[go: up one dir, main page]

WO2025146626A1 - Procédé de préparation de 1-(4-(5-(halométhyl)-1,2,4-oxadiazol-3-yl)phényl)éthan-1-one - Google Patents

Procédé de préparation de 1-(4-(5-(halométhyl)-1,2,4-oxadiazol-3-yl)phényl)éthan-1-one Download PDF

Info

Publication number
WO2025146626A1
WO2025146626A1 PCT/IB2025/050009 IB2025050009W WO2025146626A1 WO 2025146626 A1 WO2025146626 A1 WO 2025146626A1 IB 2025050009 W IB2025050009 W IB 2025050009W WO 2025146626 A1 WO2025146626 A1 WO 2025146626A1
Authority
WO
WIPO (PCT)
Prior art keywords
formula
compound
solvent
iii
acid
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Pending
Application number
PCT/IB2025/050009
Other languages
English (en)
Inventor
Kishor Bapu GAVHANE
Govind TOMAR
Girija LOHAR
Sanjay Maruti MADURKAR
Santosh Giridhar KAVITAKE
Nitin Malviya
Alexander G.M. KLAUSENER
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
PI Industries Ltd
Original Assignee
PI Industries Ltd
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by PI Industries Ltd filed Critical PI Industries Ltd
Publication of WO2025146626A1 publication Critical patent/WO2025146626A1/fr
Pending legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D271/00—Heterocyclic compounds containing five-membered rings having two nitrogen atoms and one oxygen atom as the only ring hetero atoms
    • C07D271/02—Heterocyclic compounds containing five-membered rings having two nitrogen atoms and one oxygen atom as the only ring hetero atoms not condensed with other rings
    • C07D271/06—1,2,4-Oxadiazoles; Hydrogenated 1,2,4-oxadiazoles
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
    • A61K31/4245—Oxadiazoles

