CN108276352B - Nitrogen-containing heterocyclic compound with nematicidal activity and preparation method and application thereof - Google Patents

Abstract

The invention relates to a nitrogenous heterocyclic compound with nematicidal activity, a preparation method and application thereof. Specifically, the invention discloses a compound with a formula (I) or an optical isomer, a cis-trans isomer or an agriculturally and pharmaceutically acceptable salt thereof, and a preparation method thereof. The invention also discloses an agricultural composition containing the compound and application thereof. The above compounds have excellent nematicidal activity.

Description

A kind of nitrogen-containing heterocyclic compound with nematicidal activity and its preparation method and use

technical field

The present invention belongs to the field of pesticides. Specifically, the present invention relates to a nitrogen-containing heterocyclic compound with nematicidal activity and its preparation method and use.

Background technique

Plant parasitic nematodes are a class of pathogenic microorganisms that are extremely harmful. They have a wide distribution range, a wide variety and strong environmental adaptability. They can parasitize in the roots, stems, leaves, seeds, buds and fruits of plants. Causes mechanical damage to the host plant and deprives the host plant of nutrients, especially its esophageal gland secretions, which will lead to a series of lesions in the host plant, and will also infect the host plant with other pathogenic microorganisms, causing compound diseases and yield loss. Globally, the annual agricultural losses caused by plant parasitic nematodes are as high as more than 100 billion US dollars, which seriously restricts the development of agricultural economy.

There are many ways to control nematodes in agriculture, and chemical control is the main one at present. The widely used chemical nematicides are mainly organophosphorus or carbamate pesticides with high toxicity and high residues, such as fenamiphos, fenamiphos, fenamiphos, thiazophos, aldicarb, fenamicarb and keber Wei et al., the safety of humans and other non-target organisms is low, and it will also cause different degrees of pollution to soil, water sources and agricultural products. In addition, due to the single species, the excessive and frequent use of such nematicides has caused serious drug resistance, making the control of nematodes increasingly difficult. Therefore, it is an urgent technical problem to be solved in this field to find chemical nematicides with novel structures with high efficiency, low toxicity and good environmental compatibility.

In conclusion, there is an urgent need in the art to develop new compounds with nematicidal activity.

SUMMARY OF THE INVENTION

One of the objectives of the present invention is to provide a chemical nematicide with novel structure, high efficiency, low toxicity and good environmental compatibility, and its preparation method and application.

In the first aspect of the present invention, there is provided a compound having the structure represented by the general formula (I), or an optical isomer, cis-trans isomer or agrochemically acceptable salt of the compound:

In the formula,

Ring alpha and ring beta are each independently a substituted or unsubstituted 5-7 membered aromatic ring, a substituted or unsubstituted 5-7 membered carbocyclic ring, a substituted or unsubstituted 5-7 membered aromatic heterocycle, or a substituted or unsubstituted 5-7 membered aromatic ring Substituted 5-7 membered heterocycles (including fully or partially unsaturated heterocycles);

m is 1, 2, 3, 4, 5, 6, 7 or 8;

The substituents of the ring α and ring β are selected from the following group: oxy (=O), substituted or unsubstituted C _1-6 alkyl or alkoxy, halogen, substituted or unsubstituted C _3-6 Cycloalkyl, substituted or unsubstituted C _2-6 alkenyl, substituted or unsubstituted C _2-6 alkynyl, or substituted or unsubstituted C _3-7 cycloalkyl, substituted or unsubstituted C _{5- 7} -cycloalkenyl, substituted or unsubstituted phenyl, substituted or unsubstituted naphthyl, substituted or unsubstituted 5- or 6-membered heterocyclyl, or substituted or unsubstituted 8- to 12-membered heteroaromatic bicyclic ring base;

硫羰基-氨基-羰基

羰基-氨基-磺酰基

磺酰基-氨基-羰基；当n≥2时，各个L可以是相同的或不同的；Each L is independently a group selected from the group consisting of covalent bond, _-CH2- , -NR'-, -O-, -S-, -COO-, -CONH-, -CO-, thiocarbonyl -Amino

Thiocarbonyl-amino-carbonyl

carbonyl-amino-sulfonyl

Sulfonyl-amino-carbonyl; when n ≥ 2, each L may be the same or different;

