μmol) were subsequently added. After stirring at room temperature for 15 minutes, 3,3-difluoropyrrolidine hydrochloride (20.1 mg, 140 μmol) was added and the reaction mixture was stirred at room temperature overnight. The solvent was removed under reduced pressure, and the residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/water gradient). The fractions containing the product were concentrated under reduced pressure and 35.4 mg (65% possibility) of the title compound were obtained. LC-MS (Method 4): Rt = 0.96 min; MS (ESIpos): m /z = 465 [M+H]+ ¹H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.008 (2.40), 0.008 (2.34), 1.244 (0.81), 1.259 ( 0.99), 1.273 (0.51), 1.673 (1.17), 1.682 (1.09), 1.696 (0.85), 1.740 (1.46), 1.997 (1.38), 2.012 (1.69), 2.022 (1.79), 2.037 (1.61), 2.049 ( 1.29), 2.057 (1.23), 2.064 (1.17), 2.073 (1.49), 2.085 (0.85), 2.093 (0.87), 2.100 (0.77), 2.281 (0.61), 2.328 (0.48), 2.366 (0.80), 2.382 ( 0.99), 2.393 (0.73), 2.411 (1.18), 2.430 (1.12), 2.454 (0.87), 2.519 (3.66), 2.562 (2.91), 2.576 (2.85), 2.587 (3.07), 2.602 (2.51), 2.619 ( 2.89), 2.631 (1.54), 2.650 (0.62), 2.661 (1.10), 2.670 (0.87), 2.690 (0.52), 2.710 (0.48), 2.885 (1.28), 3.535 (1.31), 3.542 (1.47), 3.553 ( 2.09), 3.562 (2.29), 3.571 (1.29), 3.582 (1.16), 3.639 (0.45), 3.673 (1.35), 3.707 (1.54), 3.726 (0.90), 3.745 (0.94), 3.779 (1.78), 3.786 ( 1.32), 3.795 (0.96), 3.812 (2.75), 3.831 (0.74), 3.893 (0.70), 3.911 (1.53), 3.930 (0.84), 3.938 (1.09), 3.956 (0.52), 3.966 (0.48), 3.995 ( 0.94), 4.009 (0.48), 4.023 (0.66), 4.037 (0.85), 4.065 (0.52), 4.150 (0.56), 4.182 (0.85), 4.207 (0.83), 4.541 (0.47), 4.776 (1.25), 4.785 ( 1.47) 5.98), 7.839 (6.03), 7.860 (5.60). Example 461 (5S)-2-[3-Chloro-4-(trifluoromethyl)benzyl]-5-{[(3S)-3-fluoropyrrolidin-1-yl]carbonyl}-5,6,7,8-tetra- hydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one

[01540] (5S)-2-[3-Chloro-4-(trifluoromethyl)benzyl]-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[ 4,3-a]pyridine-5-carboxylic acid (43.8 mg, 117 μmol) was initially loaded into THF (2.0 mL) at room temperature. Subsequently, HATU (57.6 mg, 152 μmol) and triethylamine (49 μl, 350 μmol) were added. After stirring for 15 minutes, (3S)-3-fluoropyrrolidine hydrochloride (17.6 mg, 140 μmol) was added and the reaction mixture was stirred at room temperature overnight. The reaction mixture was mixed with water and ethyl acetate. The organic phase was removed and the aqueous phase was extracted three times with ethyl acetate. The combined organic phases were washed with saturated aqueous sodium chloride solution, dried over sodium sulfate and filtered, and the filtrate was concentrated. The residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/gradient water). The fractions containing the product were concentrated under reduced pressure and 44.7 mg (86% possibility) of the title compound were obtained. LC-MS (Method 4): Rt = 0.90 min; MS (ESIpos): m /z = 447 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: 0.008 (2.72), 1.733 (2.50), 1.741 (2.71), 1.885 (0.64 ), 1.920 (0.84), 1.970 (0.43), 2.005 (0.84), 2.036 (1.45), 2.047 (1.38), 2.073 (5.69), 2.085 (2.04), 2.108 (2.42), 2.125 (1.59), 2.140 (1.69 ), 2.222 (0.93), 2.242 (0.83), 2.256 (0.88), 2.270 (1.25), 2.327 (0.64), 2.366 (0.49), 2.523 (2.19), 2.570 (1.75), 2.580 (1.91), 2.595 (1.62 ), 2.621 (2.69), 2.665 (1.42), 2.710 (0.48), 3.276 (0.75), 3.351 (0.78), 3.363 (0.72), 3.372 (0.77), 3.398 (0.88), 3.407 (0.88), 3.460 (0.65 ), 3.469 (0.68), 3.496 (0.90), 3.505 (0.85), 3.611 (0.59), 3.637 (2.74), 3.655 (2.24), 3.661 (2.19), 3.681 (1.85), 3.703 (1.17), 3.726 (1.26 ), 3,747 (2.22), 3,770 (1.72), 3,788 (1.39), 3,857 (2.72), 4,703 (1.29), 4,712 (1.56), 4,719 (1.59), 4,728 (1.26), 4,761 (1.69), 4,769 (1.88 ), 4,776 (2.09), 4,785 (1.56), 4,941 (16.00), 5,260 (1.32), 5,391 (1.77), 5,512 (0.96), 7,372 (2.79), 7,393 (3.03), 7,564 (5.99), 7,839 (5.89 ), 7,859 (5.50). Example 462 (5S)-2-(4-Chloro-3-fluorobenzyl)-5-{[(3R,4S)-3,4-difluoropyrrolidin-1-yl]carbonyl}-5,6,7,8-tetra -hydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one

[01541] hydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylic acid (80.0 mg, 233 μmol) was initially loaded into THF (2.0 mL), and HBTU (115 mg, 303 μmol) and N,N-diisopropylethylamine (120 μl, 700 μmol) were subsequently added. After stirring at room temperature for 15 minutes, (3R,4S)-3,4-difluoropyrrolidine hydrochloride (40.2 mg, 280 μmol) was added and the reaction mixture was stirred at room temperature overnight. The solvent was removed under reduced pressure, and the residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/water gradient). The fractions containing the product were concentrated under reduced pressure and 58.0 mg (60% possibility) of the title compound were obtained. LC-MS (Method 3): Rt = 1.48 min; MS (ESIpos): m /z = 415 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (0.47), -0.008 (4.35), 0.008 (4.00), 0.146 (0.45), 1665 (1.17), 1699 (0.65), 1736 (1.42), 1940 (0.53), 1973 (1.13), 2020 (1.52), 2038 (0.97), 2048 (1.03), 2056 (1.13), 2063 (1.09) (1.44) (2.10) (0.73) (0.75) (0.59) (0.81) (0.63) (0.65), 7,219 (2.81), 7,244 (2.93), 7,547 (1.88), 7,551 (2.10), 7,567 (3.46), 7,571 (3.84), 7,587 (1.78), 7,591 (2.00). Example 463 (5S)-2-(4-Chloro-3-fluorobenzyl)-5-[(3-fluoroazetidin-1-yl)carbonyl]-5,6,7,8-tetrahydro[1,2,4 ]triazolo[4,3-a]pyridin-3(2H)-one

[01542] (5S)-2-(4-Chloro-3-fluorobenzyl)-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3 -a]pyridine-5-carboxylic acid (80.0 mg, 233 μmol) was initially loaded into THF (2.0 mL), and HBTU (115 mg, 303 μmol) and N,N-diisopropylethylamine (120 μl, 700 μmol) were subsequently added. After stirring at room temperature for 15 minutes, 3-fluoroazetidine hydrochloride (31.2 mg, 280 μmol) was added and the reaction mixture was stirred at room temperature overnight. The solvent was removed under reduced pressure, and the residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/water gradient). The fractions containing the product were concentrated under reduced pressure and 36.0 mg (40% possibility) of the title compound were obtained. LC-MS (Method 3): Rt = 1.38 min; MS (ESIpos): m /z = 383 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (0.92), -0.008 (8.11), 0.146 (0.92), 1.680 (1.99) (5.08) (0.85) (0.64) (0.89), 7,106 (4.41), 7,197 (0.46), 7,568 (5.23), 7,588 (2.60). Example 464 (5S)-2-(4-Chloro-3-fluorobenzyl)-5-[(3,3-difluoropyrrolidin-1-yl)carbonyl]-5,6,7,8-tetrahydro[1,2 ,4]triazolo[4,3-a]pyridin-3(2H)-one

[01543] (5S)-2-(4-Chloro-3-fluorobenzyl)-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3 -a]pyridine-5-carboxylic acid (80.0 mg, 246 μmol) was initially loaded into THF, and HBTU (121 mg, 319 μmol) and N,N-diisopropylethylamine (130 μl, 740 μmol) were subsequently added. After stirring at room temperature for 15 minutes, 3,3-difluoropyrrolidine hydrochloride (42.3 mg, 295 μmol) was added and the reaction mixture was stirred at room temperature overnight. The solvent was removed under reduced pressure, and the residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/water gradient). The fractions containing the product were concentrated under reduced pressure and 32.0 mg (31% possibility) of the title compound were obtained. LC-MS (Method 3): Rt = 1.56 min; MS (ESIpos): m /z = 415 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (0.96), 0.146 (0.93), 1.736 (1.42), 2.013 ( 1.56), 2.366 (1.99), 2.593 (2.02), 2.609 (2.29), 2.709 (1.46), 3.557 (1.72), 3.670 (1.16), 3.703 (1.19), 3.742 (0.80), 3.774 (1.49), 3.809 ( 2.12), 3.909 (1.16), 3.935 (0.86), 3.992 (0.86), 4.035 (0.70), 4.178 (0.80), 4.202 (0.73), 4.768 (1.36), 4.848 (16.00), 7.081 (2.72), 7.102 ( 3.08), 7,217 (2.82), 7,243 (2.78), 7,549 (2.78), 7,569 (5.04), 7,589 (2.45). Example 465 (5S)-2-(4-Chloro-3-fluorobenzyl)-5-[(3,3-difluoroazetidin-1-yl)carbonyl]-5,6,7,8-tetrahydro[1,2 ,4]triazolo[4,3-a]pyridin-3(2H)-one

[01544] (5S)-2-(4-Chloro-3-fluorobenzyl)-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3 -a]pyridine-5-carboxylic acid (80.0 mg, 246 μmol) was initially loaded into THF, and HBTU (121 mg, 319 μmol) and N,N-diisopropylethylamine (130 μl, 740 μmol) were subsequently added. After stirring at room temperature for 15 minutes, 3,3-difluoroazetidine hydrochloride (38.2 mg, 295 μmol) was added and the reaction mixture was stirred at room temperature overnight. The solvent was removed under reduced pressure, and the residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/water gradient). The fractions containing the product were concentrated under reduced pressure and 69.0 mg (70% possibility) of the title compound were obtained. LC-MS (Method 3): Rt = 1.51 min; MS (ESIpos): m /z = 401 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: 1.701 (1.56), 1.711 (2.31), 1.723 (2.92), 1.736 (2.21 ), 1,960 (0.70), 1,971 (0.73), 1,982 (1.08), 1,995 (1.51), 2,008 (1.34), 2,019 (0.71), 2,026 (0.80), 2,037 (1.03), 2,051 (1.34), 2,061 (1.12 ), 2.075 (1.16), 2.096 (0.45), 2.561 (1.86), 2.577 (2.07), 2.582 (2.02), 2.596 (2.35), 2.608 (3.23), 2.621 (1.55), 2.635 (0.56), 2.650 (0.89 ), 2.664 (0.59), 4.336 (0.99), 4.365 (1.68), 4.388 (1.71), 4.419 (1.03), 4.601 (2.22), 4.616 (3.49), 4.628 (2.18), 4.725 (1.04), 4.755 (1.19 ), 4.785 (0.54), 4.817 (0.56), 4.854 (16.00), 4.875 (1.28), 7.091 (2.53), 7.112 (2.77), 7.228 (2.62), 7.233 (2.47), 7.254 (2.69), 7.258 (2.54 ), 7,550 (2.83), 7,570 (5.03), 7,590 (2.63). Example 466 (5S)-2-(3,4-Difluorobenzyl)-5-{[(3S)-3-fluoropyrrolidin-1-yl]carbonyl}-5,6,7,8-tetrahydro[1,2 ,4]triazolo[4,3-a]pyridin-3(2H)-one

[01545] (5S)-2-(3,4-Difluorobenzyl)-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a ]pyridine-5-carboxylic acid (60.0 mg, 194 μmol) was initially loaded into THF (2.0 mL), and HBTU (95.6 mg, 252 μmol) and N,N-diisopropylethylamine (100 μl, 580 μmol) were subsequently added. After stirring at room temperature for 15 minutes, (3S)-3-fluoropyrrolidine hydrochloride (29.2 mg, 233 μmol) was added and the reaction mixture was stirred at room temperature overnight. The solvent was removed under reduced pressure, and the residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/water gradient). The fractions containing the product were concentrated under reduced pressure and 42.0 mg (57% possibility) of the title compound were obtained. LC-MS (Method 4): Rt = 0.74 min; MS (ESIpos): m /z = 381 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.008 (1.32), 0.008 (1.00), 1.705 (1.55), 1.731 ( 2.78), 1.874 (0.56), 1.909 (0.73), 1.969 (0.40), 1.995 (0.87), 2.023 (1.36), 2.048 (1.03), 2.064 (1.30), 2.074 (1.68), 2.090 (1.82), 2.100 ( 2.07), 2.126 (1.27), 2.136 (1.45), 2.220 (0.82), 2.269 (1.10), 2.328 (0.48), 2.523 (1.88), 2.560 (1.65), 2.570 (1.83), 2.585 (1.51), 2.613 ( 2.42), 2.654 (0.91), 2.665 (0.74), 3.273 (0.64), 3.292 (0.87), 3.302 (1.28), 3.320 (1.58), 3.330 (1.65), 3.458 (0.74), 3.466 (0.76), 3.493 ( 0.93), 3.502 (0.85), 3.610 (0.57), 3.634 (2.77), 3.653 (2.15), 3.678 (1.49), 3.697 (1.09), 3.724 (1.18), 3.745 (1.94), 3.768 (1.62), 3.785 ( 1.30), 3.855 (2.49), 4.686 (1.18), 4.695 (1.42), 4.701 (1.48), 4.710 (1.16), 4.743 (1.56), 4.752 (1.74), 4.758 (1.95), 4.767 (1.44), 4.819 ( 16.00), 5259 (1.23), 5382 (1.53), 5390 (1.58), 5511 (0.86), 7075 (1.88), 7080 (1.96), 7091 (1.90), 7233 (1.60), 7257 (2.00), 7281 ( 1.62), 7,375 (1.67), 7,396 (3.27), 7,402 (1.91), 7,417 (1.81), 7,423 (3.19), 7,444 (1.51). Example 467 (5S)-2-(3,4-Difluorobenzyl)-5-{[(3R,4S)-3,4-difluoropyrrolidin-1-yl]carbonyl}-5,6,7,8-tetrahydro [1,2,4]triazolo[4,3-a]pyridin-3(2H)-one

[01546] (5S)-2-(3,4-Difluorobenzyl)-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a ]pyridine-5-carboxylic acid (60.0 mg, 194 μmol) was initially loaded into THF (2.0 mL), and HBTU (95.6 mg, 252 μmol) and N,N-diisopropylethylamine (100 μl, 580 μmol) were subsequently added. After stirring at room temperature for 15 minutes, (3R,4S)-3,4-difluoropyrrolidine hydrochloride (33.4 mg, 233 μmol) was added and the reaction mixture was stirred at room temperature overnight. The solvent was removed under reduced pressure, and the residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/water gradient). The fractions containing the product were concentrated under reduced pressure and 65.0 mg (84% possibility) of the title compound were obtained. LC-MS (Method 4): Rt = 0.77 min; MS (ESIpos): m /z = 399 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.150 (0.90), -0.008 (10.40), 0.008 (5.42), 0.146 (0.81) (2.17) (0.90) (0.99) (1.18), 7,398 (2.53), 7,421 (2.35), 7,447 (0.99). Example 468 (5S)-2-(3,4-Difluorobenzyl)-5-[(3,3-difluoropyrrolidin-1-yl)carbonyl]-5,6,7,8-tetrahydro[1,2,4 ]triazolo[4,3-a]pyridin-3(2H)-one

[01547] (5S)-2-(3,4-Difluorobenzyl)-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a ]pyridine-5-carboxylic acid (60.0 mg, 194 μmol) was initially loaded into THF (2.0 mL), and HBTU (95.6 mg, 252 μmol) and N,N-diisopropylethylamine (100 μl, 580 μmol) were subsequently added. After stirring at room temperature for 15 minutes, 3,3-difluoropyrrolidine hydrochloride (33.4 mg, 233 μmol) was added and the reaction mixture was stirred at room temperature overnight. The solvent was removed under reduced pressure, and the residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/water gradient). The fractions containing the product were concentrated under reduced pressure and 45.0 mg (58% possibility) of the title compound were obtained. LC-MS (Method 4): Rt = 0.81 min; MS (ESIpos): m /z = 399 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (0.73), 0.146 (0.65), (0.65), 1.670 (1.14 ), 1.731 (1.39), (2.29), 2.380 (0.98), 2.408 (1.14), (3.76), 2.591 (3.02), 2.609 (3.18), (1.47), 3.559 (2.20), 3.578 (1.14), ( 1.55), 3.743 (0.98), 3.774 (1.80), (0.73), 3.909 (1.47), 3.935 (1.06), (0.82), 4.061 (0.57), 4.145 (0.65), (0.41), 4.770 (1.71), 4,779 (1.22), (1.80), 7,230 (1.39), 7,257 (1.80), .86), 7,423 (2.94), 7,445 (1.39). Example 469 (5S)-2-(3,4-Difluorobenzyl)-5-[(3-fluoroazetidin-1-yl)carbonyl]-5,6,7,8-tetrahydro[1,2,4]triazole [4,3-a]pyridin-3(2H)-one

[01548] (5S)-2-(3,4-Difluorobenzyl)-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a ]pyridine-5-carboxylic acid (60.0 mg, 194 μmol) was initially loaded into THF (2.0 mL), and HBTU (95.6 mg, 252 μmol) and N,N-diisopropylethylamine (100 μl, 580 μmol) were subsequently added. After stirring at room temperature for 15 minutes, 3-fluoroazetidine hydrochloride (26.0 mg, 233 μmol) was added and the reaction mixture was stirred at room temperature overnight. The solvent was removed under reduced pressure, and the residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/water gradient). The fractions containing the product were concentrated under reduced pressure and 46.0 mg (65% possibility) of the title compound were obtained. LC-MS (Method 3): Rt = 1.28 min; MS (ESIpos): m /z = 367 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: 1.658 (1.01), 1.671 (1.34), 1.682 (1.98), 1.705 (3.24 ), 1,715 (3.29), 1,961 (1.99), 1,972 (1.82), 2,008 (1.60), 2,019 (1.65), 2,030 (1.77), 2,073 (1.65), 2,559 (2.65), 2,584 (3.64), 2,598 (4.93 ), 2.611 (2.51), 2.627 (0.98), 2.640 (1.60), 2.653 (0.71), 2.690 (0.79), 3.900 (0.66), 3.931 (1.37), 3.961 (1.45), 3.991 (1.40), 4.023 (0.80 ), 4.159 (0.60), 4.175 (0.66), 4.188 (0.54), 4.213 (0.76), 4.227 (1.24), 4.241 (1.20), 4.257 (1.32), 4.270 (1.45), 4.293 (1.44), 4.324 (1.20 ), 4.355 (0.84), 4.372 (0.70), 4.397 (0.86), 4.434 (0.62), 4.460 (0.86), 4.507 (0.64), 4.522 (0.75), 4.546 (3.49), 4.559 (5.42), 4.571 (3.51 ), 4.601 (0.49), 4.635 (0.58), 4.649 (0.71), 4.685 (0.64), 4.702 (0.66), 4.713 (0.59), 4.728 (0.52), 4.824 (16.00), 5.354 (0.85), 5.399 (0.75 ), 5.406 (0.83), 5.497 (0.84), 5.549 (0.83), 7.086 (2.60), 7.239 (1.90), 7.263 (2.53), 7.288 (1.94), 7.374 (1.50), 7.396 (3.14), 7.421 (3.10 ), 7,443 (1.35). Example 470 (5S)-5-[(3,3-Difluoropyrrolidin-1-yl)carbonyl]-2-[3-fluoro-4-(trifluoromethyl)benzyl]-5,6,7,8-tetrahydro[ 1,2,4]triazolo[4,3-a]pyridin- 3(2H)-one

[01549] (5S)-2-[3-Fluoro-4-(trifluoromethyl)benzyl]-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[ 4,3-a]pyridine-5-carboxylic acid (60.0 mg, 167 μmol) was initially loaded into THF (2.0 mL), and HBTU (82.3 mg, 217 μmol) and N,N-diisopropylethylamine (87 μl, 500 μmol) were subsequently added. After stirring at room temperature for 15 minutes, 3,3-difluoropyrrolidine hydrochloride (28.8 mg, 200 μmol) was added and the reaction mixture was stirred at room temperature overnight. The solvent was removed under reduced pressure, and the residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/water gradient). The fractions containing the product were concentrated under reduced pressure and 37.0 mg (49% possibility) of the title compound were obtained. LC-MS (Method 4): Rt = 0.92 min; MS (ESIpos): m /z = 449 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (0.99), 0.008 (7.37), 0.147 (0.91), 1.672 ( 1.29), 1.743 (1.60), 2.015 (2.03), 2.027 (1.90), 2.051 (1.51), 2.328 (1.55), 2.366 (2.33), 2.383 (1.12), 2.410 (1.38), 2.431 (1.29), 2.563 ( 3.54), 2.578 (3.11), 2.588 (3.54), 2.604 (3.02), 2.620 (3.19), 2.665 (2.11), 2.670 (2.11), 2.710 (1.90), 3.541 (1.68), 3.561 (2.46), 3.572 ( 1.38), 3.581 (1.29), 3.641 (0.39), 3.674 (1.42), 3.708 (1.68), 3.744 (1.12), 3.779 (1.98), 3.789 (1.29), 3.813 (2.59), 3.833 (0.82), 3.893 ( 0.73), 3.912 (1.64), 3.937 (1.12), 3.956 (0.52), 3.997 (0.99), 4.025 (0.73), 4.041 (0.91), 4.069 (0.56), 4.151 (0.65), 4.182 (0.91), 4.206 ( 0.95), 4.237 (0.43), 4.775 (1.42), 4.789 (1.81), 4.799 (1.38), 4.845 (1.34), 4.861 (1.81), 4.870 (1.29), 4.954 (16.00), 7.248 (3.62), 7.268 ( 4.05), 7,296 (3.62), 7,326 (3.62), 7,759 (2.72), 7,778 (5.18), 7,798 (2.63). Example 471 (5S)-5-{[(3S)-3-Fluoropyrrolidin-1-yl]carbonyl}-2-[3-fluoro-4-(trifluoromethyl)benzyl]-5,6,7,8-tetra- hydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one

[01550] (5S)-2-[3-Fluoro-4-(trifluoromethyl)benzyl]-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[ 4,3-a]pyridine-5-carboxylic acid (60.0 mg, 167 μmol) was initially loaded into THF (2.0 mL), and HBTU (82.3 mg, 217 μmol) and N,N-diisopropylethylamine (87 μl, 500 μmol) were subsequently added. After stirring at room temperature for 15 minutes, (3S)-3-fluoropyrrolidine hydrochloride (25.2 mg, 200 μmol) was added and the reaction mixture was stirred at room temperature overnight. The solvent was removed under reduced pressure, and the residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/water gradient). The fractions containing the product were concentrated under reduced pressure and 44.0 mg (61% possibility) of the title compound were obtained. LC-MS (Method 4): Rt = 0.86 min; MS (ESIpos): m /z = 431 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (0.49), -0.008 (4.64), 0.008 (3.55), 0.146 (0.49), 1709 (1.39), 1733 (2.38), 1744 (2.67), 1890 (0.58), 1929 (0.83), 1970 (0.41), 2005 (0.85), 2031 (1.00), 2040 (1.46), 2075 (1.75) (1.68) (0.85) (1.12) (1.63) (3.45), 7,326 (3.48), 7,758 (2.72), 7,778 (5.06), 7,797 (2.55). Example 472 (5S)-5-{[(3R,4S)-3,4-Difluoropyrrolidin-1-yl]carbonyl}-2-[3-fluoro-4-(trifluoromethyl)benzyl]-5,6,7, 8-tetrahydro[1,2,4]triazolo[4,3-a]pyridin- 3(2H)-one

[01551] (5S)-2-[3-Fluoro-4-(trifluoromethyl)benzyl]-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[ 4,3-a]pyridine-5-carboxylic acid (60.0 mg, 167 μmol) was initially loaded into THF (2.0 mL), and HBTU (82.3 mg, 217 μmol) and N,N-diisopropylethylamine (87 μl, 500 μmol) were subsequently added. After stirring at room temperature for 15 minutes, (3R,4S)-3,4-difluoropyrrolidine hydrochloride (28.8 mg, 200 μmol) was added and the reaction mixture was stirred at room temperature overnight. The solvent was removed under reduced pressure, and the residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/water gradient). The fractions containing the product were concentrated under reduced pressure and 43.0 mg (57% possibility) of the title compound were obtained. LC-MS (Method 4): Rt = 0.86 min; MS (ESIpos): m /z = 449 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (1.82), -0.008 (15.01), 0.008 (13.66), 0.146 (1.71), 1655 (1.45), 1743 (1.71), 1982 (1.30), 2022 (2.03), 2031 (2.13), 2064 (1.35), 2099 (1.14), 2327 (1.92), 2366 (2.29), 2523 (6.13) (0.62) (1.04) (0.88) (1.14) (1.14) (4.05), 7,798 (1.92). Example 473 (5S)-5-[(3-Fluoroazetidin-1-yl)carbonyl]-2-[3-fluoro-4-(trifluoromethyl)benzyl]-5,6,7,8-tetrahydro[1, 2,4]triazolo[4,3-a]pyridin- 3(2H)-one

[01552] (5S)-2-[3-Fluoro-4-(trifluoromethyl)benzyl]-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[ 4,3-a]pyridine-5-carboxylic acid (60.0 mg, 167 μmol) was initially loaded into THF (2.0 mL), and HBTU (82.3 mg, 217 μmol) and N,N-diisopropylethylamine (87 μl, 500 μmol) were subsequently added. After stirring at room temperature for 15 minutes, 3-fluoroazetidine hydrochloride (22.4 mg, 200 μmol) was added and the reaction mixture was stirred at room temperature overnight. The solvent was removed under reduced pressure, and the residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/water gradient). The fractions containing the product were concentrated under reduced pressure and 29.0 mg (42% possibility) of the title compound were obtained. LC-MS (Method 4): Rt = 0.82 min; MS (ESIpos): m /z = 417 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (1.06), 0.146 (1.06), 1.674 (1.48), 1.698 ( 2.17), 1708 (2.70), 1723 (3.07), 1977 (2.12), 2019 (1.87), 2041 (1.87), 2086 (4.07), 2327 (1.23), 2366 (1.28), 2570 (3.04), 2595 ( 3.93), 2.609 (5.35), 2.622 (2.79), 2.637 (1.09), 2.651 (1.78), 2.665 (1.64), 2.710 (1.45), 3.908 (0.75), 3.935 (1.45), 3.964 (1.48), 3.995 ( 1.53), 4.023 (0.92), 4.176 (0.75), 4.230 (1.23), 4.243 (1.20), 4.258 (1.09), 4.276 (1.59), 4.306 (1.37), 4.330 (0.89), 4.367 (1.25), 4.400 ( 0.98), 4.434 (0.67), 4.463 (0.95), 4.515 (0.67), 4.528 (0.81), 4.565 (3.93), 4.578 (5.71), 4.590 (3.71), 4.654 (0.70), 4.689 (0.72), 4.706 ( 0.72), 4.732 (0.61), 4.954 (16.00), 5.354 (0.89), 5.408 (0.92), 5.498 (0.92), 5.551 (0.86), 7.252 (4.52), 7.272 (4.88), 7.303 (4.29), 7.332 ( 4.40), 7,757 (2.70), 7,776 (5.16), 7,796 (2.62). Example 474 (5S)-2-(2-Chloro-4-fluorobenzyl)-5-{[(3R,4S)-3,4-difluoropyrrolidin-1-yl]carbonyl}-5,6,7,8-tetra -hydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one

[01553] (5S)-2-(2-Chloro-4-fluorobenzyl)-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3 -a]pyridine-5-carboxylic acid (63.2 mg, 185 μmol) was initially loaded into THF (3.0 mL), and HBTU (91.4 mg, 241 μmol) and N,N-diisopropylethylamine (130 μl , 740 μmol) were subsequently added. After stirring at room temperature for 15 minutes, (3R,4S)-3,4-difluoropyrrolidine hydrochloride (31.9 mg, 222 μmol) was added and the reaction mixture was stirred at room temperature overnight. The solvent was removed under reduced pressure, and the residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/water gradient). The fractions containing the product were concentrated under reduced pressure and 70.0 mg (91% possibility) of the title compound were obtained. LC-MS (Method 3): Rt = 1.43 min; MS (ESIpos): m /z = 415 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (1.38), -0.008 (13.47), 0.008 (11.40), 0.146 (1.38) (1.67) (1.34) (1.05) (1.09) (1.12) (8.65) (1.34), 7,201 (1.30), 7,223 (6.33), 7,228 (6.73), 7,238 (9.38), 7,244 (8.36), 7,248 (9.81), 7,254 (6.91), 7,456 (5.36), 7,479 (5.57). Example 475 (5S)-2-(2-Chloro-4-fluorobenzyl)-5-{[(3S)-3-fluoropyrrolidin-1-yl]carbonyl}-5,6,7,8-tetrahydro[1 ,2,4]triazolo[4,3-a]pyridin-3(2H)-one

[01554] (5S)-2-(2-Chloro-4-fluorobenzyl)-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3 -a]pyridine-5-carboxylic acid (63.2 mg, 185 μmol) was initially loaded into THF (3.0 mL), and HBTU (91.4 mg, 241 μmol) and N,N-diisopropylethylamine (130 μl , 740 μmol) were subsequently added. After stirring at room temperature for 15 minutes, (3S)-3-fluoropyrrolidine hydrochloride (27.9 mg, 222 μmol) was added and the reaction mixture was stirred at room temperature overnight. The solvent was removed under reduced pressure, and the residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/water gradient). The fractions containing the product were concentrated under reduced pressure and 63.6 mg (86% possibility) of the title compound were obtained. LC-MS (Method 4): Rt = 0.73 min; MS (ESIpos): m /z = 397 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (1.33), -0.008 (11.31), 0.008 (10.12), 0.146 (1.33) (2.78) (1.59) (4.95) (2.30), 4,700 (2.78), 4,706 (2.92), 4,715 (2.30), 4,748 (2.87), 4,757 (3.31), 4,763 (3.76), 4,772 (2.74), 4,823 (3.40), 4,863 (16.00), 4,878 (8.71) (8.09), 7,248 (9.15), 7,274 (1.46), 7,456 (5.70), 7,462 (5.57), 7,478 (5.79), 7,483 (5.52). Example 476 (5S)-2-(2-Chloro-4-fluorobenzyl)-5-[(3-fluoroazetidin-1-yl)carbonyl]-5,6,7,8-tetrahydro[1,2,4 ]triazolo[4,3-a]pyridin-3(2H)-one

[01555] (5S)-2-(2-Chloro-4-fluorobenzyl)-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3 -a]pyridine-5-carboxylic acid (63.2 mg, 185 μmol) was initially loaded into THF (3.0 mL), and HBTU (91.4 mg, 241 μmol) and N,N-diisopropylethylamine (130 μl , 740 μmol) were subsequently added. After stirring at room temperature for 15 minutes, 3-fluoroazetidine hydrochloride (24.8 mg, 222 μmol) was added and the reaction mixture was stirred at room temperature overnight. The solvent was removed under reduced pressure, and the residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/water gradient). The fractions containing the product were concentrated under reduced pressure and 57.0 mg (73% possibility) of the title compound were obtained. LC-MS (Method 4): Rt = 0.70 min; MS (ESIpos): m /z = 383 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.008 (3.58), 0.008 (2.92), 1.688 (2.51), 1.712 ( 4.48), 1.721 (4.07), 1.964 (2.44), 1.975 (2.30), 2.008 (1.96), 2.019 (2.00), 2.030 (2.15), 2.073 (5.14), 2.327 (0.53), 2.366 (0.51), 2.523 ( 2.70), 2.581 (3.90), 2.595 (5.88), 2.609 (3.00), 2.624 (1.16), 2.638 (1.95), 2.651 (0.89), 2.670 (0.66), 2.709 (0.55), 3.898 (0.79), 3.927 ( 1.67), 3.958 (1.70), 3.991 (1.66), 4.018 (0.96), 4.157 (0.70), 4.171 (0.81), 4.187 (0.66), 4.223 (1.42), 4.239 (1.38), 4.252 (1.29), 4.274 ( 1.71), 4.302 (1.49), 4.334 (0.93), 4.362 (1.42), 4.394 (1.05), 4.431 (0.75), 4.456 (1.03), 4.506 (0.77), 4.520 (0.88), 4.548 (4.00), 4.560 ( 6.36), 4.573 (4.15), 4.600 (0.64), 4.635 (0.68), 4.649 (0.81), 4.687 (0.81), 4.702 (0.82), 4.728 (0.62), 4.834 (1.19), 4.874 (16.00), 4.884 ( 6.86), 4.925 (0.82), 5.353 (1.00), 5.406 (1.00), 5.496 (0.99), 5.549 (1.00), 7.202 (1.12), 7.224 (4.47), 7.242 (10.36), 7.258 (7.49), 7.279 ( 2.00), 7,455 (3.92), 7,461 (3.86), 7,477 (4.01), 7,483 (3.93). Example 477 (5S)-2-(2-Chloro-4-fluorobenzyl)-5-[(3,3-difluoropyrrolidin-1-yl)carbonyl]-5,6,7,8-tetrahydro[1,2 ,4]triazolo[4,3-a]pyridin-3(2H)-one

[01556] (5S)-2-(2-Chloro-4-fluorobenzyl)-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3 -a]pyridine-5-carboxylic acid (63.2 mg, 185 μmol) was initially loaded into THF (3.0 mL), and HBTU (91.4 mg, 241 μmol) and N,N-diisopropylethylamine (130 μl , 740 μmol) were subsequently added. After stirring at room temperature for 15 minutes, 3,3-difluoropyrrolidine hydrochloride (31.9 mg, 222 μmol) was added and the reaction mixture was stirred at room temperature overnight. The solvent was removed under reduced pressure, and the residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/water gradient). The fractions containing the product were concentrated under reduced pressure and 64.5 mg (84% possibility) of the title compound were obtained. LC-MS (Method 1): Rt = 1.09 min; MS (ESIpos): m /z = 415 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (1.75), -0.008 (14.84), 0.008 (12.90), 0.146 (1.55), 1675 (2.23), 1723 (2.91), 1911 (0.82), 2004 (3.30), 2012 (3.15), 2039 (2.57), 2073 (9.41), 2327 (2.33), 2366 (2.28), 2381 (1.89) (2.96) (4.27) (1.12) (2.67) (6.69), 7,478 (6.50), 7,484 (6.40). Example 478 (5S)-5-{[(3R)-3-Fluoropyrrolidin-1-yl]carbonyl}-2-{[3-fluoro-2-(trifluoromethyl)pyridin-4-yl]methyl}-5.6 ,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one

[01557] (5S)-2-{[3-Fluoro-2-(trifluoromethyl)pyridin-4-yl]methyl}-3-oxo-2,3,5,6,7,8-hexahydro[1 ,2,4]triazolo[4,3-a]pyridine-5-carboxylic acid (60.0 mg, 167 μmol) was initially loaded into THF (2.0 mL) at room temperature. Subsequently, HATU (82.3 mg, 217 μmol) and triethylamine (70 μl, 500 μmol) were added. After stirring for 15 minutes, (3R)-3-fluoropyrrolidine hydrochloride (25.1 mg, 200 μmol) was added and the reaction mixture was stirred at room temperature overnight. The reaction mixture was mixed with water and ethyl acetate. The organic phase was removed and the aqueous phase was extracted three times with ethyl acetate. The combined organic phases were washed with saturated aqueous sodium chloride solution, dried over sodium sulfate and filtered, and the filtrate was concentrated. The residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/gradient water). The fractions containing the product were concentrated under reduced pressure and 37.0 mg (52% possibility) of the title compound were obtained. LC-MS (Method 3): Rt = 1.31 min; MS (ESIpos): m /z = 432 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (0.80), -0.008 (12.00), 0.008 (8.00), 0.146 (0.80), 1655 (0.80), 1760 (0.80), 2016 (2.00), 2027 (1.60), 2072 (2.00), 2101 (0.80), 2128 (0.80), 2263 (0.40), 2324 (1.60), 2329 (2.40), 2.333 (1.60), 2.367 (2.00), 2.410 (0.40), 2.520 (16.00), 2.524 (14.00), 2.558 (2.80), 2.584 (1.60), 2.595 (1.20), 2.615 (1.20), 2.626 (2.00), 2638 (1.20), 2666 (2.40), 2671 (3.20), 2711 (2.00), 3136 (0.40), 3176 (0.80), 3209 (0.80), 3383 (3.20), 3458 (0.80), 3528 (2.00) (0.40) (0.40), 5.481 (0.40), 7.561 (2.00), 8.564 (2.80), 8.575 (2.80). Example 479 (5S)-2-{[3-Fluoro-2-(trifluoromethyl)pyridin-4-yl]methyl}-5-{[(3S)-3-hydroxypyrrolidin-1-yl]carbonyl}-5.6 ,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one

[01558] (5S)-2-{[3-Fluoro-2-(trifluoromethyl)pyridin-4-yl]methyl}-3-oxo-2,3,5,6,7,8-hexahydro[1 ,2,4]triazolo[4,3-a]pyridine-5-carboxylic acid (30.0 mg, 83.3 μmol) was initially loaded into THF (2.0 mL) at room temperature. Subsequently, HBTU (37.9 mg, 99.9 μmol) and N,N-diisopropylethylamine (44 μl, 250 μmol) were added. After stirring for 15 minutes, (3S)-pyrrolidin-3-ol (9.43 mg, 108 μmol) was added and the reaction mixture was stirred at room temperature overnight. The reaction mixture was mixed with water and ethyl acetate. The organic phase was removed and the aqueous phase was extracted three times with ethyl acetate. The combined organic phases were washed with saturated aqueous sodium chloride solution, dried over sodium sulfate and filtered, and the filtrate was concentrated. The residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/gradient water). The fractions containing the product were concentrated under reduced pressure and 17.0 mg (48% possibility) of the title compound were obtained. LC-MS (Method 3): Rt = 1.09 min; MS (ESIpos): m /z = 430 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (1.30), -0.008 (10.80), 0.008 (9.76), 0.146 (1.30) (3.90) (5.59) (1.56) (2.86) (2.34) (4.03), 7,554 (7.93), 7,567 (4.42), 8,562 (9.76), 8,573 (9.76). Example 480 (5S)-5-{[(3R,4S)-3,4-Difluoropyrrolidin-1-yl]carbonyl}-2-{[3-fluoro-2-(trifluoromethyl)pyridin-4-yl]methyl} -5,6,7,8-tetrahydro[1,2,4]triazolo[4,3- a]pyridin-3(2H)-one