Definitions

  • the present invention relates to a method for the preparation of a compound (l-(4-(5-(halomethyl)- l,2,4-oxadiazol-3-yl)phenyl)ethan-l-one) of Formula (III). Further the present invention also relates to a method for the preparation of a compound of Formula (I), an intermediate compound of Formula (II) and N-oxides or salts thereof, useful for combating phytopathogenic fungi.
  • Oxadiazole based compounds are well known for their pesticidal activity.
  • Various oxadiazoles have been disclosed in the literature.
  • WO2017118689 discloses a microbiocidal oxadiazole compound of Formula (I), as a fungicide, wherein l-(4-(5-(trifluoromethyl)-l,2,4-oxadiazol-3-yl)phenyl)ethan-l-one was used as an intermediate for its preparation.
  • W02020208511 discloses the preparation of oxadiazole compounds bearing a carbonyl group, which includes protection of the carbonyl group of the nitrile reactant with ethylene glycol, followed by a reaction with aqueous hydroxylamine, furthermore by a cyclization with trifluoroacetic anhydride, and finally deprotection of the cyclic ether to obtain the oxadiazole compounds bearing a carbonyl group.
  • the disclosed process is lengthy, involves too many reagents and purification steps at every stage, and is eventually less atom economic.
  • the objective of the present invention is to provide a novel, cost effective and improved method for preparing the compound of Formula (I) and intermediate compounds of Formula (II) and Formula (III) and their N-oxides or salts thereof, in a reduced number of steps and with high isolated yields, suitable for commercial scale preparation.
  • the present invention provides a solution to this objective by offering a simple and economically amenable method for obtaining a compound of Formula (III). Further, the present invention also provides a method for the preparation of a compound of Formula (I), and intermediate compounds of Formula (II) or salts thereof, in high yields and a reduced number of reaction steps, wherein the said method comprises a novel and inventive step of simultaneous cyclization and de -protection of a compound of Formula (V) in a single step, by overcoming at least one of the shortcomings disclosed in the prior art.
  • the first aspect of the present invention provides a method for preparing a compound of Formula (III), or its N-oxides or salts thereof,
  • Formula (III) wherein R 1 is selected from -CHF2, -CF2-CI or CF3, comprising the steps of: a. reacting a compound of Formula (VI) with hydroxylamine or its salts in a solvent, optionally in the presence of a base, to form a dioxime compound of Formula (V), and b. cyclizing the dioxime compound of Formula (V) by reacting it with a compound of Formula (IV) in a solvent, optionally in the presence of a base, followed by treatment with an acid, to obtain the compound of Formula (III) in a single-step,
  • the present invention provides a method for preparing a compound of Formula (II), or its N-oxides or salts thereof,
  • R 1 is selected from -CHF2, -CF2-CI or CF3;
  • R 5 is selected from fluoro, chloro, bromo, or iodo, comprising the steps of: a. reacting a compound of Formula (VI) with hydroxylamine or its salts in a solvent, optionally in the presence of a base, to form a dioxime compound of Formula (V), b. cyclizing the dioxime compound of Formula (V) by reacting it with a compound of Formula (IV) in a solvent, optionally in the presence of a base, followed by treatment with an acid, to obtain the compound of Formula (III) in a single-step, wherein R 4 is selected from halogen, OH, Ci-Ce-alkoxy or O-C(O)-R'; - and c. halogenating the compound of Formula (III) using a halogenating agent and a solvent, optionally in the presence of a catalyst, to obtain a compound of Formula (II),
  • the present invention provides a method for preparing a compound of Formula (I), or its N-oxides or salts thereof,
  • R 1 is selected from -CHF2, -CF2-CI or CF3;
  • L is selected from O, NR 3 or S;
  • R 2 is selected from hydrogen, halogen, C i-Ce-alkyl, Ci-Ce-haloalkyl, Ci-Ce-alkoxy or C3-C6- cycloalkyl;
  • R 3 is selected from hydrogen or C i-Ce-alkyl; and n is an integer selected from 1-2, comprising the steps of: a. reacting a compound of Formula (VI) with hydroxylamine or its salts in a solvent, optionally in the presence of a base, to form a dioxime compound of Formula (V),
  • Formula (III) Formula (II) wherein R 5 is fluoro, chloro, bromo or iodo; and d. alkylating a compound of Formula (IX) with the compound of Formula (II) in the presence of a base, and optionally in the presence of a catalyst and a solvent, to obtain a compound of