A is V ₁ -(Q) _Z -V ₂ , wherein V ₁ is a group selected from the group consisting of unsubstituted, substituted or unsubstituted C _1-6 alkylene, substituted or unsubstituted C _3-6 Cycloalkylene, substituted or unsubstituted C _2-6 alkenylene, substituted or unsubstituted C _2-6 alkynylene, or substituted or unsubstituted C _3-7 cycloalkylene, substituted or unsubstituted C _5-7 cycloalkenylene, substituted or unsubstituted phenylene, substituted or unsubstituted naphthylene, substituted or unsubstituted 5- or 6-membered heterocyclylene, or substituted or unsubstituted 8 to 12-membered heteroarylene bicyclyl;

硫羰基-氨基-羰基

羰基-氨基-磺酰基

磺酰基-氨基-羰基；(Q) _Z is none, -CH ₂ -, -NR'-, -O-, -S-, -COO-, -CONR'-, -CO-, -SO-, -S(O) ₂ -, Thiocarbonyl-amino

Thiocarbonyl-amino-carbonyl

carbonyl-amino-sulfonyl

Sulfonyl-amino-carbonyl;

V ₂ is a group selected from the group consisting of H, substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted C _3-6 cycloalkyl, substituted or unsubstituted C _2-6 alkenyl, Substituted or unsubstituted C _2-6 alkynyl, or substituted or unsubstituted C _3-7 cycloalkyl, substituted or unsubstituted C _5-7 cycloalkenyl, substituted or unsubstituted phenyl, substituted or unsubstituted substituted naphthyl, substituted or unsubstituted 5- or 6-membered heterocyclyl, or substituted or unsubstituted 8- to 12-membered heteroaromatic bicyclyl;

And when V ₁ and (Q) _Z are both null, V ₂ is not H;

Z is 1, 2, 3, 4, 5, 6, 7 or 8;

G is each independently substituent at any one or more positions of ring α, and G is selected from the group consisting of halogen, cyano, nitro, substituted or unsubstituted C _1-6 alkoxy, substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted C _3-6 cycloalkyl, substituted or unsubstituted C _2-6 alkenyl, substituted or unsubstituted C _2-6 alkynyl, or substituted or unsubstituted C 2-6 alkynyl C _3-7 cycloalkyl, substituted or unsubstituted C _5-7 cycloalkenyl, trimethylsilylethynyl, substituted or unsubstituted phenyl, substituted or unsubstituted naphthyl, substituted or unsubstituted 5- or 6-membered heterocyclyl, substituted or unsubstituted 8- to 12-membered heteroaromatic bicyclic ring systems, OR', Si(R') ₃ , NR'R", C(O)R', C (O)OR', C(O)NR'R", SR', S(O) _m R', S(O) ₂ NR'R", OC(O)R', OC(O)NR'R ", OS(O) ₂ R', OS(O) ₂ NR'R", N(R")C(O)R', NCH ₂ R', N(R")C(O)NR'R" , N(R")S(O) ₂ R' or N(R')S(O) ₂ NR'R";

The substitution refers to the substitution of one or more groups selected from the group consisting of halogen, cyano, nitro, C _1-6 alkyl, C _1-6 alkoxy, C _1-6 haloalkyl, C _2-6 alkenyl, C _2-6 haloalkenyl, C _2-6 alkynyl, C _2-6 haloalkynyl, hydroxy, hydroxy C _1-4 alkyl, R', OR', Si(R ') ₃ , NR'R", C(O)R', C(O)OR', C(O)NR'R", SR', S(O) _m R', S(O) ₂ NR'R", OC(O)R ¹ , OC(O)NR'R", OS(O) ₂ R ¹ , OS(O) ₂ NR'R", N(R')C(O)R', N (R')C(O)NR'R", N(R')S(O) ₂ R ¹ or N(R')S(O) ₂ NR'R", or substituted or unsubstituted C _{3- 7} -cycloalkyl, substituted or unsubstituted C _5-7 cycloalkenyl, substituted or unsubstituted 6-10-membered aryl, substituted or unsubstituted 5- or 6-membered saturated or unsaturated heterocyclyl, or substituted or unsubstituted 8- to 12-membered heteroaromatic bicyclic ring systems; wherein the substitution on cycloalkyl, cycloalkenyl, aryl, heterocyclyl, heteroaromatic bicyclic ring systems is one selected from the group Substituted by or more groups: oxy (=O), halogen, cyano, nitro, C _1-6 alkyl or cycloalkyl, C _1-6 haloalkyl, C _2-6 alkenyl, C _{2 -6} haloalkenyl, C _2-6 alkynyl, C _2-6 haloalkynyl, hydroxy, hydroxy C _1-4 alkyl;