[01559] (5S)-2-{[3-Fluoro-2-(trifluoromethyl)pyridin-4-yl]methyl}-3-oxo-2,3,5,6,7,8-hexahydro[1 ,2,4]triazolo[4,3-a]pyridine-5-carboxylic acid (1.19 g, 3.15 mmol) was initially loaded into THF (25 mL), and HBTU (1.55 g, 4. 09 mmol) and N,N-diisopropylethylamine (1.6 mL, 9.4 mmol) were subsequently added. After stirring at room temperature for 15 minutes, (3R,4S)-3,4-difluoropyrrolidine (371 mg, 3.46 mmol) was added and the reaction mixture was stirred at room temperature overnight. The solvent was removed under reduced pressure, and the residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/water gradient). The fractions containing the product were concentrated under reduced pressure and 1.04 g (73% possibility) of the title compound were obtained. LC-MS (Method 3): Rt = 1.37 min; MS (ESIpos): m /z = 450 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (0.54), -0.008 (6.70), 0.008 (4.70), 0.146 (0.62) (0.62) (0.79) (0.82) (0.84), 3930 (1.06), 3944 (1.19), 3960 (0.74), 3980 (1.14), 3995 (1.11), 4009 (0.72), 4022 (0.62), 4131 (0.69), 4146 (0.79), 4160 (0.79), 4.172 (1.21), 4.186 (0.91), 4.199 (0.74), 4.214 (0.67), 4.816 (3.24), 4.830 (4.23) (6.87) (1.21), 5.431 (0.89), 5.444 (0.87), 5.457 (0.99), 7.549 (2.67), 7.561 (4.33), 8.564 (5.98), 8.576 (5.76). Example 481 (5S)-2-{[3-Fluoro-2-(trifluoromethyl)pyridin-4-yl]methyl}-5-[(3-hydroxyazetidin-1-yl)carbonyl]-5,6,7,8 -tetrahydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one

[01560] (5S)-2-{[3-Fluoro-2-(trifluoromethyl)pyridin-4-yl]methyl}-3-oxo-2,3,5,6,7,8-hexahydro[1 ,2,4]triazolo[4,3-a]pyridine-5-carboxylic acid (30.0 mg, 83.3 μmol) was initially loaded into THF (2.0 mL) at room temperature. Subsequently, HBTU (41.1 mg, 108 μmol) and N,N-diisopropylethylamine (44 μl, 250 μmol) were added. After stirring for 15 minutes, azetidin-3-ol hydrochloride (10.9 mg, 99.9 μmol) was added and the reaction mixture was stirred at room temperature overnight. The reaction mixture was mixed with water and ethyl acetate. The organic phase was removed and the aqueous phase was extracted three times with ethyl acetate. The combined organic phases were washed with saturated aqueous sodium chloride solution, dried over sodium sulfate and filtered, and the filtrate was concentrated. The residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/gradient water). The fractions containing the product were concentrated under reduced pressure and the residue was purified via preparatory HPLC (Method 10). The fractions containing the product were concentrated under reduced pressure and 10.0 mg (29% possibility) of the title compound were obtained. LC-MS (Method 4): Rt = 0.61 min; MS (ESIpos): m /z = 416 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (1.83), -0.008 (16.00), 0.008 ( 13.26), 0.146 (1.74), 1.962 (0.46), 2.327 (2.74), 2.366 (2.56), 2.523 (9.05), 2.669 (2.65), 2.710 (2 .47), 3.187 (0.55), 4.046 (0.46), 4.523 (0.55), 4.550 (0.64), 5.063 (1.74), 7.561 (0.64), 8.559 (0. 64). Example 482 (5S)-5-[(3,3-Difluoropyrrolidin-1-yl)carbonyl]-2-{[3-fluoro-2-(trifluoromethyl)pyridin-4-yl]methyl}-5,6,7 ,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one

[01561] (5S)-2-{[3-Fluoro-2-(trifluoromethyl)pyridin-4-yl]methyl}-3-oxo-2,3,5,6,7,8-hexahydro[1 ,2,4]triazolo[4,3-a]pyridine-5-carboxylic acid (180 mg, 53% purity, 266 μmol) was initially loaded into THF (2.4 mL), and HBTU (263 mg, 692 μmol) and N,N-diisopropylethylamine (280 μl, 1.6 mmol) were subsequently added. After stirring at room temperature for 15 minutes, 3,3-difluoropyrrolidine hydrochloride (91.8 mg, 639 μmol) was added and the reaction mixture was stirred at room temperature overnight. The solvent was removed under reduced pressure, and the residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/water gradient). The fractions containing the product were concentrated under reduced pressure and 106 mg (89% possibility) of the title compound were obtained. LC-MS (Method 3): Rt = 1.45 min; MS (ESIpos): m /z = 450 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (0.81), 0.145 (0.69), 1.173 (1.04), 1.191 ( 0.75), 1,225 (2.76), 1,243 (13.73), 1,259 (16.00), 1,273 (7.74), 1,673 (2.04), 1,748 (2.50), 1,902 (0.95), 1,978 (1.38), 2.019 (3.08), 2.327 ( 1.53), 2.366 (1.87), 2.382 (1.96), 2.411 (2.36), 2.432 (2.45), 2.455 (2.22), 2.583 (4.23), 2.592 (4.12), 2.608 (4.37), 2.625 (4.72), 2.669 ( 2.62), 2.710 (0.92), 3.145 (1.27), 3.541 (2.53), 3.560 (3.91), 3.573 (2.13), 3.581 (2.16), 3.641 (1.29), 3.674 (2.27), 3.709 (2.50), 3.744 ( 1.64), 3.779 (2.91), 3.814 (4.20), 3.833 (1.21), 3.891 (1.21), 3.909 (2.42), 3.936 (1.76), 3.955 (0.83), 3.967 (0.78), 3.997 (1.61), 4.025 ( 1.12), 4.040 (1.41), 4.067 (0.86), 4.150 (0.83), 4.179 (1.41), 4.205 (1.50), 4.238 (0.55), 4.782 (2.13), 4.797 (2.88), 4.806 (2.07), 4.853 ( 2.07), 4,868 (2.73), 4,877 (2.13), 5,021 (1.44), 5,063 (13.32), 5,071 (14,39), 5,113 (1.53), 6,513 (0.89), 7,547 (4.03), 7,560 (7,63), 7,573 ( 4.20), 8.564 (8.86), 8.575 (8.72). Example 483 (5S)-5-[(3-Fluoroazetidin-1-yl)carbonyl]-2-{[3-fluoro-2-(trifluoromethyl)pyridin-4-yl]methyl}-5,6,7,8 -tetrahydro[1,2,4]triazolo[4,3- a]pyridin-3(2H)-one

[01562] (5S)-2-{[3-Fluoro-2-(trifluoromethyl)pyridin-4-yl]methyl}-3-oxo-2,3,5,6,7,8-hexahydro[1 ,2,4]triazolo[4,3-a]pyridine-5-carboxylic acid (30.0 mg, 83.3 μmol) was initially loaded into THF (2.0 mL), and HBTU (41.1 mg, 108 μmol) and N,N-diisopropylethylamine (44 μl, 250 μmol) were subsequently added. After stirring at room temperature for 15 minutes, 3-fluoroazetidine hydrochloride (11.1 mg, 99.9 μmol) was added and the reaction mixture was stirred at room temperature overnight. The solvent was removed under reduced pressure, and the residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/water gradient). The fractions containing the product were concentrated under reduced pressure and 15.0 mg (43% possibility) of the title compound were obtained. LC-MS (Method 4): Rt = 0.73 min; MS (ESIpos): m /z = 418 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.150 (0.74), -0.008 (7.63), 0.008 (6.07), 0.146 (0.74) (1.38) (0.82) (1.60), 4343 (0.93), 4371 (1.64), 4398 (1.12), 4432 (0.82), 4460 (1.04), 4516 (0.74), 4530 (0.89), 4572 (4.43), 4585 (6.55), 4597 (4.24) (1.00), 5,497 (1.04), 5,551 (1.04), 7,556 (4.09), 7,569 (7.74), 7,581 (4.28), 8,561 (6.96), 8,573 (7.00). Example 484 (5S)-5-{[(3S)-3-Fluoropyrrolidin-1-yl]carbonyl}-2-{[3-fluoro-2-(trifluoromethyl)pyridin-4-yl]methyl}-5.6 ,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one

[01563] (5S)-2-{[3-Fluoro-2-(trifluoromethyl)pyridin-4-yl]methyl}-3-oxo-2,3,5,6,7,8-hexahydro[1 ,2,4]triazolo[4,3-a]pyridine-5-carboxylic acid (180 mg, 53% purity, 266 μmol) was initially loaded into THF (2.4 mL), and HBTU (263 mg, 692 μmol) and N,N-diisopropylethylamine (280 μl, 1.6 mmol) were subsequently added. After stirring at room temperature for 15 minutes, (3S)-3-fluoropyrrolidine hydrochloride (80.3 mg, 639 μmol) was added and the reaction mixture was stirred at room temperature overnight. The solvent was removed under reduced pressure, and the residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/water gradient). The fractions containing the product were concentrated under reduced pressure and 98.9 mg (86% possibility) of the title compound were obtained. LC-MS (Method 3): Rt = 1.31 min; MS (ESIpos): m /z = 432 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (1.74), -0.008 (16.00), 0.008 (13.44), 0.146 (1.64) (1.74) (1.23) (0.62), 5,260 (0.82), 5,393 (1.03), 5,515 (0.62), 7,548 (1.54), 7,561 (3.08), 7,573 (1.74), 8,564 (3.69), 8,575 (3.69). Example 485 (5S)-2-{[3-Fluoro-2-(trifluoromethyl)pyridin-4-yl]methyl}-5-(1,3-thiazolidin-3-ylcarbonyl)-5,6,7,8- tetrahydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one

[01564] (5S)-2-{[3-Fluoro-2-(trifluoromethyl)pyridin-4-yl]methyl}-3-oxo-2,3,5,6,7,8-hexahydro[1 ,2,4]triazolo[4,3-a]pyridine-5-carboxylic acid (100 mg, 278 μmol) was initially loaded into THF (2.1 mL, 26 mmol), and HBTU (137 mg, 361 μmol) and N,N-diisopropylethylamine (150 μl, 830 μmol) were subsequently added. After stirring at room temperature for 15 minutes, 1,3-thiazolidine (29.7 mg, 333 μmol) was added and the reaction mixture was stirred at room temperature overnight. The solvent was removed under reduced pressure, and the residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/water gradient). The fractions containing the product were concentrated under reduced pressure and 61.0 mg (51% possibility) of the title compound were obtained. LC-MS (Method 3): Rt = 1.40 min; MS (ESIpos): m /z = 432 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (1.81), -0.008 (16.00), 0.008 (14.45), 0.146 (1.94) (3.48), 2.710 (2.71), 3.020 (1.42), 3.036 (0.77), 3.130 (0.90), 3.145 (1.81), 3.160 (1.03), 3.643 (0.52), 3.696 (0.52), 3.801 (0.52), 3.945 (0.52), 4374 (0.90), 4400 (1.16), 4556 (1.03), 4581 (0.90), 4614 (0.65), 4637 (0.77), 4811 (0.77), 4833 (0.65), 4904 (0.65), 4991 (0.52), 5.067 (3.35), 5.075 (3.61), 7.547 (0.90), 7.560 (1.81), 7.574 (0.90), 8.564 (2.06), 8.576 (2.06). Example 486 (5S)-2-(2,4-Difluorobenzyl)-5-[(3-fluoroazetidin-1-yl)carbonyl]-5,6,7,8-tetrahydro[1,2,4]triazole [4,3-a]pyridin-3(2H)-one

[01565] (5S)-2-(2,4-Difluorobenzyl)-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a ]pyridine-5-carboxylic acid (60.0 mg, 194 μmol) was initially loaded into THF (3.0 mL), and HBTU (95.6 mg, 252 μmol) and N,N-diisopropylethylamine (140 μl, 780 μmol) were subsequently added. After stirring at room temperature for 15 minutes, 3-fluoroazetidine hydrochloride (26.0 mg, 233 μmol) was added and the reaction mixture was stirred at room temperature overnight. The solvent was removed under reduced pressure, and the residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/water gradient). The fractions containing the product were concentrated under reduced pressure and 53.1 mg (75% possibility) of the title compound were obtained. LC-MS (Method 3): Rt = 1.22 min; MS (ESIpos): m /z = 367 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: 0.008 (2.45), 1.702 (7.00), 1.942 (3.26), 2.005 (2.78 ), 2.016 (2.91), 2.073 (5.89), 2.327 (0.68), 2.366 (0.55), 2.524 (5.41), 2.566 (6.11), 2.580 (8.21), 2.593 (4.09), 2.609 (1.51), 2.622 (2.63 ), 2.635 (1.12), 2.669 (0.79), 2.710 (0.61), 3.760 (0.96), 3.778 (0.79), 3.894 (1.12), 3.923 (2.21), 3.952 (2.34), 3.985 (2.23), 4.016 (1.34 ), 4.152 (0.98), 4.167 (1.09), 4.180 (0.90), 4.205 (1.25), 4.220 (2.01), 4.235 (1.97), 4.250 (2.15), 4.264 (2.34), 4.287 (2.30), 4.319 (1.99 ), 4.348 (1.44), 4.391 (1.40), 4.426 (1.03), 4.450 (1.36), 4.496 (1.09), 4.521 (5.41), 4.533 (8.38), 4.546 (5.32), 4.566 (1.23), 4.591 (0.79 ), 4.629 (0.96), 4.642 (1.12), 4.681 (1.07), 4.697 (1.07), 4.721 (0.88), 4.784 (2.28), 4.822 (16.00), 4.877 (1.42), 5.351 (1.40), 5.405 (1.38 ), 5,494 (1.36), 5,548 (1.38), 7,056 (2.78), 7,078 (6.02), 7,097 (3.37), 7,219 (2.93), 7,244 (5.67), 7,268 (3.02), 7,284 (2.85), 7,304 (5.87 ), 7,322 (5.60), 7,343 (2.34). Example 487 (5S)-2-(2,4-Difluorobenzyl)-5-[(3,3-difluoropyrrolidin-1-yl)carbonyl]-5,6,7,8-tetrahydro[1,2,4 ]triazolo[4,3-a]pyridin-3(2H)-one

[01566] (5S)-2-(2,4-Difluorobenzyl)-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a ]pyridine-5-carboxylic acid (60.0 mg, 194 μmol) was initially loaded into THF (3.0 mL), and HBTU (95.6 mg, 252 μmol) and N,N-diisopropylethylamine (140 μl, 780 μmol) were subsequently added. After stirring at room temperature for 15 minutes, 3,3-difluoropyrrolidine hydrochloride (33.4 mg, 233 μmol) was added and the reaction mixture was stirred at room temperature overnight. The solvent was removed under reduced pressure, and the residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/water gradient). The fractions containing the product were concentrated under reduced pressure and 68.6 mg (89% possibility) of the title compound were obtained. LC-MS (Method 3): Rt = 1.42 min; MS (ESIpos): m /z = 399 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.009 (7.97), 1.707 (3.42), 1.991 (3.13), 2.072 ( 3.13), 2.327 (1.65), 2.365 (1.99), 2.408 (2.33), 2.572 (6.04), 2.590 (6.43), 2.604 (3.99), 2.633 (1.94), 2.669 (1.77), 2.710 (1.77), 3.533 ( 2.85), 3.544 (4.10), 3.554 (4.38), 3.664 (2.56), 3.697 (2.96), 3.739 (1.59), 3.772 (3.53), 3.804 (5.52), 3.904 (2.90), 3.930 (2.05), 3.989 ( 1.77), 4,031 (1.59), 4,169 (1.59), 4,196 (1.65), 4,748 (3.19), 4,779 (2,79), 4,817 (16.00), 4,836 (14,92), 4,875 (2.85), 7,059 (2.51), 7,081 ( 5.47), 7.102 (2.96), 7.218 (3.19), 7.225 (3.07), 7.244 (5.01), 7.268 (3.36), 7.275 (5.07), 7.298 (6.21), 7.315 (5.98), 7.336 (2.62). Example 488 (5S)-2-(2,4-Difluorobenzyl)-5-{[(3S)-3-fluoropyrrolidin-1-yl]carbonyl}-5,6,7,8-tetrahydro[1,2 ,4]triazolo[4,3-a]pyridin-3(2H)-one

[01567] (5S)-2-(2,4-Difluorobenzyl)-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a ]pyridine-5-carboxylic acid (60.0 mg, 194 μmol) was initially loaded into THF (3.1 mL), and HBTU (95.6 mg, 252 μmol) and N,N-diisopropylethylamine (140 μl, 780 μmol) were subsequently added. After stirring at room temperature for 15 minutes, (3S)-3-fluoropyrrolidine hydrochloride (29.2 mg, 233 μmol) was added and the reaction mixture was stirred at room temperature overnight. The solvent was removed under reduced pressure, and the residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/water gradient). The fractions containing the product were concentrated under reduced pressure and 71.0 mg (96% possibility) of the title compound were obtained. LC-MS (Method 3): Rt = 1.26 min; MS (ESIpos): m /z = 381 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (0.47), -0.008 (4.61), 0.008 (3.24), 0.146 (0.44), 1244 (0.93), 1259 (0.88), 1274 (0.58), 1710 (5.63), 1721 (6.37), 1858 (1.32), 1869 (1.26), 1882 (1.15), 1892 (1.62), 1970 (1.59) (2.14) (4.01) (1.13) (1.70) (2.42) (4.78) (3.18) (6.37) (5.52), 7,302 (4.36), 7,314 (3.68), 7,318 (5.46), 7,335 (1.65), 7,340 (1.84). Example 489 (5S)-2-(2,4-Difluorobenzyl)-5-{[(3R,4S)-3,4-difluoropyrrolidin-1-yl]carbonyl}-5,6,7,8-tetrahydro [1,2,4]triazolo[4,3-a]pyridin-3(2H)-one

[01568] (5S)-2-(2,4-Difluorobenzyl)-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a ]pyridine-5-carboxylic acid (60.0 mg, 194 μmol) was initially loaded into THF (3.1 mL), and HBTU (95.6 mg, 252 μmol) and N,N-diisopropylethylamine (140 μl, 780 μmol) were subsequently added. After stirring at room temperature for 15 minutes, (3R,4S)-3,4-difluoropyrrolidine hydrochloride (33.4 mg, 233 μmol) was added and the reaction mixture was stirred at room temperature overnight. The solvent was removed under reduced pressure, and the residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/water gradient). The fractions containing the product were concentrated under reduced pressure and 70.3 mg (91% possibility) of the title compound were obtained. LC-MS (Method 3): Rt = 1.34 min; MS (ESIpos): m /z = 399 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (0.55), -0.008 (5.38), 0.008 (5.26), 0.146 (0.55), 1.021 (0.70), 1.038 (0.74), 1.409 (0.50), 1.637 (2.21), 1.661 (2.91), 1.670 (2.58), 1.697 (2.83), 1.709 (3.33), 1.718 (3.71) (3.08), 1909 (1.50), 1951 (2.82), 1959 (2.44), 1975 (1.85), 1997 (3.57), 2021 (2.24), 2032 (2.52) (2.19) (2.28) (2.00) (2.06) (0.81) (1.92) (9.35) (2.00) (2.16) (1.25) (4.75), 7,293 (4.41), 7,301 (4.41), 7,309 (3.89), 7,317 (4.60), 7,330 (1.78), 7,339 (1.81). Example 490 (5S)-5-[(3,3-Difluoropyrrolidin-1-yl)carbonyl]-2-(2,4,5-trifluorobenzyl)-5,6,7,8-tetrahydro[1,2 ,4]triazolo[4,3-a]pyridin-3(2H)-one

[01569] (5S)-3-Oxo-2-(2,4,5-trifluorobenzyl)-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3 -a]pyridine-5-carboxylic acid (50.0 mg, 153 μmol) was initially loaded into THF (3.0 mL), and HBTU (75.3 mg, 199 μmol) and N,N-diisopropylethylamine (80 μl , 460 μmol) were subsequently added. After stirring at room temperature for 15 minutes, 3,3-difluoropyrrolidine hydrochloride (26.3 mg, 183 μmol) was added and the reaction mixture was stirred at room temperature overnight. The solvent was removed under reduced pressure, and the residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/water gradient). The fractions containing the product were concentrated under reduced pressure and 34.2 mg (54% possibility) of the title compound were obtained. LC-MS (Method 3): Rt = 1.50 min; MS (ESIpos): m /z = 417 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (0.45), -0.008 (4.97), 0.007 (3.87), 0.146 (0.52) (2.32) (2.19) (1.48) (2.52) (2.06), 3951 (0.97), 3961 (0.97), 3990 (1.87), 4003 (0.90), 4018 (1.23), 4032 (1.68), 4061 (1.03), 4143 (1.10), 4175 (1.68), 4200 (1.68) (2.77), 7.285 (3.16), 7.307 (3.16), 7.312 (2.90), 7.329 (2.45), 7.540 (2.52), 7.556 (2.77), 7.566 (3.87), 7.582 (3.87), 7.591 (2.90), 7.607 (2.65). Example 491 (5S)-5-[(3-Fluoroazetidin-1-yl)carbonyl]-2-(2,4,5-trifluorobenzyl)-5,6,7,8-tetrahydro[1,2,4 ]triazolo[4,3-a]pyridin-3(2H)-one

[01570] (5S)-3-Oxo-2-(2,4,5-trifluorobenzyl)-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3 -a]pyridine-5-carboxylic acid (50.0 mg, 153 μmol) was initially loaded into THF (3.0 mL), and HBTU (75.3 mg, 199 μmol) and N,N-diisopropylethylamine (80 μl , 460 μmol) were subsequently added. After stirring at room temperature for 15 minutes, 3-fluoroazetidine hydrochloride (20.5 mg, 183 μmol) was added and the reaction mixture was stirred at room temperature overnight. The solvent was removed under reduced pressure, and the residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/water gradient). The fractions containing the product were concentrated under reduced pressure and 27.2 mg (46% possibility) of the title compound were obtained. LC-MS (Method 3): Rt = 1.31 min; MS (ESIpos): m /z = 385 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (1.49), -0.008 (13.66), 0.008 (11.22), 0.146 (1.44) (5.72) (2.03) (2.12) (0.77) (1.22), 5,550 (1.22), 7,272 (1.89), 7,297 (3.15), 7,315 (3.20), 7,339 (1.89), 7,539 (1.89), 7,564 (3.61), 7,581 (3.65), 7,606 (1.98). Example 492 (5S)-5-{[(3R,4S)-3,4-Difluoropyrrolidin-1-yl]carbonyl}-2-(2,4,5-trifluorobenzyl)-5,6,7,8-tetra -hydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one

[01571] (5S)-3-Oxo-2-(2,4,5-trifluorobenzyl)-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3 -a]pyridine-5-carboxylic acid (50.0 mg, 153 μmol) was initially loaded into THF (3.0 mL), and HBTU (75.3 mg, 199 μmol) and N,N-diisopropylethylamine (80 μl , 460 μmol) were subsequently added. After stirring at room temperature for 15 minutes, (3R,4S)-3,4-difluoropyrrolidine hydrochloride (26.3 mg, 183 μmol) was added and the reaction mixture was stirred at room temperature overnight. The solvent was removed under reduced pressure, and the residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/water gradient). The fractions containing the product were concentrated under reduced pressure and 29.0 mg (46% possibility) of the title compound were obtained. LC-MS (Method 3): Rt = 1.41 min; MS (ESIpos): m /z = 417 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (1.81), -0.008 (16.00), 0.008 (13.82), 0.146 (1.81) (2.11) (2.07) (0.56). Example 493 (5S)-5-{[(3S)-3-Fluoropyrrolidin-1-yl]carbonyl}-2-(2,4,5-trifluorobenzyl)-5,6,7,8-tetrahydro[1 ,2,4]triazolo[4,3-a]pyridin-3(2H)-one

[01572] (5S)-3-Oxo-2-(2,4,5-trifluorobenzyl)-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3 -a]pyridine-5-carboxylic acid (50.0 mg, 153 μmol) was initially loaded into THF (3.0 mL), and HBTU (75.3 mg, 199 μmol) and N,N-diisopropylethylamine (80 μl , 460 μmol) were subsequently added. After stirring at room temperature for 15 minutes, (3S)-3-fluoropyrrolidine hydrochloride (23.0 mg, 183 μmol) was added and the reaction mixture was stirred at room temperature overnight. The solvent was removed under reduced pressure, and the residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/water gradient). The fractions containing the product were concentrated under reduced pressure and 24.7 mg (41% possibility) of the title compound were obtained. LC-MS (Method 3): Rt = 1.35 min; MS (ESIpos): m /z = 399 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (1.39), 0.008 (10.78), 0.146 (1.39), 0.934 ( 0.70), 1.728 (4.52), 1.910 (1.57), 2.073 (4.35), 2.266 (1.91), 2.327 (4.35), 2.366 (4.52), 2.524 (16.00), 2.580 (2.96), 2.609 (4.35), 2.670 ( 4.52), 2.710 (4.17), 3.395 (1.57), 3.465 (1.04), 3.493 (1.39), 3.631 (4.70), 3.651 (3.83), 3.697 (1.91), 3.741 (3.30), 3.767 (2.78), 3.851 ( 4.17) 2.61), 5.510 (1.57), 7.263 (2.09), 7.284 (2.78), 7.306 (2.96), 7.329 (1.91), 7.540 (1.91), 7.565 (3.30), 7.582 (3.48), 7.607 (2.09). Example 494 (5S)-5-[(3-Fluoroazetidin-1-yl)carbonyl]-2-{[2-(trifluoromethyl)quinolin-4-yl]methyl}-5,6,7,8-tetrahydro [1,2,4]triazolo[4,3-a]pyridin-3(2H)-one

[01573] (5S)-3-Oxo-2-{[2-(trifluoromethyl)quinolin-4-yl]methyl}- 2,3,5,6,7,8-hexahydro[1,2,4 ]triazolo[4,3-a]pyridine-5-carboxylic acid (60.0 mg, 153 μmol) was initially loaded into THF (3.0 mL), and HBTU (69.6 mg, 184 μmol) and N, N-diisopropylethylamine (80 μl, 460 μmol) was subsequently added. After stirring at room temperature for 15 minutes, 3-fluoroazetidine hydrochloride (25.6 mg, 229 μmol) was added and the reaction mixture was stirred at room temperature for 6 days. The solvent was removed under reduced pressure, and the residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/water gradient). The fractions containing the product were concentrated under reduced pressure and 63.7 mg (93% possibility) of the title compound were obtained. LC-MS (Method 3): Rt = 1.50 min; MS (ESIpos): m /z = 450 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (1.76), -0.008 (16.00) 0.008 (14.24), 0.146 ( 1.92) .20) , 2,628 (1.44), 2,641 (2.24), 2,670 (4.16), 2,710 (4.00), 3,943 (1.28), 4,002 (1.60), 4,272 (1.92), 4,298 (1.60), 4,330 (1.44), 4,358 (0.96) , 4,407 (1.12), 4,472 (0.96), 4,524 (0.80), 4,608 (3.52), 4,620 (5.12), 4,632 (3.36), 5,356 (0.96), 5,04 (3.04), 5,463 (13.44), 5,472 (6,24) , 5,484 (5.44), 5,513 (1.44), 7,747 (9.12), 7,846 (3.52), 7,863 (2.40), 7,948 (3.84), 7,966 (5.92), 7,984 (3.36), 8,214 (7.04), 8,236 (6.08) , 8,368 (4.32), 8,389 (4.00). Example 495 (5S)-5-[(3-Hydroxyazetidin-1-yl)carbonyl]-2-{[2-(trifluoromethyl)quinolin-4-yl]methyl}-5,6,7,8-tetrahydro [1,2,4]triazolo[4,3-a]pyridin-3(2H)-one

[01574] (5S)-3-Oxo-2-{[2-(trifluoromethyl)quinolin-4-yl]methyl}- 2,3,5,6,7,8-hexahydro[1,2,4 ]triazolo[4,3-a]pyridine-5-carboxylic acid (60.0 mg, 153 μmol) was initially loaded into THF (3.0 mL), and HBTU (75.4 mg, 199 μmol) and N, N-diisopropylethylamine (80 μl, 460 μmol) was subsequently added. After stirring at room temperature for 15 minutes, azetidin-3-ol hydrochloride (20.1 mg, 184 μmol) was added and the reaction mixture was stirred at room temperature for 6 days. The solvent was removed under reduced pressure, and the residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/water gradient). The fractions containing the product were concentrated under reduced pressure and 41.4 mg (61% possibility) of the title compound were obtained. LC-MS (Method 3): Rt = 1.29 min; MS (ESIpos): m /z = 448 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (0.53), -0.008 (5.42), (3.35), 1.717 ( 4.41), 1.919 (2.45), (5.95), 1.966 (5.58), 1.998 (3.61), (1.65), 2.328 (1.17), 2.333 (0.90), (4.52), 2.594 (8.50), 2.605 (4.62), (1.65) , 4,115 (2.45), (2.39), 4,341 (2.50), 4,358 (4.20), (4.36), 4,518 (7.28), 4,533 (7.44), (7.71), 4,606 (3.35), 5,413 (2.23), 61 ( 13.50) .23), 7,966 (10.79), 7,984 (6.49), 8,214 (13.29), 8,235 (11.48), 8,363 (6.64), 8,373 (7.02), 8,384 (6.43), 8,394 (6.27). Example 496 (5S)-5-{[(3S)-3-Hydroxypyrrolidin-1-yl]carbonyl}-2-{[2-(trifluoromethyl)quinolin-4-yl]methyl}-5,6,7,8 -tetrahydro[1,2,4]triazolo[4,3- a]pyridin-3(2H)-one

[01575] (5S)-3-Oxo-2-{[2-(trifluoromethyl)quinolin-4-yl]methyl}- 2,3,5,6,7,8-hexahydro[1,2,4 ]triazolo[4,3-a]pyridine-5-carboxylic acid (60.0 mg, 153 μmol) was initially loaded into THF (3.0 mL, 37 mmol), and HBTU (75.4 mg, 199 μmol) and N,N-diisopropylethylamine (80 μl, 460 μmol) were subsequently added. After stirring at room temperature for 15 minutes, (3S)-pyrrolidin-3-ol hydrochloride (22.7 mg, 184 μmol) was added and the reaction mixture was stirred at room temperature for 6 days. The solvent was removed under reduced pressure, and the residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/water gradient). The fractions containing the product were concentrated under reduced pressure and 62.3 mg (88% possibility) of the title compound were obtained. LC-MS (Method 3): Rt = 1.31 min; MS (ESIpos): m /z = 462 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.008 (3.53), 0.008 (2.56), (1.13), 1.731 (2.20 ), 1.741 (2.13), (1.43), 1.894 (1.83), 1.905 (1.43), (2.23), 2.021 (2.63), 2.031 (2.56), (1.56), 2.073 (16.00), 2.328 (0.77), ( 4.56), 2.564 (1.66), 2.608 (2.89), (1.33), 2.665 (1.03), 2.670 (0.96), (0.60), 3.350 (2.69), 3.379 (2.23), (0.83), 3.453 (0.86), 3.465 (1.06), (0.90), 3.569 (1.53), 3.591 (0.93), (1.50), 3.692 (1.60), 4.276 (1.50), (1.43), 4.757 (1.53), 4.765 (1.23), (1.16) , 4.864 (0.47), 4.970 (2.10), (4.79), 5.479 (6.35), 5.520 (1.80), (1.86), 7.825 (1.53), 7.845 (3.29), (4.46), 7.984 (2.66), 8.213 ( 5.52), 79). Example 497 (5S)-5-{[(3R,4S)-3,4-Difluoropyrrolidin-1-yl]carbonyl}-2-{[2-(trifluoromethyl)quinolin-4-yl]methyl}-5,6 ,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one

[01576] (5S)-3-Oxo-2-{[2-(trifluoromethyl)quinolin-4-yl]methyl}- 2,3,5,6,7,8-hexahydro[1,2,4 ]triazolo[4,3-a]pyridine-5-carboxylic acid (60.0 mg, 153 μmol) was initially loaded into THF (3.0 mL), and HBTU (75.4 mg, 199 μmol) and N, N-diisopropylethylamine (80 μl, 460 μmol) was subsequently added. After stirring at room temperature for 15 minutes, (3R,4S)-3,4-difluoropyrrolidine hydrochloride (26.3 mg, 184 μmol) was added and the reaction mixture was stirred at room temperature for 6 days. The solvent was removed under reduced pressure, and the residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/water gradient). The fractions containing the product were concentrated under reduced pressure and 62.0 mg (84% possibility) of the title compound were obtained. LC-MS (Method 3): Rt = 1.60 min; MS (ESIpos): m /z = 482 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (1.71), -0.008 (16.00), 0.008 (11.82), 0.147 (1.50) (1.30) (3.89) (1.17) (2.92), 8,215 (6.35), 8,236 (5.31), 8,359 (2.80), 8,367 (3.17), 8,380 (2.76), 8,388 (2.97). Example 498 (5S)-2-{[6-Fluoro-2-(trifluoromethyl)quinolin-4-yl]methyl}-5-(pyrrolidin-1-ylcarbonyl)-5,6,7,8-tetrahydro[ 1,2,4]triazolo[4,3-a]pyridin-3(2H)-one

[01577] (5S)-2-{[6-Fluoro-2-(trifluoromethyl)quinolin-4-yl]methyl}-3-oxo-2,3,5,6,7,8-hexahydro[1 ,2,4]triazolo[4,3-a]pyridine-5-carboxylic acid (44.0 mg, 107 μmol) was initially loaded into THF (2.0 mL) at room temperature. Subsequently, HATU (53.0 mg, 139 μmol) and triethylamine (45 μl, 320 μmol) were added. After stirring for 15 minutes, pyrrolidine (11 μl, 130 μmol) was added and the reaction mixture was stirred at room temperature overnight. The reaction mixture was mixed with water and ethyl acetate. The organic phase was removed and the aqueous phase was extracted three times with ethyl acetate. The combined organic phases were washed with saturated aqueous sodium chloride solution, dried over sodium sulfate and filtered, and the filtrate was concentrated. The residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/gradient water). The fractions containing the product were concentrated under reduced pressure and 28.6 mg (58% possibility) of the title compound were obtained. LC-MS (Method 3): Rt = 1.65 min; MS (ESIpos): m /z = 464 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.150 (1.01), 0.146 (1.06), 1.668 (2.28), 1.719 ( 3.21), 1,764 (2,32), 1,781 (6.04), 1,799 (10.55), 1,816 (8.53), 1,833 (2.66), 1,899 (2.58), 1,916 (7,89), 1,933 (10,26), 1,949 (6,25), 1,966 ( 1.98), 2.012 (5.91), 2.022 (5.99), 2.035 (3.80), 2.327 (2.62), 2.366 (1.94), 2.569 (3.29), 2.596 (3.08), 2.606 (4.98), 2.618 (3.17), 2.636 ( 1.60), 2.647 (2.32), 2.669 (2.96), 2.709 (2.07), 3.234 (1.52), 3.251 (3.29), 3.263 (3.29), 3.280 (5.91), 3.333 (3.55), 3.351 (5.78), 3.368 ( 3.21), 3.380 (3.42), 3.398 (1.60), 3.438 (1.77), 3.456 (3.67), 3.480 (4.64), 3.497 (2.20), 3.612 (2.07), 3.628 (4.56), 3.645 (2.70), 3.653 ( 3.63), 3.670 (1.65), 4.797 (4.18), 4.811 (5.87), 4.820 (3.93), 5.374 (2.74), 5.415 (12.37), 5.434 (12.50), 5.475 (2.70), 7.797 (16.00), ( 2.53), 7.879 (2.79), 7.894 (4.18), 7.901 (4.69), 7.916 (3.00), 7.923 (3.04), 8.151 (4.98), 8.158 (5.15), 8.177 (5.11), 8.184 (5.02), 8.295 ( 4.69), 8.309 (4.90), 8.319 (4.73), 8.333 (4.43). Example 499 (5S)-5-[(3,3-Difluoroazetidin-1-yl)carbonyl]-2-{[3-(trifluoromethyl)-1,2,4-oxadiazol-5-yl]methyl}-5, 6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one

[01578] (5S)-3-Oxo-2-{[3-(trifluoromethyl)-1,2,4-oxadiazol-5-yl]methyl}- 2,3,5,6,7,8-hexa- hydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylic acid (85.0 mg, 82% purity, 209 μmol) was initially loaded into THF (3.0 mL), and HBTU (103 mg, 272 μmol) and N,N-diisopropylethylamine (110 μl, 630 μmol) were subsequently added. After stirring at room temperature for 15 minutes, 3,3-difluoroazetidine hydrochloride (32.5 mg, 251 μmol) was added and the reaction mixture was stirred at room temperature overnight. The solvent was removed under reduced pressure, and the residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/water gradient). The fractions containing the product were concentrated under reduced pressure and 46.8 mg (55% possibility) of the title compound were obtained. LC-MS (Method 4): Rt = 0.73 min; MS (ESIpos): m /z = 409 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.008 (3.49), 0.008 (2.81), 1.723 (2.72), 1.737 ( 3.89), 1.753 (2.88), 1.766 (1.17), 1.963 (1.10), 1.975 (1.10), 1.987 (1.10), 1.999 (1.76), 2.012 (1.52), 2.023 (0.68), 2.048 (0.75), 2.063 ( 1.38), 2.083 (1.48), 2.098 (1.38), 2.117 (0.80), 2.327 (0.63), 2.366 (0.84), 2.523 (1.99), 2.576 (0.82), 2.601 (1.90), 2.619 (3.02), 2.629 ( 2.08) 1.27), 4.620 (2.51), 4.635 (3.98), 4.648 (2.51), 4.727 (1.12), 4.758 (1.31), 4.787 (0.68), 4.803 (0.70), 4.835 (1.41), 4.863 (1.31), 5.392 ( 0.40), 5.437 (16.00), 5.481 (0.45). Example 500 (5S)-5-{[(3R,4S)-3,4-Difluoropyrrolidin-1-yl]carbonyl}-2-{[3-(trifluoromethyl)-1,2,4-oxadiazol-5-yl ]methyl}-5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one

[01579] (5S)-3-Oxo-2-{[3-(trifluoromethyl)-1,2,4-oxadiazol-5-yl]methyl}- 2,3,5,6,7,8-hexa- hydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylic acid (85.0 mg, 82% purity, 209 μmol) was initially loaded into THF (3.0 mL), and HBTU (103 mg, 272 μmol) and N,N-diisopropylethylamine (110 μl, 630 μmol) were subsequently added. After stirring at room temperature for 15 minutes, (3R,4S)-3,4-difluoropyrrolidine hydrochloride (36.0 mg, 251 μmol) was added and the reaction mixture was stirred at room temperature overnight. The solvent was removed under reduced pressure, and the residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/water gradient). The fractions containing the product were concentrated under reduced pressure and 49.1 mg (56% possibility) of the title compound were obtained. LC-MS (Method 4): Rt = 0.72 min; MS (ESIpos): m /z = 423 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (0.99), -0.008 (9.46), 0.008 (7.63), 0.146 (0.99) (2.09) (1.31) (1.41) (0.78) (4.55), 4,844 (3.61), 5,266 (1.25), 5,377 (2.14), 5,416 (16.00), 5,419 (13.91), 5,427 (10.88), 5,470 (1.78). Example 501 (5S)-5-[(3,3-Difluoropyrrolidin-1-yl)carbonyl]-2-{[3-(trifluoromethyl)-1,2,4-oxadiazol-5-yl]methyl}-5, 6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one

[01580] (5S)-3-Oxo-2-{[3-(trifluoromethyl)-1,2,4-oxadiazol-5-yl]methyl}- 2,3,5,6,7,8-hexa- hydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylic acid (85.0 mg, 82% purity, 209 μmol) was initially loaded into THF (3.0 mL), and HBTU (103 mg, 272 μmol) and N,N-diisopropylethylamine (110 μl, 630 μmol) were subsequently added. After stirring at room temperature for 15 minutes, 3,3-difluoropyrrolidine hydrochloride (36.0 mg, 251 μmol) was added and the reaction mixture was stirred at room temperature overnight. The solvent was removed under reduced pressure, and the residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/water gradient). The fractions containing the product were concentrated under reduced pressure and 69.8 mg (77% possibility) of the title compound were obtained. LC-MS (Method 3): Rt = 1.44 min; MS (ESIpos): m /z = 423 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (0.41), -0.008 (3.87), 0.008 (3.12), 0.146 (0.41) (1.01) (1.40) (1.03), 2710 (0.95), 3532 (2.57), 3551 (4.23), 3570 (2.05), 3637 (0.47), 3670 (1.52), 3704 (1.66), 3737 (1.50), 3768 (2.33), 3786 (1.36) (1.09) (1.70) (0.45). Example 502 (5S)-2-[(1RS)-1-(4-Methylphenyl)ethyl]-5-(pyrrolidin-1-ylcarbonyl)-5,6,7,8-tetrahydro[1,2,4 ]triazolo[4,3-a]pyridin-3(2H)-one (mixture of diastereomer, 2 isomers)