  • the present invention provides a method for the synthesis of compounds of Formula (VI) and salts thereof, comprising the steps of: i. acetylating a compound of Formula (VIII) with acetyl chloride or acetic anhydride in the presence of a suitable catalyst and optionally in the presence of a solvent to obtain a compound of Formula (VII),
  • R 4 is selected from halogen, Ci-Ce-alkoxy, OH or O-C(O)-R'.
  • the present invention further relates to an intermediate compound of formula (X) or formula (XI),
  • the compounds of the present disclosure may be present either in pure form or as mixtures of different possible isomeric forms such as stereoisomers or constitutional isomers.
  • the various stereoisomers include enantiomers, diastereomers, chiral isomers, atropisomers, conformers, rotamers, tautomers, optical isomers, polymorphs, and geometric isomers. Any desired mixtures of these isomers fall within the scope of the claims of the present disclosure.
  • one stereoisomer may be more active and/or may exhibit beneficial effects when enriched relative to the other isomer(s) or when separated from the other isomer(s). Additionally, the person skilled in the art knows processes or methods or technology to separate, enrich, and/or to selectively prepare said isomers.
  • the compounds of the present disclosure may be present in the form of N -oxides or salts.
  • the compounds of the present invention may be an acid addition or base addition salt.
  • the acid addition salt includes inorganic or organic acid preferably hydrochloric acid, trifluoroacetic acid, methanesulfonic acid, p-toluenesulfonic acid.
  • the base addition salt includes inorganic or organic base preferably alkali metal or alkaline earth metal salt.
  • halogen used in the present invention refers to fluoro, chloro, bromo or iodo.
  • Ci-Ce alkyl used in the present invention refers to a linear or branched alkyl with 1 to 6 carbon atoms.
  • Examples of Ci-Ce includes but not limited to methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, sec-butyl, t-butyl, //-pentyl or //-hexyl and the like.
  • Ci-Ce haloalkyl used in the present invention refers to a linear or a branched alkyl with 1 to 6 carbon atoms, which is substituted with one or more halogen. Examples includes but not limited to chloromethyl, dichloromethyl, trichloromethyl, trifluoromethyl, difluoromethyl, trifluoroethyl, perfluoroethyl and the like.
  • Ci-Ce alkoxy used in the present invention refers to a linear or a branched alkoxy with 1 to 6 carbon atoms. Examples includes but not limited to methoxy, ethoxy, propoxy, isopropoxy, //-butoxy, t-butoxy and the like.
  • C3-C6 cycloalkyl used in the present invention refers to a 3- to 6-membered saturated monocyclic carbocyclic ring. Examples includes but not limited to cyclopropyl, cyclobutyl, cyclopentyl and the like.
  • Formula (VI) HO' N Formula (V) b. cyclizing the dioxime compound of Formula (V) by reacting it with a compound of Formula (IV) in a solvent, optionally in the presence of a base, followed by treatment with an acid, to obtain the compound of Formula (III) in a single-step, wherein R 4 is selected from halogen, OH, Ci-Ce-alkoxy or O-C(O)-R'; and c. halogenating the compound of Formula (III) using a halogenating agent and a solvent, optionally in the presence of a catalyst, to obtain a compound of Formula (II),
  • R 3 is selected from hydrogen or C i-CT-alkyl; and n is an integer selected from 1-2, comprising the steps of: a. reacting the compound of Formula (VI) with hydroxylamine or its salt in a solvent, optionally in the presence of a base, to form a dioxime compound of Formula (V), b. cyclizing the dioxime compound of Formula (V) by reacting it with a compound of Formula (IV) in a solvent, optionally in the presence of a base, followed by treatment with an acid, to obtain the compound of Formula (III) in a single-step,
  • Embodiment-004 The present invention still further provides a method for the synthesis of a compound of Formula (VI), comprising the steps of: i. acetylating a compound of Formula (VIII) with acetyl chloride or acetic anhydride in the presence of a suitable catalyst and optionally in the presence of a solvent to obtain a compound of Formula (VII),