Wherein, R' and R" are each independently H, C _1-6 alkyl, C _3-6 cycloalkyl, C _1-6 haloalkyl, C _3-6 halocycloalkyl, C _2-6 alkene base, C _2-6 haloalkenyl, C _2-6 alkynyl, C _2-6 haloalkynyl, or substituted or unsubstituted C _3-7 cycloalkyl, substituted or unsubstituted C _5-7 Cycloalkenyl, substituted or unsubstituted phenyl, substituted or unsubstituted naphthyl, substituted or unsubstituted 5- or 6-membered saturated or unsaturated heterocyclyl, or substituted or unsubstituted 8- to 12-membered heterocyclyl Aromatic bicyclic ring system; wherein, the substituents on R', R" are substituted by one or more groups selected from the following group: oxy (=O), halogen, cyano, nitro, C _{1- 6} alkyl or cycloalkyl, C _1-6 haloalkyl, C _2-6 alkenyl, C _2-6 haloalkenyl, C _2-6 alkynyl, C _2-6 haloalkynyl, hydroxy, hydroxy C _1-4 alkyl.

In another preferred embodiment, the compound has the structure shown in the following formula II:

Y is C(O) or S(O ₂ );

X ₁ and X ₄ are each independently C(Ra)(Rb) or N(Rb);

X ₂ is N(Rb) or C(Ra)(Rb), O or S;

X ₃ is none, N(Rb), or C(Ra)(Rb), C(O), S(O), S(O) ₂ , C=C(Rb), CH ₂ CH ₂ ;

n is 0 or 1; and when n is 0, X ₁ is N(Rb);

And when there is a double bond between X ₂ and X ₃ , Rb in X ₂ and X ₃ is none;

Ra is selected from the group consisting of H, halogen, cyano, nitro, substituted or unsubstituted C _1-6 alkoxy, substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted C _3-6 Cycloalkyl, substituted or unsubstituted C _2-6 alkenyl, substituted or unsubstituted C _2-6 alkynyl, or substituted or unsubstituted C _3-7 cycloalkyl, substituted or unsubstituted C _{5- 7} -cycloalkenyl, trimethylsilylethynyl, substituted or unsubstituted phenyl, substituted or unsubstituted naphthyl, substituted or unsubstituted 5- or 6-membered heterocyclyl, substituted or unsubstituted 8-membered to 12-membered heteroaromatic bicyclic ring systems, OR', Si(R') ₃ , NR'R", C(O)R', C(O)OR', C(O)NR'R", SR' , S(O) _m R', S(O) ₂ NR'R", OC(O)R', OC(O)NR'R", OS(O) ₂ R', OS(O) ₂ NR'R",N(R")C(O)R', NCH ₂ R', N(R")C(O)NR'R", N(R")S(O) ₂ R' or N(R ')S(O) ₂ NR'R";

Rb is selected from the group consisting of none, H, halogen, cyano, nitro, substituted or unsubstituted C _1-6 alkoxy, substituted or unsubstituted C _1-6 alkyl.

具有选自下组的结构：In another preferred embodiment, the structural unit

has a structure selected from the group consisting of:

具有选自下组的结构：In another preferred embodiment, the structural unit

has a structure selected from the group consisting of:

In another preference, the G group has a structure selected from the group consisting of:

wherein R _D is selected from the group consisting of H, C _1-6 alkyl or alkoxy, C _1-6 haloalkyl, C _2-6 alkenyl, C _2-6 haloalkenyl, C _2-6 alkyne base, C _2-6 haloalkynyl, or substituted or unsubstituted C _3-7 cycloalkyl, substituted or unsubstituted C _5-7 cycloalkenyl, substituted or unsubstituted phenyl, substituted or unsubstituted naphthyl, substituted or unsubstituted 5- or 6-membered heterocyclic group, or substituted or unsubstituted 8- to 12-membered heteroaromatic bicyclic ring system.

In another preferred embodiment, V ₁ is a substituted or unsubstituted 5- to 7-membered heterocycle containing at least one N atom (referring to a 5-, 6- or 7-membered heterocycle).

In another preferred embodiment, V ₁ contains 0-3 substituents; in another preferred embodiment, the at least one substituent is -QV ₂ .

In another preferred embodiment, the V ₁ contains 2-3 heteroatoms. Preferably, the 5-7 membered heterocycle contains 2 or 3 heteroatoms, including at least one N atom and at least one O atom.