[01581] (5S)-2-[(1RS)-1-(4-Methylphenyl)ethyl]-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4] triazolo[4,3-a]pyridine-5-carboxylic acid (isomer 1) (58.0 mg, 192 μmol) was initially loaded into THF (2.3 mL) at room temperature. Subsequently, HBTU (94.9 mg, 250 μmol) and N,N-diisopropylethylamine (130 μl, 770 μmol) were added. After stirring for 15 minutes, pyrrolidine (19 μl, 230 μmol) was added and the reaction mixture was stirred at room temperature overnight. The reaction mixture was mixed with water and ethyl acetate. The organic phase was removed and the aqueous phase was extracted three times with ethyl acetate. The combined organic phases were washed with saturated aqueous sodium chloride solution, dried over sodium sulfate and filtered, and the filtrate was concentrated. The residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/gradient water). The fractions containing the product were concentrated under reduced pressure and 49.8 mg (73% possibility) of the title compound were obtained. LC-MS (Method 3): Rt = 1.46 min; MS (ESIpos): m /z = 355 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (1.79), -0.008 (16.00), 0.008 (13.92), 0.146 (1.84) (15.10) (1.04) (5.71), 7,160 (6.75), 7,180 (2.88). Example 503 (5S)-5-(1,3-Thiazolidin-3-ylcarbonyl)-2-{[6-(trifluoromethyl)pyridin-3-yl]methyl}-5,6,7,8-tetrahydro[ 1,2,4]triazolo[4,3-a]pyridin-3(2H)-one

[01582] (5S)-3-Oxo-2-{[6-(trifluoromethyl)pyridin-3-yl]methyl}-2,3,5,6,7,8-hexahydro[1,2,4 ]triazolo[4,3-a]pyridine-5-carboxylic acid (100 mg, 292 μmol) was initially loaded into THF (2.0 mL), and HBTU (144 mg, 380 μmol) and N,N-diisopropylethylamine ( 150 μl, 880 μmol) were subsequently added. After stirring at room temperature for 15 minutes, 1,3-thiazolidine (31.3 mg, 351 μmol) was added and the reaction mixture was stirred at room temperature overnight. The solvent was removed under reduced pressure, and the residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/water gradient). The fractions containing the product were concentrated under reduced pressure and 36.5 mg (30% possibility) of the title compound were obtained. LC-MS (Method 1): Rt = 0.97 min; MS (ESIpos): m /z = 414 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (0.48), -0.008 (3.99), 0.008 (4.42), 0.146 (0.48) (2.66) (2.21) (0.51) (1.88) (10.37), 5,058 (0.48), 7,910 (15.09), 7,913 (16.00), 8,642 (5.60). Example 504 (5S)-2-[(5-Bromopyridin-2-yl)methyl]-5-{[(3R,4S)-3,4-difluoropyrrolidin-1-yl]carbonyl}-5,6,7, 8-tetrahydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one

[01583] (5S)-2-[(5-Bromopyridin-2-yl)methyl]-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[ 4,3-a]pyridine-5-carboxylic acid (100 mg, 283 μmol) was initially loaded into THF (23 μl), and (3R,4S)-3,4-difluoropyrrolidine hydrochloride (48.8 mg, 340 μmol ) and (200 μl, 1.4 mmol) were added subsequently. After stirring at room temperature for 15 minutes, HBTU (140 mg, 368 μmol) was added and the reaction mixture was stirred at room temperature for 4 hours. The solvent was removed under reduced pressure, and the residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/water gradient). The fractions containing the product were concentrated under reduced pressure and 36.5 mg (30% possibility) of the title compound were obtained. LC-MS (Method 3): Rt = 0.97 min; MS (ESIpos): m /z = 442 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) delta [ppm]: -0.149 (1.70), -0.008 (12.77), 0.008 (16.00), 0.146 (1.62) (3.06) (0.68) (3.15). Example 505 (5S)-2-[(5-Chloropyridin-2-yl)methyl]-5-(1,3-thiazolidin-3-ylcarbonyl)-5,6,7,8-tetrahydro[1,2 ,4]triazolo[4,3-a]pyridin-3(2H)-one

[01584] (5S)-2-[(5-Chloropyridin-2-yl)methyl]-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[ 4,3-a]pyridine-5-carboxylic acid (100 mg, 324 μmol) was initially loaded into THF (2.0 mL), and HBTU (160 mg, 421 μmol) and N,N-diisopropylethylamine (170 μl, 970 μmol) were subsequently added. After stirring at room temperature for 15 minutes, 1,3-thiazolidine (34.7 mg, 389 μmol) was added and the reaction mixture was stirred at room temperature overnight. The solvent was removed under reduced pressure, and the residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/water gradient). The fractions containing the product were concentrated under reduced pressure and 45.0 mg (37% possibility) of the title compound were obtained. LC-MS (Method 3): Rt = 1.15 min; MS (ESIpos): m /z = 380 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.008 (2.72), 0.008 (2.67), 1.245 (0.93), 1.261 ( 1.57), 1.278 (0.76), 1.661 (0.95), 1.746 (1.42), 1.796 (0.77), 1.980 (0.76), 2.016 (1.80), 2.073 (1.11), 2.327 (0.55), 2.524 (1.84), 2.578 ( 2.03), 2.592 (2.04), 2.610 (2.62), 2.622 (1.51), 2.640 (0.63), 2.652 (0.92), 2.665 (0.84), 2.913 (0.50), 3.002 (1.47), 3.018 (3.08), 3.034 ( 1.74), 3.130 (2.02), 3.146 (4.22), 3.161 (2.18), 3.596 (0.43), 3.614 (0.67), 3.629 (0.91), 3.644 (1.14), 3.659 (0.60), 3.673 (0.63), 3.690 ( 1.14), 3.707 (0.71), 3.720 (0.60), 3.761 (0.51), 3.777 (0.94), 3.788 (0.91), 3.803 (1.24), 3.818 (0.61), 3.932 (0.60), 3.947 (1.19), 3.961 ( 0.83), 3.973 (0.92), 3.989 (0.43), 4.244 (0.93), 4.373 (1.89), 4.399 (2.43), 4.486 (0.45), 4.553 (2.48), 4.578 (1.94), 4.618 (1.41), 4.640 ( 1.72), 4.808 (1.68), 4.831 (1.34), 4.875 (1.22), 4.891 (1.45), 4.900 (1.35), 4.916 (16.00), 4.958 (1.10), 4.974 (1.11), 7.200 (4.68), 7.221 ( 5.05), 7,914 (4.06), 7,920 (4.18), 7,935 (3.90), 7,941 (4.01), 8,572 (4.54), 8,578 (4.62). Example 506 (5S)-2-[(5-Bromopyridin-3-yl)methyl]-5-{[(3R,4S)-3,4-difluoropyrrolidin-1-yl]carbonyl}-5,6,7, 8-tetrahydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one

[01585] (5S)-2-[(5-Bromopyridin-3-yl)methyl]-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[ 4,3-a]pyridine-5-carboxylic acid (100 mg, 283 μmol) was initially loaded into THF (1.7 mL), and HBTU (140 mg, 368 μmol) and N,N-diisopropylethylamine (250 μl, 1.4 mmol) were subsequently added. After stirring at room temperature for 15 minutes, (3R,4S)-3,4-difluoropyrrolidine hydrochloride (48.8 mg, 340 μmol) was added and the reaction mixture was stirred at room temperature overnight. The solvent was removed under reduced pressure, and the residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/water gradient). The fractions containing the product were concentrated under reduced pressure and 51.1 mg (41% possibility) of the title compound were obtained. LC-MS (Method 3): Rt = 1.19 min; MS (ESIpos): m /z = 442 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (0.64), -0.008 (5.43), 0.008 (5.61), 0.146 (0.67) (1.01) (1.22) (0.60) (0.71) (3.52), 8,446 (5.61), 8,450 (5.65), 8,639 (5.35), 8,644 (5.37). Example 507 (5S)-2-[(5-Chloro-3-Fluoropyridin-2-yl)methyl]-5-(1,3-thiazolidin-3-ylcarbonyl)-5,6,7,8-tetrahydro [1,2,4]triazolo[4,3-a]pyridin-3(2H)-one

[01586] (5S)-2-[(5-Chloro-3-fluoropyridin-2-yl)methyl]-3-oxo-2,3,5,6,7,8-hexahydro[1,2, 4]triazolo[4,3-a]pyridine-5-carboxylic acid (100 mg, 306 μmol) was initially loaded into THF (4.6 mL), and HBTU (139 mg, 367 μmol) and N,N-diisopropylethylamine (160 μl, 920 μmol) were subsequently added. After stirring at room temperature for 15 minutes, 1,3-thiazolidine (35.5 mg, 398 μmol) was added and the reaction mixture was stirred at room temperature for 72 hours. The solvent was removed under reduced pressure, and the residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/water gradient). The fractions containing the product were concentrated under reduced pressure and 40.0 mg (33% possibility) of the title compound were obtained. LC-MS (Method 3): Rt = 1.19 min; MS (ESIpos): m /z = 398 [M+H]+ ¹H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (1.06), -0.008 (9.48), 0.008 (8.72), 0.147 (1.06) (8.95) (8.27) (1.82) (2.35) (3.79), 4,900 (5.61), 4,905 (5.84), 4,939 (16.00), 4,943 (15.17), 4,991 (11,98), 5,030 (4,85), 8,42), 8,094 (8,95), 8,113 (8,87), 8,118 (8.95), 8,478 (9.33), 8,482 (9.25). Example 508 (5S)-2-[(5-Chloropyridin-2-yl)methyl]-5-{[(3S)-3-fluoropyrrolidin-1-yl]carbonyl}-5,6,7,8-tetra- hydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one

[01587] (5S)-2-[(5-Chloropyridin-2-yl)methyl]-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[ 4,3-a]pyridine-5-carboxylic acid (100 mg, 324 μmol) was initially loaded into THF (2.0 mL), and HBTU (160 mg, 421 μmol) and N,N-diisopropylethylamine (280 μl, 1.6 mmol) were subsequently added. After stirring at room temperature for 15 minutes, (3S)-3-fluoropyrrolidine hydrochloride (48.8 mg, 389 μmol) was added and the reaction mixture was stirred at room temperature overnight. The solvent was removed under reduced pressure, and the residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/water gradient). The fractions containing the product were concentrated under reduced pressure and 67.0 mg (54% possibility) of the title compound were obtained. LC-MS (Method 3): Rt = 1.06 min; MS (ESIpos): m /z = 380 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (0.82), -0.008 (6.88), 0.008 (6.28), 0.146 (0.82) (0.69) (1.03) (1.36) (2.11) (1.09), 5.944 (0.39), 7.200 (6.85), 7.221 (7.37), 7.913 (5.80), 7.920 (5.89), 7.934 (5.40), 7.941 (5.68), 8.572 (6.67), 8.578 (6.70). Example 509 (5S)-2-[(5-Bromopyridin-3-yl)methyl]-5-{[(3S)-3-fluoropyrrolidin-1-yl]carbonyl}-5,6,7,8-tetra- hydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one

[01588] (5S)-2-[(5-Bromopyridin-3-yl)methyl]-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[ 4,3-a]pyridine-5-carboxylic acid (100 mg, 283 μmol) was initially loaded into THF (1.7 mL), and HBTU (140 mg, 368 μmol) and N,N-diisopropylethylamine (250 μl, 1.4 mmol) were subsequently added. After stirring at room temperature for 15 minutes, (3S)-3-fluoropyrrolidine hydrochloride (42.7 mg, 340 μmol) was added and the reaction mixture was stirred at room temperature overnight. The solvent was removed under reduced pressure, and the residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/water gradient). The fractions containing the product were concentrated under reduced pressure and 42.7 mg (36% possibility) of the title compound were obtained. LC-MS (Method 3): Rt = 1.05 min; MS (ESIpos): m /z = 424 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (1.52), -0.008 (13.23), 0.008 (14.75), 0.146 (1.57) (1.63) (1.08) (1.46), 4,901 (16.00), 5,259 (1.25), 5,390 (1.63), 5,515 (0.87), 7,893 (4.99), 8,448 (5.91), 8,639 (4.72), 8,644 (4.99). Example 510 (5S)-2-[(5-Bromopyridin-2-yl)methyl]-5-{[(3S)-3-fluoropyrrolidin-1-yl]carbonyl}-5,6,7,8-tetra- hydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one

[01589] (5S)-2-[(5-Bromopyridin-2-yl)methyl]-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[ 4,3-a]pyridine-5-carboxylic acid (100 mg, 283 μmol) was initially loaded into THF (23 μl), and (3S)-3-fluoropyrrolidine hydrochloride (42.7 mg, 340 μmol) and (3S )-3-fluoropyrrolidine hydrochloride (200 μl, 1.4 mmol) was added subsequently. After stirring at room temperature for 15 minutes, HBTU (140 mg, 368 μmol) was added and the reaction mixture was stirred at room temperature for 4 hours. The solvent was removed under reduced pressure, and the residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/water gradient). The fractions containing the product were concentrated under reduced pressure and 56.0 mg (47% possibility) of the title compound were obtained. LC-MS (Method 3): Rt = 1.13 min; MS (ESIpos): m /z = 424 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (0.76), -0.008 (6.64), 0.008 (6.30), 0.146 (0.76) (1.19) (1.19) (3.68) (1.72) (11.27) (5.64), 8,648 (6.83), 8,654 (6.93). Example 511 (2S)-1-{[(5S)-3-Oxo-2-{[6-(trifluoromethyl)pyridin-3-yl]methyl}-2,3,5,6,7,8-hexa- hydro[1,2,4]triazolo[4,3-a]pyridin-5-yl]carbonyl}pyrrolidine-2-carbonitrile

[01590] (5S)-3-Oxo-2-{[6-(trifluoromethyl)pyridin-3-yl]methyl}-2,3,5,6,7,8-hexahydro[1,2,4 ]triazolo[4,3-a]pyridine-5-carboxylic acid (97.0 mg, 283 μmol) was initially loaded into THF (2.0 mL), and HBTU (140 mg, 368 μmol) and N,N- diisopropylethylamine (150 μl, 850 μmol) were subsequently added. After stirring at room temperature for 15 minutes, (2S)-pyrrolidine-2-carbonitrile hydrochloride (45.1 mg, 340 μmol) was added and the reaction mixture was stirred at room temperature overnight. The solvent was removed under reduced pressure, and the residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/water gradient). The fractions containing the product were concentrated under reduced pressure and 36.0 mg (30% possibility) of the title compound were obtained. LC-MS (Method 1): Rt = 0.97 min; MS (ESIpos): m /z = 421 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (1.50), 0.146 (1.50), 1.244 (1.05), 1.260 ( 1.05), 1.641 (1.50), 1.780 (1.64), 2.045 (4.49), 2.061 (6.88), 2.077 (5.98), 2.094 (2.99), 2.117 (2.54), 2.136 (2.39), 2.150 (2.99), 2.161 ( 2.54), 2.189 (1.35), 2.209 (2.99), 2.228 (2.84), 2.240 (1.79), 2.259 (1.50), 2.327 (3.89), 2.366 (2.84), 2.570 (3.29), 2.586 (2.39), 2.597 ( 2.39) 4.49), 4.830 (4.93), 4.847 (2.54), 4.971 (1.05), 5.011 (9.12), 5.021 (8.52), 5.061 (1.05), 7.915 (16.00), 8.642 (6.13). Example 512 (2S)-1-({(5S)-2-[(5-Chloropyridin-2-yl)methyl]-3-oxo-2,3,5,6,7,8-hexahydro[1 ,2,4]triazolo[4,3-a]pyridin-5-yl}carbonyl)pyrrolidine-2-carbonitrile

[01591] (5S)-2-[(5-Chloropyridin-2-yl)methyl]-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[ 4,3-a]pyridine-5-carboxylic acid (100 mg, 324 μmol) was initially loaded into THF (2.0 mL), and HBTU (160 mg, 421 μmol) and N,N-diisopropylethylamine (170 μl, 970 μmol) were subsequently added. After stirring at room temperature for 15 minutes, (2S)-pyrrolidine-2-carbonitrile (37.4 mg, 389 μmol) was added and the reaction mixture was stirred at room temperature for 72 hours. The solvent was removed under reduced pressure, and the residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/water gradient). The fractions containing the product were concentrated under reduced pressure and 31.0 mg (25% possibility) of the title compound were obtained. LC-MS (Method 3): Rt = 1.16 min; MS (ESIpos): m /z = 387 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (0.55), -0.008 (4.70), 0.008 (4.51), 0.146 (0.56), 1675 (0.88), 1791 (1.13), 2028 (1.26), 2047 (3.33), 2063 (4.78), 2079 (4.08), 2095 (1.90), 2106 (1.56), 2120 (1.82), 2130 (1.52) (0.96) (1.02) (1.88), 4.915 (16.00), 7.195 (4.32), 7.216 (4.66), 7.921 (3.06), 7.927 (3.05), 7.942 (2.91), 7.949 (2.99), 8.573 (3.80), 8.579 (3.82). Example 513 (2S)-1-({(5S)-2-[(3,5-Dichloropyridin-2-yl)methyl]-3-oxo-2,3,5,6,7,8-hexahydro [1,2,4]triazolo[4,3-a]pyridin-5-yl}carbonyl)pyrrolidine-2-carbonitrile

[01592] (5S)-2-[(3,5-Dichloropyridin-2-yl)methyl]-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4] triazolo[4,3-a]pyridine-5-carboxylic acid (70.0 mg, 204 μmol) was initially loaded into THF (1.7 mL), and HBTU (155 mg, 408 μmol) and N,N-diisopropylethylamine (140 μl, 820 μmol) were subsequently added. After stirring at room temperature for 15 minutes, (2S)-pyrrolidine-2-carbonitrile hydrochloride (40.6 mg, 306 μmol) was added and the reaction mixture was stirred at room temperature overnight. The solvent was removed under reduced pressure, and the residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/water gradient). The fractions containing the product were concentrated under reduced pressure and the residue was purified via preparatory HPLC (Method 10). The fractions containing the product were concentrated under reduced pressure and 7.50 mg (94% purity, 8% chance) of the title compound were obtained. LC-MS (Method 4): Rt = 0.70 min; MS (ESIpos): m /z = 421 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (1.95), -0.008 (16.00), 0.008 (15.18), 0.146 (1.88) (0.75) (2.51) (1.19), 5,004 (6.40), 5,018 (6.53), 5,058 (1.25), 8,251 (2.51), 8,256 (2.70), 8,566 (2.89), 8,572 (2.82). Example 514 (2S)-1-({(5S)-2-[(5-Chloro-3-fluoropyridin-2-yl)methyl]-3-oxo-2,3,5,6,7,8-hexa -hydro[1,2,4]triazolo[4,3-a]pyridin-5-yl}carbonyl)pyrrolidine-2-carbonitrile

[01593] (5S)-2-[(5-Chloro-3-fluoropyridin-2-yl)methyl]-3-oxo-2,3,5,6,7,8-hexahydro[1,2, 4]triazolo[4,3-a]pyridine-5-carboxylic acid (100 mg, 306 μmol) was initially loaded into THF (4.6 mL), and HBTU (139 mg, 367 μmol) and N,N-diisopropylethylamine (160 μl, 920 μmol) were subsequently added. After stirring at room temperature for 15 minutes, (2S)-pyrrolidine-2-carbonitrile (38.3 mg, 398 μmol) was added and the reaction mixture was stirred for 72 hours. The solvent was removed under reduced pressure, and the residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/water gradient). The fractions containing the product were concentrated under reduced pressure and 35.0 mg (28% possibility) of the title compound were obtained. LC-MS (Method 3): Rt = 1.19 min; MS (ESIpos): m /z = 405 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.008 (3.01), 0.008 (2.62), 1.247 (1.39), 1.264 ( 2.35), 1.281 (1.26), 1.655 (2.13), 1.746 (2.54), 1.757 (2.62), 1.772 (1.94), 1.982 (1.68), 2.001 (2.40), 2.017 (3.51), 2.025 (4.06), 2.046 ( 5.71), 2059 (9.52), 2078 (9.69), 2094 (5.49), 2104 (3.31), 2115 (3.01), 2129 (2.61), 2137 (3.62), 2149 (4.47), 2160 (3.59), 2176 ( 1.91), 2.182 (2.56), 2.202 (4.62), 2.214 (1.69), 2.221 (4.22), 2.234 (2.64), 2.241 (1.72), 2.253 (2.06), 2.274 (0.86), 2.287 (0.55), 2.328 ( 1.08), 2.567 (3.13), 2.584 (3.05), 2.597 (5.37), 2.610 (2.96), 2.627 (1.37), 2.639 (2.19), 2.651 (0.94), 2.665 (0.85), 2.670 (1.04), 3.502 ( 0.56), 3,521 (0.44), 3,670 (7.94), 3,687 (16.00), 3.703 (7.75), 4,739 (0.60), 4,783 (6,98), 4,786 (5,83), 4,793 (8.96), 4,802 (12,61), 4,812 ( 9.58) 3 ( 0.87), 7.101 (0.90), 7.229 (0.82), 8.090 (7.00), 8.095 (7.61), 8.114 (7.09), 8.118 (7.72), 8.480 (9.30), 8.483 (9.78). Example 515 (5S)-5-{[(3S)-3-Fluoropyrrolidin-1-yl]carbonyl}-2-{[5-(trifluoromethyl)pyridin-3-yl]methyl}-5,6,7,8 -tetrahydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one

[01594] (5S)-3-Oxo-2-{[5-(trifluoromethyl)pyridin-3-yl]methyl}-2,3,5,6,7,8-hexahydro[1,2,4 ]triazolo[4,3-a]pyridine-5-carboxylic acid (46.5 mg, 136 μmol) was initially loaded into THF (11 μl), and (3S)-3-fluoropyrrolidine hydrochloride (20.5 mg, 163 μmol) and (3S)-3-fluoropyrrolidine hydrochloride (95 μl, 680 μmol) were subsequently added. After stirring at room temperature for 15 minutes, HBTU (67.0 mg, 177 μmol) was added and the reaction mixture was stirred at room temperature overnight. The solvent was removed under reduced pressure, and the residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/water gradient). The fractions containing the product were concentrated under reduced pressure and the residue was purified via preparatory HPLC (Method 11). The fractions containing the product were concentrated under reduced pressure and 29.5 mg (53% possibility) of the title compound were obtained. LC-MS (Method 3): Rt = 1.16 min; MS (ESIpos): m /z = 414 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: 1.695 (1.26), 1.734 (2.23), 1.888 (0.52), 1.924 (0.76 ), 1.999 (0.84), 2.034 (1.38), 2.047 (1.33), 2.068 (1.37), 2.088 (1.85), 2.104 (2.27), 2.138 (1.59), 2.221 (0.85), 2.242 (0.78), 2.256 (0.80 ), 2.270 (1.14), 2.327 (0.56), 2.569 (1.57), 2.577 (1.70), 2.591 (1.48), 2.617 (2.57), 2.660 (1.13), 2.670 (0.97), 3.361 (1.30), 3.371 (1.17 ), 3.398 (1.01), 3.406 (0.99), 3.460 (0.64), 3.468 (0.71), 3.495 (0.89), 3.504 (0.86), 3.613 (0.59), 3.630 (2.11), 3.637 (2.26), 3.654 (2.41 ), 3,666 (1.56), 3,681 (1.50), 3,698 (1.11), 3,725 (1.28), 3,746 (1.94), 3,770 (1.64), 3,784 (1.49), 3,855 (2.48), 4,703 (1.17), 4,712 (1.42 ), 4,719 (1.49), 4,728 (1.18), 4,762 (1.50), 4,770 (1.68), 4,777 (1.93), 4,786 (1.45), 5,017 (16.00), 5,260 (1.25), 5,384 (1.52), 5,391 (1.57 ), 5,512 (0.89), 8,059 (5.28), 8,742 (5.83), 8,917 (5.45). Example 516 (5S)-5-{[(3S)-3-Fluoropyrrolidin-1-yl]carbonyl}-2-[2-(4-methylphenyl)-2-oxoethyl]-5,6,7,8-tetra -hydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one

[01595] (5S)-2-[2-(4-Methylphenyl)-2-oxoethyl]-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazole [4,3-a]pyridine-5-carboxylic acid (121 mg, 383 μmol) was initially loaded into THF (7.0 mL), and HBTU (189 mg, 498 μmol) and N,N-diisopropylethylamine (200 μl , 1.1 mmol) were subsequently added. After stirring at room temperature for 15 minutes, (3S)-3-fluoropyrrolidine hydrochloride (1:1) (57.7 mg, 459 μmol) was added and the reaction mixture was stirred at room temperature overnight. The solvent was removed under reduced pressure, and the residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/water gradient). The fractions containing the product were concentrated under reduced pressure and 77.3 mg (52% possibility) of the title compound were obtained. LC-MS (Method 3): Rt = 1.27 min; MS (ESIpos): m /z = 387 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (1.36), -0.008 (16.00), 0.008 (8.62), 0.146 (1.10) (1.89) (2.46), 7,378 (2.55), 7,908 (2.59), 7,927 (2.37). Example 517 (5S)-2-[2,2-Difluoro-2-(4-methylphenyl)ethyl]-5-{[(3S)-3-fluoropyrrolidin-1-yl]carbonyl}-5,6,7, 8-tetrahydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one

[01596] (5S)-5-{[(3S)-3-Fluoropyrrolidin-1-yl]carbonyl}-2-[2-(4-methylphenyl)-2-oxoethyl]-5,6,7,8- tetrahydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one (51.5 mg, 133 μmol) was dissolved in 1,2-dichloroethane (2.0 mL) and diethylamino sulfur trifluoride (1.0 mL, 90% purity, 6.8 mmol) and 1 drop of ethanol were added. The reaction mixture was stirred at 70°C for 3 hours. The reaction mixture was added dropwise to a saturated aqueous sodium hydrogen carbonate solution. Dichloromethane was added and the organic phase was removed. The organic phase was washed with saturated aqueous sodium chloride solution, dried over sodium sulfate and filtered, and the filtrate was concentrated. The residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/gradient water). The fractions containing the product were concentrated under reduced pressure and 16.8 mg (31% possibility) of the title compound were obtained. LC-MS (Method 3): Rt = 1.49 min; MS (ESIpos): m /z = 409 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: 0.007 (6.14), 1.148 (1.48), 1.729 (2.36), 2.084 (1.37 ), 2,347 (16.00), 2,365 (1.48), 2,568 (2.08), 2,608 (1.70), 2,669 (1.37), 2,710 (0.99), 3,615 (1.92), 3,640 (1.48), 3,726 (1.32), 3,750 (1.04 ), 3,839 (1.70), 4,275 (1.26), 4,315 (1.64), 4,658 (0.99), 4,716 (1.26), 5,383 (1.15), 7,288 (3.84), 7,308 (5.81), 7,393 (4.88), 7,413 (3.18 )

[01597] The following examples 518-546 were prepared as described in Example 517: Example 518 (5S)-2-{[3-Chloro-5-(trifluoromethyl)pyridin-2-yl]ethyl}-5-[( 3-fluoroazetidin-1-yl)carbonyl]-5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one

[01598] (5S)-2-{2-[3-Chloro-5-(trifluoromethyl)pyridin-2-yl]ethyl}-3-oxo-2,3,5,6,7,8-hexahydro [1,2,4]triazolo[4,3-a]pyridine-5-carboxylic acid (75.0 mg, 72% purity, 138 μmol) N,N-diisopropylethylamine (110 μl, 620 μmol), HBTU ( 99.6 mg, 263 μmol), 3-fluoroazetidine hydrochloride (1:1) (26.2 mg, 235 μmol). Stir at room temperature overnight. After purification, 44.1 mg (71% possibility) of the title compound were obtained. LC-MS (Method 3): Rt = 1.43 min; MS (ESIpos): m /z = 448 [M+H]+1H- NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (3.72), 0.146 (3.72), 1.707 (9.96), 1.931 ( 3.82), 1992 (4.03), 2072 (3.02), 2327 (5.53), 2366 (4.03), 2584 (7.95), 2625 (2.72), 2669 (5.53), 2709 (3.52), 3283 (11.07), 3910 ( 2.92), 4.024 (5.94), 4.041 (13.08), 4.059 (9.96), 4.235 (3.62), 4.324 (2.72), 4.441 (6.14), 4.454 (9.86), 4.468 (6.44), 4.658 (1.81), 5.385 ( 1.81), 5,517 (1.81), 8,413 (16.00), 8,876 (14.79). Example 519 (5S)-5-[(3,3-Difluoropyrrolidin-1-yl)carbonyl]-2-[2-(4-fluorophenyl)ethyl]-5,6,7,8-tetrahydro[1, 2,4]triazolo[4,3-a]pyridin-3(2H)-one

[01599] (5S)-2-[2-(4-Fluorophenyl)ethyl]-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4, 3-a]pyridine-5-carboxylic acid (73.1 mg, 240 μmol) N,N-diisopropylethylamine (130 μl, 720 μmol), HBTU (118 mg, 311 μmol), 3,3-difluoropyrrolidine hydrochloride (1: 1) (41.3 mg, 287 μmol). Stir at room temperature for 72 hours. After purification, 53.2 mg (56% possibility) of the title compound were obtained. LC-MS (Method 3): Rt = 1.48 min; MS (ESIpos): m /z = 395 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: 0.008 (2.61), 1.683 (1.93), 1.709 (3.74), 1.891 (1.36 ), 1,971 (3.06), 2,011 (1.82), 2,026 (1.70), 2,037 (1.82), 2,328 (1.93), 2,353 (0.68), 2,367 (2.16), 2,400 (1.59), 2,523 (7.72), 2,567 (4.43 ), 2,576 (4.99), 2,591 (3.40), 2,604 (2.50), 2,616 (4.31), 2,660 (2.16), 2,670 (2.84), 2,710 (1.70), 2,895 (5.90), 2,914 (12.26), 2,932 (6.47 ), 3.518 (3.29), 3.538 (5.22), 3.557 (2.50), 3.623 (0.68), 3.658 (1.93), 3.691 (2.16), 3.721 (1.48), 3.751 (4.20), 3.767 (5.56), 3.785 (13.39 ), 3.803 (10.55), 3.822 (3.86), 3.838 (2.04), 3.857 (1.13), 3.882 (2.27), 3.909 (1.70), 3.928 (0.79), 3.949 (0.68), 3.979 (1.48), 4.008 (1.02 ), 4.020 (1.36), 4.050 (0.79), 4.115 (0.79), 4.147 (1.36), 4.174 (1.36), 4.204 (0.57), 4.668 (1.82), 4.683 (2.61), 4.693 (1.82), 4.744 (1.93 ), 4,759 (2.61), 4,769 (1.82), 7,062 (7.15), 7,085 (16.00), 7,107 (10.33), 7,203 (8.74), 7,217 (9.87), 7,225 (8.17), 7,239 (6.70). Example 520 (5S)-5-[(3-Fluoroazetidin-1-yl)carbonyl]-2-[2-(4-fluorophenyl)ethyl]-5,6,7,8-tetrahydro[1,2, 4]triazolo[4,3-a]pyridin-3(2H)-one

[01600] (5S)-2-[2-(4-Fluorophenyl)ethyl]-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3- a]pyridine-5-carboxylic acid (73.1 mg, 240 µmol) N,N-diisopropylethylamine (130 µl, 720 µmol), HBTU (118 mg, 311 µmol), 3-fluoroazetidine hydrochloride (1:1) (32 .1 mg, 287 µmol). Stir at room temperature for 72 hours. After purification, 37.7 mg (43% possibility) of the title compound were obtained. LC-MS (Method 3): Rt = 1.49 min; MS (ESIpos): m /z = 363 [M+H]+ ¹H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (2.06), -0.008 (15.54), 0.008 (16.00), 0.146 (2.06) (1.83) (4.00) (0.57), 5,520 (0.57), 7,064 (2.29), 7,085 (5.03), 7,106 (3.09), 7,223 (4.00). Example 521 (5S)-2-[2-(4-Methylphenyl)ethyl]-5-(pyrrolidin-1-ylcarbonyl)-5,6,7,8-tetrahydro[1,2,4]triazolo[4, 3-a]pyridin-3(2H)-one

[01601] (5S)-2-[2-(4-Methylphenyl)ethyl]-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4, 3-a]pyridine-5-carboxylic acid (200 mg, 664 μmol), N,N-diisopropylethylamine (460 μl, 2.7 mmol), HBTU (327 mg, 863 μmol), pyrrolidine (66 μl, 800 μmol) . Stir at room temperature overnight. After purification, 163 mg (69% possibility) of the title compound were obtained. LC-MS (Method 3): Rt = 1.45 min; MS (ESIpos): m /z = 355 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.008 (1.86), 0.008 (1.55), 1.703 (0.76), 1.714 ( 1.01), 1.733 (0.71), 1.746 (0.55), 1.764 (1.00), 1.781 (1.71), 1.798 (1.34), 1.815 (0.41), 1.883 (0.41), 1.900 (1.27), 1.916 (1.67), 1.933 ( 1.07), 1.951 (0.54), 1.962 (0.61), 1.973 (0.54), 1.982 (0.43), 1.997 (0.44), 2.018 (0.40), 2.257 (9.36), 2.560 (0.68), 2.580 (0.44), 2.602 ( 0.42), 2.613 (0.87), 2.626 (0.44), 2.848 (1.00), 2.868 (1.97), 2.887 (1.03), 3.233 (0.51), 3.246 (0.52), 3.263 (0.91), 3.280 (0.45), 3.328 ( 1.08), 3.346 (0.51), 3.357 (0.53), 3.440 (0.58), 3.447 (0.42), 3.465 (0.74), 3.589 (0.70), 3.606 (0.41), 3.613 (0.54), 3.729 (0.62), 3.748 ( 0.95), 3.758 (0.65), 3.766 (0.59), 3.777 (0.97), 3.797 (0.54), 4.659 (0.65), 4.669 (0.75), 4.675 (0.88), 4.684 (0.64), 7.085 (16.00). Example 522 (5S)-5-{[(3R,4S)-3,4-Difluoropyrrolidin-1-yl]carbonyl}-2-[2-(4-methoxyphenyl)ethyl]-5,6,7,8- tetrahydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one

[01602] (5S)-2-[2-(4-Methoxyphenyl)ethyl]-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4, 3-a]pyridine-5-carboxylic acid (92.0 mg, 290 μmol), N,N-diisopropylethylamine (150 μl, 870 μmol), HBTU (143 mg, 377 μmol), (3R,4S)-3, 4-difluoropyrrolidine hydrochloride (49.9 mg, 348 μmol). Stir at room temperature for 72 hours. After purification, 71.1 mg (60% possibility) of the title compound were obtained. LC-MS (Method 4): Rt = 0.72 min; MS (ESIpos): m /z = 407 [M+H]+ [ppm]: 1.680 (0.47), 1.704 (0.90), (0.47), 1.976 (0.55), 1.986 (0.65), (0.42), 2.028 ( 0.46), 2.036 (0.44), (0.77), 2.575 (0.79), 2.586 (0.63), (0.51), 2.830 (1.48), 2.848 (2.93), (0.42), 3.509 (0.44), 3.532 (0.49), (16.00) ), 7,104 (2.47), 7,116 (1.95), 7,125 (2.09). Example 523 (5S)-5-[(3,3-Difluoroazetidin-1-yl)carbonyl]-2-[2-(4-methoxyphenyl)ethyl]-5,6,7,8-tetrahydro[1, 2,4]triazolo[4,3-a]pyridin-3(2H)-one

[01603] (5S)-2-[2-(4-Methoxyphenyl)ethyl]-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4, 3-a]pyridine-5-carboxylic acid (92.0 mg, 290 μmol), N,N-diisopropylethylamine (150 μl, 870 μmol), HBTU (143 mg, 377 μmol), 3,3-difluoroazetidine hydrochloride (45 .1 mg, 348 μmol). Stir at room temperature for 72 hours. After purification, 64.5 mg (57% possibility) of the title compound were obtained. LC-MS (Method 3): Rt = 1.46 min; MS (ESIpos): m /z = 393 [M+H]+ ¹H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.008 (0.90), 0.008 (0.75), 1.711 (0.65), 1.726 ( 1.00), 1.738 (0.92), 1.749 (0.63), 1.960 (0.54), 1.971 (0.50), 2.016 (0.41), 2.028 (0.40), 2.037 (0.48), 2.569 (0.65), 2.589 (0.83), 2.605 ( 0.98), 2.618 (1.19), 2.632 (0.57), 2.835 (1.24), 2.854 (2.48), 2.872 (1.35), 3.713 (16.00), 3.743 (0.87), 3.750 (0.92), 3.760 (1.69), 3.770 ( 1.68), 3.779 (0.83), 3.789 (0.76), 4.342 (0.64), 4.357 (0.64), 4.501 (0.86), 4.515 (1.44), 4.528 (0.85), 4.700 (0.45), 4.807 (0.43), 6.825 ( 3.10), 6,847 (3.66), 6,854 (0.44), 7,102 (3.30), 7,123 (2.85). Example 524 (5S)-5-[(3,3-Difluoropyrrolidin-1-yl)carbonyl]-2-{[1-(4-methylphenyl)cyclopropyl]methyl}-5,6,7,8-tetrahydro [1,2,4]triazolo[4,3-a]pyridin- 3(2H)-one

[01604] (5S)-2-{[1-(4-Methylphenyl)cyclopropyl]methyl}-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazole [4,3-a]pyridine-5-carboxylic acid (45.0 mg, 137 μmol), N,N-diisopropylethylamine (72 μl, 410 μmol), HBTU (67.8 mg, 179 μmol), 3.3 -difluoropyrrolidine hydrochloride (23.7 mg, 165 μmol). Stir at room temperature overnight. After purification, 27.3 mg (48% possibility) of the title compound were obtained. LC-MS (Method 3): Rt = 1.72 min; MS (ESIpos): m /z = 417 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.008 (2.67), 0.008 (2.32), 0.677 (0.52), 0.687 ( 0.71), 0.702 (1.17), 0.713 (1.14), 0.720 (0.89), 0.786 (1.23), 0.796 (1.02), 0.811 (0.74), 0.821 (0.61), 0.921 (0.53), 0.931 (0.55), 0.945 ( 1.24), 0.955 (1.62), 0.966 (2.20), 0.974 (1.56), 0.988 (1.08), 0.998 (0.49), 1.662 (0.70), 1.688 (1.08), 1.958 (0.93), 1.972 (0.93), 1.985 ( 0.91), 2.012 (0.58), 2.022 (0.44), 2.073 (1.06), 2.235 (16.00), 2.327 (0.53), 2.366 (0.85), 2.393 (0.59), 2.416 (0.56), 2.435 (0.42), 2.467 ( 0.58), 2.523 (2.70), 2.566 (1.36), 2.580 (1.61), 2.622 (0.61), 2.669 (0.58), 2.710 (0.45), 3.509 (0.99), 3.528 (1.58), 3.549 (0.71), 3.644 ( 1.67), 3.649 (1.91), 3.680 (2.35), 3.685 (2.14), 3.712 (0.55), 3.744 (1.27), 3.772 (1.06), 3.869 (0.74), 3.895 (0.58), 3.915 (1.88), 3.922 ( 1.67), 3.951 (1.38), 3.958 (1.74), 4.000 (0.47), 4.133 (0.47), 4.159 (0.42), 4.657 (0.64), 4.671 (0.88), 4.681 (0.62), 4.731 (0.67), 4.747 ( 0.85), 4.756 (0.62), 7.025 (3.25), 7.045 (5.44), 7.105 (6.96), 7.125 (4.16). Example 525 (5S)-5-{[(3S)-3-Hydroxypyrrolidin-1-yl]carbonyl}-2-{[1-(4-methylphenyl)cyclopropyl]methyl}-5,6,7,8-tetra -hydro[1,2,4]triazolo[4,3-a]pyridin- 3(2H)-one