  • Embodiment-005 in yet another aspect, the present invention further relates to a method of preparing a compound of Formula (III), or its salts or N-oxides thereof, wherein the said method comprises the step (step-b) of cyclizing the dioxime compound of Formula (V) with a compound of Formula (IV) in a solvent and optionally in the presence of a base, followed by treatment with an acid, to obtain the compound of Formula (III) in a single-step, wherein, R 1 is selected from -CHF2, -CF2-CI or CF3 and
  • R 4 is selected from halogen, OH, C i-Ce-alkoxy or O-C(O)-R
  • Embodiment-006 In yet another aspect, the present invention provides a method for a compound of Formula (III), or its N-oxides or salts thereof,
  • R 1 is selected from -CHF2, -CF2-CI or CF3, comprising the steps of:
  • Formula (VIII) Formula (VII) . ii. reacting the compound of Formula (VII) with a cyanide source in a solvent, optionally in the presence of a catalyst, to obtain a compound of Formula (VI),
  • Formula (VII) Formula (VI) a. reacting the compound of Formula (VI) obtained in step (A) with hydroxylamine or its salts in a solvent, optionally in the presence of a base, to form a dioxime compound of Formula (V), and b. cyclizing the dioxime compound of Formula (V) by reacting it with a compound of Formula (IV) in a solvent, optionally in the presence of a base, followed by treatment with an acid, to obtain the compound of Formula (III) in a single-step, wherein R 4 is selected from halogen, -OH, Ci-Ce-alkoxy or O-C(O)-R'.
  • R 1 is selected from -CHF2, -CF2-CI or CF3;
  • R 5 is selected from fluoro, chloro, bromo, or iodo, comprising the steps of:
  • Embodiment-028 The methods of the present invention according to embodiments 001 , 002, 003, 004, 005, 006, 007, and 008, wherein the solvent can be selected from aliphatic or aromatic hydrocarbon, halogenated hydrocarbon, ethers, cyclic ethers, cyclic esters, cyclic carbonate ester, nitro based solvents, nitriles, amides, ketones, acids, alcohols, organosulfur, ionic liquids, water or mixture thereof.
  • the solvent can be selected from aliphatic or aromatic hydrocarbon, halogenated hydrocarbon, ethers, cyclic ethers, cyclic esters, cyclic carbonate ester, nitro based solvents, nitriles, amides, ketones, acids, alcohols, organosulfur, ionic liquids, water or mixture thereof.
  • Embodiment-030 The methods of the present invention according to embodiments 001 , 002, 003, 004, 005, 006, 007, and 008, wherein the base, if used, can be selected from an inorganic or organic base such as alkali metal hydrogen carbonate, alkali/alkaline earth metal carbonate, alkali/alkaline earth metal hydroxide, alkali metal phosphate, alkali metal hydride, alkali metal alkoxide, ethylamine, triethylamine, isopropylamine diisopropylamine, triisopropylamine, pyridine, picoline, piperidine, methylmorpholine, /V-mcthylpipcridinc N,N- (dimethylamino)pyridine (DMAP), lutidine, collidine, tetramethylammonium hydroxide, tetrabutylammonium hydroxide, choline hydroxide, l
  • Embodiment-031 The methods of the present invention according to embodiments 001, 002, 003, 005, 006, 007, and 008, wherein the reagent hydroxylamine used in step-a can be either in an aqueous form or in a solid form such as a salt form.
  • Embodiment-034 The methods of the present invention according to embodiment-031, wherein the reagent hydroxylamine is hydroxylamine hydrochloride salt.
  • Hydroxylamine hydrochloride is soluble in polar organic solvents and is more stable to oxidation and is easy to handle on large quantity as compared to free hydroxylamine or aqueous hydroxylamine, and as a result, step-c of the present method was carried out using hydroxylamine hydrochloride.
  • step-a was carried out in the presence of a base to neutralize the hydrochloride salt.
  • Embodiment-035 The methods of the present invention according to embodiment-034, wherein the base can be selected from alkali metal hydrogen carbonate, alkaline earth metal hydrogen carbonate, alkali metal carbonate, alkaline earth metal carbonate, triethylamine, diisopropylamine, triisopropylamine, pyridine, or picoline.
  • Embodiment-037 The methods of the present invention according to embodiments 001, 002, 003 and embodiments 005, 006, 007, 008, wherein step-a was performed in a suitable solvent selected from but not limited to alcohol such as ethanol, methanol, isopropanol, diethyl ether, /V,/V-di methyl f rm am ide, tetrahydrofuran or water or a mixture thereof.
  • a suitable solvent selected from but not limited to alcohol such as ethanol, methanol, isopropanol, diethyl ether, /V,/V-di methyl f rm am ide, tetrahydrofuran or water or a mixture thereof.