In another preferred embodiment, V ₁ contains 2 or 3 N atoms.

In another preferred example, V ₁ includes an aromatic heterocycle or a non-aromatic heterocycle.

In another preferred embodiment, the 5-7 membered heterocycle is an N-containing 6 membered heterocycle.

In another preferred example, V ₁ is a five-membered aromatic ring containing W ₁ , W ₂ and W ₃ selected from the following group, a non-aromatic ring, an aromatic heterocyclic ring or a non-aromatic heterocyclic ring:

In the formula,

W ₁ , W ₂ and W ₃ are each independently CR ₄ , NR ₅ , O or S;

R ₃ , R ₄ , R ₅ are each independently halogen, cyano, nitro, substituted or unsubstituted C _1-6 alkoxy, substituted or unsubstituted C _1-6 alkyl, substituted or unsubstituted C _3-6 cycloalkyl, substituted or unsubstituted C _2-6 alkenyl, substituted or unsubstituted C _2-6 alkynyl, or substituted or unsubstituted C _3-7 cycloalkyl, substituted or unsubstituted C _5-7 cycloalkenyl, trimethylsilylethynyl, substituted or unsubstituted phenyl, substituted or unsubstituted naphthyl, substituted or unsubstituted 5- or 6-membered heterocyclyl, substituted or unsubstituted Substituted 8- to 12-membered heteroaromatic bicyclic ring systems, OR', Si(R') ₃ , NR'R", C(O)R', C(O)OR', C(O)NR'R ", SR', S(O) _m R', S(O) ₂ NR'R", OC(O)R', OC(O)NR'R", OS(O) ₂ R', OS(O ) ₂ NR'R", N(R")C(O)R', NCH ₂ R', N(R")C(O)NR'R", N(R")S(O) ₂ R' or N(R')S(O) ₂ NR'R";

Wherein, R' and R" are each independently H, C _1-6 alkyl or cycloalkyl, C _1-6 haloalkyl, C _2-6 alkenyl, C _2-6 haloalkenyl, C _{2- 6} alkynyl or C _2-6 haloalkynyl.

In another preferred example, V ₁ is a non-aromatic heterocycle containing N.

In another preferred embodiment, the V ₁ is a group selected from the following group:

none,

In another preferred embodiment, the compound is selected from compounds I-1 to I-200.

In another preferred embodiment, the compound is selected from the following group:

The second aspect of the present invention provides an agricultural composition, the composition comprising: 0.001-99.99 wt % of the compound described in the first aspect of the present invention, or an optical isomer, cis-trans isomeric compound of the compound Constituents or agrochemically acceptable salts, or combinations thereof; and agrochemically acceptable carriers and/or excipients.

The third aspect of the present invention provides a compound according to the first aspect of the present invention, or an optical isomer, cis-trans isomer or pesticide acceptable salt of the compound, or a compound according to the first aspect of the present invention. Use of the agricultural composition described in the second aspect, for killing or preventing nematodes or for preparing a nematicidal composition.

In another preferred embodiment, the composition is used for killing or preventing agroforestry plant parasitic nematodes.

The third aspect of the present invention provides a method for preparing the compound according to the first aspect of the present invention, or an optical isomer, cis-trans isomer or a pesticide acceptable salt of the compound, wherein The methods described include:

与

反应，得到式I化合物；in an inert solvent, with

and

reaction to obtain the compound of formula I;

Wherein, LG is a leaving group, and the definitions of other groups are as described in the first aspect of the present invention.

In another preferred embodiment, the method includes the steps:

反应，得到式II化合物；其中，LG为离去基团，其他各基团的定义如本发明第一方面中所述。in an inert solvent, in the presence of a base, with

After reaction, the compound of formula II is obtained; wherein, LG is a leaving group, and the definitions of other groups are as described in the first aspect of the present invention.

It should be understood that within the scope of the present invention, the above-mentioned technical features of the present invention and the technical features specifically described in the following (eg, the embodiments) can be combined with each other to form new or preferred technical solutions. Due to space limitations, it is not repeated here.

Detailed ways

After long-term and in-depth research, the inventors have unexpectedly discovered and synthesized a series of triazine heterocyclic compounds with novel structures and remarkable insecticidal activity. On this basis, the inventors have completed the present invention.

group definition

The term "C _1-6 alkyl" refers to a straight or branched chain alkyl group having 1-6 carbon atoms, such as methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl , tert-butyl, or similar groups.