[01605] (5S)-2-{[1-(4-Methylphenyl)cyclopropyl]methyl}-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazole [4,3-a]pyridine-5-carboxylic acid (45.0 mg, 137 μmol), N,N-diisopropylethylamine (72 μl, 410 μmol), HBTU (67.8 mg, 179 μmol), (3S) -pyrrolidin-3-ol hydrochloride (1:1) (20.4 mg, 165 μmol). Stir at room temperature overnight. After purification, 24.4 mg (45% possibility) of the title compound were obtained. LC-MS (Method 4): Rt = 0.74 min; MS (ESIpos): m /z = 397 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.008 (2.87), 0.008 (2.23), 0.683 (0.77), 0.706 ( 1.23), 0.786 (1.29), 0.809 (0.80), 0.820 (0.58), 0.921 (0.45), 0.933 (0.56), 0.944 (1.00), 0.956 (1.70), 0.966 (2.06), 0.992 (0.79), 1.387 ( 0.55), 1.692 (1.47), 1.703 (1.54), 1.752 (0.58), 1.762 (0.51), 1.831 (0.77), 1.842 (0.86), 1.853 (0.73), 1.863 (0.91), 1.874 (0.74), 1.930 ( 0.79), 1.964 (1.45), 1.975 (1.42), 1.987 (1.40), 1.997 (0.95), 2.013 (0.66), 2.072 (1.15), 2.236 (16.00), 2.327 (0.57), 2.366 (0.53), 2.447 ( 0.64), 2464 (0.80), 2523 (1.85), 2565 (0.86), 2577 (1.36), 2619 (0.60), 2669 (0.51), 2709 (0.44), 3243 (0.42), 3276 (2.35), 3287 ( 2.17), 3.297 (1.50), 3.404 (1.13), 3.413 (0.96), 3.427 (0.92), 3.434 (1.00), 3.456 (0.55), 3.464 (0.45), 3.528 (0.58), 3.549 (0.45), 3.606 ( 0.87), 3.617 (1.32), 3.634 (3.12), 3.644 (1.09), 3.671 (2.81), 3.918 (1.76), 3.928 (1.40), 3.954 (1.38), 3.964 (1.11), 4.251 (0.78), 4.349 ( 0.85), 4.591 (0.77), 4.599 (0.88), 4.606 (0.95), 4.614 (0.77), 4.633 (0.63), 4.647 (0.81), 4.656 (0.57), 7.026 (3.04), 7.046 (4.91), 7.106 ( 4.38), 7.112 (4.57), 7.126 (2.87), 7.132 (2.62). Example 526 (5S)-5-{[(3S)-3-Fluoropyrrolidin-1-yl]carbonyl}-2-{[1-(4-methylphenyl)cyclopropyl]methyl}-5,6,7,8-tetra -hydro[1,2,4]triazolo[4,3-a]pyridin- 3(2H)-one

[01606] (5S)-2-{[1-(4-Methylphenyl)cyclopropyl]methyl}-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazole [4,3-a]pyridine-5-carboxylic acid (45.0 mg, 137 μmol), N,N-diisopropylethylamine (72 μl, 410 μmol), HBTU (67.8 mg, 179 μmol), (3S) -3-fluoropyrrolidine hydrochloride (20.7 mg, 165 μmol). Stir at room temperature overnight. After purification, 21.6 mg (39% possibility) of the title compound were obtained. LC-MS (Method 3): Rt = 1.58 min; MS (ESIpos): m /z = 399 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (0.60), -0.008 (5.27), 0.008 (4.23), 0.146 (0.55) (1.54) (1.07) (1.80) (1.23) (0.63), 5,499 (0.44), 7,026 (2.90), 7,046 (4.72), 7,102 (3.47), 7,108 (4.33), 7,123 (2.35), 7,128 (2.45). Example 527 (5S)-5-[(3-Fluoroazetidin-1-yl)carbonyl]-2-({1-[4-(trifluoromethyl)phenyl]cyclopropyl}methyl)-5,6,7,8-tetra- hydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one

[01607] (5S)-3-Oxo-2-({1-[4-(trifluoromethyl)phenyl]cyclopropyl}methyl)- 2,3,5,6,7,8-hexahydro[1,2, 4]triazolo[4,3-a]pyridine-5-carboxylic acid (57.4 mg, 151 μmol), N,N-diisopropyethylamine (79 μl, 450 μmol), HBTU (74.2 mg, 196 μmol), 3-fluoroazetidine hydrochloride (20.1 mg, 181 μmol). Stir at room temperature overnight. After purification, 37.9 mg (57% possibility) of the title compound were obtained. LC-MS (Method 4): Rt = 0.92 min; MS (ESIpos): m /z = 439 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (1.76), -0.008 (16.00), 0.008 (14.16), 0.146 (1.84) (2.85) (1.34) (0.75) (10.05), 7,592 (7.71). Example 528 (5S)-5-{[(3S)-3-Fluoropyrrolidin-1-yl]carbonyl}-2-{[1-(4-methoxyphenyl)cyclopropyl]methyl}-5,6,7,8-tetra -hydro[1,2,4]triazolo[4,3- a]pyridin-3(2H)-one

[01608] (5S)-2-{[1-(4-Methoxyphenyl)cyclopropyl]methyl}-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazole [4,3-a]pyridine-5-carboxylic acid (93.2 mg, 50% purity, 136 μmol), N,N-diisopropylethylamine (140 μl, 810 μmol), HBTU (134 mg, 353 μmol), (3S)-3-fluoropyrrolidine hydrochloride (1:1) (20.4 mg, 163 μmol). Stir at room temperature overnight. After purification, 42.9 mg (76% possibility) of the title compound were obtained. LC-MS (Method 4): Rt = 0.79 min; MS (ESIpos): m /z = 415 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.008 (1.55), 0.008 (1.21), 0.659 (0.47), 0.676 ( 0.69), 0.686 (0.80), 0.756 (0.77), 0.780 (0.43), 0.922 (0.63), 0.940 (1.59), 1.712 (1.04), 1.987 (0.54), 1.997 (0.67), 2.009 (0.56), 2.021 ( 0.47), 2.035 (0.49), 2.050 (0.46), 2.073 (7.98), 2.523 (1.28), 2.591 (0.77), 3.282 (0.42), 3.613 (1.24), 3.621 (1.22), 3.636 (0.59), 3.649 ( 1.32), 3.657 (1.14), 3.702 (16.00), 3.736 (0.53), 3.821 (0.80), 3.862 (0.89), 3.881 (1.07), 3.898 (0.68), 3.918 (0.80), 4.598 (0.45), 4.605 ( 0.46), 4.647 (0.48), 4.662 (0.62), 4.670 (0.45), 6.777 (2.71), 6.798 (2.98), 7.123 (1.91), 7.130 (2.47), 7.145 (1.88), 7.152 (2.06). Example 529 (5S)-5-[(3,3-Difluoropyrrolidin-1-yl)carbonyl]-2-{[1-(4-methoxyphenyl)cyclopropyl]methyl}-5,6,7,8-tetrahydro [1,2,4]triazolo[4,3- a]pyridin-3(2H)-one

[01609] (5S)-2-{[1-(4-Methoxyphenyl)cyclopropyl]methyl}-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazole [4,3-a]pyridine-5-carboxylic acid (93.2 mg, 50% purity, 136 μmol), N,N-diisopropylethylamine (140 μl, 810 μmol), HBTU (134 mg, 353 μmol), 3,3-difluoropyrrolidine hydrochloride (1:1) (23.4 mg, 163 μmol). Stir at room temperature overnight. After purification, 41.1 mg (70% possibility) of the title compound were obtained. LC-MS (Method 4): Rt = 0.86 min; MS (ESIpos): m /z = 433 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (0.44), -0.008 (4.06), 0.008 (3.72), 0.147 (0.48) (0.78), 2366 (1.19), 2392 (0.41), 2523 (3.21), 2584 (1.13), 2628 (0.44), 2670 (0.92), 2710 (0.92), 3508 (0.65), 3527 (1.06), 3547 (0.58) (0.55), 4,752 (0.41), 6,776 (3.14), 6,798 (3.58), 7,127 (3.79), 7,149 (3.38). Example 530 (5S)-2-{[1-(2,4-Difluorophenyl)cyclopropyl]methyl}-5-(pyrrolidin-1-ylcarbonyl)-5,6,7,8-tetrahydro[1,2, 4]triazolo[4,3-a]pyridin-3(2H)-one

[01610] (5S)-2-{[1-(2,4-Difluorophenyl)cyclopropyl]methyl}-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4 ]triazolo[4,3-a]pyridine-5-carboxylic acid (78.0 mg, 223 μmol), N,N-diisopropylethylamine (120 μl, 670 μmol), HBTU (110 mg, 290 μmol), pyrrolidine (22 μl, 270 μmol). Stir at room temperature overnight. After purification, 9.80 mg (11% possibility) of the title compound were obtained. LC-MS (Method 3): Rt = 1.53 min; MS (ESIpos): m /z = 403 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (0.71), 0.146 (0.71), 0.705 (1.90), 0.730 ( 7.14), 0.761 (8.00), 0.786 (2.29), 0.968 (1.24), 1.001 (16.00), 1.036 (0.90), 1.237 (0.71), 1.676 (5.05), 1.684 (5.29), 1.695 (4.43), 1.707 ( 2.24), 1.732 (1.52), 1.749 (5.90), 1.766 (10.43), 1.783 (8.14), 1.800 (2.48), 1.865 (2.33), 1.881 (6.90), 1.898 (8.90), 1.915 (6.19), 1.939 ( 6.10), 1,953 (5.67), 1,975 (2.43), 1,990 (1.90), 2,073 (5.00), 2,327 (1.29), 2,367 (1.00), 2,418 (1.19), 2,435 (1.48), 2,459 (3.52), 2,574 ( 1.67), 2.586 (2.48), 2.670 (1.43), 2.710 (1.10), 3.196 (1.29), 3.213 (2.71), 3.225 (3.05), 3.242 (5.24), 3.259 (2.57), 3.281 (3.24), 3.345 ( 2.14), 3.388 (1.76), 3.405 (3.52), 3.412 (2.76), 3.430 (4.52), 3.447 (2.05), 3.533 (2.05), 3.550 (4.19), 3.566 (2.48), 3.574 (3.24), 3.600 ( 7.00), 3.636 (9.14), 3.813 (8.90), 3.849 (6.48), 4.598 (3.76), 4.612 (5.62), 4.622 (3.81), 6.883 (1.90), 6.889 (2.10), 6.904 (4.05), 6.910 ( 4.43), 6.925 (2.33), 6.932 (2.43), 7.087 (2.14), 7.094 (2.33), 7.116 (3.86), 7.137 (3.90), 7.144 (2.67), 7.156 (5.05), 7.173 (4.71), 7.195 ( 2.19). Example 531 (5S)-5-(Pyrrolidin-1-ylcarbonyl)-2-{[5-(trifluoromethyl)pyridin-2-yl]methyl}-5,6,7,8-tetrahydro[1,2, 4]triazolo[4,3-a]pyridin-3(2H)-one

[01611] (5S)-3-Oxo-2-{[5-(trifluoromethyl)pyridin-2-yl]methyl}-2,3,5,6,7,8-hexahydro[1,2,4 ]triazolo[4,3-a]pyridine-5-carboxylic acid (60.0 mg, 175 μmol), triethylamine (73 μl, 530 μmol), HATU (86.6 mg, 228 μmol), pyrrolidine (15.0 mg, 210 μmol). Stir at room temperature overnight. After purification, 51.6 mg (74% possibility) of the title compound were obtained. LC-MS (Method 3): Rt = 1.23 min; MS (ESIpos): m /z = 396 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.008 (2.08), 0.008 (1.90), 1.154 (3.17), 1.172 ( 6.53), 1.190 (3.27), 1.689 (0.90), 1.702 (1.25), 1.713 (1.69), 1.725 (2.58), 1.738 (3.07), 1.748 (2.44), 1.756 (2.05), 1.774 (4.73), 1.792 ( 7.66), 1.809 (5.78), 1.826 (1.71), 1.894 (1.71), 1.909 (6.12), 1.927 (5.83), 1.944 (3.53), 1.961 (1.02), 1.977 (0.83), 1.989 (0.80), 2.002 ( 1.29), 2.013 (2.31), 2.026 (2.61), 2.038 (1.76), 2.053 (1.85), 2.063 (1.34), 2.070 (1.25), 2.078 (1.22), 2.089 (0.73), 2.104 (0.42), 2.328 ( 0.69), 2.367 (0.47), 2.523 (3.17), 2.565 (2.44), 2.574 (2.24), 2.589 (1.92), 2.600 (1.83), 2.612 (3.36), 2.624 (1.90), 2.642 (0.85), 2.654 ( 1.29), 2.666 (1.14), 2.710 (0.56), 2.866 (1.29), 3.008 (1.19), 3.026 (3.44), 3.044 (3.36), 3.062 (1.12), 3.235 (1.08), 3.252 (2.19), 3.265 ( 2.12), 3.282 (3.95), 3.328 (3.27), 3.347 (4.14), 3.359 (1.61), 3.364 (2.17), 3.376 (2.29), 3.394 (1.03), 3.449 (1.15), 3.467 (2.46), 3.475 ( 1.83), 3.485 (1.49), 3.492 (3.15), 3.509 (1.42), 3.598 (1.47), 3.615 (2.86), 3.623 (1.51), 3.632 (1.69), 3.640 (2.25), 3.656 (1.05), 4.760 ( 2.66), 4.769 (2.95), 4.775 (3.56), 4.784 (2.64), 5.026 (16.00), 7.194 (0.95), 7.383 (4.80), 7.404 (5.03), 8.207 (3.02), 8.212 (3.10), 8.228 ( 2.95), 8.233 (2.97), 8.929 (4.64). Example 532 (5S)-5-[(3,3-Difluoroazetidin-1-yl)carbonyl]-2-[(5-methoxypyridin-2-yl)methyl]-5,6,7,8-tetrahydro[ 1,2,4]triazolo[4,3-a]pyridin-3(2H)-one

[01612] (5S)-2-[(5-Methoxypyridin-2-yl)methyl]-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[ 4,3-a]pyridine-5-carboxylic acid (45.0 mg, 148 μmol), N,N-diisopropylethylamine (77 μl, 440 μmol), HBTU (72.9 mg, 192 μmol), 3,3- difluoroazetidine hydrochloride (23.0 mg, 177 μmol). Stir at room temperature for 72 hours. After purification, 20.0 mg (36% possibility) of the title compound were obtained. LC-MS (Method 4): Rt = 0.54 min; MS (ESIpos): m /z = 380 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: 1.710 (1.02), 1.725 (1.59), 1.739 (1.12), 1.755 (0.41 ), 1.977 (0.42), 1.989 (0.76), 2.001 (0.67), 2.043 (0.64), 2.061 (0.68), 2.078 (0.51), 2.524 (0.77), 2.608 (0.64), 3.809 (16.00), 4.331 (0.41 ), 4.361 (0.69), 4.384 (0.69), 4.414 (0.42), 4.582 (0.92), 4.597 (1.47), 4.610 (0.91), 4.730 (0.43), 4.760 (0.50), 4.838 (6.91), 4.876 (0.46 ), 7,128 (1.79), 7,149 (2.18), 7,352 (1.38), 7,360 (1.40), 7,374 (1.15), 7,381 (1.19), 8,205 (1.83), 8,212 (1.80). Example 533 (5S)-2-{[3-Chloro-4-(trifluoromethyl)pyridin-2-yl]methyl}-5-(pyrrolidin-1-ylcarbonyl)-5,6,7,8-tetrahydro[ 1,2,4]triazolo[4,3-a]pyridin-3(2H)-one

[01613] (5S)-2-{[3-Chloro-4-(trifluoromethyl)pyridin-2-yl]methyl}-3-oxo-2,3,5,6,7,8-hexahydro[1 ,2,4]triazolo[4,3-a]pyridine-5-carboxylic acid (53.0 mg, 141 μmol), triethylamine (59 μl, 420 μmol), HATU (69.5 mg, 183 μmol), pyrrolidine (14 μl, 170 μmol). Stir at room temperature overnight. After purification, 40.0 mg (66% possibility) of the title compound were obtained. LC-MS (Method 4): Rt = 0.74 min; MS (ESIpos): m /z = 430 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.150 (0.42), -0.008 (3.83), 0.008 (3.11), 0.146 (0.41), 1.171 (0.73), 1.189 (0.45), 1.271 (0.69), (3.53), 1.677 (1.03), 1.691 (2.06), (4.67), 1.744 (2.31), 1.753 (1.98) , 1,822 (2.66), 1,891 (2.78), (6.73), 1,958 (3.14), 1,972 (2.09), (1.77), 2,025 (2.72), 2,039 (2.05), (1.11), 2,097 (0.59), 2,327 ( 0.67), (3.36), 2.569 (3.11), 2.581 (6.08), (2.17), 2.636 (0.92), 2.669 (0.75), (1.62), 3.246 (3.50), 3.259 (3.55), (6.78), 3.351 (2.56), 3.356 (3.48), (1.84), 3.459 (3.97), 3.466 (2.95), (2.19), 3.596 (2.28), 3.613 (5.03) , (0.61), 4.042 (0.59), 4.099 (0.61), 4.200 (0.53), 4.216 (0.50), 4.738 (4.37), 4.747 (5.06), 4.754 (5.78), 4.763 (4.33), 5.093 (4.67), 5,133 (16.00), 5,161 (15.97), 5,201 (4.61), 7,843 (9.97), 7,855 (10.39), 8,738 (8.03), 8,750 (7.84). Example 534 (5S)-5-[(3-Fluoroazetidin-1-yl)carbonyl]-2-[(1-methyl-1H-pyrazol[3,4-b]pyridin-3-yl)methyl]-5, 6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one

[01614] (5S)-2-[(1-Methyl-1H-pyrazolo[3,4-b]pyridin-3-yl)methyl]-3-oxo- 2,3,5,6,7,8- hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylic acid (38.0 mg, 116 μmol), N,N-diisopropylethylamine (60 μl, 350 μmol), HBTU (57.1 mg, 150 μmol), 3-fluoroazetidine hydrochloride (1:1) (15.5 mg, 139 μmol). Stir at room temperature overnight. After purification, 24.7 mg (100% purity, 55% chance) of the title compound was obtained. LC-MS (Method 3): Rt = 0.93 min; MS (ESIpos): m /z = 386 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ 1.677 (1.65), 1.935 (0.83), 2.004 2.523 (4.40), 2.562 (1.52), 2.578 2,669 (0.72), 2,709 (0.83), 3,931 4,025 (16.00), 4,231 (0.51), 4,260 4,541 (1.41), 4,553 (2.10), 4,566 7,196 (1.14), 7,204 (1.34), 7,216 8 .543 (2.21), 8.547 (2.23), 8.554 (2. 21), 8.558 (2.01). Example 535 (5S)-5-(Pyrrolidin-1-ylcarbonyl)-2-{[5-(trifluoromethyl)pyridin-3-yl]methyl}-5,6,7,8-tetrahydro[1,2, 4]triazolo[4,3-a]pyridin-3(2H)-one

[01615] (5S)-3-Oxo-2-{[5-(trifluoromethyl)pyridin-3-yl]methyl}-2,3,5,6,7,8-hexahydro[1,2,4 ]triazolo[4,3-a]pyridine-5-carboxylic acid (35.4 mg, 103 μmol), triethylamine (43 μl, 310 μmol), HATU (59.0 mg, 155 μmol), pyrrolidine (13 μl, 160 μmol). Stir at room temperature overnight. After purification, 16.7 mg (41% possibility) of the title compound were obtained. LC-MS (Method 3): Rt = 1.20 min; MS (ESIpos): m /z = 396 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (0.71), -0.008 (6.63), 0.008 (5.76), 0.146 (0.68) (4.48) (1.86) (3.54) (1.16), 3593 (1.20), 3610 (2.57), 3627 (1.49), 3635 (2.01), 3652 (1.01), 4754 (2.38), 4763 (2.67), 4769 (3.12), 4778 (2.34), 5012 (16.00), 8,063 (5.22), 8,737 (5.29), 8,912 (4.96). Example 536 (5S)-5-[(3,3-Difluoropyrrolidin-1-yl)carbonyl]-2-[(6-fluoropyridin-3-yl)methyl]-5,6,7,8-tetrahydro[ 1,2,4]triazolo[4,3-a]pyridin-3(2H)-one

[01616] (5S)-2-[(6-Fluoropyridin-3-yl)methyl]-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[ 4,3-a]pyridine-5-carboxylic acid (60.0 mg, 205 μmol), N,N-diisopropylethylamine (110 μl, 620 μmol), HBTU (101 mg, 267 μmol), 3,3-difluoropyrrolidine hydrochloride (35.4 mg, 246 μmol). Stir at room temperature overnight. After purification, 43.3 mg (55% possibility) of the title compound were obtained. LC-MS (Method 3): Rt = 1.05 min; MS (ESIpos): m /z = 382 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (0.48), -0.008 (5.78), 0.008 (3.49), 0.146 (0.48) (1.32) (1.33), 2519 (5.01), 2524 (4.66), 2567 (3.46), 2576 (3.26), 2591 (3.81), 2607 (3.64), 2619 (1.71), 2635 (0.71), 2650 (1.07), 2665 (0.89) (1.63) (1.61) (0.63) (16.00) (3.54), 7,728 (3.59), 7,742 (1.73), 7,750 (1.76), 8,512 (5.68), 8,520 (5.44). Example 537 (5S)-5-[(3,3-Difluoroazetidin-1-yl)carbonyl]-2-[(6-fluoropyridin-3-yl)methyl]-5,6,7,8-tetrahydro[ 1,2,4]triazolo[4,3-a]pyridin-3(2H)-one

[01617] (5S)-2-[(6-Fluoropyridin-3-yl)methyl]-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[ 4,3-a]pyridine-5-carboxylic acid (60.0 mg, 205 μmol), N,N-diisopropylethylamine (110 μl, 620 μmol), HBTU (101 mg, 267 μmol), 3,3-difluoroazetidine hydrochloride (31.9 mg, 246 μmol). Stir at room temperature for 72 hours. After purification, 41.5 mg (55% possibility) of the title compound were obtained. LC-MS (Method 3): Rt = 1.20 min; MS (ESIpos): m /z = 368 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.008 (1.07), 1.716 (2.85), 1.730 (4.22), 1.745 ( 2.96), 1.759 (1.15), 1.961 (0.99), 1.974 (1.04), 1.985 (1.17), 1.997 (1.96), 2.009 (1.75), 2.021 (0.75), 2.034 (0.84), 2.050 (1.58), 2.070 ( 1.74), 2.085 (1.40), 2.103 (0.84), 2.560 (1.95), 2.618 (1.73), 2.632 (0.58), 2.647 (0.96), 2.661 (0.43), 4.333 (1.13), 4.363 (1.88), 4.385 ( 1.88), 4.416 (1.14), 4.597 (2.54), 4.612 (3.97), 4.624 (2.50), 4.705 (0.40), 4.734 (1.19), 4.763 (1.35), 4.794 (0.66), 4.816 (0.68), 4.847 ( 1.36), 4.877 (1.28), 4.918 (16.00), 7.251 (2.70), 7.262 (2.75), 7.272 (3.02), 7.283 (2.90), 7.699 (1.82), 7.706 (1.90), 7.721 (3.45), 7.728 ( 3.55), 7,742 (1.69), 7,750 (1.72), 8,507 (4.62), 8,514 (4.60). Example 538 (5S)-2-[(6-Methoxypyridin-3-yl)methyl]-5-(pyrrolidin-1-ylcarbonyl)-5,6,7,8-tetrahydro[1,2,4]triazole [4,3-a]pyridin-3(2H)-one

[01618] (5S)-2-[(6-Methoxypyridin-3-yl)methyl]-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[ 4,3-a]pyridine-5-carboxylic acid (467 mg, 1.53 mmol), N,N-diisopropylethylamine (800 μl, 4.6 mmol), HBTU (757 mg, 2.00 mmol), pyrrolidine ( 150 μl, 1.8 mmol). Stir at room temperature overnight. After purification, 40.0 mg (95% purity, 7% possibility) of the title compound was obtained. LC-MS (Method 4): Rt = 0.58 min; MS (ESIpos): m /z = 358 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (0.63), -0.008 (5.45), 0.008 (4.76), 0.146 (0.63), 1.706 (0.80), 1.772 (1.20), 1.789 (2.01), 1.806 (1.61), 1.823 (0.52), 1.891 (0.69), 1.908 (1.55), 1.924 (1.89), 1.941 (1.20) (0.57), 1971 (0.80), 2017 (0.52), 2327 (1.38), 2366 (1.20), 2523 (5.10), 2570 (0.92), 2583 (1.15), 2625 (0.46), 2665 (1.20), 2670 (1.55) (0.52) (0.75), 4,760 (5.79), 6,782 (1.72), 6,803 (1.89), 7,552 (1.15), 7,558 (1.15), 7,573 (1.09), 7,580 (1.15), 8,050 (1.43), 8,056 (1.38). Example 539 (5S)-5-{[(3S)-3-Fluoropyrrolidin-1-yl]carbonyl}-2-{[2-(trifluoromethyl)quinolin-4-yl]methyl}-5,6,7,8 -tetrahydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one

[01619] (5S)-3-Oxo-2-{[2-(trifluoromethyl)quinolin-4-yl]methyl}-2,3,5,6,7,8-hexahydro[1,2,4 ]triazolo[4,3-a]pyridine-5-carboxylic acid (38.5 mg, 98.1 μmol), N,N-diisopropylethylamine (51 μl, 290 μmol), HBTU (48.4 mg, 128 μmol) , (3S)-3-fluoropyrrolidine hydrochloride (14.8 mg, 118 μmol). Stir at room temperature overnight. After purification, 30.9 mg (68% possibility) of the title compound were obtained. LC-MS (Method 3): Rt = 1.54 min; MS (ESIpos): m /z = 464 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (1.85), -0.008 (16.00), 0.008 (13.66), 0.146 (1.95), 1732 (2.93), 2006 (3.22), 2327 (4.10), (4.39), 2709 (2.24), 3527 (2.54), (2.34), 3748 (2.44), 3777 (11.02), (6.54) , 4,759 (1.46), 4,810 (1.66), (3.22), 5,459 (6.15), 5,481 (6.54), (3.22), 7,741 (7.32), 7,748 (5.56), (3.02), 7,946 (4.10), 7,966 ( 6.15), .02), 8.371 (4.10), 8.387 (3.90). Example 540 (5S)-5-[(3-Fluoroazetidin-1-yl)carbonyl]-2-{[3-(trifluoromethyl)-1,2,4-oxadiazol-5-yl]methyl}-5,6, 7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one

[01620] (5S)-3-Oxo-2-{[3-(trifluoromethyl)-1,2,4-oxadiazol-5-yl]methyl}- 2,3,5,6,7,8-hexa- hydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylic acid (85.0 mg, 82% purity, 209 μmol), N,N-diisopropylethylamine (110 μl, 630 μmol), HBTU (103 mg, 272 μmol), 3-fluoroazetidine hydrochloride (28.0 mg, 251 μmol). Stir at room temperature overnight. After purification, 53.0 mg (65% possibility) of the title compound were obtained. LC-MS (Method 3): Rt = 1.24 min; MS (ESIpos): m /z = 391 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (0.75), -0.008 (6.77), 0.008 (6.05), 0.146 (0.77), 1706 (3.09), 1728 (5.31), 1738 (4.23), 1954 (2.13), 1967 (2.27), 1976 (1.96), 2041 (1.91), 2053 (2.07), 2073 (4.26), 2328 (0.77) (2.40) (1.52) (0.69) (1.05), 5,421 (16.00), 5,476 (0.88), 5,492 (1.13), 5,546 (1.05). Example 541 (5S)-5-[(3,3-Difluoropyrrolidin-1-yl)carbonyl]-2-{[5-(trifluoromethyl)-1,3,4-oxadiazol-2-yl]methyl}-5, 6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one

[01621] 5S)-3-Oxo-2-{[5-(trifluoromethyl)-1,3,4-oxadiazol-2-yl]methyl}- 2,3,5,6,7,8-hexahydro [1,2,4]triazolo[4,3-a]pyridine-5-carboxylic acid (100 mg, 80% purity, 240 μmol), N,N-diisopropylethylamine (130 μl, 720 μmol), HBTU (118 mg, 312 μmol), 3,3-difluoropyrrolidine hydrochloride (1:1) (41.4 mg, 288 μmol). Stir at room temperature for 72 hours. After purification, 18.0 mg (18% possibility) of the title compound were obtained. LC-MS (Method 3): Rt = 1.27 min; MS (ESIpos): m /z = 423 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (0.80), -0.008 (6.76), 0.008 (5.45), 0.146 (0.80) (1.45) (3.35) (0.95), 3908 (2.25), 3934 (1.60), 3954 (0.80), 3993 (1.38), 4035 (1.16), 4064 (0.73), 4148 (0.87), 4173 (1.16), 4205 (1.24), 4769 (1.82) (0.65). Example 542 (5S)-5-[(3-Fluoroazetidin-1-yl)carbonyl]-2-{[5-(trifluoromethyl)-1,3,4-oxadiazol-2-yl]methyl}-5,6, 7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one

[01622] (5S)-3-Oxo-2-{[5-(trifluoromethyl)-1,3,4-oxadiazol-2-yl]methyl}- 2,3,5,6,7,8-hexa- hydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylic acid (100 mg, 80% purity, 240 μmol), N,N-diisopropylethylamine (130 μl, 720 μmol), HBTU ( 118 mg, 312 μmol), 3-fluoroazetidine hydrochloride (32.1 mg, 288 μmol). Stir at room temperature overnight. After purification, 21.0 mg (22% possibility) of the title compound were obtained. LC-MS (Method 3): Rt = 1.06 min; MS (ESIpos): m /z = 391 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (0.62), -0.008 (4.52), 0.008 (4.71), 0.146 (0.67) (4.56) (1.39) (3.51) (0.96), 6.510 (1.20). Example 543 (5S)-5-{[(3R,4S)-3,4-Difluoropyrrolidin-1-yl]carbonyl}-2-{[5-(trifluoromethyl)-1,3,4-oxadiazol-2-yl ]methyl}-5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one

[01623] (5S)-3-Oxo-2-{[5-(trifluoromethyl)-1,3,4-oxadiazol-2-yl]methyl}- 2,3,5,6,7,8-hexa- hydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylic acid (100 mg, 80% purity, 240 μmol), N,N-diisopropylethylamine (130 μl, 720 μmol), HBTU ( 118 mg, 312 μmol), (3R,4S)-3,4-difluoropyrrolidine hydrochloride (1:1) (41.4 mg, 288 μmol). Stir at room temperature overnight. After purification, 30.0 mg (30% possibility) of the title compound were obtained. LC-MS (Method 3): Rt = 1.23 min; MS (ESIpos): m /z = 423 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (1.10), -0.008 (9.43), 0.008 (8.71), 0.146 (1.14) (1.86) (3.81), 2630 (4.95), 2643 (2.95), 2670 (3.29), 2710 (1.86), 3455 (0.90), 3489 (1.62), 3513 (1.67), 3535 (1.48), 3545 (1.67), 3557 (1.10) (1.52) (0.81) (5.48) (1.71), 5.407 (1.43), 5.473 (1.24), 5.481 (1.24). Example 544 (5S)-5-{[(3S)-3-Fluoropyrrolidin-1-yl]carbonyl}-2-{[5-(trifluoromethyl)-1,3,4-oxadiazol-2-yl]methyl}- 5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one

[01624] (5S)-3-Oxo-2-{[5-(trifluoromethyl)-1,3,4-oxadiazol-2-yl]methyl}- 2,3,5,6,7,8-hexa- hydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylic acid (100 mg, 80% purity, 240 μmol), N,N-diisopropylethylamine (130 μl, 720 μmol), HBTU ( 118 mg, 312 μmol), (3S)-3-fluoropyrrolidine hydrochloride (36.2 mg, 288 μmol). Stir at room temperature overnight. After purification, 18.9 mg (19% possibility) of the title compound were obtained. LC-MS (Method 3): Rt = 1.16 min; MS (ESIpos): m /z = 405 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.150 (4.07), 0.145 (4.07), 1.740 (4.95), 1.910 ( 1.45), 2,029 (2.04), 2,110 (3.49), 2,268 (1.75), 2,327 (8.44), 2,366 (9,89), 2,584 (4,95), 2,631 (5,53), 2,669 (10.18), 2.709 (11,35), 3.395 ( 2.62), 3.501 (1.75), 3.651 (3.20), 3.722 (2.91), 3.745 (3.49), 3.770 (2.91), 3.857 (4.07), 4.715 (2.33), 4.774 (3.20), 5.246 (2.91), 5.288 ( 16.00), 5,297 (9.02), 5,303 (10.47), 5,346 (1.75), 5,388 (2.91), 5,512 (1.75). Example 545 (5S)-2-{[5-Chloro-6-(trifluoromethyl)pyridin-3-yl]methyl}-5-(pyrrolidin-1-ylcarbonyl)-5,6,7,8-tetrahydro[ 1,2,4]triazolo[4,3-a]pyridin-3(2H)-one

[01625] (5S)-2-{[5-Chloro-6-(trifluoromethyl)pyridin-3-yl]methyl}-3-oxo-2,3,5,6,7,8-hexahydro[1 ,2,4]triazolo[4,3-a]pyridine-5-carboxylic acid (35.0 mg, 92.9 μmol), N,N-diisopropylethylamine (49 μl, 280 μmol), HBTU (45.8 mg , 121 μmol), pyrrolidine (9.3 μl, 110 μmol). Stir at room temperature for 72 hours. After purification, 25.0 mg (63% possibility) of the title compound were obtained. LC-MS (Method 3): Rt = 1.49 min; MS (ESIpos): m /z = 430 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.008 (3.06), 0.008 (2.74), 1.243 (2.70), 1.259 ( 3.33), 1.647 (1.15), 1.667 (1.47), 1.681 (1.59), 1.691 (1.31), 1.708 (1.15), 1.734 (2.34), 1.744 (2.18), 1.757 (2.50), 1.775 (5.76), 1.792 ( 9.37), 1809 (7.07), 1826 (1.99), 1894 (1.91), 1910 (5.56), 1927 (6.87), 1943 (4.17), 1960 (1.23), 1979 (0.91), 1992 (0.87), 2006 ( 1.67), 2.019 (3.69), 2.028 (4.01), 2.044 (2.18), 2.056 (1.63), 2.063 (1.67), 2.071 (1.59), 2.328 (0.91), 2.366 (0.67), 2.523 (4.09), 2.564 ( 3.10), 2.575 (2.78), 2.590 (2.30), 2.605 (2.26), 2.616 (3.93), 2.628 (2.34), 2.646 (1.07), 2.660 (1.67), 2.670 (1.79), 2.690 (0.71), 2.710 ( 0.79), 2.885 (3.65), 3.033 (1.91), 3.235 (1.23), 3.251 (2.54), 3.264 (2.66), 3.281 (4.96), 3.330 (3.73), 3.348 (4.96), 3.360 (1.99), 3.366 ( 2.62), 3.378 (2.90), 3.396 (1.67), 3.403 (2.02), 3.442 (1.43), 3.459 (3.06), 3.466 (2.26), 3.476 (1.87), 3.484 (3.89), 3.501 (1.75), 3.593 ( 1.95), 3.610 (3.77), 3.618 (2.14), 3.627 (2.38), 3.635 (3.06), 3.652 (1.43), 4.760 (3.30), 4.769 (3.73), 4.775 (4.53), 4.784 (3.18), 4.992 ( 0.60), 5.035 (16.00), 5.078 (0.56), 8.067 (6.83), 8.537 (6.95), 8.541 (6.83). Example 546 (5S)-5-[(3-Fluoroazetidin-1-yl)carbonyl]-2-(4-fluorobenzyl)-5,6,7,8-tetrahydro[1,2,4]triazolo[4 ,3-a]pyridin-3(2H)-one

[01626] (5S)2-(4-Fluorobenzyl)-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine- 5-carboxylic acid (62.8 mg, 215 μmol) N,N-diisopropylethylamine (110 μl, 650 μmol), HBTU (106 mg, 280 μmol), 3-fluoroazetidine hydrochloride (1:1) (28.8 mg, 259 μmol). Stir at room temperature overnight. After purification, 15.9 mg (21% possibility) of the title compound were obtained. LC-MS (Method 4): Rt = 0.65 min; MS (ESIpos): m /z = 349 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.150 (0.69), -0.008 (9.17), 0.008 (5.47), 0.146 (0.72) (0.61), 2571 (4.19), 2585 (5.22), 2598 (2.61), 2613 (1.08), 2627 (1.61), 2640 (0.72), 2669 (0.81), 2709 (0.67), 3894 (0.78), 3.927 (1.42) (1.33) (3.61) (0.86), 7,140 (4.42), 7,161 (9.78), 7,184 (5.97), 7,263 (5.64), 7,277 (6.94), 7,295 (3.83). Example 547 (5S,8RS)-2-[(5-Chloropyridin-2-yl)methyl]-5-{[(3S)-3-fluoropyrrolidin-1-yl]carbonyl}-8-hydroxy-5,6, 7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one (mixture of diastereomer; 2 isomers)

[01627] (5S)-2-[(5-Chloropyridin-2-yl)methyl]-5-{[(3S)-3-fluoropyrrolidin-1-yl]carbonyl}-5,6,7,8-tetra -hydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one (66.6 mg, 175 μmol) and cerium(IV) sulfate (350 mg, 1.05 mmol) were suspended in tert-butanol (230 μl) at room temperature. Subsequently, 1 N aqueous sulfuric acid (230 μl, 4.4 mmol) was added, and the reaction mixture was stirred at 70 °C overnight. The reaction mixture was cooled to room temperature and adjusted to pH 9 with 2 N aqueous sodium hydroxide solution. The suspension was filtered and the filtrate was extracted three times with dichloromethane. The combined organic phases were dried over sodium sulfate and filtered, and the filtrate was concentrated. 40.4 mg (55% possibility) of the title compound was obtained. LC-MS (Method 1): Rt = 0.73 min; MS (ESIpos): m /z = 396 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.008 (3.50), 1.167 (0.78), 1.215 (0.80), 1.236 ( 1.14), 1.273 (0.68), 1.283 (0.48), 1.352 (0.59), 1.425 (0.57), 1.526 (0.41), 1.743 (1.70), 1.754 (2.02), 1.767 (2.20), 1.780 (2.30), 1.799 ( 1.41), 1.812 (1.70), 1.822 (2.02), 1.855 (1.40), 1.873 (0.98), 1.906 (1.16), 1.942 (1.08), 1.988 (0.74), 2.026 (0.56), 2.107 (1.89), 2.124 ( 1.73), 2.132 (1.74), 2.222 (1.05), 2.234 (1.05), 2.270 (1.43), 2.327 (0.99), 2.366 (1.04), 2.391 (1.34), 2.403 (1.29), 2.432 (0.84), 2.669 ( 0.72), 3.269 (0.74), 3.343 (0.69), 3.361 (0.68), 3.388 (0.77), 3.398 (0.71), 3.451 (0.53), 3.459 (0.60), 3.486 (0.83), 3.495 (0.78), 3.629 ( 1.85), 3.641 (2.63), 3.657 (2.17), 3.665 (2.21), 3.685 (1.68), 3.738 (1.68), 3.759 (1.83), 3.779 (1.65), 3.801 (1.05), 3.834 (0.50), 3.866 ( 2.24), 4.488 (0.63), 4.501 (0.59), 4.526 (3.47), 4.537 (3.85), 4.554 (0.99), 4.673 (0.62), 4.742 (1.35), 4.754 (1.28), 4.798 (1.71), 4.809 ( 1.65), 4.896 (0.56), 4.906 (0.72), 4.937 (2.42), 4.956 (16.00), 4.998 (0.56), 5.258 (1.44), 5.388 (2.08), 5.517 (1.20), 5.754 (6.83), 5.778 ( 4.87) 4.26), 8.582 (4.62), 8.588 (4.12). Example 548 (5S)-2-[(5-Chloropyridin-3-yl)methyl]-5-{[trans-3,4-difluoropyrrolidin-1-yl]carbonyl}-5,6,7,8-tetra- hydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one (diastereomer mixture; 2 isomers)