  • Embodiment-039 The methods of the present invention according to embodiments 001 , 002, 003, 005, 006, 007 and 008, wherein in step-a: i. the solvent is selected from ethanol, methanol, isopropanol, diethyl ether, N,N- dimethylformamide, tetrahydrofuran or water or a mixture thereof; and ii. the base if used, is selected from alkali metal hydrogen carbonate or alkaline earth metal hydrogen carbonate, alkali metal carbonate or alkaline earth metal carbonate, triethylamine, diisopropylamine, triisopropylamine, pyridine, or picoline.
  • the solvent is selected from ethanol, methanol, isopropanol, diethyl ether, N,N- dimethylformamide, tetrahydrofuran or water or a mixture thereof
  • the base if used is selected from alkali metal hydrogen carbonate or alkaline earth metal
  • Embodiment-045 The methods of the present invention according to embodiments-041 and 042, wherein the acid used for the acidic treatment, can be selected from but not limited to sulphuric acid, hydrochloric acid, or hydrobromic acid.
  • Embodiment-046 The methods of the present invention according to embodiment-045, wherein the acid is selected from hydrochloric acid and particularly from an aqueous hydrochloric acid.
  • Embodiment-047 The step-b of the present methods according to embodiments 001, 002, 003 and embodiments 005, 006, 007, 008, wherein the solvent includes alcohol, tetrahydrofuran, 2- methyltetrahydrofuran, acetonitrile, or V,V-dimethylformamide or water.
  • the solvent includes alcohol, tetrahydrofuran, 2- methyltetrahydrofuran, acetonitrile, or V,V-dimethylformamide or water.
  • Embodiment-048 The methods of the present invention according to embodiment-047, wherein the solvent is selected from methanol, ethanol, isopropanol, tetrahydrofuran or water and particularly, it is selected from methanol, ethanol or tetrahydrofuran.
  • the solvent is selected from methanol, ethanol, isopropanol, tetrahydrofuran or water and particularly, it is selected from methanol, ethanol or tetrahydrofuran.
  • Embodiment-049 The methods of the present invention according to embodiments 001, 002, 003 and embodiments 005, 006, 007, 008, wherein in step-b: i. the solvent is selected from methanol, ethanol, isopropanol, tetrahydrofuran, 2- methyltetrahydrofuran, acetonitrile, V,V-dimethylformamide or water; ii. the base if used, is selected from alkali metal alkoxide or alkaline earth metal alkoxide; iii. the acid is selected from sulphuric acid, hydrochloric acid, or hydrobromic acid.
  • the solvent is selected from methanol, ethanol, isopropanol, tetrahydrofuran, 2- methyltetrahydrofuran, acetonitrile, V,V-dimethylformamide or water
  • the base if used is selected from alkali metal alkoxide or alkaline earth metal al
  • Embodiment-050 The step-b of the present methods according to embodiments 001, 002, 003 and embodiments 005, 006, 007, 008, wherein the reaction temperature is between 0 °C-120 °C, and particularly, it is between 0 °C-40 °C during the cyclization and 70 °C -100 °C during the acidic treatment to obtain the compound of Formula (III).
  • Embodiment-051 The step-c of the present methods according to embodiments 002, 003 and 007, 008, wherein the halogenating agent can be selected from but not limited to F2, CI2, Br2, 12, B in acetic acid, /V-bromosuccinimidc, copper bromide (CuB ). HBr, NaBr, NtBBr, phosphorus tribromide (PBi ;).
  • phosphorus pentabromide a mixture of NJBBr and potassium peroxymonosulfate sulfate, Trimethylphenylammonium tribromide, N-chlorosuccinimide, phosphorus trichloride (PCh), phosphorus pentachloride (PCI5), sulfonyl chloride (SOCI2), sulfuryl chloride (SO2CI2), selenium oxychloride, benzyltrimethylammonium dichloroiodate, or trichloroisocyanuric acid.
  • PCh phosphorus trichloride
  • PCI5 phosphorus pentachloride
  • SOCI2 sulfuryl chloride
  • selenium oxychloride benzyltrimethylammonium dichloroiodate
  • trichloroisocyanuric acid trichloroisocyanuric acid.
  • Embodiment-052 The methods of the present invention according to embodiment-051, wherein the halogenating agent can be selected from B , /V-bromosuccinimidc, CI2, or N- chlorosuccinimide .
  • Embodiment-054 The methods of the present invention according to embodiments-002, 003 and 007, 008, wherein the halogenating agent can be used in the presence of a catalyst selected from but not limited to p-toluenesulfonic acid, aluminium chloride (AlCh), monopotassium phosphate (K2HSO4), sulphuric acid, silica, amberlyst 15, or trimethylsilyl triflate.
  • a catalyst selected from but not limited to p-toluenesulfonic acid, aluminium chloride (AlCh), monopotassium phosphate (K2HSO4), sulphuric acid, silica, amberlyst 15, or trimethylsilyl triflate.