The term "C _2-6 alkenyl" refers to a straight or branched chain alkenyl group having 2-6 carbon atoms, such as vinyl, allyl, 1-propenyl, isopropenyl, 1-butenyl, 2-butenyl, or similar groups.

The term "C _2-6 alkynyl" refers to a straight or branched chain alkynyl group having 2 to 6 carbon atoms, such as ethynyl, propynyl, or the like.

The term " _{C3-7cycloalkyl} " refers to a cyclic alkyl group having 3-7 carbon atoms, such as cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, or the like.

The term "C _5-7 cycloalkenyl" refers to a cyclic alkenyl group having 5-7 carbon atoms having one or more double bonds, such as cyclopentenyl, cyclohexenyl, cycloheptenyl, 1 ,3-cyclohexadienyl, 1,4-cyclohexadienyl, or similar groups.

As used herein, the term "C _1-4 alkoxy" refers to a straight or branched chain alkoxy group having 1-4 carbon atoms, such as methoxy, ethoxy, propoxy, isopropoxy, Butoxy, isobutoxy, sec-butoxy, tert-butoxy, or similar groups.

The term "halogen" refers to fluorine, chlorine, bromine, or iodine. The term "halogenated" refers to a group substituted with one or more of the same or different halogen atoms described above, eg, trifluoromethyl, pentafluoroethyl, heptafluoroisopropyl, or the like.

The term "ring" or "ring system" refers to a carbocyclic or heterocyclic ring.

The term "heterocycle" means that at least one of the atoms forming the heterocyclic skeleton is not carbon, but is nitrogen, oxygen or sulfur. Typically, heterocycles contain no more than 4 nitrogens, no more than 2 oxygens, and/or no more than 2 sulfurs. Unless otherwise specified, heterocycles may be saturated, partially unsaturated or fully unsaturated rings.

The term "ring system" refers to a fused ring in which two or more rings are joined together.

As used herein, the term "5- or 6-membered heterocyclyl" refers to a five- or six-membered ring containing one or more heteroatoms selected from nitrogen, oxygen, or sulfur, such as pyridyl, thiazolyl, isothiazolyl, thienyl, furyl, pyrrolyl, pyrazolyl, pyrimidinyl, tetrahydrofuranyl, 4,5-dihydrothiazol-2-yl, 2-cyanoimino-4-oxo-1,3-thiazolidine- 3-yl, 2-cyanoimino-4-oxo-1,3-thiazin-3-yl, oxazolyl, isoxazolyl, 1H-tetrazolyl, 1H-1,2,3 -triazolyl, 4H-1,2,4-triazolyl, 1,2,3-thiadiazolyl, 1,2,4-thiadiazolyl, 1,3,4-thiadiazolyl, 1,2,4-oxadiazolyl, 1,2,5-oxadiazolyl, 1,3,4-oxadiazolyl or tetrazolyl and the like.

The term "heterocyclic ring system" refers to a ring system in which at least one ring in the ring system is a heterocyclic ring.

The term "heteroaromatic ring system" refers to a system in which at least one ring in the ring system is an aromatic ring.

As used herein, the term "8- to 12-membered heteroaromatic bicyclic ring system" or "8- to 14-membered heteroaromatic bicyclic or tricyclic ring system" may be selected from the group consisting of benzofuran, benzo[b] Thiophene, indole, quinoline, isoquinoline, 1H-indazole, 1H-benzo[d]imidazole, benzo[d]thiazole, benzo[d]oxazole, benzo[d]isoxazole, Benzo[d][1,2,3]thiadiazole, 2,3-dihydroimidazo[1,2-a]pyridine, quinazoline, quinoxaline, cinnoline, phthalazine, 1,8 -Naphthyridine, 4,5,6,7-tetrahydrobenzo[b]thiophene, benzo[b]thiophene-1,1-dioxane, 8H-indeno[2,1-b]thiophene, 7 ,8-Dihydro-6H-cyclopenta[4,5]thieno[2,3-d]pyrimidine, 3,5,6,7-tetrahydro-4H-cyclopenta[4,5]thieno[2 ,3-d]pyrimidin-4-one, spiro[indoline-3,2'-[1,3]dioxolane]-2-one, spiro[indoline-3,2'-[1 ,3] Dioxane]-2-one, or indoline-2,3-dione, etc.

The term "alkyl" refers to a group in which one hydrogen atom is missing from an alkane molecule; the term "alkylene"

It refers to the group formed by missing two hydrogen atoms in the alkane molecule. Similarly, "alkenylene", "alkynylene", "cycloalkylene", "cycloalkenylene", "phenylene", "naphthylene", "heterocyclylene" or "cycloalkylene" "Heteroaromatic bicyclic or tricyclic ring system" is defined similarly.