[01628] (5S)-2-[(5-Chloropyridin-3-yl)methyl]-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[ 4,3-a]pyridine-5-carboxylic acid (162 mg, 525 μmol) was initially loaded into THF (11 mL) at room temperature. Subsequently, HBTU (259 mg, 683 μmol) and N,N-diisopropylethylamine (460 μl, 2.6 mmol) were added. After stirring for 5 minutes, trans-3,4-difluoropyrrolidine hydrochloride (90.5 mg, 630 μmol) was added and the reaction mixture was stirred at room temperature overnight. HBTU (259 mg, 683 μmol) and N,N-diisopropylethylamine (460 μl, 2.6 mmol) were added again and the mixture was stirred at room temperature overnight. The reaction mixture was mixed with saturated aqueous sodium hydrogen carbonate solution and extracted twice with ethyl acetate. The combined organic phases were washed with saturated aqueous sodium chloride solution, dried over sodium sulfate and filtered, and the filtrate was concentrated. The residue was purified via preparatory HPLC (Method 12). The fractions containing the product were concentrated under reduced pressure and 2.90 mg (1.4% possibility) of the title compound were obtained. LC-MS (Method 3): Rt = 1.09 min; MS (ESIpos): m /z = 398 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (1.68), -0.008 (14.62), 0.008 (11.46), 0.146 (1.68) (2.67) (1.19) (2.12), 4,780 (1.58), 4,916 (16.00), 5,309 (1.78), 5,444 (2.22), 5,537 (0.84), 7,760 (7.85), 8,425 (7.90), 8,564 (7.26), 8,570 (7.26). Example 549 (5S)-2-[(5-Chloro-3-fluoropyridin-3-yl)methyl]-5-{[trans-3,4-difluoropyrrolidin-1-yl]carbonyl}-5,6,7, 8-tetrahydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one (diastereomer mixture; 2 isomers)

[01629] (5S)-2-[(5-Chloro-3-fluoropyridin-2-yl)methyl]-3-oxo-2,3,5,6,7,8-hexahydro[1,2, 4]triazolo[4,3-a]pyridine-5-carboxylic acid (212 mg, 650 μmol) was initially loaded into THF (14 mL) at room temperature. Subsequently, HBTU (320 mg, 845 μmol) and N,N-diisopropylethylamine (570 μl, 3.2 mmol) were added. After stirring for 5 minutes, trans-3,4-difluoropyrrolidine hydrochloride (112 mg, 780 μmol) was added and the reaction mixture was stirred at room temperature overnight. HBTU (320 mg, 845 μmol) and N,N-diisopropylethylamine (570 μl, 3.2 mmol) were added again and the mixture was stirred at room temperature overnight. The reaction mixture was mixed with saturated aqueous sodium hydrogen carbonate solution and extracted twice with ethyl acetate. The combined organic phases were washed with saturated aqueous sodium chloride solution, dried over sodium sulfate and filtered, and the filtrate was concentrated. The residue was purified via preparatory HPLC (Method 12). The fractions containing the product were concentrated under reduced pressure and 26.5 mg (10% possibility) of the title compound were obtained. LC-MS (Method 3): Rt = 1.18 min; MS (ESIpos): m /z = 416 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (2.07), -0.008 (16.00), 0.008 (12.99), 0.146 (1.88) (2.35) 2,709 (2.45), 3,527 (1.32), 3,563 (1.60), 3,627 (6.12), 3,665 (1.88), 3,711 (4.24), 3,745 (2.45), 3,782 (1.69), 3,813 (3.01), 3,850 (2.35), 3,936 (5.84), 4,015 (3.67), 4,127 (1.88), 4,160 (1.60), 4,190 (1.98), 4,223 (1.69), 4,726 (2.73), 4,737 (3.48), 4,742 (3.67), 4,752 (2.92), 4,855 (2.73), 4,870 (3.58), 4,880 (2.64), 4,902 (4.42), 4,941 (10.82), 4,990 (10.82), 5,029 (4.24), 5,308 (2.73), 5,427 (3.86), 5,441 (3.58), 5,533 (1.51), 5,565 (1.41), 8,089 (6.59), 8,094 (7.25), 8,114 (7.06), 8,118 (7.44), 8,478 (8.19), 8,482 (8.38). Example 550 (5S)-2-[(6-Chloropyridin-3-yl)methyl]-5-{[trans-3,4-difluoropyrrolidin-1-yl]carbonyl}-5,6,7,8-tetra- hydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one (diastereomer mixture; 2 isomers)

[01630] (5S)-2-[(6-Chloropyridin-3-yl)methyl]-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[ 4,3-a]pyridine-5-carboxylic acid (200 mg, 649 μmol) was initially loaded into THF (14 mL) at room temperature. Subsequently, HBTU (320 mg, 843 μmol) and N,N-diisopropylethylamine (570 μl, 3.2 mmol) were added. After stirring for 5 minutes, trans-3,4-difluoropyrrolidine hydrochloride (112 mg, 779 μmol) was added and the reaction mixture was stirred at room temperature overnight. The suspension was filtered and the filtrate was mixed with saturated aqueous sodium hydrogencarbonate solution and extracted twice with ethyl acetate. The aqueous phase was acidified with 1N aqueous hydrochloric acid and extracted with ethyl acetate. The combined organic phases were washed with saturated aqueous sodium chloride solution, dried over sodium sulfate and filtered, and the filtrate was concentrated. The residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 40mm; eluent: gradient (acetonitrile/water with 0.1% formic acid). The fractions containing the product were concentrated under reduced pressure and 71. 5 mg (28% possibility) of the title compound. LC-MS (Method 3): Rt = 1.10 min; MS (ESIpos): m / z = 398 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (0.57), -0.008 (4.53), 0.008 (5.49), 0.146 (0.57), 1.648 (0.77), 1.672 (0.75), 1.720 (2.21), 1.730 (2.59) , 1.742 (2.35), 1.887 (0.75), 1.912 (0.77), 1.928 (0.99), 1.959 (0.50), 1.995 (1.10), 2.020 (0.70), 2.030 (0.70), 2.037 (0.68), 2.045 (0.79) , 2.057 (0.75), 2.065 (0.88), 2.073 (1.22), 2.082 (0.95), 2.099 (1.10), 2.108 (1.02), 2.116 (0.83), 2.124 (0.84), 2.134 (0.72), 2.327 (0.79) , 2.366 (0.75), 2.524 (3.00), 2.566 (2.71), 2.576 (2.64), 2.591 (3.79), 2.604 (4.17), 2.616 (2.26), 2.633 (0.83), 2.646 (1.29), 2.660 (0.77) , 2.665 (0.74), 2.669 (0.88), 2.710 (0.74), 3.528 (0.65), 3.565 (0.90), 3.633 (3.32), 3.667 (1.08), 3.709 (1.83), 3.730 (1.33), 3.753 (1.42) , 3.766 (0.63), 3.789 (1.08), 3.820 (1.85), 3.845 (0.77), 3.857 (1.15), 3.914 (0.65), 3.936 (3.36), 4.013 (1.96), 4.023 (1.35), 4.132 (1.02) , 4,166 (0.88), 4,196 (1.06), 4,230 (0.83), 4,739 (1.67), 4,749 (2.03), 4,755 (2.15), 4,765 (1.63), 4,883 (16.00), 4,907 (1.53), 5,257 (0.41) , 5,310 (1.56), 5,399 (0.84), 5,425 (1.87), 5,442 (1.99), 5,533 (0.75), 5,567 (0.74), 7,506 (6.29), 7,527 (7.96), 7,690 (4.02), 7,696 (4.04) , 7,710 (3.34), 7,716 (3.29), 8,299 (5.30), 8,304 (5.14). Example 551 (5S)-2-[(6-Chloropyridin-3-yl)methyl]-5-{[trans-3,4-difluoropyrrolidin-1-yl]carbonyl}-5,6,7,8-tetra- hydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one (isomer 1) CL

[01631] (5S)-2-[(6-Chloropyridin-3-yl)methyl]-5-{[trans-3,4-difluoropyrrolidin-1-yl]carbonyl}-5,6,7,8-tetra -hydro[1,2,4]triazolo[4,3- a]pyridin-3(2H)-one (diastereomer mixture; 2 isomers) was separated by chiral preparatory HPLC [sample preparation: 71.5 mg dissolved in 2 mL of ethanol and 2 mL of dichloromethane; injection volume: 0.3 mL; column: Daicel Chiralpak® IF 5 μm, 250 x 20 mm; eluent: n-heptane/ethanol 35:65; flow rate: 15 ml/min; temperature 25°C; UV detection: 210 nm]. After separation, 19.2 mg of isomer 1, which elutes first, and 20.3 mg of isomer 2, which elutes later, were isolated. Isomer 1:

[01632] Analytical chiral HPLC: Rt = 2.66 min, de = 99% [column: Daicel Chiralpak® IF-350 50 x 4.6 mm; eluent: n-heptane/ethanol 50:50; flow rate: 1 ml/min; UV detection: 220 nm]. LC-MS (Method 4): Rt = 0.59 min; MS (ESIpos): m /z = 398 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (0.77), -0.008 (5.90), 0.008 (6.28), 0.146 (0.70), 1237 (0.41), 1647 (0.98), 1732 (1.32), 1741 (1.34), 1755 (1.01), 1958 (0.70), 1995 (1.68), 2020 (1.08), 2029 (1.03), 2045 (1.15) (3.05), 2616 (1.80), 2634 (0.72), 2646 (1.01), 2669 (1.61), 2710 (1.03), 3092 (1.49), 3633 (4.37), 3672 (0.67), 3708 (2.37), 3729 (1.63) (1.25) (2.69), 7,715 (2.81), 8,299 (3.72), 8,304 (3.79). Example 552 (5S)-2-[(6-Chloropyridin-3-yl)methyl]-5-{[trans-3,4-difluoropyrrolidin-1-yl]carbonyl}-5,6,7,8-tetra- hydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one (isomer 2)

[01633] (5S)-2-[(6-Chloropyridin-3-yl)methyl]-5-{[trans-3,4-difluoropyrrolidin-1-yl]carbonyl}-5,6,7,8-tetra -hydro[1,2,4]triazolo[4,3- a]pyridin-3(2H)-one (diastereomer mixture; 2 isomers) was separated by chiral preparatory HPLC [sample preparation: 71.5 mg dissolved in 2 mL of ethanol and 2 mL of dichloromethane; injection volume: 0.3 mL; column: Daicel Chiralpak® IF 5 μm, 250 x 20 mm; eluent: n-heptane/ethanol 35:65; flow rate: 15 ml/min; temperature 25°C; UV detection: 210 nm]. After separation, 19.2 mg of isomer 1, which elutes first, and 20.3 mg of isomer 2, which elutes later, were isolated. Isomer 2:

[01634] Analytical chiral HPLC: Rt = 3.85 min, de = 99% [column: Daicel Chiralpak® IF-350 50 x 4.6 mm; eluent: n-heptane/ethanol 50:50; flow rate: 1 ml/min; UV detection: 220 nm]. LC-MS (Method 4): Rt = 0.60 min; MS (ESIpos): m /z = 398 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (0.56), -0.008 (4.82), 0.008 (5.43), 0.146 (0.58) (1.07) (1.15) (1.89) (2.23) (2.87), 8,298 (4.10), 8,304 (4.34). Example 553 (5S)-5-{[trans-3,4-Difluoropyrrolidin-1-yl]carbonyl}-2-{[6-(trifluoromethyl)pyridin-3-yl]methyl}-5,6,7,8 -tetrahydro[1,2,4]triazolo[4,3- a]pyridin-3(2H)-one (isomer 1)

[01635] (5S)-3-Oxo-2-{[6-(trifluoromethyl)pyridin-3-yl]methyl}-2,3,5,6,7,8-hexahydro[1,2,4 ]triazolo[4,3-a]pyridine-5-carboxylic acid (389 mg, 88% purity, 1.00 mmol) was initially loaded into THF (21 mL) at room temperature. Subsequently, HBTU (493 mg, 1.30 mmol) and N,N-diisopropylethylamine (870 μl, 5.0 mmol) were added. After stirring for 5 minutes, trans-3,4-difluoropyrrolidine hydrochloride (172 mg, 1.20 mmol) was added and the reaction mixture was stirred at room temperature overnight. The suspension was filtered and the filtrate was mixed with saturated aqueous sodium hydrogen carbonate solution and extracted twice with ethyl acetate. The aqueous phase was acidified with 1N aqueous hydrochloric acid and extracted with ethyl acetate. The combined organic phases were washed with saturated aqueous sodium chloride solution, dried over sodium sulfate and filtered, and the filtrate was concentrated. The residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 40mm; eluent: gradient (acetonitrile/water with 0.1% formic acid). The fractions containing the product were concentrated under reduced pressure and 128. 5 mg (84% purity, 25% possibility) of a diastereomer mixture (2 isomers). The diastereomer mixture (2 isomers) was separated by chiral preparatory HPLC [sample preparation: 128.5 mg dissolved in 2 mL of ethanol and 2 mL of n-heptane; injection volume: 0.4 mL; column: Daicel Chiralpak® IC 5 μm, 250 x 20 mm; /min; temperature 40°C; UV detection: 220 nm]. After separation, 43 mg of isomer 1, which elutes first, and 45.5 mg of isomer 2, which elutes later, were isolated.

[01636] Analytical chiral HPLC: Rt = 1.74 min, de = 99% [column: Daicel Chiralpak® IC-3 3 μm, 50 x 4.6 mm; eluent: n-heptane/ethanol 50:50; flow rate: 1 ml/min; UV detection: 220 nm]. LC-MS (Method 3): Rt = 1.25 min; MS (ESIpos): m /z = 432 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (1.66), -0.008 (13.19), 0.008 (12.41), 0.146 (1.56) (1.36) (4.24) (1.39) (1.93), 5,533 (1.19), 7,911 (14.88), 7,915 (16.00), 8,644 (5.59). Example 554 (5S)-5-{[trans-3,4-Difluoropyrrolidin-1-yl]carbonyl}-2-{[6-(trifluoromethyl)pyridin-3-yl]methyl}-5,6,7,8 -tetrahydro[1,2,4]triazolo[4,3- a]pyridin-3(2H)-one (isomer 2)

[01637] (5S)-5-{[trans-3,4-Difluoropyrrolidin-1-yl]carbonyl}-2-{[6-(trifluoromethyl)pyridin-3-yl]methyl}-5,6,7, 8-tetrahydro[1,2,4]triazolo[4,3- a]pyridin-3(2H)-one (diastereomer mixture; 2 isomers) was separated by chiral preparatory HPLC [sample preparation: 128.5 mg dissolved in 2 mL of ethanol and 2 mL of n-heptane; injection volume: 0.4 mL; column: Daicel Chiralpak® IC 5 μm, 250 x 20 mm; eluent: n-heptane/ethanol 50:50; flow rate: 15 ml/min; temperature 40°C; UV detection: 220 nm]. After separation, 43 mg of isomer 1, which elutes first, and 45.5 mg of isomer 2, which elutes later, were isolated. Isomer 2:

[01638] Analytical chiral HPLC: Rt = 2.51 min, de = 99% [column: Daicel Chiralpak® IC-3 3 μm, 50 x 4.6 mm; eluent: n-heptane/ethanol 50:50; flow rate: 1 ml/min; UV detection: 220 nm]. LC-MS (Method 8): Rt = 1.80 min; MS (ESIpos): m /z = 432 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (1.97), -0.008 (16.00), 0.146 (1.86), 1.726 (1.43) (1.20) (0.85), 3940 (2.90), 4019 (1.97), 4755 (1.43), 4770 (1.97), 4780 (1.51), 5010 (9.89), 5310 (0.85), 5446 (1.35), 5574 (0.73), 7912 (8.81), 7.915 (10.01), 8.645 (3.29). Example 555 (5S)-2-[(5-Chloropyridin-2-yl)methyl]-8,8-difluoro-5-{[(3S)-3-fluoropyrrolidin-1-yl]carbonyl}-5,6, 7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one

[01639] Under argon: (5S)-2-[(5-chloropyridin-2-yl)methyl]-5-{[(3S)-3-fluoropyrrolidin-1-yl]carbonyl}-6,7-di- hydro[1,2,4]triazolo[4,3-a]pyridine-3,8(2H,5H)-dione (20.7 mg, 71% purity, 37.2 μmol) was initially loaded into dichloromethane ( 3.8 mL) at room temperature. Subsequently, diethylamino sulfur trifluoride (15 μl, 110 μmol) was added, and the mixture was stirred at 40°C overnight. The reaction mixture was mixed with water and saturated aqueous sodium hydrogen carbonate solution. The aqueous phase was extracted four times with dichloromethane, and the combined organic phases were dried over sodium sulfate and filtered, and the filtrate was concentrated. The residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: gradient (acetonitrile/water with 0.1% formic acid). The fractions containing the product were concentrated under reduced pressure and 7. 00 mg (44% chance) of the title compound. LC-MS (Method 4): Rt = 0.77 min; MS (ESIpos): m / z = 416 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (1.99), -0.008 (15.19), 0.008 (16.00), 0.146 (1.74), 1.072 (1.31), 1.126 (1.25), 1.146 (1.31), 1.178 (1.56) , 1,190 (1.43), 1,364 (0.93), 2,151 (1.06), 2,327 (5.23), 2,366 (3.24), 2,669 (4.86), 2,710 (2.24), 3,526 (0.75), 3,645 (1.43), 3,673 (1.31) , 3,700 (1.12), 3,777 (1.18), 3,889 (1.25), 4,896 (0.81), 4,960 (1.12), 5,064 (5.60), 5,078 (3.55), 5,276 (0.75), 5,406 (1.00), 7,282 (2.93) , 7.303 (3.18), 7.951 (2.18), 7.957 (2.37), 7.972 (2.24), 7.979 (2.30), 8.440 (0.68), 8.590 (2.49). 3-fluoropyridin-2-yl)methyl]-8,8-difluoro-5-{[(3S)-3-fluoropyrrolidin-1-yl]carbonyl}-5,6,7,8-tetrahydro[1, 2,4]triazolo[4,3- a]pyridin-3(2H)-one

[01640] Under argon: (5S)-2-[(5-chloro-3-fluoropyridin-2-yl)methyl]-5-{[(3S)-3-fluoropyrrolidin-1-yl]carbonyl}-6, 7-dihydro[1,2,4]triazolo[4,3- a]pyridine-3,8(2H,5H)-dione (25.8 mg, 79% purity, 49.4 μmol) was initially charged in dichloromethane (5.1 mL) at room temperature. Subsequently, diethylamino sulfur trifluoride (20 μl, 150 μmol) was added, and the mixture was stirred at 40°C overnight. Diethylamino sulfur trifluoride (8 μl, 59 μmol) was added again, and the mixture was stirred at 40°C for 2 hours. The reaction mixture was mixed with water and saturated aqueous sodium hydrogen carbonate solution. The aqueous phase was extracted four times with dichloromethane, and the combined organic phases were dried over sodium sulfate and filtered, and the filtrate was concentrated. The residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: gradient (acetonitrile/water with 0.1% formic acid). The fractions containing the product were concentrated under reduced pressure and 9. 10 mg (42% possibility) of the title compound. LC-MS (Method 3): Rt = 1.42 min; MS (ESIpos): m / z = 434 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (1.72), -0.008 (14.25), 0.008 (16.00), 0.146 (1.68), 1.148 (0.62), 2.144 (1.21), 2.249 (1.13), 2.327 (4.24) , 2,366 (2.01), 2,670 (3.11), 2,710 (1.46), 3,416 (0.95), 3,477 (0.69), 3,520 (0.77), 3,611 (0.62), 3,637 (1.86), 3,668 (1.72), 3,698 (1.28) , 3.745 (0.99), 3.767 (1.53), 3.790 (1.21), 3.813 (0.88), 3.881 (1.79), 4.893 (1.13), 4.952 (1.46), 5.084 (1.02), 5.123 (4.05), 5.144 (2.63) , 5,183 (0.73), 5,273 (0.99), 5,403 (1.21), 5,528 (0.66), 8,136 (2.30), 8,155 (2.23), 8,160 (2.37), 8,501 (3.14). (6-Chloropyridin-3-yl)methyl]-5-[(3,3-difluoropyrrolidin-1-yl)carbonyl]-8,8-difluoro-5,6,7,8-tetrahydro[1,2 ,4]triazolo[4,3-a]pyridin-3(2H)-one

[01641] (5S)-2-[(6-Chloropyridin-3-yl)methyl]-5-[(3,3-difluoropyrrolidin-1-yl)carbonyl]-6,7-dihydro[1,2 ,4]triazolo[4,3-a]pyridine-3,8(2H,5H)-dione (47.3 mg, 115 μmol) was initially charged under argon in dichloromethane (12 mL, 180 mmol) at room temperature. Subsequently, diethylamino sulfur trifluoride (46 μl, 340 μmol) was added, and the mixture was stirred at 40°C overnight. The reaction mixture was mixed with water and saturated aqueous sodium hydrogen carbonate solution. The aqueous phase was extracted four times with dichloromethane, and the combined organic phases were dried over sodium sulfate and filtered, and the filtrate was concentrated. The residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: gradient (acetonitrile/water with 0.1% formic acid). The fractions containing the product were concentrated under reduced pressure and 40 mg were obtained (80% possibility) of the title compound. LC-MS (Method 3): Rt = 1.50 min; MS (ESIpos): m /z = 434 [M+H]+ 1H-NMR (400 MHz, DMSO- d6) δ [ppm]: -0.149 (0.94), -0.008 (7.23), 0.008 (7.13), 0.146 (0.88), 2.281 (2.47), 2.323 (2.09), 2.327 (2.43), 2.366 (1.18), 2.416 (1.59), 2442 (1.91), 2463 (1.83), 2523 (3.29), 2564 (1.51), 2580 (1.04), 2597 (0.78), 2617 (0.48), 2665 (1.00), 2670 (1.26), 2710 (0.58) (0.80) (0.66), 4204 (0.70), 4936 (1.59), 5008 (1.59), 5045 (16.00), 7539 (4.94), 7560 (6.24), 7724 (3.37), 7730 (3.41), 7744 (2.75), 7750 (2.87), 8,334 (4.38), 8,340 (4.38). Example 558 (5S)-5-{[(3R,4S)-3,4-Difluoropyrrolidin-1-yl]carbonyl}-2-{[6-(trifluoromethyl)pyridin-3-yl]methyl}-5,6 -dihydro[1,2,4]triazolo[4,3-a]pyridin- 3(2H)-one

[01642] (5S)-5-{[(3R,4S)-3,4-Difluoropyrrolidin-1-yl]carbonyl}-2-{[6-(trifluoromethyl)pyridin-3-yl]methyl}-5, 6,7,8-tetrahydro[1,2,4]triazolo[4,3- a]pyridin-3(2H)-one (176 mg, 408 μmol) and cerium(IV) sulfate (542 mg, 1.63 mmol) were suspended in tert-butanol (1.7 mL) at room temperature. Subsequently, 1N aqueous sulfuric acid (1.7 mL, 32 mmol) was added, and the reaction mixture was stirred at 70 ° C for 72 hours. The reaction mixture was cooled to room temperature and adjusted to pH 9 with 2 N aqueous sodium hydroxide solution. The suspension was filtered and the filtrate was extracted three times with dichloromethane. The combined organic phases were dried over sodium sulfate and filtered, and the filtrate was concentrated. The residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 40mm; eluent: gradient (acetonitrile/water with 0.1% formic acid). The fractions containing the product were concentrated under reduced pressure and the residue was separated by Chiral preparatory HPLC [sample preparation: 34.8 mg dissolved in 3 mL ethanol; injection volume: 0.3 mL column: Daicel Chiralcel OX-H 5 μm, 250 x 20 mm; 25:75; flow rate: 15 ml/min; temperature 50°C; UV detection: 220 nm]. of the title compound. LC-MS (Method 1): Rt = 1.01 min; : -0.149 (1.91), -0.008 (15.66) (5S)-5-{[(3S)-3-Fluoropyrrolidin-1-yl]carbonyl}-2-{[2-(trifluoromethyl)pyrimidin-5-yl] methyl}-5,6,7,8-tetrahydro[1,2,4]triazolo[4,3- a]pyridin-3(2H)-one 0.008 (16.00), 0.146 (1.78), 0.996 (3.35 ), 1,006 (3.56), 1,131 (1.98), 1,150 (3.83), 1,168 (2.05), 1,223 (2.53), 1,240 (2.74), 1,347 (2.87), 1,475 (2.74), 2,287 (7.04), 2,327 (2.46 ), 2.366 (1.85), 2.670 (2.94), 2.709 (1.85), 2.906 (1.37), 3.777 (0.62), 3.896 (0.62), 3.950 (0.55), 5.087 (4.85), 5.108 (0.82), 6.250 (0.62 ), 6,316 (1.23), 7,923 (4.72), 8,661 (2.05). Example 559(5S)-5-{[(3S)-3-Fluoropyrrolidin-1-yl]carbonyl}-2-{[2-(trifluoromethyl)pyrimidin-5-yl]methyl}-5,6,7,8 -tetrahydro[1,2,4]triazolo[4,3- a]pyridin-3(2H)-one

[01643] (5S)-3-Oxo-2-{[2-(trifluoromethyl)pyrimidin-5-yl]methyl}-2,3,5,6,7,8-hexahydro[1,2,4 ]triazolo[4,3-a]pyridine-5-carboxylic acid (22.0 mg, 79% purity, 26.9 μmol) was initially loaded into THF (2.0 mL) at room temperature. Subsequently, HBTU (31.6 mg, 83.3 μmol) and N,N-diisopropylethylamine (56 μl, 320 μmol) were added. After stirring for 5 minutes, (3S)-3-fluoropyrrolidine hydrochloride (9.66 mg, 76.9 μmol) was added and the reaction mixture was stirred at room temperature overnight. The reaction mixture was mixed with ethyl acetate. The organic phase was washed with saturated sodium hydrogen carbonate solution, water and saturated aqueous sodium chloride solution, dried over sodium sulfate and filtered, and the filtrate was concentrated. The residue was purified via preparatory HPLC (Method 14). The fractions containing the product were concentrated under reduced pressure and 0.4 mg (3.6% possibility) of the title compound were obtained. LC-MS (Method 3): Rt = 1.30 min; MS (ESIpos): m /z = 415 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (2.02), -0.008 (16.00), 0.008 ( 15.11), 0.146 (1.96), 1.148 (0.70), 1.405 (2.85), 2.327 (4.62), 2.366 (1.96), 2.393 (5.82), 2.670 (4 .17), 2.710 (1.71), 3.876 (0.57), 9.068 (1.90). Example 560 (5S)-2-[(3-Chloro-5-fluoropyridin-2-yl)methyl]-5-{[(3S)-3-fluoropyrrolidin-1-yl]carbonyl}-5,6,7, 8-tetrahydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one

[01644] (5S)-2-[(3-Chloro-5-fluoropyridin-2-yl)methyl]-3-oxo-2,3,5,6,7,8-hexahydro[1,2, 4]triazolo[4,3-a]pyridine-5-carboxylic acid (150 mg, 459 μmol) was initially loaded into THF (37 μl), and HBTU (226 mg, 597 μmol) and N,N-diisopropylethylamine (240 μl, 1.4 mmol) were subsequently added. After stirring at room temperature for 15 minutes, (3S)-3-fluoropyrrolidine hydrochloride (63.4 mg, 505 μmol) was added and the reaction mixture was stirred at room temperature overnight. The solvent was removed under reduced pressure, and the residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/water gradient). The fractions containing the product were concentrated under reduced pressure and 42.7 mg (23% possibility) of the title compound were obtained. LC-MS (Method 3): Rt = 1.04 min; MS (ESIpos): m /z = 398 [M+H]+ ¹H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (0.48), -0.008 (3.94), 0.008 (3.64), 0.146 (0.42), 1243 (0.46), 1258 (0.46), 1726 (1.88), 1894 (0.48), 2016 (0.71), 2073 (16.00), 2094 (1.03), 2264 (0.57), 2327 (1.25), 2366 (0.69), 2578 (1.45), 2621 (0.53), 2669 (1.25), 2710 (0.67), 3359 (0.42), 3405 (0.48), 3501 (0.46), 3628 (1.23), 3651 (1.19), 3680 (0.77) (0.89) (0.85), 5.509 (0.51), 8.101 (1.66), 8.107 (1.82), 8.122 (1.78), 8.129 (1.84), 8.546 (3.25), 8.553 (3.19). Example 561 (5RS)-2-[(6-Chlorpyridin-3-yl)methyl]-5-{[(3S)-3-fluoropyrrolidin-1-yl]carbonyl}-5,6,7,8-tetra- hydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one (racemate)

[01645] (5RS)-2-[(6-Chloropyridin-3-yl)methyl]-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4]triazolo[ 4,3-a]pyridine-5-carboxylic acid (racemate) (130 mg, 421 μmol) was initially loaded into THF (34 μl), and 1-[bis(dimethylamino)methylene]-1H-benzotriazol-1-io Hexafluorophosphate 3-oxide (208 mg, 547 μmol) and N,N-diisopropylethylamine (220 μl, 1.3 mmol) were subsequently added. After stirring at room temperature for 15 minutes, (3S)-3-fluoropyrrolidine hydrochloride (58.2 mg, 463 μmol) was added and the reaction mixture was stirred at room temperature overnight. The solvent was removed under reduced pressure, and the residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/water gradient). The fractions containing the product were concentrated under reduced pressure and 73.6 mg (46% possibility) of the title compound were obtained. LC-MS (Method 3): Rt = 1.02 min; MS (ESIpos): m /z = 380 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (1.02), -0.008 (13.52), 0.008 (9.53), 0.146 (1.12) (12.01) (1.60) (1.22) (16.00) (3.21), 7,704 (2.48), 7,710 (4.38), 7,717 (2.33), 8,297 (5.25). Example 562 (5RS,7RS)-2-{[3-Chloro-5-(trifluoromethyl)pyridin-2-yl]methyl}-5-{[(3S)-3-fluoropyrrolidin-1-yl]carbonyl}-7 -(trifluoromethyl)-5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one (mixture of diastereomer, 2 isomers)

[01646] (5RS,7RS)-2-{[3-Chloro-5-(trifluoromethyl)pyridin-2-yl]methyl}-3-oxo-7-(trifluoromethyl)-2,3,5,6,7 ,8-hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylic acid (mixture of diastereomer; 4 isomers) (423 mg, 50% purity, 476 μmol) was initially loaded in THF (4.5 mL), and HBTU (234 mg, 618 μmol) and N,N-diisopropylethylamine (250 μl, 1.4 mmol) were subsequently added. After stirring at room temperature for 15 minutes, (3S)-3-fluoropyrrolidine hydrochloride (71.7 mg, 571 μmol) was added and the reaction mixture was stirred at room temperature overnight. The solvent was removed under reduced pressure, and the residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/water gradient). The fractions containing the product were concentrated under reduced pressure and 54.6 mg (22% possibility) of the title compound were obtained. LC-MS (Method 3): Rt = 1.70 min; MS (ESIpos): m /z = 516 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (1.14), -0.008 (16.00), 0.008 (8.79), 0.146 (1.14) (1.84) (0.54) (2.55). Example 563 (5RS,7RS)-2-{[3-Chloro-5-(trifluoromethyl)pyridin-2-yl]methyl}-5-{[(3S)-3-fluoropyrrolidin-1-yl]carbonyl}-7 -(trifluoromethyl)-5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one (isomer 2)

[01647] (5RS,7RS)-2-{[3-Chloro-5-(trifluoromethyl)pyridin-2-yl]methyl}-5-{[(3S)-3-fluoropyrrolidin-1-yl]carbonyl}- 7-(trifluoromethyl)-5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one (diastereomer mixture; 2 isomers) was separated by chiral preparatory HPLC [sample preparation: 55 mg dissolved in 8 mL of acetonitrile; injection volume: 0.9 mL; column: Daicel Chiralpak® AD, 250 x 20 mm; eluent: CO2/isopropanol 85:15; flow rate: 80 ml/min; temperature 40°C; UV detection: 210 nm]. After separation, 17 mg of isomer 1, which eluted first, and 18 mg of isomer 2, which eluted later, were isolated. Isomer 2:

[01648] Analytical chiral HPLC: Rt = 2.4 min, de = 98% [column: Daicel Chiralpak® AD 50 x 4.6 mm; eluent: CO2/isopropanol 85:15; flow rate: 3 ml/min; UV detection: 210 nm]. LC-MS (Method 3): Rt = 1.70 min; MS (ESIpos): m /z = 516 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (0.86), -0.008 (6.12), 0.008 (5.73), 0.068 (0.53), 0.146 (0.79), 1.029 (0.66), 1.045 (0.66), 1.146 (0.66), 1.999 (1.05), 2.104 (2.17) (4.48), 2.231 (5.40), 2.245 (4.61), 2.280 (6.98), 2.322 (4.48), 2.327 (4.81), 2.366 (1.51), 2.523 (10.01), 2.652 (2.77), 2.669 (5.86), 2.685 (4.41) (2.17) (4.81) (2.50) (2.44) (16.00), 8,894 (15.54). Example 564 (5RS,7RS)-2-{[3-Chloro-5-(trifluoromethyl)pyridin-2-yl]methyl}-5-[(3,3-difluoropyrrolidin-1-yl)carbonyl]-7-( trifluoromethyl)-5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one (diastereomer 1; racemate)

[01649] (5RS,7RS)-2-{[3-Chloro-5-(trifluoromethyl)pyridin-2-yl]methyl}-3-oxo-7-(trifluoromethyl)-2,3,5,6,7 ,8-hexahydro[1,2,4]triazolo[4,3- a]pyridine-5-carboxylic acid (mixture of diastereomer; 4 isomers) (423 mg, 951 μmol) was initially loaded into THF (9, 0 mL), and 1-[bis(dimethylamino)methylene]-1H-benzotriazol-1-io-3-oxide hexafluorophosphate (469 mg, 1.24 mmol) and N,N-diisopropylethylamine (500 μl, 2.9 mmol) were subsequently added. After stirring at room temperature for 15 minutes, 3,3-difluoropyrrolidine hydrochloride (164 mg, 1.14 mmol) was added and the reaction mixture was stirred at room temperature overnight. The solvent was removed under reduced pressure, and the residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/gradient water) and diastereomer 1 was isolated. The fractions containing the product were concentrated under reduced pressure and 48.0 mg (9% possibility) of the title compound were obtained. LC-MS (Method 3): Rt = 1.85 min; MS (ESIpos): m /z = 534 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (0.81), -0.008 (6.61), 0.008 (7.06), 0.146 (0.71), 2073 (16.00), 2158 (0.58), 2194 (0.81), 2240 (0.58), 2272 (1.10), 2323 (1.45), 2327 (1.74), 2366 (0.84), 2424 (0.87), 2440 (0.87), 2523 (4.03), 2669 (2.06), 2702 (1.32), 2710 (1.58), 2734 (0.81), 2959 (2.10), 2996 (1.35), 3540 (0.68), 3560 (1.32), 3581 (1.16) (0.55) (4.48), 5,214 (1.23), 8,505 (3.45), 8,890 (3.42). Example 565 (5RS,7RS)-2-{[3-Chloro-5-(trifluoromethyl)pyridin-2-yl]methyl}-5-[(3,3-difluoropyrrolidin-1-yl)carbonyl]-7-( trifluoromethyl)-5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one (enantiomer 2)

[01650] (5RS,7RS)-2-{[3-Chloro-5-(trifluoromethyl)pyridin-2-yl]methyl}-5-[(3,3-difluoropyrrolidin-1-yl)carbonyl]-7- (trifluoromethyl)-5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one (diastereomer 1; racemate) was separated by chiral preparatory HPLC [sample preparation: 48 mg dissolved in 2.5 mL of ethanol/acetonitrile (1:1); injection volume: 0.15 mL; column: Daicel Chiralcel® OX-H 5 μm, 250 x 20 mm; eluent: n-heptane/ethanol (10:80) + 0.2% diethylamine; flow rate: 30 ml/min; temperature 28°C; UV detection: 220 nm]. After separation, 9.9 mg of enantiomer 1, which eluted first, and 9.1 mg of enantiomer 2, which eluted later, were isolated. Enantiomer 2:

[01651] Analytical chiral HPLC: Rt = 6.38 min, ee = 100% [column: Daicel Chiralcel® OX-H-3 250 x 4.6 mm; eluent: heptane/ethanol (1:1) + 0.2% diethylamine; flow rate: 1 ml/min; UV detection: 220 nm]. LC-MS (Method 3): Rt = 1.82 min; MS (ESIpos): m /z = 534 [M+H]+ ¹H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (2.14), -0.008 (15.25), 0.008 (16.00), 0.146 (1.94) (3.43) (5.22) (1.49) (2.43), 5.051 (2.53), 5.065 (2.48), 5.107 (2.78), 5.148 (10.68), 5.174 (11.33), 5.214 (2.93), 8.502 (7.90), 8.890 (7.90). Example 566 (5RS,7RS)-2-[(5-Chloropyridin-2-yl)methyl]-5-[(3,3-difluoropyrrolidin-1-yl)carbonyl]-7-(trifluoromethyl)-5,6, 7,8-tetrahydro[1,2,4]triazolo[4,3- a]pyridin-3(2H)-one (diastereomer 1; racemate)

[01652] (5RS,7RS)-2-[(5-Chloropyridin-2-yl)methyl]-3-oxo-7-(trifluoromethyl)-2,3,5,6,7,8-hexahydro[ 1,2,4]triazolo[4,3-a]pyridine-5-carboxylic acid (mixture of diastereomer; 4 isomers) (393 mg, 76% purity, 793 μmol) was initially loaded into THF (3.8 mL ), and HBTU (391 mg, 1.03 mmol) and N,N-diisopropylethylamine (410 μl, 2.4 mmol) were subsequently added. After stirring at room temperature for 15 minutes, 3,3-difluoropyrrolidine hydrochloride (137 mg, 951 μmol) was added and the reaction mixture was stirred at room temperature overnight. The solvent was removed under reduced pressure, and the residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/water gradient). The fractions containing the product were concentrated under reduced pressure and 171 mg (45% possibility) of the title compound were obtained. LC-MS (Method 4): Rt = 0.87 min; MS (ESIpos): m /z = 466 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: 2.125 (0.60), 2.141 (0.72), 2.161 (1.46), 2.172 (1.67 ), 2,192 (1.64), 2,206 (2.29), 2,220 (1.51), 2,235 (1.39), 2,251 (1.32), 2,273 (2.84), 2,290 (3.01), 2,327 (2.24), 2,377 (0.97), 2,396 (1.79 ), 2.426 (2.36), 2.443 (2.27), 2.461 (1.61), 2.565 (2.70), 2.583 (2.16), 2.603 (1.46), 2.686 (1.65), 2.714 (2.61), 2.723 (3.94), 2.732 (2.44 ), 2,754 (2.45), 2,936 (2.06), 2,972 (5.32), 3,013 (2.95), 3,518 (0.44), 3,538 (0.84), 3,549 (1.85), 3,567 (4.66), 3,586 (3.76), 3,602 (1.90 ), 3.681 (0.54), 3.714 (1.84), 3.753 (3.10), 3.785 (3.25), 3.816 (1.94), 3.850 (0.49), 3.879 (0.44), 3.905 (1.92), 3.922 (3.99), 3.939 (4.34 ), 3.957 (1.84), 3.982 (0.44), 4.112 (0.52), 4.141 (1.65), 4.169 (1.47), 4.181 (2.52), 4.211 (2.65), 4.239 (1.52), 4.896 (2.75), 4.937 (14.75 ), 4,953 (16.00), 4,979 (3.36), 4,993 (3.14), 5,046 (3.20), 5,060 (3.14), 7,221 (8.97), 7,242 (9.62), 7,919 (6.01), 7,926 (6.46), 7,941 (5.80 ), 7,947 (6.12), 8,574 (8.32), 8,579 (8.50). Example 567 (5RS,7RS)-2-[(5-Chloropyridin-2-yl)methyl]-5-[(3,3-difluoropyrrolidin-1-yl)carbonyl]-7-(trifluoromethyl)-5,6, 7,8-tetrahydro[1,2,4]triazolo[4,3- a]pyridin-3(2H)-one (enantiomer 2)