  • phosphorus pentabromide a mixture of NfhBr and potassium peroxymonosulfate sulfate, trimethylphenylammonium tribromide, N-chlorosuccinimide, phosphorus trichloride (PCI3), phosphorus pentachloride (PCI5), sulfonyl chloride (SOCI2), sulfuryl chloride (SO2CI2), selenium oxychloride, benzyltrimethylammonium dichloroiodate, or trichloroisocyanuric acid; ii.
  • the solvent is selected from dichloromethane, dichloroethane (ethylene dichloride), chloroform, acetonitrile, diethyl ether, methyl tertiary-butyl ether, tetrahydrofuran, 2- methyl-tetrahydrofuran, ethyl acetate, alcoholic solvent selected from methanol, ethanol, or isopropanol, acetic acid or water or a mixture thereof; iii.
  • the catalyst if used is selected from p-toluenesulfonic acid, aluminium chloride (AlCh), monopotassium phosphate (K2HSO4), sulphuric acid, silica, amberlyst 15, or trimethylsilyl triflate.
  • Embodiment-058 The step-c of the present methods according to embodiments 002, 003 and 007, 008, wherein when the compound of formula (III) is subjected to halogenation using bromine or chlorine and in the presence of an alcoholic solvent such as methanol, ethanol or isopropanol followed by ketal de -protection in the presence of an acid to obtain a compound of formula (Ila), as shown below wherein,
  • R 5a is selected from bromo or chloro
  • R 6 is selected from methyl, ethyl, n-propyl or isopropyl, wherein the intermediate compound of formula (X) Formula (X) or f ormu ) a (XI)
  • Formula (XI) is/are optionally isolated.
  • Embodiment-059 The methods of the present invention according to embodiment-058, wherein the acid used for ketal deprotection is selected from hydrochloric acid.
  • Embodiment-063 The step-d of the present methods according to embodiments 003 and 008, can be carried out with or without a solvent.
  • Embodiment-090 The present invention further provides an intermediate compound of formula (XI),
  • the isolation of the reaction product can be carried out by a technique which includes but is not limited to decantation, filtration, centrifugation, evaporation, liquid-liquid extraction, distillation, recrystallization, chromatography and the like or a combination thereof.
  • Scheme 1 A process for preparing a compound of Formula (I) and its intermediate compounds of Formula (II) and Formula (III)
  • reaction mixture was cooled to 25-30 °C and quenched by the addition of water (150 mL), and extracted with methyl tert-butyl ether (MTBE) (3 X 100 mL). The combined organic layers were washed with brine (100 mL), dried over anhydrous sodium sulfate (NazSCH) and concentrated under reduced pressure to afford 4-acetylbenzonitrile (8.3 g, 78.99%) as an off-white solid.
  • MTBE methyl tert-butyl ether
  • Reagents 4-acetylbenzonitrile (300 g, 2046 mmol); hydroxylamine sulphate (402g, 2456 mmol); methanol (600 mL) and triethylamine (TEA) (371 mL, 2660 mmol).
  • Step-b Preparation of l-(4-(5-(trifluoromethyl)-l,2,4-oxadiazol-3-yl)phenyl)ethan-l-one
  • Method-2 Using Ethyl trifluoroacetate and NaOMe in MeOH To a stirred solution of /V'-hydroxy-4-(4 -(hydroxyimino) ethyl)benzimidamide (20 g, 104 mmol) in ethyl trifluoroacetate (36.8 g, 259 mmol), 30% sodium methoxide (NaOMe) in methanol (MeOH) (93.2 g, 518 mmol) was added in a dropwise manner at a temperature between 25 to 40 °C, and continued to stir further for 3 hours.
  • reaction mixture was added into aqueous 5N hydrochloric acid (HC1) solution (200 mL) and further heated to a temperature between 70 to 80°C. The reaction mixture was then continued to stir for 6 hours at 80°C. During the reaction, the distillate was collected to recover ethyl trifluoroacetate and methyl trifluoroacetate formed in situ due to transesterification. After completion of the reaction, the reaction mixture was cooled to a temperature between 20 to25°C. The solid obtained was filtered.
  • HC1 hydrochloric acid
  • Step-c Preparation of 2-bromo-l-(4-(5-(trifluoromethyl)-l,2,4-oxadiazol-3-yl)phenyl)ethan-l- one
  • Method-1 To a stirred solution of l-(4-(5-(trifluoromethyl)-l,2,4-oxadiazol-3-yl)phenyl)ethan-l-one (50 g, 195 mmol) in ethylene dichloride (EDC) (1.0 L), a solution of bromine (37.4 g, 234 mmol) in ethylene dichloride (500 mL) was added at a temperature between 40 to 45 °C in a drop wise manner. The reaction mixture was then stirred for 2 hours at a temperature between 40 to 45 °C. After the completion of the reaction, the reaction mixture was quenched by the addition of water (250 mL) and extracted with ethylene dichloride (2 x 250 mL).
  • EDC ethylene dichloride