Unless specifically stated that the group described in the present invention is "substituted or unsubstituted", the group of the present invention can be substituted by a substituent selected from the following group: halogen, cyano, nitro, C _1-6 Alkyl, C _1-6 haloalkyl, C _2-6 alkenyl, C _2-6 haloalkenyl, C _2-6 alkynyl, C _2-6 haloalkynyl, hydroxy, hydroxy C _1-4 alkane base, OR', Si(R') ₃ , NR'R", C(O)R', C(O)OR', C(O)NR'R", SR', S(O) _m R' , S(O) ₂ NR'R", OC(O)R', OC(O)NR'R", OS(O) ₂ R', OS(O) ₂ NR'R", N(R") C(O)R', NCH ₂ R', N(R")C(O)NR'R", N(R")S(O) ₂ R' or N(R')S(O) ₂ NR 'R', etc., wherein the R' and R'' are as defined above, and m is 1 or 2.

Inert solvents refer to various solvents that do not react with raw materials, including various linear, branched or cyclic alcohols, ethers or ketones, haloalkanes, 1,4-dioxane, acetonitrile, tetrahydrofuran, N, N-dimethylformamide (DMF), dimethyl sulfoxide (DMSO), etc.

The compounds of the present invention may contain one or more asymmetric centers and thus occur as racemates, racemic mixtures, single enantiomers, diastereomeric compounds and single diastereomers. The number of asymmetric centers that can exist depends on the nature of the various substituents on the molecule. Each such asymmetric center will independently produce two optical isomers, and all possible optical isomers and diastereomeric mixtures and pure or partially pure compounds are included within the scope of the present invention. The present invention includes all isomeric forms of the compounds.

In the compound of formula I of the present invention, when Y or Q is a covalent bond, it means that the groups on both sides of Y or Q are connected to each other through a covalent bond. even.

Nematicidal activity of the active substances according to the invention

The term "active substance of the present invention" or "active compound of the present invention" refers to the compound of the structure represented by general formula (I), its optical isomer, cis-trans isomer or agrochemically acceptable salt. The heterocyclic structure containing N and S has significant nematicidal activity, wide nematicidal spectrum and strong stability.

The term "pesticidally acceptable salt" means that the anion of the salt is known and acceptable to form a nematicide pharmaceutically acceptable salt. Preferably, the salt is water soluble. Suitably, acid addition salts formed from compounds of formula (I) include salts formed from inorganic acids, such as hydrochlorides, phosphates, sulfates, nitrates; and salts formed from organic acids, such as acetates, Benzoate etc.

The active substances of the present invention can be used for the control and eradication of a wide range of agroforestry plant-parasitic nematodes. In this specification, "nematicide" is a general term for substances that have the effect of controlling all plant-parasitic nematodes mentioned herein.

Examples of plant parasitic nematodes include, but are not limited to: root-knot nematodes such as Meloidogyne nematode, Meloidogyne chitwoodi, Meloidogyneexigua, northern root-knot nematode (Meloidogyne hapla), southern Meloidogyne incognita, Meloidogyne javanica, and other Meloidogyne genera; cyst nematodes such as Globodera rostochiensis, Globodera pallida, tobacco spores Globodera tabacum, and other Globodera genera; Heterodera, such as Heterodera avenae, Heterodera glycines, Heteroderaschachtii, clover Cyst nematodes (Heterodera trifolii), and other Heterodera spp. (Heterodera); nematodes such as Anguina funesta, Anguina tritici, and other Anguina nematodes; stem nematodes and leaf bud nematodes, such as Aphelenchoides besseyi, Aphelenchoides fragariae, Aphelenchoides ritzemabosi, and other Aphelenchoides; spiny nematodes, such as weed nematodes (Belonolaimus longicaudatus) and other genus Belonolaimus; pine nematodes such as Bursaphelenchus xylophilus and other genera Bursaphelenchus; ring nematodes such as Criconema, Criconema Criconemella, Criconemoides, and Mesocriconema; bulb nematodes such as Ditylenchus destructor, Ditylenchus dipsaci, Ditylenchus myceliophagus, and others Ditylenchus; trypanosomes, such as Trypanosoma (Do lichodorus); helical nematodes, such as Helicotylenchus dihystera, Helicotylenchus multicintus, and other Helicotylenchus; sheath nematodes, such as Helicotylenchus and Helicotylenchus ( Hemicriconemoides); crown nematodes, such as Hoploaimus columbus and other Hoploaimus; pseudorhizobium nematodes, such as Nacobbus aberrans and other pearl nematodes (Nacobbus); needle nematodes, such as escape Longidorus elongatus and other Longidorus; pinworms, such as Paratylenchus; root-rot nematodes, such as Pratylenchus brachyurus, Pratylenchus coffee ), Pratylenchus zeae, Pratylenchus penetrans, and other genus Pratylenchus; piercing nematodes such as Radopholus similis and other genera Radopholus; Reniform nematodes such as Rotylenchus robustus and other genera Rotylenchus; stump nematodes such as Trichodorus primitivus and other genera Trichodorus; dwarf nematodes such as Tylenchorhynchus claytoni, adventitious dwarf nematode (Tylenchorhynchus dubius), and other dwarf nematodes (Tylenchorhynchus); citrus nematodes such as Tylenchulus semipenetrans and other dwarf nematodes (Tylenchulus); Xiphinema, such as Xiphinema americanum, Xiphinema index, Xiphinemadiversicaudatum, and other Xiphinema.