[01653] (5RS,7RS)-2-[(5-Chloropyridin-2-yl)methyl]-5-[(3,3-difluoropyrrolidin-1-yl)carbonyl]-7-(trifluoromethyl)-5,6 ,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one (diastereomer 1; racemate) was separated by chiral preparatory HPLC [sample preparation: 170 mg dissolved in 5 mL of ethanol/n-heptane (3:2); injection volume: 0.5 mL; column: Daicel Chiralpak® ID, 250 x 20 mm; eluent: n-heptane/ethanol 60:40; flow rate: 15 ml/min; temperature 45°C; UV detection: 210 nm]. After separation, 77 mg of isomer 1, which eluted first, and 75 mg of isomer 2, which eluted later, were isolated. Enantiomer 2:

[01654] Analytical chiral HPLC: Rt = 3.17 min, ee = 100% [column: Daicel Chiralpak® IC-3 50 x 4.6 mm; eluent: n-heptane/ethanol 70:30; flow rate: 1 ml/min; UV detection: 220 nm]. LC-MS (Method 3): Rt = 1.58 min; MS (ESIpos): m /z = 466 [M+H]+ ¹H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (1.00), -0.008 (7.03), 0.008 (7.68), 0.146 (0.79) (2.37) (2.51) (2.80) (2.37) (9.26), 7,920 (6.67), 7,926 (6.82), 7,941 (6.39), 7,947 (6.67), 8,574 (5.96), 8,579 (6.10). Example 568 (5S)-2-[(5-Chloro-3-fluoropyridin-2-yl)methyl]-5-{[(3S)-3-fluoropyrrolidin-1-yl]carbonyl}-5,6,7, 8-tetrahydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one

[01655] (5S)-2-[(5-Chloro-3-fluoropyridin-2-yl)methyl]-3-oxo-2,3,5,6,7,8-hexahydro[1,2, 4]triazolo[4,3-a]pyridine-5-carboxylic acid (500 mg, 1.53 mmol) was initially loaded into THF (10 mL), and HBTU (755 mg, 1.99 mmol) and N,N -diisopropylethylamine (800 μl, 4.6 mmol) were subsequently added. After stirring at room temperature for 15 minutes, (3S)-3-fluoropyrrolidine hydrochloride (211 mg, 1.68 mmol) was added and the reaction mixture was stirred at room temperature overnight. The solvent was removed under reduced pressure, and the residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/water gradient). The fractions containing the product were concentrated under reduced pressure and 224 mg (37% possibility) of the title compound were obtained. LC-MS (Method 4): Rt = 0.64 min; MS (ESIpos): m /z = 398 [M+H]+ ¹H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (0.47), -0.008 (4.50), 0.008 (3.40), 0.146 (0.48) (2.11) (1.24) (1.76) (1.40) (3.42) (3.80) (3.12) (15.45). Example 569 (5RS,7RS)-2-[(3,5-Difluoropyridin-2-yl)methyl]-5-{[(3S)-3-fluoropyrrolidin-1-yl]carbonyl}-7-(trifluoromethyl)- 5,6,7,8-tetrahydro[1,2,4]triazolo[4,3- a]pyridin-3(2H)-one (diastereomer mixture; 4 isomers)

[01656] (5RS,7RS)-2-[(3,5-Difluoropyridin-2-yl)methyl]-3-oxo-7- (trifluoromethyl)-2,3,5,6,7,8-hexa- hydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylic acid (mixture of diastereomer; 4 isomers) (123 mg, 96% purity, 312 μmol) was initially loaded into THF (10 mL ), and HBTU (154 mg, 406 μmol) and N,N-diisopropylethylamine (160 μl, 940 μmol) were subsequently added. After stirring at room temperature for 15 minutes, (3S)-3-fluoropyrrolidine hydrochloride (47.0 mg, 375 μmol) was added and the reaction mixture was stirred at room temperature overnight. The solvent was removed under reduced pressure, and the residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/water gradient). The fractions containing the product were concentrated under reduced pressure and 92.9 mg (63% possibility) of the title compound were obtained. LC-MS (Method 4): Rt = 0.73 min; MS (ESIpos): m /z = 450 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (0.66), -0.008 (5.04), 0.008 (4.55), 0.146 (0.66), 1312 (0.45), 2000 (0.83), 2073 (1.32), 2118 (3.31), 2149 (5.50), 2168 (3.97), 2185 (5.50), 2199 (5.37), 2216 (5.04), 2262 (4.38) (8.19) (1.45) (1.45) (2.36) (2.48) (4.51), 7,990 (4.80), 8,467 (15.71), 8,472 (16.00). Example 570 (5RS,7RS)-2-[(3,5-Difluoropyridin-2-yl)methyl]-5-{[(3S)-3-fluoropyrrolidin-1-yl]carbonyl}-7-(trifluoromethyl)- 5,6,7,8-tetrahydro[1,2,4]triazolo[4,3- a]pyridin-3(2H)-one (isomer 2)

[01657] (5RS,7RS)-2-[(3,5-Difluoropyridin-2-yl)methyl]-5-{[(3S)-3-fluoropyrrolidin-1-yl]carbonyl}-7-(trifluoromethyl) -5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one (diastereomer mixture; 4 isomers) was separated by chiral preparatory HPLC [ sample preparation: 82.6 mg dissolved in 4 mL of ethanol/acetonitrile (3:1); injection volume: 0.30 mL; column: Daicel Chiralcel® IC 5 μm, 250 x 20 mm; eluent: n-heptane/ethanol (1:1); flow rate: 15 ml/min; temperature 30°C; UV detection: 210 nm]. After separation, 34.4 mg of isomer 1, which eluted first, and 36.6 mg of isomer 2, which eluted later, were isolated. Isomer 2:

[01658] Analytical chiral HPLC: Rt = 2.237 min, de = 100% [column: Daicel Chiralcel® IC-3 50 x 4.6 mm; eluent: n-heptane/ethanol (1:1); flow rate: 1 ml/min; UV detection: 220 nm]. LC-MS (Method 3): Rt = 1.35 min; MS (ESIpos): m /z = 450 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.150 (1.82), -0.008 (12.17), 0.008 (12.50), 0.146 (1.68) 2.89), 2.710 (5.38), 2.946 (8.07), 2.981 (6.45), 3.390 (2.62), 3.434 (1.95), 3.523 (1.82), 3.646 (3.03), 3.668 (4.64), 3.692 (4.91), 3.722 ( 2.29), 3.820 (3.23), 3.845 (3.83), 3.867 (2.08), 3.919 (2.62), 3.976 (1.88), 4.917 (7.13), 4.956 (11.83), 5.012 (6.45), 5.052 (3.03), 5.265 ( 2.62), 5.396 (4.17), 5.530 (1.95), 7.937 (4.10), 7.943 (4.64), 7.967 (6.79), 7.985 (4.37), 7.991 (4.37), 8.467 (16.00), 8.472 (15.93). Example 571 (5RS,7RS)-2-[(3-Chloro-5-fluoropyridin-2-yl)methyl]-5-{[(3S)-3-fluoropyrrolidin-1-yl]carbonyl}-7-(trifluoromethyl )-5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one (mixture of diastereomer 1; 2 isomers)

[01659] (5RS,7RS)-2-[(3-chloro-5-fluoropyridin-2-yl)methyl]-3-oxo-7- (trifluoromethyl)-2,3,5,6,7,8- Hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylic acid (mixture of diastereomer; 4 isomers) (100 mg, 253 μmol) was initially loaded into THF (3.0 mL) , and HBTU (125 mg, 329 μmol) and N,N-diisopropylethylamine (130 μl, 760 μmol) were subsequently added. After stirring at room temperature for 15 minutes, (3S)-3-fluoropyrrolidine hydrochloride (38.2 mg, 304 μmol) was added and the reaction mixture was stirred at room temperature overnight. The solvent was removed under reduced pressure, and the residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/water gradient). The fractions containing the product were concentrated under reduced pressure and 85.0 mg (72% possibility) of the title compound were obtained. LC-MS (Method 3): Rt = 1.45 min; MS (ESIpos): m /z = 466 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.150 (0.48), -0.008 (4.20), 0.146 (0.46), 1.197 (4.10) (4.66) (1.65) (1.39) (1.47) (0.76) (2.03) (15.62). Example 572 (5RS,7RS)-2-[(3-Chloro-5-fluoropyridin-2-yl)methyl]-5-{[(3S)-3-fluoropyrrolidin-1-yl]carbonyl}-7-(trifluoromethyl )-5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one (isomer 2)

[01660] (5RS,7RS)-2-[(3-Chloro-5-fluoropyridin-2-yl)methyl]-5-{[(3S)-3-fluoropyrrolidin-1-yl]carbonyl}-7-( trifluoromethyl)-5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one (mixture of diastereomer 1; 2 isomers) was separated by HPLC chiral preparatory [sample preparation: 83.0 mg dissolved in 5 mL of i-propanol/acetonitrile (1:1); injection volume: 0.30 mL; column: Daicel Chiralcel® IB 5 μm, 250 x 20 mm; eluent: n-heptane/i-propanol (25:75); flow rate: 15 ml/min; temperature 35°C; UV detection: 220 nm]. After separation, 32.5 mg of isomer 1, which eluted first, and 32.6 mg of isomer 2, which eluted later, were isolated. Isomer 2:

[01661] Analytical chiral HPLC: Rt = 4.109 min, de = 100% [column: Daicel Chiralcel® IB-3 50 x 4.6 mm; eluent: n-heptane/i-propanol (1:1); flow rate: 1 ml/min; UV detection: 220 nm]. LC-MS (Method 3): Rt = 1.46 min; MS (ESIpos): m /z = 466 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.150 (1.21), -0.008 (9.38), 0.008 (8.11), 0.146 (1.05) (4.86), 2.240 (4.14), 2.273 (6.68), 2.297 (2.92), 2.322 (2.37), 2.327 (3.20), 2.366 (2.10), 2.523 (7.12), 2.643 (2.37), 2.660 (2.98), 2.665 (2.92) (7.50) (2.04) (4.14) (4.91) (8.17), 8,119 (8.77), 8,134 (8.33), 8,140 (8.99), 8,543 (16.00), 8,549 (15.78). Example 573 (5RS,7RS)-2-[(3,5-Difluoropyridin-2-yl)methyl]-5-[(3,3-difluoropyrrolidin-1-yl)carbonyl]-7-(trifluoromethyl)-5, 6,7,8-tetrahydro[1,2,4]triazolo[4,3- a]pyridin-3(2H)-one (diastereomer 1; racemate)

[01662] (5RS,7RS)-2-[(3,5-Difluoropyridin-2-yl)methyl]-3-oxo-7- (trifluoromethyl)-2,3,5,6,7,8-hexa- hydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylic acid (mixture of diastereomer; 4 isomers) (90.0 mg, 96% purity, 228 μmol) was initially loaded into THF ( 2.0 mL), and HBTU (113 mg, 297 μmol) and N,N-diisopropylethylamine (120 μl, 690 μmol) were subsequently added. After stirring at room temperature for 15 minutes, 3,3-difluoropyrrolidine hydrochloride (39.4 mg, 274 μmol) was added and the reaction mixture was stirred at room temperature overnight. The solvent was removed under reduced pressure, and the residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/water gradient). The fractions containing the product were concentrated under reduced pressure and 68.7 mg (62% possibility) of the title compound were obtained. LC-MS (Method 4): Rt = 0.83 min; MS (ESIpos): m /z = 468 [M+H]+ ¹H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.008 (1.74), 1.404 (2.01), 2.098 (1.04), 2.114 ( 1.19), 2.133 (2.22), 2.144 (2.67), 2.163 (2.48), 2.179 (3.71), 2.194 (2.19), 2.209 (2.15), 2.225 (2.01), 2.257 (4.64), 2.283 (2.63), 2.328 ( 0.83), 2.375 (1.44), 2.394 (2.76), 2.412 (2.48), 2.424 (3.58), 2.441 (3.18), 2.460 (2.18), 2.469 (1.85), 2.524 (2.66), 2.562 (4.10), 2.582 ( 3.23), 2.602 (2.30), 2.620 (1.20), 2.639 (1.82), 2.648 (2.48), 2.673 (4.46), 2.683 (6.28), 2.692 (4.09), 2.716 (3.58), 2.724 (3.18), 2.940 ( 9.27), 2.981 (5.71), 3.512 (0.75), 3.531 (1.47), 3.542 (3.00), 3.560 (7.48), 3.580 (5.90), 3.596 (2.96), 3.609 (1.20), 3.626 (0.72), 3.673 ( 0.89), 3.707 (2.73), 3.746 (4.58), 3.776 (4.66), 3.808 (2.96), 3.844 (1.14), 3.873 (0.81), 3.892 (1.79), 3.899 (2.90), 3.917 (7.20), 3.936 ( 7.09), 3956 (2.73), 3962 (1.95), 3982 (0.81), 4105 (0.92), 4134 (2.60), 4146 (0.99), 4163 (2.09), 4176 (4.09), 4204 (3.97), 4237 ( 2,24), 4,266 (0.65), 4,925 (5,80), 4,936 (5,21), 4,961 (13.01), 5,015 (15,41), 5,034 (4,96), 5,050 (5,57), 7,938 (4,48), 7,943 (4,78), 7,962 ( 6.94), 7.966 (7.24), 7.985 (4.63), 7.991 (4.78), 8.465 (16.00), 8.471 (15.52). Example 574 (5RS,7RS)-2-[(3,5-Difluoropyridin-2-yl)methyl]-5-[(3,3-difluoropyrrolidin-1-yl)carbonyl]-7-(trifluoromethyl)-5, 6,7,8-tetrahydro[1,2,4]triazolo[4,3- a]pyridin-3(2H)-one (enantiomer 1)

[01663] (5RS,7RS)-2-[(3,5-Difluoropyridin-2-yl)methyl]-5-[(3,3-difluoropyrrolidin-1-yl)carbonyl]-7-(trifluoromethyl)-5 ,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one (diastereomer 1; racemate) was separated by chiral preparatory HPLC [sample preparation: 59.9 mg dissolved in 4 mL of ethanol/acetonitrile (1:1); injection volume: 0.20 mL; column: Daicel Chiralcel® IC 5 μm, 250 x 20 mm; eluent: n-heptane/ethanol (1:1); flow rate: 15 ml/min; temperature 30°C; UV detection: 210 nm]. After separation, 27.8 mg of enantiomer 1, which eluted first, and 27.2 mg of enantiomer 2, which eluted later, were isolated. Enantiomer 1:

[01664] Analytical chiral HPLC: Rt = 1.483 min, ee = 100% [column: Daicel Chiralcel® IC-3 50 x 4.6 mm; eluent: n-heptane/ethanol (1:1); flow rate: 1 ml/min; UV detection: 220 nm]. LC-MS (Method 3): Rt = 1.50 min; MS (ESIpos): m /z = 468 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: 0.008 (6.37), 2.179 (2.78), 2.257 (3.92), 2.327 (2.12 ), 2,366 (2.22), 2,673 (4.20), 2,682 (4.63), 2,710 (3.16), 2,941 (6.80), 2,978 (4.11), 3,541 (2.22), 3,560 (5.90), 3,580 (4.44), 3,707 (2.22 ), 3,747 (3.40), 3,776 (3.59), 3,809 (1.98), 3,899 (2.31), 3,917 (5.47), 3,936 (5.24), 3,956 (2.03), 4,133 (1.89), 4,177 (2.97), 4,204 (2.97 ), 4,235 (1.79), 4,924 (4.34), 4,961 (9.82), 5,014 (11.66), 5,034 (3.87), 5,052 (4.20), 7,938 (3.82), 7,944 (4.29), 7,967 (6.18), 7,985 (3.73 ), 7,991 (4.20), 8,465 (16.00), 8,471 (15.24). Example 575 (5RS,7RS)-2-[(3-Chloro-5-fluoropyridin-2-yl)methyl]-5-[(3,3-difluoropyrrolidin-1-yl)carbonyl]-7-(trifluoromethyl)- 5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one (diastereomer 1; racemate)

[01665] (5RS,7RS)-2-[(3-Chloro-5-fluoropyridin-2-yl)methyl]-3-oxo-7- (trifluoromethyl)-2,3,5,6,7,8- Hexahydro[1,2,4]triazolo[4,3-a]pyridine-5-carboxylic acid (mixture of diastereomer; 4 isomers) (100 mg, 253 μmol) was initially loaded into THF (3.0 mL) , and HBTU (125 mg, 329 μmol) and N,N-diisopropylethylamine (130 μl, 760 μmol) were subsequently added. After stirring at room temperature for 15 minutes, 3,3-difluoropyrrolidine hydrochloride (43.6 mg, 304 μmol) was added and the reaction mixture was stirred at room temperature overnight. The solvent was removed under reduced pressure, and the residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/water gradient). The fractions containing the product were concentrated under reduced pressure and 98.5 mg (80% possibility) of the title compound were obtained. LC-MS (Method 3): Rt = 1.60 min; MS (ESIpos): m /z = 484 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: 2.073 (6.45), 2.189 (2.26), 2.257 (2.86), 2.328 (1.53 ), 2.425 (2.10), 2.693 (3.86), 2.736 (2.40), 2.950 (5.52), 2.983 (3.83), 3.541 (1.70), 3.560 (4.29), 3.581 (3.93), 3.598 (1.83), 3.710 (1.43 ), 3,745 (2.73), 3,779 (3.03), 3,807 (1.76), 3,920 (4.22), 3,939 (4.29), 3,958 (1.66), 4,134 (1.40), 4,178 (2.49), 4,206 (2.23), 4,238 (1.56 ), 4,953 (2.89), 4,977 (4.86), 5,017 (12.87), 5,038 (3.29), 5,056 (13.87), 5,097 (4.56), 8,113 (6.82), 8,119 (7.38), 8,134 (6.69), 8,140 (7.32 ), 8,540 (16.00), 8,546 (15.67). Example 576 (5RS,7RS)-2-[(3-Chloro-5-fluoropyridin-2-yl)methyl]-5-[(3,3-difluoropyrrolidin-1-yl)carbonyl]-7-(trifluoromethyl)- 5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one (enantiomer 2)

[01666] (5RS,7RS)-2-[(3-Chloro-5-fluoropyridin-2-yl)methyl]-5-[(3,3-difluoropyrrolidin-1-yl)carbonyl]-7-(trifluoromethyl) -5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one (diastereomer 1; racemate) was separated by chiral preparatory HPLC [preparation of sample: 93.0 mg dissolved in 4 mL of ethanol/acetonitrile (1:1); injection volume: 0.20 mL; column: Daicel Chiralcel® IC 5 μm, 250 x 20 mm; eluent: n-heptane/ethanol (1:1); flow rate: 15 ml/min; temperature 30°C; UV detection: 220 nm]. After separation, 40.9 mg of enantiomer 1, which eluted first, and 38.3 mg of enantiomer 2, which eluted later, were isolated. Enantiomer 2:

[01667] Analytical chiral HPLC: Rt = 1.874 min, ee = 100% [column: Daicel Chiralcel® IC-3 50 x 4.6 mm; eluent: n-heptane/ethanol (1:1); flow rate: 1 ml/min; UV detection: 220 nm]. LC-MS (Method 3): Rt = 1.60 min; MS (ESIpos): m /z = 484 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (2.11), -0.008 (16.00), 0.008 (13.37), 0.146 (1.89) (3.05) (3.79), 8,113 (5.89), 8,119 (6.11), 8,134 (5.47), 8,140 (5.89), 8,540 (13.47), 8,546 (12.42). Example 577 (5S)-5-{[(3S)-3-Fluoropyrrolidin-1-yl]carbonyl}-2-{[5-(trifluoromethyl)pyridin-3-yl]methyl}-5,6,7,8 -tetrahydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one

[01668] (5S)-3-Oxo-2-{[5-(trifluoromethyl)pyridin-3-yl]methyl}-2,3,5,6,7,8-hexahydro[1,2,4 ]triazolo[4,3-a]pyridine-5-carboxylic acid (46.5 mg, 136 μmol) was initially loaded into THF (1.1 mL), and HBTU (67.0 mg, 177 μmol) and N, N-diisopropylethylamine (95 μl, 680 μmol) was subsequently added. After stirring at room temperature for 15 minutes, (3S)-3-fluoropyrrolidine hydrochloride (20.5 mg, 163 μmol) was added and the reaction mixture was stirred at room temperature overnight. The solvent was removed under reduced pressure, and the residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/water gradient). The fractions containing the product were concentrated under reduced pressure and 29.5 mg (53% possibility) of the title compound were obtained. LC-MS (Method 3): Rt = 1.16 min; MS (ESIpos): m /z = 414 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: 1.695 (1.26), 1.734 (2.23), 1.888 (0.52), 1.924 (0.76 ), 1.999 (0.84), 2.034 (1.38), 2.047 (1.33), 2.068 (1.37), 2.088 (1.85), 2.104 (2.27), 2.138 (1.59), 2.221 (0.85), 2.242 (0.78), 2.256 (0.80 ), 2.270 (1.14), 2.327 (0.56), 2.569 (1.57), 2.577 (1.70), 2.591 (1.48), 2.617 (2.57), 2.660 (1.13), 2.670 (0.97), 3.361 (1.30), 3.371 (1.17 ), 3.398 (1.01), 3.406 (0.99), 3.460 (0.64), 3.468 (0.71), 3.495 (0.89), 3.504 (0.86), 3.613 (0.59), 3.630 (2.11), 3.637 (2.26), 3.654 (2.41 ), 3,666 (1.56), 3,681 (1.50), 3,698 (1.11), 3,725 (1.28), 3,746 (1.94), 3,770 (1.64), 3,784 (1.49), 3,855 (2.48), 4,703 (1.17), 4,712 (1.42 ), 4,719 (1.49), 4,728 (1.18), 4,762 (1.50), 4,770 (1.68), 4,777 (1.93), 4,786 (1.45), 5,017 (16.00), 5,260 (1.25), 5,384 (1.52), 5,391 (1.57 ), 5,512 (0.89), 8,059 (5.28), 8,742 (5.83), 8,917 (5.45). Example 578 (5S)-5-{[(3R,4S)-3,4-Difluoropyrrolidin-1-yl]carbonyl}-2-{[5-(trifluoromethyl)pyridin-3-yl]methyl}-5,6 ,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one

[01669] (5S)-3-Oxo-2-{[5-(trifluoromethyl)pyridin-3-yl]methyl}-2,3,5,6,7,8-hexahydro[1,2,4 ]triazolo[4,3-a]pyridine-5-carboxylic acid (130 mg, 380 μmol) was initially loaded into THF (3.1 mL), and HBTU (187 mg, 494 μmol) and N,N-diisopropylethylamine ( 200 μl, 1.1 mmol) were subsequently added. After stirring at room temperature for 15 minutes, (3R,4S)-3,4-difluoropyrrolidine hydrochloride (60.0 mg, 418 μmol) was added and the reaction mixture was stirred at room temperature overnight. The solvent was removed under reduced pressure, and the residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/water gradient). The fractions containing the product were concentrated under reduced pressure and 28.1 mg (17% possibility) of the title compound were obtained. LC-MS (Method 4): Rt = 0.71 min; MS (ESIpos): m /z = 432 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (1.89), -0.008 (14.86), 0.008 (16.00), 0.146 (1.81) (2.02), 2.674 (1.52), 2.710 (1.26), 3.684 (0.55), 3.729 (0.46), 4.825 (1.09), 5.020 (5.09), 8.061 (1.56), 8.740 (1.73), 8.915 (1.52). Example 579 (5S)-5-[(3,3-Difluoropyrrolidin-1-yl)carbonyl]-2-{[5-(trifluoromethyl)pyridin-3-yl]methyl}-5,6,7,8-tetra -hydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one

[01670] (5S)-3-Oxo-2-{[5-(trifluoromethyl)pyridin-3-yl]methyl}-2,3,5,6,7,8-hexahydro[1,2,4 ]triazolo[4,3-a]pyridine-5-carboxylic acid (130 mg, 380 μmol) was initially loaded into THF (3.1 mL), and HBTU (187 mg, 494 μmol) and N,N-diisopropylethylamine ( 200 μl, 1.1 mmol) were subsequently added. After stirring at room temperature for 15 minutes, 3,3-difluoropyrrolidine hydrochloride (60.0 mg, 418 μmol) was added and the reaction mixture was stirred at room temperature overnight. The solvent was removed under reduced pressure, and the residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/water gradient). The fractions containing the product were concentrated under reduced pressure and 32.6 mg (20% possibility) of the title compound were obtained. LC-MS (Method 3): Rt = 1.34 min; MS (ESIpos): m /z = 432 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (1.49), -0.008 (11.08), 0.008 (11.23), 0.146 (1.49), 1656 (1.12), 1735 (1.37), 2009 (1.73), 2072 (2.13), 2088 (0.97), 2327 (2.00), 2366 (1.46), 2425 (1.28), 2571 (3.49), 2582 (2.49) (1.24) (0.82) (1.18), 5,019 (16.00), 8,060 (5.25), 8,741 (5.22), 8,918 (4.80). Example 580 (5S)-2-[(3-Chloro-5-fluoropyridin-2-yl)methyl]-5-{[(3S)-3-fluoropyrrolidin-1-yl]carbonyl}-5,6,7, 8-tetrahydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one

[01671] (5S)-2-[(3-Chlor-5-fluoropyridin-2-yl)methyl]-3-oxo-2,3,5,6,7,8-hexahydro[1,2, 4]triazolo[4,3-a]pyridine-5-carboxylic acid (150 mg, 459 μmol) was initially loaded into THF (3.4 mL), and HBTU (226 mg, 597 μmol) and N,N-diisopropylethylamine (240 μl, 1.4 mmol) were subsequently added. After stirring at room temperature for 15 minutes, (3S)-3-fluoropyrrolidine hydrochloride (63.4 mg, 505 μmol) was added and the reaction mixture was stirred at room temperature overnight. The solvent was removed under reduced pressure, and the residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/water gradient). The fractions containing the product were concentrated under reduced pressure and 42.7 mg (23% possibility) of the title compound were obtained. LC-MS (Method 3): Rt = 1.04 min; MS (ESIpos): m /z = 398 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (0.48), -0.008 (3.94), 0.008 (3.64), 0.146 (0.42), 1243 (0.46), 1258 (0.46), 1726 (1.88), 1894 (0.48), 2016 (0.71), 2073 (16.00), 2094 (1.03), 2264 (0.57), 2327 (1.25), 2366 (0.69), 2578 (1.45), 2621 (0.53), 2669 (1.25), 2710 (0.67), 3359 (0.42), 3405 (0.48), 3501 (0.46), 3628 (1.23), 3651 (1.19), 3680 (0.77) (0.89) (0.85), 5.509 (0.51), 8.101 (1.66), 8.107 (1.82), 8.122 (1.78), 8.129 (1.84), 8.546 (3.25), 8.553 (3.19). Example 581 (5S)-2-[(3,5-Difluoropyridin-2-yl)methyl]-5-{[(3S)-3-fluoropyrrolidin-1-yl]carbonyl}-5,6,7,8- tetrahydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one

[01672] (5S)-2-[(3,5-Difluoropyridin-2-yl)methyl]-3-oxo-2,3,5,6,7,8-hexahydro[1,2,4] triazolo[4,3-a]pyridine-5-carboxylic acid (185 mg, 596 μmol) was initially loaded into THF (5.0 mL), and HBTU (294 mg, 775 μmol) and N,N-diisopropylethylamine (520 μl, 3.0 mmol) were subsequently added. After stirring at room temperature for 5 minutes, (S)(+)-3-fluoropyrrolidine hydrochloride (89.9 mg, 716 μmol) was added, and the reaction mixture was stirred at room temperature over a weekend. The reaction mixture was mixed with water and ethyl acetate, and the organic phase was removed. The organic phase was washed with saturated aqueous sodium hydrogen carbonate solution, water and saturated aqueous sodium chloride solution, dried over sodium sulfate and filtered, and the filtrate was concentrated. The residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: gradient (acetonitrile/water with 0.1% formic acid). The fractions containing the product were concentrated under reduced pressure and 38. 2 mg (17% possibility) of the title compound. LC-MS (Method 3): Rt = 0.96 min; MS (ESIpos): m / z = 382 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: 0.008 (2.60), 1.706 (9.68), 1.715 (10.82), 1.847 (1.79), 1.857 (1.68), 1.871 (1.71), 1.883 (2.85), 1.893 (2.55), 1.968 (2.44), 1.994 (4.47), 2.029 (2.47), 2.050 (4.18), 2.067 (6.02), 2.084 (5.61), 2.103 (5.56), 2.120 (2.96), 2.134 (3.42), 2.187 (0.87), 2.220 (2.22) (0.98) (1.87) (5.88) (4.61) (5.13), 5.510 (2.74), 7.924 (4.47), 7.930 (4.66), 7.948 (7.65), 7.953 (7.86), 7.972 (4.58), 7.978 (4.69), 8.465 (16.00), 8.471 (15.38). Example 582 (5RS,7RS)-5-{[rel-(3R,4R)-3,4-Difluoropyrrolidin-1-yl]carbonyl}-7-(trifluoromethyl)-2-{[6-(trifluoromethyl)pyridin- 3-yl]methyl}-5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one (diastereomer mixture; 8 isomers)

[01673] (5RS,7RS)-3-Oxo-7-(trifluoromethyl)-2-{[6-(trifluoromethyl)pyridin-3-yl]methyl}-2,3,5,6,7,8-hexa -hydro[1,2,4]triazolo[4,3- a]pyridine-5-carboxylic acid (mixture of diastereomer; 4 isomers) (259 mg, 92% purity, 581 μmol) was initially loaded into THF (5 .3 mL), and HBTU (286 mg, 755 μmol) and N,N-diisopropylethylamine (300 μl, 1.7 mmol) were subsequently added. After stirring at room temperature for 5 minutes, rel-(3R,4R)-3,4-difluoropyrrolidine hydrochloride (100 mg, 697 μmol) was added and the reaction mixture was stirred at room temperature overnight. The reaction mixture was mixed with water and ethyl acetate, and the organic phase was removed. The organic phase was washed three times with saturated aqueous sodium hydrogen carbonate solution and 1N aqueous hydrochloric acid. The aqueous phase was extracted with ethyl acetate and the combined organic phases were dried over sodium sulfate and filtered and the filtrate was concentrated. The residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: gradient (acetonitrile/water with 0.1% formic acid). The fractions containing the product were concentrated under reduced pressure and 311 mg were obtained (97% possibility) of the title compound. LC-MS (Method 3): Rt = 1.56 and 1.62 min MS (ESIpos): m /z = 500 [M +H]+ 1H-NMR (400; MHz, DMSO-d6) δ [ppm]: -0.008 (1.18), 0.008 (1.10), 1.171(2.12), 1.194 (15.97), 1.210 (16.00), 2.073 (1.12), 2.200 (0.77), 2.216 (1.54 ), 2.229 (1.70), 2.254 (1.42), 2.289 (0.48), 2.451 (1.81), 2.489 (6.72), 2.564 (1.85), 2.690 (0.88), 2.701 (0.92), 2.729 (1.49), 2.739 (1.37 ), 2.769 (1.51), 2.895 (0.95), 2.933 (0.63), 2.975 (1.58), 2.985 (2.01), 3.014 (1.57), 3.023 (1.95), 3.501 (0.87), 3.627 (0.56), 3.661 (0.78 ), 3.676 (1.06), 3.729 (0.55), 3.754 (2.19), 3.795 (0.53), 3.825 (0.69), 3.863 (0.48), 3.982 (0.54), 4.050 (0.44), 4.094 (1.10), 4.126 (0.41 ), 4.157 (0.66), 4.192 (0.96), 4.225 (0.54), 4.256 (0.68), 4.289 (0.48), 4.985 (1.04), 5.021 (0.69), 5.052 (8.26), 5.107 (1.17), 5.118 (1.11 ), 5.322 (0.83), 5.440 (1.32), 5.457 (1.10), 5.549 (0.50), 7.920 (10.95), 7.923 (10.77), 7.945 (0.58), 8.147 (2.92), 8.646 (4.33), 8.678 (0.41 ). Example 583 (5RS,7RS)-5-{[rel-(3R,4R)-3,4-Difluoropyrrolidin-1-yl]carbonyl}-7-(trifluoromethyl)-2-{[6-(trifluoromethyl)pyridin- 3-yl]methyl}-5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one (isomer 3)

[01674] (5RS,7RS)-5-{[rel-(3R, 3R)-3,4-Difluoropyrrolidin-1-yl]carbonyl}-7-(trifluoromethyl)-2-{[6-(trifluoromethyl)pyridin -3-yl]methyl}-5,6,7,8- tetrahydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one (mixture of diastereomer; 8 isomers) was separated by chiral preparatory HPLC [sample preparation: 311 mg dissolved in 5 mL of ethanol/acetonitrile (1:1); injection volume: 0.1 mL; column: Daicel Chiralcel® OX-H 5 μm, 250 x 20 mm; eluent: n-heptane/ethanol (7:3); flow rate: 40 ml/min; temperature 35°C; UV detection: 220 nm]. After separation, 4 largest diastereomers were isolated. (82 mg of diastereomeric mixture (isomer 1 and isomer 2), which eluted first, 46.7 mg of isomer 3, which eluted later, and 39.4 mg of isomer 4, which eluted last) Isomer 3:

[01675] Analytical chiral HPLC: Rt = 2.63 min, de = 99% [column: Daicel Chiralpak® IA-3, 50 x 4.6 mm; eluent: i-hexane/ethanol (1:1); flow rate: 1 ml/min; UV detection: 220 nm]. LC-MS (Method 3): Rt = 1.62 min; MS (ESIpos): m /z = 500 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (0.84), -0.008 (6.67), 0.008 (6.52), 0.146 (0.70), 1100 (0.43), 1243 (3.42), 1258 (3.30), 1273 (2.09), 2163 (0.64), 2198 (1.62), 2214 (1.45), 2228 (1.77), 2256 (2.75), 2291 (1.16) (2.41) (1.71) (16.00), 7,923 (15.77), 8,645 (5.74). Example 584 (5RS,7RS)-5-{[rel-(3R,4R)-3,4-Difluoropyrrolidin-1-yl]carbonyl}-7-(trifluoromethyl)-2-{[6-(trifluoromethyl)pyridin- 3-yl]methyl}-5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one (isomer 4)

[01676] (5RS,7RS)-5-{[rel-(3R, 3R)-3,4-Difluoropyrrolidin-1-yl]carbonyl}- 7-(trifluoromethyl)-2-{[6-(trifluoromethyl)pyridin -3-yl]methyl}-5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one (diastereomer mixture; 8 isomers) was separated by chiral preparatory HPLC [sample preparation: 311 mg dissolved in 5 mL of ethanol/acetonitrile (1:1); injection volume: 0.1 mL; column: Daicel Chiralcel® OX-H 5 μm, 250 x 20 mm; eluent: n-heptane/ethanol (7:3); flow rate: 40 ml/min; temperature 35°C; UV detection: 220 nm]. After separation, 4 largest diastereomers were isolated. (82 mg of diastereomeric mixture (isomer 1 and isomer 2), which eluted first, 46.7 mg of isomer 3, which eluted later, and 39.4 mg of isomer 4, which eluted last) Isomer 4:

[01677] Analytical chiral HPLC: Rt = 3.25 min, d = 96.7% [Daicel Chiralpak® IA-3 column, 50 x 4.6 mm; eluent: i-hexane/ethanol (1:1) flow rate: 1 ml/min; UV detection: 220 nm] LC-MS (Method 3): Rt = 1.62 min; MS (ESIpos): m /z = 500 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.148 (0.80), -0.008 (5.80) 0.008 (5.01), 0.146 ( 0.89), 1.243 (4.40), 1.259 (4.16), 1.273 (2.95), 2.224 (3.88), 2.327 (1.96), 2.367 (1.68), 2.670 (2.85), 2.710 (1.82), 2.726 (2.15), 2.736 ( 2.95), 2.767 (1.73), 2.986 (2.95), 3.022 (2.11), 3.626 (1.50), 3.728 (1.22), 3.755 (1.96), 3.791 (1.08), 3.823 (1.96), 3.860 (1.08), 3.993 ( 1.22), 4094 (2.71), 4125 (1.22), 4155 (1.92), 4190 (1.03), 4983 (2.99), 5045 (7.77), 5051 (8.05), 5322 (1.08), 5456 (1.73), 5589 ( 1.12), 7,919 (16.00), 7,923 (15.20), 8,645 (5.80). Example 585 (5S,8SR)-2-[(3,5-Difluoropyridin-2-yl)methyl]-5-{[(3S)-3-fluoropyrrolidin-1-yl]carbonyl}-8-hydroxy-5, 6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one (mixture of diastereomer; 2 isomers)

[01678] (5S)-2-[(3,5-Difluoropyridin-2-yl)methyl]-5-{[(3S)-3-fluoropyrrolidin-1-yl]carbonyl}-5,6,7,8 -tetrahydro[1,2,4]triazolo[4,3- a]pyridin-3(2H)-one (46.0 mg, 121 μmol) and cerium(IV) sulfate (240 mg, 724 μmol) were suspended in tert-butanol (160 μl) at room temperature. Subsequently, 1 N aqueous sulfuric acid (160 μl, 3.0 mmol) was added, and the reaction mixture was stirred at 70 °C overnight. Cerium(IV) sulfate (240 mg, 724 μmol) and 1 N aqueous sulfuric acid (160 μl, 3.0 mmol) were added again, and at 70°C overnight. The reaction mixture was cooled to room temperature and adjusted to pH 9 with 1 N aqueous sodium hydroxide solution. The suspension was filtered and the filtrate was extracted three times with dichloromethane. The combined organic phases were dried over sodium sulfate and filtered, and the filtrate was concentrated. The residue was purified via preparatory HPLC (Phenomenex, 5μm silica gel, 21.2mm x 100mm; eluent: acetonitrile/gradient water). The fractions containing the product were concentrated under reduced pressure and 4.40 mg (9% possibility) of the title compound were obtained. LC-MS (Method 3): Rt = 0.76 min; MS (ESIpos): m /z = 398 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: 1.735 (4.24), 2.100 (3.29), 2.327 (11.14), 2.366 (8.63 ), 2,669 (9.73), 2,709 (6.27), 3,636 (5.65), 3,751 (4.08), 3,770 (4.08), 3,860 (5.33), 4,485 (7.84), 4,717 (3.29), 4,772 (3.92), 4,931 (4.08 ), 4,971 (10.04), 5,015 (7.53), 5,056 (3.76), 5,256 (2.82), 5,383 (4,86), 5,743 (10,82), 5,755 (11,29), 7,945 (4,55), 7,964 (7,53), 7,993 (3.92 ), 8,479 (16.00). Example 586 (5S)-2-[(5-Chloropyridin-2-yl)methyl]-5-[(3,3-difluoropyrrolidin-1-yl)carbonyl]-8,8-difluoro-5,6,7, 8-tetrahydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one

[01679] (5S)-2-[(5-Chloropyridin-2-yl)methyl]-5-[(3,3-difluoropyrrolidin-1-yl)carbonyl]-6,7-dihydro[1,2 ,4]triazolo[4,3-a]pyridine-3,8(2H,5H)-dione (79.4 mg, 88% purity, 170 μmol) was initially loaded into a Teflon flask under argon in dichloromethane ( 3 mL) at room temperature. Subsequently, diethylamino sulfur trifluoride (67 μl, 510 μmol) was added, and the mixture was stirred at 40°C overnight. The reaction mixture was mixed with water and saturated aqueous sodium hydrogen carbonate solution. The aqueous phase was extracted four times with dichloromethane, and the combined organic phases were dried over sodium sulfate and filtered, and the filtrate was concentrated. The residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: gradient (acetonitrile/water with 0.1% formic acid). The fractions containing the product were concentrated under reduced pressure and were obtained 53.6 mg (72% possibility) of the title compound. LC-MS (Method 3): Rt = 1.51 min MS (ESIpos): m / z = 434 [M+H]+ 1H-NMR (500; MHz, DMSO-d6) δ [ppm]: -0.120 (1.43), -0.007 (16.00), 0.006 (9.20), 0.116 (1.20), 2.292 (2.63), 2.340 (1.37), 2.358 (2.34), 2.361 ( 2.74), 2.365 (2.23), 2.440 (2.40), 2.518 (1.89), 2.522 (1.49), 2.566 (1.14), 2.580 (0.86), 2.593 (0.63), 2.631 (1.43), 2.635 (1.94), 2.639 ( 1.31), 3.563 (2.29), 3.578 (3.77), 3.593 (2.17), 3.705 (1.14), 3.732 (1.26), 3.766 (0.69), 3.792 (1.37), 3.818 (1.20), 3.825 (1.03), 3.831 ( 0.97), 3.846 (1.66), 3.861 (0.69), 3.893 (0.69), 3.908 (1.54), 3.923 (0.86), 3.929 (0.97), 3.944 (0.40), 4.027 (0.40), 4.050 (0.86), 4.061 ( 0.46), 4.072 (0.57), 4.085 (0.69), 4.107 (0.46), 4.159 (0.51), 4.183 (0.69), 4.203 (0.74), 4.961 (1.71), 5.036 (2.40), 5.047 (1.37), 5.068 ( 6.91) 6.34). Example 587 (5S)-2-[(5-Chloropyridin-2-yl)methyl]-8,8-difluoro-5-[(3-fluoroazetidin-1-yl)carbonyl]-5,6,7,8- tetrahydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one