Landscapes

  • Chemical & Material Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Organic Chemistry (AREA)
  • Animal Behavior & Ethology (AREA)
  • Epidemiology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Medicinal Chemistry (AREA)
  • Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)

Abstract

La présente invention concerne un procédé de préparation d'un composé de formule (I) et de ses composés intermédiaires représentés par la formule (II) et la formule (III), où R1, R2, L, R4, R5 et n sont tels que définis dans la description. Le présent procédé comprend une étape de conversion d'un composé dioxime de formule (V) en un composé de formule (III) en une seule étape par cyclisation et déprotection simultanées de cétoxime pour obtenir le composé de formule (III), qui a ensuite été soumis à une halogénation et une réaction ultérieures avec un composé de formule (IX) pour obtenir le composé de formule (I).
PCT/IB2025/050009 2024-01-03 2025-01-02 Procédé de préparation de 1-(4-(5-(halométhyl)-1,2,4-oxadiazol-3-yl)phényl)éthan-1-one Pending WO2025146626A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
IN202411000327 2024-01-03
IN202411000327 2024-01-03

Publications (1)

Publication Number Publication Date
WO2025146626A1 true WO2025146626A1 (fr) 2025-07-10

Family

ID=96300136

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/IB2025/050009 Pending WO2025146626A1 (fr) 2024-01-03 2025-01-02 Procédé de préparation de 1-(4-(5-(halométhyl)-1,2,4-oxadiazol-3-yl)phényl)éthan-1-one

Country Status (2)

Country Link
TW (1) TW202542121A (fr)
WO (1) WO2025146626A1 (fr)

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2017220485A1 (fr) * 2016-06-21 2017-12-28 Syngenta Participations Ag Dérivés d'oxadiazole microbiocides
WO2020208511A1 (fr) * 2019-04-08 2020-10-15 Pi Industries Limited Nouveaux composés d'oxadiazole pour la lutte ou la prévention contre des champignons phytopathogènes
WO2022249074A1 (fr) * 2021-05-26 2022-12-01 Pi Industries Ltd. Composition fongicide contenant des composés oxadiazoles

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2017220485A1 (fr) * 2016-06-21 2017-12-28 Syngenta Participations Ag Dérivés d'oxadiazole microbiocides
WO2020208511A1 (fr) * 2019-04-08 2020-10-15 Pi Industries Limited Nouveaux composés d'oxadiazole pour la lutte ou la prévention contre des champignons phytopathogènes
WO2022249074A1 (fr) * 2021-05-26 2022-12-01 Pi Industries Ltd. Composition fongicide contenant des composés oxadiazoles

Also Published As

Publication number Publication date
TW202542121A (zh) 2025-11-01

Similar Documents

Publication Publication Date Title
JP7553689B2 (ja) フェニルイソオキサゾリン系化合物の製造方法
JPH1045733A (ja) ２−（４−アルコキシ−３−シアノフェニル）チアゾール誘導体の製造法
WO2024194896A1 (fr) Procédé de préparation de diamides anthraniliques
DE102004041531A1 (de) Verfahren zum Herstellen von Biphenylaminen
WO2025146626A1 (fr) Procédé de préparation de 1-(4-(5-(halométhyl)-1,2,4-oxadiazol-3-yl)phényl)éthan-1-one
US20120029202A1 (en) Process for the Preparation of 5-Substituted 3-Aryl-3-(trifluoromethyl)-3,4-dihydro-2H-pyrroles
JP5140776B1 (ja) １−置換−３−フルオロアルキルピラゾール−４−カルボン酸エステルの製造方法
US5922916A (en) Process to chloroketoamines using carbamates
WO2025196653A1 (fr) Procédé de préparation de 1-(4-(5-(halométhyl)-1,2,4-oxadiazol-3-yl)phényl)éthan-1-one substitué
US20040199002A1 (en) Process for producing(2-nitrophenyl)acetonitrile derivative and intermediate therefor
JP3006237B2 (ja) アミノピラゾール誘導体の製法
JP7547414B2 (ja) シス－アルコキシ置換スピロ環式１－ｈ－ピロリジン－２，４－ジオン誘導体の製造方法
RU2846415C2 (ru) Способ получения ингибитора нуклеокапсида вируса гепатита в
KR101308227B1 (ko) 니코틴산 유도체 또는 그의 염의 제조 방법
Nagano et al. Synthesis of unsymmetrically and highly substituted thiophenes utilizing regioselective ring-expansion of gem-dichlorocyclopropyl ketones with Lawesson’s reagent
US7601847B2 (en) Preparation and purification of 4-(indazol-3-yl)phenols
CN110914250B (zh) 用于合成非罗考昔的新工艺
CN121039088A (zh) 3-羟基联苯化合物及其衍生物的制造方法
JP2003171359A (ja) （２−ニトロ−フェニル）アセトニトリル誘導体の製造方法及びその合成中間体
JP4356917B2 (ja) ビスアミノメチル−１，４−ジチアン類の製造方法及びその中間体
WO2003045934A1 (fr) Procede de production de 2 (5h)-furanone 5-substituee
JP2004244362A (ja) １，２−ジ置換−１，４−ジヒドロ−オキソキノリン誘導体の製造方法
JP2008195697A (ja) ３−アルキル−７，７，９，９−テトラメチル−１，３，８−トリアザスピロ〔４，５〕デカン誘導体の製造方法
JP2013010739A (ja) イソキサゾリン化合物を製造する方法
JP2006008617A (ja) ５−フタランカルボニトリル化合物の製造方法、その中間体およびその製造方法

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 25736470

Country of ref document: EP

Kind code of ref document: A1