The compounds involved in the present invention especially have better control effect on Meloidogyne incognita.

Nematicidal compositions containing active substances according to the invention

The active substances of the present invention can be prepared in a conventional manner into nematicidal compositions. The active compounds can be formulated into the customary formulations such as solutions, emulsions, suspensions, powders, foams, pastes, granules, aerosols, natural and synthetic materials impregnated with active substances, in polymeric Microcapsules in cigarettes, coating formulations for seeds, and formulations for use with combustion devices such as smoking cartridges, smoking pots and smoking trays, as well as ULV Cold mist and Warmmist )preparation.

These formulations can be produced by known methods, for example, by mixing the active compounds with extenders, which are liquid or liquefied gas or solid diluents or carriers, optionally with surfactants, ie emulsifiers and/or Dispersants and/or foam formers. For example, when water is used as an extender, organic solvents can also be used as auxiliaries.

When using liquid solvents as diluents or carriers, it is basically suitable, such as: aromatic hydrocarbons, such as xylene, toluene or alkylnaphthalene; chlorinated aromatic or chlorinated aliphatic hydrocarbons, such as chlorobenzene, vinyl chloride or dichloromethane; aliphatic hydrocarbons such as cyclohexane or paraffins such as mineral oil fractions; alcohols such as ethanol or ethylene glycol and their ethers and lipids; ketones such as acetone, methyl ethyl ketone, methyl isobutyl ketone or cyclohexanone; or unusual polar solvents such as dimethylformamide and dimethylsulfoxide, and water.

A diluent or carrier for a liquefied gas refers to a liquid that will become a gas at normal temperature and pressure, such as aerosol propellants, such as halogenated hydrocarbons and butane, propane, nitrogen and carbon dioxide.

The solid carrier may be ground natural minerals, such as kaolin, clay, talc, quartz, activated clay, montmorillonite, or diatomaceous earth; and ground synthetic minerals, such as highly dispersed silicic acid, alumina and silicates. Solid supports for granules are ground and graded natural zircon such as calcite, marble, pumice, sepiolite and dolomite, as well as granules synthesized from inorganic and organic coarse powders, and organic materials such as sawdust, coconut shells, Particles of corn cobs and tobacco stems, etc.

Nonionic and anionic emulsifiers can be used as emulsifiers and/or foam formers. For example, polyoxyethylene-fatty acid esters, polyoxyethylene-fatty alcohol ethers, such as alkyl aryl polyglycol ethers, alkyl sulfonates, alkyl sulfates, aryl sulfonates and white protein hydrolysate. Dispersants include lignin sulfite waste liquor and methyl cellulose.

Binders such as carboxymethyl cellulose and natural and synthetic polymers in the form of powders, granules or emulsions such as acacia, polyvinyl alcohol and polyvinyl acetate can be used in the formulation.

Colorants such as inorganic dyes such as iron oxide, cobalt oxide and Prussian blue; organic dyes such as azo dyes or metal phthalocyanine dyes; and trace nutrients such as iron, manganese, boron, copper, cobalt, aluminum can be used and zinc salts, etc.