[01680] (5S)-2-[(5-Chloropyridin-2-yl)methyl]-5-[(3-fluoroazetidin-1-yl)carbonyl]-6,7-dihydro[1,2,4 ]triazolo[4,3-a]pyridine-3,8(2H,5H)-dione (37.1 mg, 63% purity, 61.5 μmol) was initially charged under argon in dichloromethane (1.7 mL) at room temperature. Subsequently, diethylamino sulfur trifluoride (39 μl, 290 μmol) was added, and the mixture was stirred at 40°C overnight. The reaction mixture was mixed with water and saturated aqueous sodium hydrogen carbonate solution. The aqueous phase was extracted twice with dichloromethane, and the combined organic phases were dried over sodium sulfate and filtered, and the filtrate was concentrated. The residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: gradient (acetonitrile/water with 0.1% formic acid). The fractions containing the product were concentrated under reduced pressure and 12. 4 mg (48% possibility) of the title compound. LC-MS (Method 3): Rt = 1.33 min; MS (ESIpos): m / z = 402 [M+H]+ 1H-NMR (500 MHz, DMSO-d6) δ [ppm]: -0.120 (1.40), -0.007 (15.46), 0.006 (8.74), 0.117 (1.13), 1.058 (0.72), 1.067 (0.90), 1.072 (1.35), 1.087 (0.77) , 1.097 (0.81), 1.104 (0.77), 1.112 (1.26), 1.119 (1.35), 1.126 (1.13), 1.133 (0.95), 1.165 (0.68), 1.179 (0.86), 1.190 (0.86), 1.273 (1.62) , 1.345 (0.41), 2.224 (2.07), 2.237 (2.07), 2.303 (3.38), 2.312 (3.29), 2.358 (3.06), 2.361 (3.65), 2.365 (2.66), 2.405 (1.31), 2.428 (2.57) , 2,518 (1.94), 2,522 (1.22), 2,631 (1.76), 2,635 (2.52), 2,639 (1.67), 3,313 (10.05), 3.955 (1.58), 3,978 (1.80), 4,003 (1.53), 4,026 (1.58) , 4.201 (0.81), 4.216 (0.86), 4.227 (0.77), 4.248 (1.53), 4.260 (1.53), 4.272 (1.40), 4.283 (1.31), 4.302 (0.90), 4.315 (0.77), 4.328 (0.68) , 4,360 (0.95), 4,381 (1.76), 4,403 (1.76), 4,430 (1.85), 4,451 (1.04), 4,574 (0.77), 4,589 (0.90), 4,618 (0.81), 4,642 (1.31), 4,654 (1.26) , 4,682 (0.90), 4,698 (0.86), 4,705 (0.86), 4,727 (3.43), 4,735 (6,58), 5,040 (1.31), 5,071 (16.00), 5,080 (7,53), 5,112 (0.86), 5,373 (1.13) , 5,429 (1.13), 5,487 (1.13), 5,537 (0.99), 5,543 (1.08), 7,292 (7.12), 7,309 (7.44), 7,953 (4.91), 7,956 (4.96), 7,970 (4.64), 7,973 (4.60) , 8,288 (15.95), 8,583 (5.09), 8,589 (7.35), 8,595 (4.60). Example 588 (5S)-2-[(3,5-Difluoropyridin-2-yl)methyl]-5-[(3,3-difluoropyrrolidin-1-yl)carbonyl]-8,8-difluoro-5,6, 7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one

[01681] (5S)-2-[(3,5-Difluoropyridin-2-yl)methyl]-5-[(3,3-difluoropyrrolidin-1-yl)carbonyl]-6,7-dihydro[1 ,2,4]triazolo[4,3-a]pyridine-3,8(2H,5H)-dione (67.3 mg, 163 μmol) was initially charged under argon in dichloromethane (7 mL) at room temperature. Subsequently, diethylamino sulfur trifluoride (86 μl, 650 μmol) was added, and the mixture was stirred at 40°C overnight. Diethylamino sulfur trifluoride (86 μl, 650 μmol) was added again, and the mixture was stirred at 40°C overnight. The reaction mixture was diluted with dichloromethane and washed with saturated aqueous sodium hydrogen carbonate solution and saturated sodium chloride solution. The organic phase was dried over sodium sulfate and filtered, and the filtrate was concentrated. The residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: acetonitrile/gradient water). The fractions containing the product were concentrated under reduced pressure and dissolved in ethyl acetate. The organic phase was washed with 1N aqueous hydrochloric acid and water, dried over sodium sulfate and filtered, and the filtrate was concentrated. 13.6 mg (19% chance) of the title compound was obtained. LC-MS (Method 3): Rt = 1.42 min; MS (ESIpos): m /z = 436 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.150 (2.27), 0.008 (12.80), 1.348 (3.47), 1.504 ( 5.73), 1.908 (2.27), 2.271 (6.53), 2.327 (7.60), 2.366 (6.13), 2.670 (4.40), 2.710 (4.93), 3.553 (5.33), 3.573 (8.67), 3.591 (4.53), 3.694 ( 3.07), 3.729 (3.47), 3.783 (4.00), 3.814 (4.27), 3.900 (4.00), 4.035 (2.00), 4.197 (2.00), 4.950 (4.40), 5.028 (3.73), 5.076 (2.27), 5.117 ( 12.40), 5.133 (12.27), 5.169 (2.67), 7.969 (4.67), 7.975 (4.80), 7.999 (6.40), 8.015 (4.40), 8.484 (16.00), 8.490 (15.07). Example 589 (5S)-2-{[3-Chloro-5-(trifluoromethyl)pyridin-2-yl]methyl}-8,8-difluoro-5-{[(3S)-3-fluoropyrrolidin-1-yl] carbonyl}-5,6,7,8-tetrahydro[1,2,4]triazolo[4,3- a]pyridin-3(2H)-one

[01682] (5S)-2-{[3-Chloro-5-(trifluoromethyl)pyridin-2-yl]methyl}-5-{[(3S)-3-fluoropyrrolidin-1-yl]carbonyl}-6, 7-dihydro[1,2,4]triazolo[4,3-a]pyridine-3,8(2H,5H)-dione (75.0 mg, 162 μmol) was initially loaded into a Teflon flask under argon in dichloromethane (10 mL) at room temperature. Subsequently, diethylamino sulfur trifluoride (110 μl, 810 μmol) was added, and the mixture was stirred at 40°C overnight. A saturated aqueous solution of sodium hydrogen carbonate was then added, and the aqueous phase was extracted with dichloromethane. The organic phase was dried over sodium sulfate and filtered, and the filtrate was concentrated. The residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: gradient (acetonitrile/water with 0.1% formic acid). The fractions containing the product were concentrated under reduced pressure and 55. 5 mg (71% possibility) of the title compound. LC-MS (Method 4): Rt = 0.88 min; MS (ESIpos): m / z = 484 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (0.66), -0.008 (4.35), 0.008 (3.90), 0.147 (0.51), 1.168 (0.96), 1.185 (1.97), 1.203 (0.91), 1.292 (0.86) , 1,310 (1.87), 1,328 (0.81), 2,012 (0.46), 2,117 (1.57), 2,150 (1.92), 2,251 (1.57), 2,282 (2.38), 2,332 (4.56), 2,346 (3.09), 2,366 (3.80) , 2,407 (1.37), 2,447 (1.82), 2,524 (4.86), 2,670 (1.77), 2,710 (1.77), 3,349 (1.62), 3,394 (1.11), 3,421 (1.11), 3,483 (0.91), 3,519 (1.11) , 3.614 (0.76), 3.639 (3.44), 3.667 (3.49), 3.696 (2.28), 3.732 (1.06), 3.755 (1.52), 3.777 (2.43), 3.799 (2.13), 3.823 (1.47), 3.887 (3.04) , 3,900 (1.06), 3,910 (0.96), 3,918 (1.06), 4,925 (2.13), 4,984 (2.63), 5,274 (1.82), 5,299 (16.00), 5,348 (0.76), 5,406 (2.03), 5,527 (1.16) , 8,531 (7.49), 8,916 (7.59). Example 590 (5S)-2-{[3-Chloro-5-(trifluoromethyl)pyridin-2-yl]methyl}-5-[(3,3-difluoropyrrolidin-1-yl)carbonyl]-8,8-difluoro -5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one

[01683] (5S)-2-{[3-Chloro-5-(trifluoromethyl)pyridin-2-yl]methyl}-5-[(3,3-difluoropyrrolidin-1-yl)carbonyl]-6,7- dihydro[1,2,4]triazolo[4,3-a]pyridine-3,8(2H,5H)-dione (65.0 mg, 48% purity, 65.0 μmol) was initially loaded into a Teflon bottle under argon in dichloromethane (2.0 mL) at room temperature. Subsequently, diethylamino sulfur trifluoride (26 μl, 200 μmol) was added, and the mixture was stirred at 40°C overnight. Diethylamino sulfur trifluoride (26 μl, 200 μmol) was added again, and the mixture was stirred at 40°C overnight. Diethylamino sulfur trifluoride (86 μl, 650 μmol) was added again, and the mixture was stirred at 40°C overnight. A saturated aqueous solution of sodium hydrogencarbonate was then added, and the aqueous phase was extracted with dichloromethane. The organic phase was washed with water and saturated sodium chloride solution, dried over sodium sulfate and filtered, and the filtrate was concentrated. The residue was purified via preparatory HPLC (Method 14). The fractions containing the product were concentrated under reduced pressure and 4.00 mg (12% possibility) of the title compound were obtained. LC-MS (Method 3): Rt = 1.76 min; MS (ESIpos): m /z = 502 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: 0.008 (16.00), 0.146 (3.40), 2.327 (13.00), 2.366 (8.00 ), 2,669 (12.60), 2,710 (6.60), 3,576 (4.00), 5,305 (13.80), 8,531 (6.80), 8,915 (5.60). Example 591 (5S,8RS)-2-[(6-Chloropyridin-3-yl)methyl]-5-[(3,3-difluoropyrrolidin-1-yl)carbonyl]-8-hydroxy-5,6,7, 8-tetrahydro[1,2,4]triazolo[4,3-a]pyridin- 3(2H)-one (mixture of diastereomer; 2 isomers)

[01684] (5S)-2-[(6-Chloropyridin-3-yl)methyl]-5-[(3,3-difluoropyrrolidin-1-yl)carbonyl]-5,6,7,8-tetrahydro [1,2,4]triazolo[4,3-a]pyridin-3(2H)-one (100 mg, 244 μmol) and cerium(IV) sulfate (486 mg, 1.46 mmol) were suspended in tert -butanol (330 μl) at room temperature. Subsequently, 1 N aqueous sulfuric acid (330 μl, 6.1 mmol) was added, and the reaction mixture was stirred at 70 °C overnight. The reaction mixture was cooled to room temperature and adjusted to pH 9 with 2 N aqueous sodium hydroxide solution. The suspension was filtered and the filtrate was extracted three times with dichloromethane. The combined organic phases were dried over sodium sulfate and filtered, and the filtrate was concentrated. 66.9 mg (90% purity, 60% chance) of the title compound was obtained. LC-MS (Method 3): Rt = 0.98 min; MS (ESIpos): m /z = 414 [M+H]+ Example 592 (5S,8RS)-2-[(5-Chloro-3-fluoropyridin-2-yl)methyl]-5-{[(3S) -3-fluoropyrrolidin- 1-yl]carbonyl}-8-hydroxy-5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridin- 3(2H)-one (mixture of diastereomer; 2 isomers)

[01685] (5S)-2-[(5-Chloro-3-fluoropyridin-2-yl)methyl]-5-{[(3S)-3-fluoropyrrolidin-1-yl]carbonyl}-5,6,7 ,8-tetrahydro[1,2,4]triazolo[4,3- a]pyridin-3(2H)-one (95.7 mg, 229 μmol) and cerium(IV) sulfate (456 mg, 1 .37 mmol) were suspended in tert-butanol (310 μl) at room temperature. Subsequently, 1 N aqueous sulfuric acid (310 μl, 5.7 mmol) was added, and the reaction mixture was stirred at 70 °C overnight. The reaction mixture was cooled to room temperature and adjusted to pH 9 with 2 N aqueous sodium hydroxide solution. The suspension was filtered and the filtrate was extracted three times with dichloromethane. The combined organic phases were dried over sodium sulfate and filtered, and the filtrate was concentrated. 51.7 mg (86% purity, 47% chance) of the title compound was obtained. LC-MS (Method 1): Rt = 0.74 min; MS (ESIpos): m /z = 414 [M+H]+ Example 593 (5S,8RS)-2-{[3-Chloro-5-(trifluoromethyl)pyridin-2-yl]methyl}-5-{[ (3S)-3-fluoropyrrolidin-1-yl]carbonyl}-8-hydroxy-5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridin-3(2H )-one (diastereomer mixture; 2 isomers)

[01686] (5S)-2-{[3-Chloro-5-(trifluoromethyl)pyridin-2-yl]methyl}-5-{[(3S)-3-fluoropyrrolidin-1-yl]carbonyl}-5, 6,7,8-tetrahydro[1,2,4]triazolo[4,3- a]pyridin-3(2H)-one (685 mg, 1.53 mmol) and cerium(IV) sulfate (3 .05 g, 9.18 mmol) were suspended in tert-butanol (2 mL) at room temperature. Subsequently, 1N aqueous sulfuric acid (2.0 mL, 38 mmol) was added, and the reaction mixture was stirred at 70 ° C overnight. The reaction mixture was cooled to room temperature and adjusted to pH 9 with 2 N aqueous sodium hydroxide solution. The suspension was filtered and the filtrate was extracted three times with dichloromethane. The combined organic phases were dried over sodium sulfate and filtered, and the filtrate was concentrated. The residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 30mm; eluent: gradient (acetonitrile/water with 0.1% formic acid). The fractions containing the product were concentrated under reduced pressure and 93. 8 mg (13% possibility) of the title compound. LC-MS (Method 4): Rt = 0.64 min; MS (ESIpos): m / z = 464 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (1.95), -0.008 (11.35), 1.747 (4.47), 1.844 (3.91), 2.136 (3.53), 2.268 (3.44), 2.328 (4.00), 2.365 (5.86) , 2,669 (3.26), 2,710 (3.81), 3,485 (2.05), 3,613 (4.09), 3,639 (5.30), 3,655 (5.02), 3,755 (4.00), 3,865 (4.84), 4,502 (7.53), 4,512 (7.26) , 4,727 (3.35), 4,783 (4.00), 4,794 (3.72), 5,117 (3.44), 5,156 (15.35), 5,171 (8.47), 5,180 (10.33), 5,221 (3.07), 5,256 (3.35), 5,381 (4.56 ) , 5.513 (2.51), 5.748 (10.05), 5.760 (10.05), 6.606 (1.49), 8.501 (16.00), 8.915 (14.88). trifluoromethyl)pyridin-2-yl]methyl}-5-[(3,3-difluoropyrrolidin-1-yl)carbonyl]-8-hydroxy-5,6,7,8-tetrahydro[1,2,4] triazolo[4,3-a]pyridin-3(2H)-one (diastereomer mixture; 2 isomers)

[01687] (5S)-2-{[3-Chloro-5-(trifluoromethyl)pyridin-2-yl]methyl}-5-[(3,3-difluoropyrrolidin-1-yl)carbonyl]-5,6, 7,8-tetrahydro[1,2,4]triazolo[4,3- a]pyridin-3(2H)-one (630 mg, 95% purity, 1.28 mmol) and cerium(IV) sulfate ) (2.56 g, 7.71 mmol) were suspended in tert-butanol (1.7 mL) at room temperature. Subsequently, 1N aqueous sulfuric acid (1.7 mL, 32 mmol) was added, and the reaction mixture was stirred at 70 ° C for 20 hours. Additional 1N aqueous sulfuric acid (1.7 mL, 32 mmol) was added, and the reaction mixture was stirred at 70 ° C overnight. The reaction mixture was cooled to room temperature and adjusted to pH 9 with 2 N aqueous sodium hydroxide solution. The suspension was filtered and the filtrate was extracted three times with dichloromethane. The combined organic phases were dried over sodium sulfate and filtered, and the filtrate was concentrated. The residue was purified via preparatory HPLC (Chromatorex C18, 10μm, 125mm x 40mm; eluent: gradient (acetonitrile/water with 0.1% formic acid). The fractions containing the product were concentrated under reduced pressure and 58. 7 mg (9% chance) of the title compound. LC-MS (Method 3): Rt = 1.28 min; MS (ESIpos): m / z = 482 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: -0.149 (1.45), -0.008 (10.12), 0.008 (9.85), 1.424 (2.44), 1.445 (1.90), 1.742 (3.98), 1.815 (3.07), 1.898 (2.80) , 2,132 (2.26), 2,327 (4.43), 2,366 (5.06), 2,405 (3.25), 2,669 (2.89), 2,709 (3.34), 3,521 (4.16), 3,540 (7.32), 3,560 (4.34), 3,658 (2.44) , 3,692 (2.53), 3,725 (2.71), 3,758 (2.89), 3,791 (4.07), 3,819 (3.07), 3,916 (3.07), 3,996 (1.81), 4,188 (2.17), 4,212 (1.90), 4,501 (6.51) , 4,797 (3.07), 4,807 (2.98), 4,884 (2.98), 5,123 (2.26), 5,163 (15.82), 5,176 (16.00), 5,217 (2.62), 5,763 (11.30), 5,775 (11.39), 8,505 (14 .73) , 8,914 (13.02). 5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one (diastereomer mixture; 2 isomers)

[01688] (5S)-2-[(5-Chloropyridin-2-yl)methyl]-5-[(3,3-difluoropyrrolidin-1-yl)carbonyl]-5,6,7,8-tetrahydro [1,2,4]triazolo[4,3-a]pyridin-3(2H)-one (174 mg, 74 mg purity, 324 μmol) and cerium(IV) sulfate (645 mg, 1.94 mmol ) were suspended in tert-butanol (430 μl) at room temperature. Subsequently, 1 N aqueous sulfuric acid (430 μl, 8.1 mmol) was added, and the reaction mixture was stirred at 70 °C overnight. The reaction mixture was cooled to room temperature and adjusted to pH 9 with 2 N aqueous sodium hydroxide solution. The suspension was filtered and the filtrate was extracted three times with dichloromethane. The combined organic phases were washed with water and saturated aqueous sodium chloride solution, dried over sodium sulfate and filtered, and the filtrate was concentrated. 103 mg (85% purity, 65% chance) of the title compound was obtained. LC-MS (Method 1): Rt = 0.82 min; MS (ESIpos): m /z = 414 [M+H]+ Example 596 (5S,8RS)-2-[(5-Chloropyridin-2-yl)methyl]-5-[(3-fluoroazetidin-1-yl )carbonyl]- 8-hydroxy-5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one (mixture of diastereomer; 2 isomers)

[01689] (5S)-2-[(5-Chloropyridin-2-yl)methyl]-5-[(3-fluoroazetidin-1-yl)carbonyl]-5,6,7,8-tetrahydro[1 ,2,4]triazolo[4,3-a]pyridin-3(2H)-one (166 mg, 98 mg purity, 445 μmol) and cerium(IV) sulfate (887 mg, 2.67 mmol) were suspended in tert-butanol (590 μl) at room temperature. Subsequently, 1 N aqueous sulfuric acid (590 μl, 11 mmol) was added, and the reaction mixture was stirred at 70 °C overnight. The reaction mixture was cooled to room temperature and adjusted to pH 9 with 2 N aqueous sodium hydroxide solution. The suspension was filtered and the filtrate was extracted three times with dichloromethane. The combined organic phases were washed with water and saturated aqueous sodium chloride solution, dried over sodium sulfate and filtered, and the filtrate was concentrated. 48.1 mg (84% purity, 24% chance) of the title compound was obtained. LC-MS (Method 3): Rt = 0.83 min; MS (ESIpos): m /z = 382 [M+H]+ Example 597 (5S,8RS)-2-[(3,5-Difluoropyridin-2-yl)methyl]-5-[(3,3-difluoropyrrolidin -1- yl)carbonyl]-8-hydroxy-5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridin- 3(2H)-one (diastereomer mixture ; 2 isomers)

[01690] (5S)-2-[(3,5-Difluoropyridin-2-yl)methyl]-5-[(3,3-difluoropyrrolidin-1-yl)carbonyl]-5,6,7,8-tetra -hydro[1,2,4]triazolo[4,3- a]pyridin-3(2H)-one (226 mg, 567 μmol) and cerium(IV) sulfate (1.13 g, 3.40 mmol) were suspended in tert-butanol (770 μl) at room temperature. Subsequently, 1 N aqueous sulfuric acid (770 μl, 770 μmol) was added, and the reaction mixture was stirred at 70°C overnight. The reaction mixture was cooled to room temperature and adjusted to pH 9 with 2N aqueous sodium hydroxide solution. The aqueous phase was extracted three times with ethyl acetate, and the combined organic phases were dried over sodium sulfate and filtered. , and the filtrate was concentrated. 116 mg (49% chance) of the title compound was obtained. LC-MS (Method 3): Rt = 0.91 min; MS (ESIpos): m /z = 416 [M+H]+ 1H-NMR (400 MHz, DMSO-d6) δ [ppm]: 1.097 (3.87), 1.110 (1.22), 1.135 (4.05), 1.157 (1.27 ), 1.175 (2.34), 1.193 (1.34), 1.227 (16.00), 1.736 (6.08), 1.768 (0.64), 1.797 (0.65), 1.845 (0.62), 1.858 (0.55), 1.880 (1.03), 1.892 (0.81 ), 1.939 (0.47), 1.959 (0.47), 1.988 (4.06), 2.328 (0.69), 2.359 (0.53), 2.378 (0.68), 2.407 (0.68), 2.425 (0.68), 2.448 (0.57), 2.570 (0.72 ), 2.589 (0.50), 3.518 (0.78), 3.538 (1.26), 3.559 (0.77), 3.653 (0.55), 3.687 (0.65), 3.722 (0.49), 3.758 (0.71), 3.790 (0.95), 3.812 (0.72 ), 3.914 (0.65), 3.940 (0.50), 3.991 (0.42), 4.002 (0.53), 4.021 (1.25), 4.038 (1.17), 4.056 (0.42), 4.186 (0.45), 4.388 (1.59), 4.486 (1.30 ), 4.495 (1.21), 4.776 (0.62), 4.786 (0.63), 4.853 (0.63), 4.863 (0.64), 4.940 (0.71), 4.978 (2.02), 5.018 (2.18), 5.056 (0.84), 5.280 (0.84 ), 5.294 (0.72), 5.757 (2.51), 5.769 (2.47), 5.780 (0.44), 5.794 (0.41), 7.940 (0.81), 7.945 (0.83), 7.964 (1.33), 7.968 (1.37), 7.987 (0.86 ), 7,993 (0.84), 8,446 (0.74), 8,452 (0.75), 8,477 (3.04), 8,483 (2.64). B. Assessment of pharmacological efficacy

[01691] The pharmacological activity of the compounds of the invention can be demonstrated by in vitro and in vivo studies as known to the person skilled in the art. The following application examples describe the biological action of the compounds of the invention, without restricting the invention to these examples. Abbreviations and acronyms: ATP adenosine triphosphate COPD chronic obstructive pulmonary disease LPS lipopolysaccharide PGP proline-glycine-proline Poly(I:C) polynosinic-polycytidylic acid B-1 Human prolyl endopeptidase (PREP) biochemical assay for identification of inhibitors of PREP activity using a fluorescently labeled substrate Assay principle:

[01692] Enzymatic conversion of the fluorescent peptide substrate was observed based on measurement of fluorescence intensity. Enzymatic activity was determined by investigating the initial slope in the increase in fluorescence. Compounds that inhibit PREP were identified based on the decrease in initial slope compared to a reaction mixture without test compound. Activity determination:

[01693] IC50 values were determined by plotting the percentage of PREP activity against the concentration of the test substance by interpolation. Test description:

[01694] To prolylate endopeptidase (PREP, R&D-Systems, 4308- SE recombinant full-length human; final concentration, e.g., 0.4 nM, volume: 25 μl) in reaction buffer (50 mM Tris-HCl, pH 7, 5; 150 mM NaCl; 0.13% BSA, 5 mM EDTA, 3 mM GSH, 0.005% Brij-35) a test compound was added (in DMSO, in a final concentration range of 1 nM to 30 μM, volume : 1 μl) in one well of a 384-well microtiter plate. The reaction was initiated by adding the substrate Z-Gly-Pro-AMC (final concentration 50 μM; Z = carboxybenzyl; AMC = 7-amino-4-methylcoumarin, volume: 25 μl). The progress of the PREP reaction was observed by measuring the fluorescence intensity on a Tecan SAFIRE II plate spectrophotometer at 32°C over a period of 60 min. (excitation wavelength: 360 nm, emission wavelength: 465 nm).

[01695] Table B-1 below groups the IC50 values thus obtained from the human prolyl endopeptidase assay for individual working examples of the invention (some as average values from several independent individual determinations). Table B-1 B-2 Murine biochemistry prolyl endopeptidase (PREP) assay Determination of activity:

[01696] IC50 values were determined by plotting the percentage of PREP activity against the concentration of the test substance by interpolation. Preparation of rat brain homogenate:

[01697] BalbC rat brain in 0.8 mL of a mixture of 100 mM sodium phosphate (pH 7.0) and 3 mM dithiothreitol was homogenized 4x25s in an OmniBead Ruptor. The resulting homogenate was centrifuged at 13000 rpm and 4 °C for 20 min. The supernatant in aliquots was frozen at −80°C. Test description:

[01698] The rat brain homogenate was diluted 1:100 in a reaction buffer (50 mM Tris-HCl, pH 7.5; 150 mM NaCl; 0.13% BSA, 5 mM EDTA, 3 mM GSH, 0.005 % Brij-35) and 25 μl of the solution was introduced into one well of a 384-well microtiter plate. A test compound (in DMSO, in an appropriate final concentration range of, e.g., 1 nM to 30 μM, volume: 1 μl) was added. The reaction is initiated by adding the substrate Z-Gly-Pro-AMC (final concentration 50 μM; Z = carboxybenzyl; AMC = 7-amino-4-methylcoumarin, volume: 25 μl). The progress of the PREP reaction was observed by measuring the fluorescence intensity on a suitable plate spectrometer at 32°C over a period of, for example, 60 min. (excitation wavelength: 360 nm, emission wavelength: 465 nm).

[01699] Table 1 below groups the IC50 values thus obtained from the KDR and PDGFRβ kinase assays for individual working examples of the invention (some as average values from multiple independent individual determinations). B-3 Efficacy of PREP inhibitors in rats exposed to cigarette smoke

[01700] The suitability of the substances of the invention for the treatment/prophylaxis of the mentioned diseases can be shown in the following animal model. Material and methods:

[01701] Mice: Group: BALB/C, origin: Charles River Netherlands, sex: male, age: 8 to 10 weeks, weight: 25 g, n = 21. Vehicle: Solutol, EtOH, water (S: 40%, EtOH 10%, water 50% (v/v))

[01702] For the administration of PREP inhibitors by gavage, they were dissolved in the vehicle described above (c = 3750 μg/mL).

[01703] The rats were divided into three groups of seven animals each and treated as follows: Group 1: no exposure to smoke (room air), two daily doses of 200 μl of vehicle without active ingredient Group 2: exposure to smoke, two daily doses of 200 μl of vehicle without active ingredient Group 3: exposure to smoke, two daily doses of 200 μl of vehicle with active ingredient (30 mg/kg in each case) Exposure to smoke:

[01704] For exposure to cigarette smoke, animals in groups 2 and 3 (animals in group 1 were not exposed to smoke and remained in holding cages) were introduced twice a day into an exposure chamber with a volume total of 52 liters in 16 individual cages dividing the grids. For smoke exposure, the animals, which were kept in groups (7 animals per cage), were introduced into a single cage in the exposure chamber (7 animals per cage). Between the two daily exposures, there was a 5-hour smoke-free period. In total, the animals were exposed to smoke on five successive days. The cigarettes were burned in pairs. Current cigarette smoke was introduced into the exposure chamber.

[01705] Smoke exposure was conducted according to the following scheme: • Day 1: 1st smoking period: 2 x 2 cigarettes, 2nd smoking period: 3 x 2 cigarettes • Day 2: 1st smoking period : 4 x 2 cigarettes, 2nd smoking period: 5 x 2 cigarettes • Day 3: 1st smoking period: 6 x 2 cigarettes, 2nd smoking period: 7 x 2 cigarettes • Days 4 and 5: 1st and 2nd smoking periods: each 7 x 2 cigarettes

[01706] Treatment of animals with PREP inhibitors or vehicle was initiated 15 minutes before the first smoking period on day 1. Subsequently, animals received two daily doses 8 hours apart of PREP inhibitors or vehicle at the above dosage described.

[01707] On day 6, the animals were sacrificed by intraperitoneal administration of 150 mg/kg of pentobarbital (Euthesate®). The tracheas were exposed and incised for insertion of cannulas. These cannulas were used to purge the lungs four times with saline at 37°C. Cells from these four fractions in each case of bronchoalveolar lavage fluid (BALF) were centrifuged at 4°C at 400 x g/5 minutes. Subsequently, the cell pellets were combined and resuspended in 150 µl of saline (4°C) in each case. After staining with Türk's solution, the total number of cells was counted by light microscopy. For quantification of neutrophil granulocytes (neutrophils for short), cells were transferred to microscope slides (Cytospin) and stained with DiffQuick (Dade A.G., Düdingen, Switzerland). Finally, neutrophils, macrophages, and lymphocytes were counted, and the relative proportions of the previously determined total number were calculated. To determine the concentration of PGP in BALF, 200 μl in each case of the supernatant from the first BALF fraction was mixed with bestatin (final concentration: 1 mM) and stored at −20°C until analysis. Quantification of PGP in bronchoalveolar lavage fluid (BALF)

[01708] PGP was determined by the method of Hardison et al. [Hardison et al., J. Immunol. 2009, 182:4423-4431] with the use of the following equipment: ESI-LC-MS/MS (Shimadzu HPLC, Columbia, MA, USA) with a Finnigan TSQ quantum discovery Max quadrupole mass spectrometer in conjunction with thermal ionization by electrospray (Thermo Fisher Scientific, San José, CA, USA) and an Atlantis dC18 column (100 mm x 2.1 mm, dp = 3 mm, Waters Chromatography, Milford, MA, USA) or an Atlantis precolumn (10 mm x 2.1 mm, dp = 3 μm, Waters). B-4 Purification, crystallization and determination of single crystal structure of PREP (porcine) in a complex with Examples 26, 108, 113, 157, 237, 358 and 454 Abbreviations: GST = glutathione-S-transferases IPTG = isopropyl-β -D-thiogalactopyranoside OD600 = optical density at 600 nM TRIS-HCl = tris(hydroxymethyl)aminomethane hydrochloride EDTA = ethylenediaminetetraacetic acid DTT = dithiothreitol PAGE = polyacrylamide gel electrophoresis TEV = tobacco etch virus SEC = size exclusion chromatography FPLC = chromatography fast protein liquid NaCl = sodium chloride PEG = polyethylene glycol MES = 2-(N-morpholino)ethanesulfonic acid DMSO = dimethyl sulfoxide CCD = charge-coupled arrangement 4.1 PREP expression and purification Expression system: Formation of an expression vector of E. coli for production of GST- PREP (porcine) - Uniprot number P23687

[01709] The PREP (porcine) expression vector used (based on pET-22b) encodes a fusion protein consisting of GST tag, attB1-5 # (Gateway, Invitrogen), TEV cleavage site, PREP region ( porcine) (1-710) and attB2 -3 #, (Gateway, Invitrogen). E. coli expression in a bioreactor:

[01710] The E. coli BL21 DE3 group was transformed with the above expression vector and a stable group was established by ampicillin selection. This transformed group was used for expression in a 10 l bioreactor (Sartorius). The conditions for running the bioreactor were: Circle growth medium, incubation at 17°C for 16 h, induction with 500 μM IPTG at OD600, 200 μg/mL ampicillin). PREP purification (porcine):

[01711] The E. coli pellet from 9 l of bioreactor culture was suspended in 200 ml of lysis buffer (50 mM TRIS-HCl pH 7.5; 150 mM NaCl; 5 mM EDTA; 5 mM DTT), 20 μL of Benzonase pf (Roche) were added, and digestion was carried out in a microfluidizer (3 x 900 bar). The soluble fraction of the lysate (centrifugation 100,000 x g 40 min, 4) was used for further chromatographic purification.

[01712] In subsequent affinity chromatography, a glutathione matrix (Protino GST/4B) was incubated with the soluble lysate fraction, which resulted in the binding of GST-PREP (porcine) to the matrix and washed with lysis buffer (50 mM Tris HCl pH 7.5; 150mM NaCl; 5mM EDTA; 5mM DTT) and buffer A (50mM TRIS-HCl, pH 7.5; 150mM NaCl; 1mM EDTA; 1mM DTT). Subsequently, the GST-PREP fusion protein (porcine) was eluted with buffer B (50 mM Tris-HCl, pH 7.5; 150 mM NaCl; 1 mM EDTA; 15 mM glutathione; 1 mM DTT). The elution fractions were analyzed on Coomassie/PAGE and the elution peak fractions containing GST-PREP (porcine) were combined. (Yield of 172 mg of fusion protein from 9 l of E. coli culture).

[01713] To separate the GST tag, an incubation with TEV protease was conducted in solution during dialysis. For this purpose, purified GST-PREP (porcine) (172 mg) was mixed with TEV protease (produced in-house) at a TEV fusion protein ratio of 1:50 w/w and dialyzed in a dialysis system (SlideA- Lyzer cut 10,000 Da) against 2 x 2 liters of buffer A (17 h, 6°C). Using Coomassie/PAGE, the cleavage mixture was analyzed and a 90% conversion was determined.

[01714] In another column affinity chromatography with glutathione matrix (Protino GST/4B), the PREP (porcine) protein (without GST tag) (110 mg) was isolated from the cleavage mixture in the eluate and concentrated by using an ultrafiltration unit (Amicon Ultra millipore cutoff 50 kDa) for further processing.

[01715] Subsequently, size exclusion chromatography was performed to isolate the monomeric fraction of PREP (porcine). For this purpose, a Superdex S200 26/60 (GE) column with SEC buffer (50 mM Tris HCl pH 7.5; 150 mM NaCl; 1 mM EDTA; 1 mM DTT) was used. Final samples were aliquoted (1 mL), shock-frozen in liquid nitrogen, and stored at −80°C. Storage buffer: 50 mM Tris-Cl pH 7.5; 150 mM NaCl; 1mM EDTA.

[01716] Final concentration of PREP (porcine): 3.24 mg/mL, 20 mL, 64.8 mg total, yield of 9 l of E. coli culture of 7.2 mg/L.

[01717] To transfer PREP (porcine) from the storage buffer (see above) to the crystallization buffer (10 mM TRIS-HCl pH 7.5; 100 mM NaCl), a trans buffering operation was performed by means of a system FPLC with a desalting column (at 6°C) and subsequent concentration (Millipore UFC 905096 ultrafiltration unit, cutoff 50,000 Da). 4.2 Complex formation and crystallization of PREP (porcine)

[01718] Pork PREP protein was present at a concentration of ~34 mg/mL in 10 mM Tris at pH = 7.5 and 100 mM NaCl. The protein solution was mixed in each case with DMSO solutions of the exemplary compounds, so that there was a final concentration of the exemplary compounds of 4 mM in the protein buffer. The protein complex solution was incubated on a shaker at 4°C for at least 3 hours, and the solution was subsequently centrifuged for 5 minutes. Analyzable single crystals were obtained at 20°C using the hanging drop method. To this end, equal volumes of the protein solution and reservoir solution (13-15% PEG8000, 0.2 M magnesium acetate tetrahydrate, 0.1 M MES at pH = 6.25) were pipetted together and mixed with pork PREP crystal seeds. Pork PREP crystals usually form overnight. 4.3 Data collection and processing

[01719] A single crystal of good visual appearance was introduced for a very short time into a solution containing 13-15% PEG8000, 0.2 M magnesium acetate tetrahydrate, 0.1 MES at pH = 6.25 and 20% glycerol, and then frozen in liquid nitrogen. Crystals from examples [237, 108, 113] were analyzed on a Rigaku 007HF generator from Rigaku at 100 K and a wavelength of 1.5418 Å. The detection instrument used was a Pilatus 2K counter. The data were processed with the HKL3000 program. Crystals from examples [358, 474, 157, 026] were analyzed on a Bruker Proteum system at 100 K and a wavelength of 1.5148 Å. The detection instrument used was a CCD counter. Data were integrated with the SAINT program and resized with the SADABS program (both part of the Bruker Proteum software package).

[01720] The crystals crystallized in the orthorhombic space group P2 (1) 2 (1) 2 (1) with one molecule in the asymmetric unit. 4.4 Structure determination and refinement

[01721] It was possible to solve the structure of PREP (porcine) by the molecular replacement method with another internal structure as a search model and the MOLREP program (CCP4 software package). All examples [xxx] were generated as a 3D model with the help of the Discovery Studio program, and a parameter file was generated with the PRODRG program. All examples were manually positioned at their respective electron density and minimized in terms of electron density in the COOT program. Further refinement was carried out by iterative means with the REFMAC 5.5 and COOT programs (both CCP4 software packages). Refinement data and statistics for all examples are summarized in Tables B2-8:

[01722] Table B-2-8: Data collection and refinement statistics for pork PREP in a complex with examples 237, 358, 454, 108, 113, 157 and 26. Values in brackets are for the outermost resolution capsule b Rfusion = ∑hkl |Ihkl - <Ihkl>| / ∑hkl <Ihkl>; Ihkl is the intensity of hkl reflections and <Ihkl> is the average value of repeatedly measured intensities c Rcrist = ∑ |Fobs- Fcalc| / ∑ Fobs; Fobs and Fcalc are observed and calculated structure factors d 5% test set and RMSD, root mean square deviation of the defined parameter from the ideal bond geometry 4.5 Determination of the absolute structure of Example 237 in PREP (porcine)

[01723] The pork PREP complex with Example 237 crystallizes with one molecule in the asymmetric unit. The stereochemistry of Example 237 is unambiguously determined through knowledge of the stereochemistry of the porcine PREP protein. In Example 237, the S configuration is unambiguously present at stereocenters C31 and C2, and the R configuration is present at C6 (Figure 1).

[01724] Structure of example 237: (5S, 7R)-5-{[(3S)-3-Fluoropyrrolidin-1-yl]carbonyl}-7-(trifluoromethyl)-2-{[6-(trifluoromethyl)pyridin- 3-yl]methyl}-5},6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one with the following formula: 4.6 Determination of the absolute structure of Example 358 in PREP (porcine)

[01725] The pork PREP complex with Example 358 crystallizes with one molecule in the asymmetric unit. The stereochemistry of Example 358 is unambiguously determined through knowledge of the stereochemistry of the porcine PREP protein. In Example 358, the S configuration is unambiguously present at both stereocenters C26 and C2 (Figure 2). Structure of example 358: (5S)-5-[(3-Fluoroazetidin-1-yl)carbonyl]-2- {[1-(4-methoxyphenyl)cyclopropyl]methyl}-5,6,7,8-tetra- hydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one with the following formula: 4.7 Determination of the absolute structure of Example 454 in PREP (porcine)

[01726] The pork PREP complex with Example 454 crystallizes with one molecule in the asymmetric unit. The stereochemistry of Example 454 is unambiguously determined through knowledge of the stereochemistry of the porcine PREP protein. In Example 454, the S configuration is unambiguously present at both stereocenters C25 and C6 (Figure 3).

[01727] Structure of example 454: (5S)-2-(3-Chloro-4-fluorobenzyl)-5-{[(3S)-3-fluoropyrrolidin-1-yl]carbonyl}-5,6,7,8 -tetrahydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one with the following formula: 4.8 Determination of the absolute structure of Example 108 in PREP (porcine)

[01728] The pork PREP complex with Example 108 crystallizes with one molecule in the asymmetric unit. The stereochemistry of Example 108 is unambiguously determined through knowledge of the stereochemistry of the porcine PREP protein. In Example 108, the S configuration is unambiguously present at the C8 stereocenter (Figure 4).

[01729] Structure of example 108: (2-{[(1S)-1-(3-chlorophenyl)-2-fluoroethyl]amino}-7-methoxy-1,3-benzoxazol-5-yl) [(2S, 5S)-5-(2-hydroxyethyl)-2-methylmorpholin-4-yl]methanone with the following Formula: (5S)-2-(4-Methylbenzyl)-5-(1,3-thiazolidin-3-ylcarbonyl) -5,6,7,8-tetrahydro[1,2,4]triazolo[4,3-a]pyridin-3(2H)-one 4.9 Determination of the absolute structure of Example 113 in PREP (porcine)

[01730] The pork PREP complex with Example 113 crystallizes with one molecule in the asymmetric unit. The stereochemistry of Example 113 is unambiguously determined through knowledge of the stereochemistry of the porcine PREP protein. In Example 113, the S configuration is unambiguously present at the C3 stereocenter (Figure 5).

[01731] Structure of example 113: (5S)-5-[(3-Fluoroazetidin-1-yl)carbonyl]-2-(4-methylbenzyl)-5,6,7,8-tetrahydro[1,2 ,4]triazolo[4,3- a]pyridin-3(2H)-one with the following formula: 4.10 Determination of the absolute structure of Example 157 in PREP (porcine)

[01732] The pork PREP complex with Example 157 crystallizes with one molecule in the asymmetric unit. The stereochemistry of Example 157 is unambiguously determined through knowledge of the stereochemistry of the porcine PREP protein. In Example 157, the S configuration is unambiguously present at the C1 stereocenter (Figure 6).

[01733] Structure of example 157: (5S)-2-(4-methylbenzyl)-5- (pyrrolidin-1-ylcarbonyl)-2,5,6,7-tetrahydro-3H-pyrrole [2,1- c] [1,2,4]triazol-3-one with the following formula: 4.11 Determination of the absolute structure of Example 26 in PREP (porcine)

[01734] The pork PREP complex with Example 26 crystallizes with one molecule in the asymmetric unit. The stereochemistry of Example 26 is unambiguously determined through knowledge of the stereochemistry of the porcine PREP protein. In Example 26, the S configuration is unambiguously present at the C3 stereocenter (Figure 7).

[01735] Structure of example 26: (5S)-2-(4-methylbenzyl)-5-(pyrrolidin-1-ylcarbonyl)-5,6,7,8-tetrahydro[1,2,4]triazolo[ 4,3-a]pyridin-3(2H)-one with the following formula: Literature B-4: Emsley P. et al. (2010) Acta Cryst. D66:486-501 Evans PR, (2005) Acta Cryst. D62, 72-82 Long et al. F (2008) Acta Cryst. D64, 125-132 Murshudo GN et al. (1997) Acta Cryst. D53, 240-255 C. Functional examples of pharmaceutical compositions

[01736] The compounds of the invention can be converted into pharmaceutical preparations as follows: Tablet: Composition:

[01737] 100 mg of the compound according to the invention, 50 mg of lactose (monohydrate), 50 mg of starch (native), 10 mg of polyvinylpyrrolidone (PVP 25) (from BASF, Ludwigshafen, Germany) and 2 mg of magnesium stearate.

[01738] Tablet weight: 212 mg, Diameter 8 mm, radius of curvature 12 mm. Production:

[01739] The mixture of the compound of the invention, lactose and starch is granulated with a solution of 5% (w/w) of PVP in water. The granules are dried and then mixed with magnesium stearate for 5 minutes. The mixture is compressed using conventional tablet pressure (see above for tablet shape). The reference value used for pressing is a pressing force of 15 kN. Suspension for oral administration: Composition:

[01740] 1000 mg of the compound of the invention, 1000 mg of ethanol (96%), 400 mg of Rhodigel® (xanthan gum from FMC, Pennsylvania, USA) and 99 g of water.

[01741] 10 mL of oral solution corresponding to a single dose of 100 mg of the compound of the invention. Production:

[01742] Rhodigel is suspended in ethanol; the compound of the invention is added to the suspension. Water is added while stirring. The mixture is stirred for about 6 hours until the Rhodigel expansion is complete. Solution for oral administration: Composition:

[01743] 500 mg of the compound of the invention, 2.5 g of polysorbate and 97 g of polyethylene glycol 400. 20 g of oral solution corresponding to a single dose of 100 mg of the compound of the invention. Production:

[01744] The compound of the invention is suspended in the mixture of polyethylene glycol and polysorbate with stirring. The stirring process continued until the compound according to the invention was completely dissolved. i.v. solution:

[01745] The compound, according to the invention, is dissolved at a concentration below saturation solubility in a physiologically tolerated solvent (e.g., isotonic saline solution, 5% glucose solution and/or PEG 400 solution at 30 %). The solution is sterilized by filtration and used to fill sterile, pyrogen-free injection containers.

Claims (14)

1. Compound, characterized by the fact that it presents Formula (I), in which A is (C1-C4)-alkylene or CD2, wherein (C1-C4)-alkylene is optionally substituted by hydroxyl and (C1-C4)-alkoxy and optionally even pentassubstituted by fluorine, or A is a group of Formula , in which n is 0 or 1, p is 0 or 1, q is 1 or 2, where # 1 marks the bond to the nitrogen atom of the 5-oxo-4,5-dihydro-1H-1,2 ring ,4-triazol-1-yl, # marks the bond to R1, -**, with #2 marking the bond to the carbon atom of the CR4R5- group, with ** marking the bond to the carbon atom of the 5-oxo-4,5-dihydro-1H-1,2 ring ,4-triazol-1-yl, where R6 is hydrogen, fluorine, (C1-C4)-alkyl, where (C1-C4)-alkyl is optionally even trisubstituted by fluorine, R7 is hydrogen, fluorine or (C1 -C4)-alkyl, where (C1-C4)-alkyl is optionally even trisubstituted by fluorine; R8 is hydrogen, (C1-C4)-alkyl or hydroxyl, where (C1-C4)-alkyl is optionally even trisubstituted by fluorine, R9 is hydrogen, fluorine or (C1-C4)-alkyl, where (C1-C4 )-alkyl is optionally even trisubstituted by fluorine; R10 is hydrogen, (C1-C4)-alkyl or hydroxyl, where (C1-C4)-alkyl is optionally even trisubstituted by fluorine, R11 is hydrogen, fluorine or (C1-C4)-alkyl, where (C1- C4)-alkyl is optionally even trisubstituted by fluorine; R1 is (C3-C7)-cycloalkyl, phenyl or heteroaryl with 5 to 6 members, wherein (C3-C7)-cycloalkyl is optionally substituted by 1 to 3 substituents independently selected from the group halgen, cyano, trifluoromethyl, (C1-C4 )-alkyl and (C1-C4)-alkoxy, where (C1-C4)-alkyl is optionally up to pentasubstituted by fluorine, with phenyl being substituted by 1 to 4 substituents independently selected from the halgen group, cyano, (C1-C4 )-alkyl, (C3-C6)-cycloalkyl, trifluoromethyl, (C1-C4)-alkoxy, (C3-C5)-cycloalkoxy, monofluoromethoxy, difluoromethoxy, trifluoromethoxy, hydroxycarbonyl, (C1-C4)-alkoxycarbonyl, aminocarbonyl, mono- (C1-C4)-alkylaminocarbonyl, di-(C1-C4)-alkylaminocarbonyl, (C3-C5)-cycloalkylaminocarbonyl, (C1-C4)-alkylsulfanyl, (C1-C4)-alkylsulfonyl, (C1-C4)-alkylsulfonimidoyl, (C1-C4)-cycloalkylsulfonyl, aminosulfonyl, mono-(C1-C4)-alkylaminosulfonyl, di-(C1-C4)-alkylaminosulfonyl, (C1-C4)-alkylsulfinyl, amino, mono-(C1-C4)-alkylamino or di-(C1-C4)-alkylamino, or wherein phenyl is optionally fused to (C3-C7)-cycloalkyl, (C3-C7)-heterocyclyl or 5- to 6-membered heteroaryl, with phenyl being optionally substituted by methyl , ethyl, chlorine, fluorine or methoxy, where (C3-C7)-cycloalkyl, (C3-C7)-heterocyclyl and 5- to 6-membered heteroaryl are optionally substituted by 1 or 2 substituents (C1-C4)-alkyl, being which (C1-C4)-alkyl is optionally substituted by (C1-C4)-alkoxy, hydroxyl, mono-(C1-C4)-alkylamino or di-(C1-C4)-alkylamino and is optionally even pentasubstituted by fluorine, or wherein 5 to 10 membered heteroaryl is optionally substituted by 1 to 4 substituents independently selected from the group halgen, cyano, (C1-C4)-alkyl, (C3-C6)-cycloalkyl, trifluoromethyl, (C1-C4)-alkoxy, (C3-C5)-cycloalkoxy, difluoromethoxy, trifluoromethoxy, 2,2,2-trifluoroethoxy, phenyl, hydroxycarbonyl, (C1-C4)-alkoxycarbonyl, aminocarbonyl, mono-(C1-C4)-alkylaminocarbonyl, di-(C1-C4 )-alkylaminocarbonyl, (C3-C5)-cycloalkylaminocarbonyl, (C1-C4)-alkylsulfanyl, (C1-C4)-alkylsulfonyl, (C1-C4)-alkylsulfonimidoyl, (C1-C4)-cycloalkylsulfonyl, aminosulfonyl, mono-(C1 -C4)-alkylaminosulfonyl, di-(C1-C4)-alkylaminosulfonyl, (C1-C4)-alkylsulfinyl, amino, mono-(C1-C4)-alkylamino or di-(C1-C4)-alkylamino, with phenyl is optionally substituted by methyl, ethyl, chloro, fluorine, or methoxy, or where the 5- to 6-membered heteroaryl of R1 is optionally fused to (C3-C7)-cycloalkyl or (C3-C7)-heterocyclyl, phenyl, or heteroaryl with 5 to 6 members, said 5 to 6 membered heteroaryl of R1 being optionally substituted by methyl, ethyl, chlorine, fluorine or methoxy, wherein (C3-C7)-cycloalkyl, (C3-C7)-heterocyclyl, phenyl and 5 to 6 membered heteroaryl fused to said 5 to 6 membered heteroaryl fused to said 5 to 6 membered heteroaryl are optionally substituted by 1 or 2 substituents (C1-C4)-alkyl, wherein (C1-C4)-alkyl is optionally substituted by (C1-C4)-alkoxy, hydroxyl, mono-(C1-C4)-alkylamino or di-(C1-C4)-alkylamino and even pentassubstituted by fluorine, R2 is a group of the Formula, in which #3 marks the bond to the carbonyl carbon atom; r is 0 or 1; Z is O, NR18, S, SO, SO2 or CR14AR14B; R14A is hydrogen, fluorine, (C1-C4)-alkyl, trifluoromethyl, difluoromethyl, fluoromethyl, hydroxyl, (C1-C4)-alkoxy, difluoromethoxy; wherein (C1-C4)-alkyl is optionally substituted by hydroxyl; R14B is hydrogen, fluorine or (C1-C4)-alkyl, or R14A and R14B together with the carbon atom to which they are attached form a carbonyl group, R18 is hydrogen or methyl, R12 is hydrogen, cyano, (C1-C4) -alkyl, acetyl or formyl, where acetyl is optionally substituted by hydroxyl; R13 is hydrogen, fluorine or (C1-C4)-alkyl, or R12 and R13, together with the carbon atoms to which they are attached, form a cyclopropyl ring, with the cyclopropyl ring being optionally even disubstituted by fluorine, or R13 and R14A, together with the carbon atoms to which they are attached, form a cyclopropyl ring, with the cyclopropyl ring being optionally even disubstituted by fluorine, or R14A and R14B, together with the carbon atom to which they are attached, form a cyclopropyl ring , with the cyclopropyl ring being optionally even disubstituted by fluorine, with R13, R14A and R14B being hydrogen when R12 is not hydrogen, with R12 being hydrogen when one of the substituents R13, R14A and R14B is not hydrogen, or is a group of the Formula, in which #4 marks the bond to the carbonyl carbon atom; Y is NR15, CR16AR16B, oxygen or sulfur; R15 is hydrogen or methyl; R16A is hydrogen or methyl; R 16B is hydrogen or methyl; R3 is hydrogen or (C1-C4)-alkyl; R4 is hydrogen, (C1-C4)-alkyl, fluorine, hydroxyl; wherein (C1-C4)-alkyl is optionally even trisubstituted by fluorine; R5 is hydrogen or (C1-C4)-alkyl; or a salt thereof. 2. Compound according to claim 1, characterized by the fact that: A is (C1-C4)-alkylene, wherein (C1-C4)-alkylene is optionally substituted by hydroxyl and methoxy and is optionally even trisubstituted by fluorine , or is a group of the Formula, , where n is 1; p is 0; q is 1; #1 marks the bond to the nitrogen atom of the 5-oxo-4,5-dihydro-1H-1,2,4-triazol-1-yl ring; # marks the bond to R1, of the 5-oxo-4,5-dihydro-1H-1,2,4-triazol-1-yl ring, with R6 being hydrogen, fluorine, methyl and ethyl; wherein methyl and ethyl are optionally even trisubstituted by fluorine, R7 is hydrogen, fluorine or methyl, with methyl being optionally even trisubstituted by fluorine; R8 is hydrogen, fluorine, methyl, ethyl and hydroxyl, with methyl and ethyl optionally even being trisubstituted by fluorine; R9 is hydrogen, fluorine or methyl, with methyl being optionally even trisubstituted by fluorine; R1 is (C5-C6)-cycloalkyl, phenyl or 5-6 membered heteroaryl, wherein (C5-C6)-cycloalkyl is optionally substituted by 1 to 3 substituents independently selected from the group consisting of fluorine, cyano, trifluoromethyl, methyl, ethyl, methoxy and ethoxy, where methyl and ethyl are optionally even trisubstituted by fluorine, with phenyl being substituted by 1 to 4 substituents independently selected from the group consisting of halgen, cyano, (C1-C4)-alkyl, (C3-C6 )-cycloalkyl, trifluoromethyl, (C1-C4)-alkoxy, (C3-C5)-cycloalkoxy, monofluoromethoxy, difluoromethoxy, trifluoromethoxy, hydroxycarbonyl, (C1-C4)-alkoxycarbonyl, aminocarbonyl, mono-(C1-C4)-alkylaminocarbonyl, di-(C1-C4)-alkylaminocarbonyl, (C1-C4)-alkylsulfanyl, (C1-C4)-alkylsulfonyl, (C1-C4)-alkylsulfonimidoyl, aminosulfonyl, mono-(C1-C4)-alkylaminosulfonyl, di-(C1 -C4)-alkylaminosulfonyl, (C1-C4)-alkylsulfinyl, amino, mono-(C1-C4)-alkylamino or di-(C1-C4)-alkylamino, or where phenyl is optionally fused to cyclopentyl, cyclohexyl , 5- to 6-membered heterocyclyl or 5 to 6-membered heteroaryl, with phenyl being optionally substituted by methyl, ethyl, chlorine, fluorine or methoxy, with cyclopentyl, cyclohexyl, 5- to 6-membered heterocyclyl and heteroaryl with 5 to 6 members are optionally substituted by 1 or 2 methyl or ethyl substituents, with methyl and ethyl being optionally substituted by methoxy, hydroxyl, monomethylamino or diethylamino and even optionally trisubstituted by fluorine, or with the 5 to 10 membered heteroaryl being optionally substituted by 1 to 4 substituents independently selected from the group halgen, cyano, (C1-C4)-alkyl, (C3-C6)-cycloalkyl, trifluoromethyl, (C1-C4)-alkoxy, (C3-C5)-cycloalkoxy, difluoromethoxy , trifluoromethoxy, 2,2,2-trifluoroethoxy, hydroxycarbonyl, (C1-C4)-alkoxycarbonyl, aminocarbonyl, mono-(C1-C4)-alkylaminocarbonyl, di-(C1-C4)-alkylaminocarbonyl, (C1-C4)-alkylsulfanyl , (C1-C4)-alkylsulfonyl, (C1-C4)-alkylsulfonimidoyl, aminosulfonyl, mono-(C1-C4)-alkylaminosulfonyl, di-(C1-C4)-alkylaminosulfonyl, (C1-C4)-alkylsulfinyl, amino, mono -(C1-C4)-alkylamino or di-(C1-C4)-alkylamino, or wherein the 5- to 6-membered heteroaryl of R1 is optionally fused to cyclopentyl, cyclohexyl, phenyl or 5- to 6-membered heterocyclyl, wherein the 5 to 6 membered heteroaryl of R1 is optionally substituted by methyl, ethyl, chlorine, fluorine or methoxy, with the cyclopentyl, cyclohexyl, phenyl and 5 to 6 membered heterocyclyl fused to said 5 to 6 membered heterocyclyl of R1 are optionally substituted by 1 or 2 substituents (C1-C4)-alkyl, with (C1-C4)-alkyl being optionally substituted by (C1-C4)-alkoxy, hydroxyl, mono-(C1-C4)-alkylamino or di-(C1-C4)-alkylamino and even pentassubstituted by fluorine, R2 is a group of the Formula, in which #3 marks the bond to the carbon atom; " is 0 or 1; Z is S, SO, SO2 or CR14AR14B; R14A is hydrogen, fluorine, (C1-C4)-alkyl, trifluoromethyl, difluoromethyl, fluoromethyl, hydroxyl, methoxy, ethoxy, difluoromethoxy, where (C1-C4)-alkyl is optionally substituted by hydroxyl, R14B is hydrogen, fluorine, methyl or trifluoromethyl, or R14A and R14B, together with the carbon atom to which they are attached, form a carbonyl group, R12 is hydrogen, cyano, methyl, ethyl, acetyl or formyl, with acetyl being replaced by hydroxyl, R13 is hydrogen, fluorine or methyl, or R12 and R13, together with the carbon atoms to which they are attached, form a cyclopropyl ring, with the cyclopropyl ring being optionally even disubstituted by fluorine, or R13 and R14A, together with the carbon atoms to which are linked, form a cyclopropyl ring, with the cyclopropyl ring being optionally even disubstituted by fluorine, or R14A and R14B, together with the carbon atom to which they are linked, form a cyclopropyl ring, with the cyclopropyl ring being optionally even disubstituted by fluorine, where R13, R14A and R14B are hydrogen when R12 is not hydrogen, and R12 is hydrogen when one of the substituents R13, R14A and R14B is not hydrogen, or is a group of the Formula, in which #4 marks the bond to the carbonyl carbon atom; Y is NR15, CR16AR16B, oxygen or sulfur; R15 is hydrogen or methyl; R16A is hydrogen or methyl; R 16B is hydrogen or methyl; R3 is hydrogen or methyl; R4 is hydrogen, fluorine, methyl, ethyl, or hydroxyl, where methyl and ethyl are optionally even trisubstituted by fluorine, R5 is hydrogen or methyl, or a salt thereof. 3. Compound according to claim 1 or 2, characterized by the fact that: A is -CH2-, -CH(CH3)-, -CH2CH2-, #5-CH2CH(CH3)-***, #5-CH2C(CH3)2-***, #5-CH2CHF-*** or #5-CH2CF2-***, with #5 marking the bond to the nitrogen atom of the 5-oxo-4 ring, 5-dihydro-1H-1,2,4-triazol-1-yl, where *** marks the bond to the R1 group, X is - #2-CR6R7-CR8R9-**, where #2 marks the bond to the carbon atom of the CR4R5- group, with ** marking the bond to the carbon atom of the 5-oxo-4,5-dihydro-1H-1,2,4-triazol-1-yl ring, R6 is hydrogen, fluorine, methyl or trifluoromethyl, R7 is hydrogen, fluorine or methyl, R8 is hydrogen, (C1-C4)-alkyl, fluorine, hydroxyl, where (C1-C4)-alkyl is optionally even trisubstituted by fluorine, R9 is hydrogen, fluorine or (C1-C4)-alkyl, where (C1-C4)-alkyl is optionally even trisubstituted by fluorine, R1 is phenyl or heteroaryl with 5 to 6 members, with phenyl being substituted by 1 to 3 substituents independently selected from the group consisting of fluorine, chlorine, cyano, methyl, ethyl, trifluoromethyl, methoxy, difluoromethoxy, trifluoromethoxy, hydroxycarbonyl, methoxycarbonyl, ethoxycarbonyl, tert-butoxycarbonyl, methylaminocarbonyl, dimethylaminocarbonyl, methylsulfanyl, methylsulfonyl, methylsulfonimidoyl, aminosulfonyl or methylsulfinyl, or wherein the phenyl is optionally fused to cyclopentyl, cyclohexyl, 5 to 6 membered heterocyclyl or 5 to 6 membered heteroaryl, wherein cyclopentyl, cyclohexyl, 5 to 6 membered heterocyclyl and 5 to 6 membered heteroaryl are optionally substituted by 1 or 2 methyl or ethyl substituents; or wherein the 5- to 6-membered heteroaryl is optionally substituted by 1 to 3 substituents independently selected from the group consisting of fluorine, chlorine, cyano, methyl, ethyl, trifluoromethyl, methoxy, ethoxy, difluoromethoxy, trifluoromethoxy, 2,2,2- trifluoroethoxy, methylaminocarbonyl, tert-butylaminocarbonyl, dimethylaminocarbonyl, or the 5- to 6-membered heteroaryl of R1 is optionally fused to cyclopentyl, cyclohexyl, 5- to 6-membered heterocyclyl, phenyl, or 5- to 6-membered heteroaryl, with the 5-membered heteroaryl the 6-membered R1 is optionally substituted by methyl, ethyl, chlorine, fluorine or methoxy, and cyclopentyl, cyclohexyl, 5- to 6-membered heterocyclyl fused to said 5- to 6-membered heteroaryl of R1 are optionally substituted by 1 or 2 (C1-C4)-alkyl substituents, R2 is a group of the Formula, in which #3 marks the bond to the carbon atom; " is 0 or 1; Z is S or CR14AR14B when " is 0, Z is S, SO, SO2 or CR14AR14B when " is 1, in each of which R14A is hydrogen, fluorine, methyl, trifluoromethyl, difluoromethyl, fluo"omethyl, hydroxyl, methoxy or difluo"omethoxy; R14B is hydrogen or fluorine; or R14A and R14B, together with the carbon atom to which they are attached, form a cabonyl group, R12 is hydrogen, cyano, methyl, acetyl or fomyl, with acetyl being substituted powder"hydroxyl; R13 is hydrogen, fluorine or methyl; or R12 and R13, together with the carbon atoms to which they are bonded, form a cyclopyl ring; or R13 and R14A, together with the carbon atom to which they are bonded, form a ring cyclop"opyl, with the cyclop"opyl ring being optionally even disubstituted by "fluo", or R14A and R14B, together with the carbon atom to which they are attached, form a cyclopropyl ring, with the cyclopropyl ring being optionally even disubstituted by fluorine, with R13, R14A and R14B being hydrogen when R12 is not hydrogen, with R12 being hydrogen when one of the substituents R13, R14A and R14B is not hydrogen; hydrogen; or a salt thereof. 4. Compound according to claim 1, characterized by the fact that: A is -CH2-, -CH(CH3)-, -CH2CH2-, #5-CH2CH(CH3)-***, #5-CH2C (CH3)2-***, #5-CH2CHF-*** or #5-CH2CF2-***, with #5 marking the bond to the nitrogen atom of the 5-oxo-4,5-di- ring hydro-1H-1,2,4-triazol-1-yl, where *** marks the bond to the R1 group, X is - #2-CR6R7-CR8R9-**, where #2 marks the bond to the atom of the CR4R5- group, with ** marking the bond to the carbon atom of the 5-oxo-4,5-dihydro-1H-1,2,4-triazol-1-yl ring, with R6 being hydrogen, fluorine, methyl or trifluoromethyl; R7 is hydrogen, fluorine or methyl; R8 is hydrogen, fluorine, methyl or trifluoromethyl; R9 is hydrogen, fluorine or methyl; R1 is 5- to 6-membered phenyl or heteroaryl, with phenyl being substituted by 1 to 3 substituents independently selected from the group consisting of fluorine, chlorine, cyano, methyl, ethyl, trifluoromethyl, methoxy, difluoromethoxy, trifluoromethoxy, hydroxycarbonyl, methoxycarbonyl, ethoxycarbonyl, tert-butoxycarbonyl, methylaminocarbonyl, dimethylaminocarbonyl, methylsulfanyl, methylsulfonyl, methylsulfonimidoyl, aminosulfonyl and methylsulfinyl, or wherein phenyl is optionally fused to cyclopentyl, cyclohexyl, 5- to 6-membered heterocyclyl or 5- to 6-membered heteroaryl, being wherein cyclopentyl, cyclohexyl, 5 to 6 membered heterocyclyl and 5 to 6 membered heteroaryl are optionally substituted by 1 or 2 methyl or ethyl substituents, or wherein the 5 to 6 membered heteroaryl is optionally substituted by 1 to 3 substituents independently selected from the group consisting of fluorine, chlorine, cyano, methyl, ethyl, trifluoromethyl, methoxy, ethoxy, difluoromethoxy, trifluoromethoxy, 2,2,2-trifluoroethoxy, methylaminocarbonyl, tert-butylaminocarbonyl, dimethylaminocarbonyl, or said heteroaryl with 5 to 6 members of R1 is optionally fused to cyclopentyl, cyclohexyl, 5- to 6-membered heterocyclyl, phenyl or 5- to 6-membered heteroaryl, with said 5- to 6-membered heteroaryl of R1 being optionally substituted by methyl, ethyl, chloro, fluorine or methoxy, wherein cyclopentyl, cyclohexyl, 5 to 6 membered heterocyclyl, phenyl and 5 to 6 membered heteroaryl fused to said 5 to 6 membered heteroaryl of R1 are optionally substituted by 1 or 2 substituents of (C1-C4)- alkyl, R2 is a group of the Formula, in which #3 marks the bond to the carbonyl carbon atom; r is 0 or 1; Z is S or CR14AR14B when r is 0; Z is S, SO, SO2 or CR14AR14B when r is 1, in each of which R14A is hydrogen, fluorine, methyl, trifluoromethyl, difluoromethyl, fluoromethyl, hydroxyl, methoxy or difluoromethoxy; R14B is hydrogen or fluorine; or R14A and R14B, together with the carbon atom to which they are attached, form a carbonyl group, R12 is hydrogen, cyano, methyl, acetyl or formyl, with acetyl being replaced by hydroxyl; R13 is hydrogen, fluorine or methyl, or R12 and R13, together with the carbon atoms to which they are attached, form a cyclopropyl ring, or R13 and R14A, together with the carbon atom to which they are attached, form a cyclopropyl ring, with the cyclopropyl ring being optionally even disubstituted by fluorine, or R14A and R14B, together with the carbon atom to which they are attached, form a cyclopropyl ring, with the cyclopropyl ring being optionally even disubstituted by fluorine, with R13, R14A and R14B are hydrogen when R12 is not hydrogen, with R12 being hydrogen when one of the substituents R13, R14A and R14B is not hydrogen; R3 is hydrogen; R4 is hydrogen, fluorine or methyl; R5 is hydrogen; or a salt thereof. 5. Compound according to claim 1, characterized by the fact that: A is -CH2-, -CH(CH3)-, -CH2CH2-, #5-CH2CH(CH3)-***, #5-CH2C (CH3)2-***, #5-CH2CHF-*** or #5-CH2CF2-***, with #5 marking the bond to the nitrogen atom of the 5-oxo-4,5-di- ring hydro-1H-1,2,4-triazol-1-yl, where *** marks the bond to the R1 group, X is - #2-CR6R7-CR8R9-**, where #2 marks the bond to the atom carbon of the CR4R5- group, with ** marking the bond to the carbon atom of the 5-oxo-4,5-dihydro-1H-1,2,4-triazol-1-yl ring; R6 is hydrogen, fluorine, methyl or trifluoromethyl; R7 is hydrogen, fluorine or methyl, or R8 is hydrogen, fluorine, methyl or trifluoromethyl; R9 is hydrogen, fluorine or methyl; R1 is phenyl, pyrazolyl, imidazolyl, thiazolyl, thiophenyl, oxazolyl, oxadiazolyl or pyridyl, wherein phenyl is substituted by 1 to 3 substituents independently selected from the group consisting of fluorine, chlorine, cyano, methyl, ethyl, trifluoromethyl, methoxy, difluoromethoxy , trifluoromethoxy, hydroxycarbonyl, methoxycarbonyl, ethoxycarbonyl, tert-butoxycarbonyl, methylaminocarbonyl, dimethylaminocarbonyl, methylsulfanyl, methylsulfonyl, methylsulfonimidoyl, aminosulfonyl or methylsulfinyl; or wherein the phenyl is optionally fused to cyclopentyl, cyclohexyl, pyrazolyl or pyridyl, wherein cyclopentyl, cyclohexyl, pyrazolyl or pyridyl is optionally substituted by 1 or 2 methyl or ethyl substituents; or wherein said pyrazolyl, imidazolyl, thiazolyl, thiophenyl, oxazolyl, oxadiazolyl or pyridyl of R1 are optionally substituted by 1 to 3 substituents independently selected from the group consisting of fluorine, chlorine, cyano, methyl, ethyl, trifluoromethyl, methoxy, ethoxy, difluoromethoxy, trifluoromethoxy, 2,2,2-trifluoroethoxy, methylaminocarbonyl, tert-butylaminocarbonyl, dimethylaminocarbonyl; said pyrazolyl, imidazolyl, thiazolyl, thiophenyl, oxazolyl, oxadiazolyl or pyridyl of R1 being optionally fused to cyclopentyl, cyclohexyl, phenyl or pyridyl, said pyridyl of R1 being optionally substituted by methyl, ethyl, chlorine, fluorine or methoxy, wherein the cyclopentyl, cyclohexyl, phenyl and pyridyl fused to said pyrazolyl, imidazolyl, thiazolyl, thiophenyl, oxazolyl, oxadiazolyl or pyridyl of R1 are optionally substituted by 1 or 2 substituents (C1-C4)-alkyl, R2 is a Formula group, in which #3 marks the bond to the carbonyl carbon atom; r is 0 or 1; Z is S or CR14AR14B when r is 0; Z is S, SO, SO2 or CR14AR14B when r is 1, in each of which R14A is hydrogen, fluorine, methyl, trifluoromethyl, difluoromethyl, fluoromethyl, hydroxyl, methoxy or difluoromethoxy; R14B is hydrogen or fluorine, or R14A and R14B, together with the carbon atom to which they are attached, form a carbonyl group, R12 is hydrogen, cyano, methyl, acetyl or formyl, with acetyl being replaced by hydroxyl; R13 is hydrogen, fluorine or methyl; or R12 and R13, together with the carbon atoms to which they are attached, form a cyclopropyl ring, or R13 and R14A, together with the carbon atom to which they are attached, form a cyclopropyl ring, the cyclopropyl ring being optionally even disubstituted by fluorine, or R14A and R14B, together with the carbon atom to which they are attached, form a cyclopropyl ring, with the cyclopropyl ring being optionally even disubstituted by fluorine, with R13, R14A and R14B being hydrogen when R12 is not hydrogen, with R12 being hydrogen when one of the substituents R13, R14A and R14B is not hydrogen; R3 is hydrogen; R4 is hydrogen, fluorine or methyl; R5 is hydrogen; or a salt thereof. 6. Compound of Formula (I), according to claim 1, characterized by the fact that it is (5RS, 7RS) -2 - [(6-Chloropyridin-3-yl) methyl] -5-{[(3R, 4S)-3,4-difluoropyrrolidin-1-yl]carbonyl}-7-trifluoromethyl)-5,6,7,8-tetrahydro[1,2,4]triazol[4,3-a]pyridin-3 (2H)-one (isomer 1), from the Formula, 7. Compound of Formula (I), according to claim 1, characterized by the fact that it is (5S, 7R)-5-{[(3S)-3-Fluoropyrrolidin-1-yl]carbonyl}-7-( trifluoromethyl)-2-{[6-(trifluoromethyl)pyridin-3-yl]methyl}-5,6,7,8-tetrahydro[1,2,4] triazol[4,3-a]pyridin-3 (2H)-one (isomer 1), from the Formula, 8. Compound of Formula (I) according to claim 1, characterized by the fact that it is (5S)-5-{[(3R, 4S)-3,4-difluoropyrrolidin-1-yl]carbonyl}-2 -{[3-fluoro-2-trifluoromethyl) pyridin-4-yl]methyl}-5,6,7,8-tetrahydro[1,2,4]triazol[4,3-a] pyridin-3 2H )-one Formula, 9. Compound of Formula (I), according to claim 1, characterized by the fact that it is (5S)-5-{[(3S)-3-fluoropyrrolidin-1-yl]carbonyl}-2-{[6 -(trifluoromethyl)pyridin-3-yl]methyl}-5,6,7,8-tetrahydro[1,2,4]triazol[4,3-a]pyridin-3(2H)-one, of Formula , 10. Process for preparing a compound of Formula (I), as defined in claim 1, wherein A is -CH2-, -CH(CH3)-, -CH2CH2-, #5-CH2CH(CH3)-***, #5- CH2C(CH3)2-***, #5-CH2CHF-*** or #5-CH2CF2-***, where #5 marks the bond to the nitrogen atom of the 5-oxo-4,5-dihydro-1H-1,2,4 ring -triazol-1-yl, where *** marks the bond to the R1 group, and where R1, R2, R3, R4, R5 and X are as defined in claim 1, said process being characterized by the fact that it comprises : [A] react with a compound of Formula (II), wherein R3, R4, R5 and X are as defined in claim 1; and T1 is (C1-C4)-alkyl or benzyl; in an inert solvent, in the presence of a suitable base, with a compound of Formula (III), RH 1^A (III), in which A1 is -CH2-, -CH(CH3)-, -CH2CH2-, #5-CH2CH(CH3)-***, #5-CH2C(CH3)2-** *, #5-CH2CHF-*** or #5-CH2CF2-***, with #5 marking the bond to the nitrogen atom of the 5-oxo-4,5-dihydro-1H-1,2 ring ,4-triazol-1-yl, where *** marks the connection to the R1 group; R1 is as defined in claim 1; and -nitrophenyl)sulfonyl]oxy} or {[(4-methylphenyl)sulfonyl]oxy} tosylate, to produce a compound of Formula (IV), wherein A1, R1, R3, R4, R5, X and T1 are each as defined above; convert the compound of Formula (IV) into a compound of Formula (V) by removing the "T1" group in an inert solvent in the presence of a suitable base or acid, in which A1, R1, R3, R4, R5 and X are each as defined above, react the compound of Formula (V) in an inert solvent under amide coupling conditions with an amine of Formula (VI-A) or ( VI-B), wherein Y, Z, R12 and R13 are as defined in claim 1; thereby providing the compound of Formula (I); and the resulting compounds of Formula (I) are optionally converted with appropriate solvents (i) and/or (ii) acids or bases to salts thereof; or [B] react a compound of Formula (II), wherein R3, R4, R5 and X are as defined in claim 1; and T1 is (C1-C4)-alkyl or benzyl; in an inert solvent in the presence of a suitable base with an amine of Formula (VI-A) or (VI-B), wherein Y, Z, R12 and R13 are as defined in claim 1, to produce a compound of Formula (XXIII-A) or (XXIII-B), in which R3, R4, R5, R12, R13, X, Y, Z and r are each as defined above, react the compound of Formula (XXIII-A) or the compound of Formula (XXIII-B) in an inert solvent, in the presence of a suitable base, with a compound of Formula (III), where A1 is -CH2-, -CH(CH3)-, -CH2CH2-, #5-CH2CH(CH3)-***, #5-CH2C(CH3)2-***, #5-CH2CHF-* ** or #5-CH2CF2-***, where #5 marks the bond to the nitrogen atom of the 5-oxo-4,5-dihydro-1H-1,2,4-triazol-1-yl ring , where *** marks the bond to the group R1, R1 as defined in claim 1, and X1 is a suitable leaving group, thereby providing the compound of Formula (I); and optionally further converting the compound of Formula (I) with appropriate solvents (i) and/or (ii) acids or bases to salts thereof; or [C] convert a compound of Formula (VII), wherein R3, R4, R5 and X are as defined in claim 1; T1 is (C1-C4)-alkyl or benzyl; T2 is 4-methoxybenzyl, benzyl, allyl, β-(trimethylsilyl)ethoxymethyl (SEM), methoxymethyl (MOM) or benzyloxymethyl, by hydrolysis of the ester group in an inert solvent in the presence of a base or acid suitable for a compound of the Formula ( VIII), in which R3, R4, R5, T2 and X are as defined above, react the compound of Formula (VII) in an inert solvent in the presence of a suitable base with an amine of Formula (VI-A) or (VI-B) , in which Z, R12 and R13 are as defined in claim 1, to produce a compound of Formula (IX-A) or (IX-B) , in which R3, R4, R5, R12, R13, T2, X, Y, Z and r are each as defined above, the protecting group "T2" is removed in an inert solvent in the presence of a suitable base or acid or optionally in the presence of a suitable palladium catalyst and the resulting compound of Formula (XA) or (XB), in which R3, R4, R5, R12, R13, X, Y, Z and r are each as defined above, react the compound of Formula (XA) or (ZB) in an inert solvent, in the presence of a suitable base, with a compound of Formula (III), in which A1 is A; R1 is defined as in claim 1; and X1 is a suitable leaving group; thereby providing the compound of Formula (I); and optionally further converting the compound of Formula (I) with appropriate solvents (i) and/or (ii) acids or bases to salts thereof. 11. Compound of Formula (I), according to any one of claims 1 to 9, characterized by the fact that it is for treatment and/or prophylaxis of inflammatory lung disorders, particularly chronic obstructive pulmonary disease (COPD), pulmonary emphysema , chronic bronchitis, bronchiectasis, pulmonary hypertension in COPD (PH-COPD), acute exacerbation in COPD, cystic fibrosis (mucoviscidosis, CF), asthma and idiopathic pulmonary fibrosis (IPF), bronchiolitis obliterans syndrome ( SBO), arteriosclerosis, myocarditis and inflammatory disorders of the skin and eyes or inflammatory disorders of internal organs. 12. Use of a compound of Formula (I), as defined in any one of claims 1 to 9, characterized by the fact that it is for the production of a medicine for the treatment and/or prophylaxis of pulmonary inflammatory disorders, particularly obstructive pulmonary disease chronic (COPD), pulmonary emphysema, chronic bronchitis, bronchiectasis, pulmonary hypertension in COPD (PH-COPD), acute exacerbation in COPD, cystic fibrosis (mucoviscidosis, CF), asthma and idiopathic pulmonary fibrosis (IPF ), bronchiolitis obliterans syndrome (BOS), arteriosclerosis, myocarditis and inflammatory disorders of the skin and eyes or inflammatory disorders of internal organs. 13. Medicament, characterized by the fact that it comprises a compound, as defined in any one of claims 1 to 9, in combination with one or more pharmaceutically suitable inert, non-toxic excipients. 14. Medication according to claim 13, characterized in that it is indicated for the treatment and/or prophylaxis of inflammatory lung disorders, particularly chronic obstructive pulmonary disease (COPD), pulmonary emphysema, chronic bronchitis, bronchiectasis, pulmonary hypertension in COPD (PH-COPD), acute exacerbation in COPD, cystic fibrosis (mucoviscidosis, CF), asthma and idiopathic pulmonary fibrosis (IPF), bronchiolitis obliterans syndrome (BOS), arteriosclerosis, myocarditis and from inflammatory disorders of the skin and eyes or inflammatory disorders of internal organs.