The active compounds of the present invention may be present in their commercial formulations or in use forms prepared from these formulations in a mixture with other active compounds, such as insecticides, bactericides, fungicides, Herbicides, growth control agents, etc. Insecticides include, for example, phosphates, carbamates, chlorinated hydrocarbons and substances produced by microorganisms, such as abamectin, etc. Fungicides include methoxyacrylates, amides, triazoles Wait.

Furthermore, the active compounds of the present invention may also be present in their commercial formulations or in use dosage forms prepared from these formulations in a mixture with synergists, which are compounds which enhance the action of the active compounds, due to their active The compound itself is active, and it is not necessary to add a synergist.

These formulations generally contain from 0.001 to 99.99% by weight, preferably from 0.01 to 99.9% by weight, more preferably from 0.05 to 90% by weight of the active compound of the invention, based on the total weight of the nematicide composition. The concentration of active compound in the commercial formulation or in the dosage form for use can vary within wide limits. The concentration of active compound in the dosage form used may be from 0.0000001 to 100% (g/v), preferably between 0.0001 and 1% (g/v).

The preparation method of the compound of the present invention

The compound represented by the general formula of the present invention can be prepared by the following method, however, the conditions of the method, such as reactants, solvent, base, amount of the compound used, reaction temperature, time required for the reaction, etc., are not limited to the following explanations. The compounds of the present invention can also be conveniently prepared by optionally combining various synthetic methods described in this specification or known in the art, and such combinations can be easily carried out by those skilled in the art to which the present invention belongs. If feasible, reagents can be purchased commercially.

Exemplary embodiments of the compounds of the present invention can be synthesized using the general reaction schemes described below. It is apparent from the description given herein that the general scheme can be modified by substituting other materials with similar structures to obtain correspondingly different products. Synthetic methods are available as needed to provide high volume production. Starting materials can be obtained by commercial methods or synthesized using published methods. In the examples given herein, the characterization of the final product generally makes the characterization of the necessary raw materials apparent through simple verification procedures.

Synthetic Reaction Parameters The compounds of the invention can be prepared from readily available starting materials using, for example, the following general methods and procedures. It will be recognized that where typical or optimized process conditions (ie, reaction temperatures, times, molar ratios of reactants, solvents, catalysts, pressures, etc.) are given, other process conditions may also be used unless otherwise indicated. Optimum reaction conditions may vary with the particular reactants or solvents used, but such conditions can be determined by one skilled in the art through routine optimization procedures.

The starting materials for the following reactions are generally known compounds, or can be prepared by known procedures or obvious modifications thereof. For example, many starting materials are available from commercial suppliers, and others can be prepared by procedures described in the text of standard references, or by obvious modifications, eg, by the methods described in CN 104530037 A.

In the preparation method of the present invention, each reaction is usually carried out in an inert solvent at a reaction temperature of -20 to 120°C (preferably -10 to 0°C or 20 to 30°C or 80 to 100°C). The reaction time is usually 2 to 24 hours, preferably 4 to 18 hours, and the reaction time can be appropriately extended according to the needs of the reaction, and the specific reaction time is determined according to the degree of the reaction.

The bases used in the reaction include (but are not limited to): triethylamine, diisopropylethylamine, diethylamine, piperidine, piperazine, morpholine, N-methylmorpholine, triethylenediamine ( DABCO), 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU), 1,5-diazabicyclo[4.3.0]non-5-ene (DBN) , potassium carbonate, potassium bicarbonate, sodium carbonate, sodium bicarbonate, cesium carbonate, sodium hydroxide, potassium hydroxide, sodium methoxide, sodium ethoxide, or a combination thereof, the LG used in the scheme is a leaving group, which is passed through conventional The method synthesizes the intermediate, and then reacts through the LG-containing moiety to obtain the corresponding final product.

plan 1

In one embodiment, 1-5 is used to react first with N,N _- carbonyldiimidazole to give 1-6, then to give 1-7, which is cyclized via KI, TBHP, CH3NO2 to give _1-8 .

In another embodiment, 1-3 is obtained after triphosgene ammonolysis, then cyclized by diazotization, and then reacted with an intermediate containing a leaving group under the action of a base to obtain 1-8.

In another embodiment, 1-5 is used to react first with N,N-carbonyldiimidazole to give 1-6, then to give 1-7, and a diazotization reaction to cyclize to give 1-8.

Among them, intermediates 1-4 can also be prepared by the reaction of 1-9.

Scenario 2

In one embodiment, 2-2 is obtained from 2-1 through an intermediate in the presence of an acid binding agent, and then reduced. The reduction can be performed with hydrogen and palladium carbon or iron, zinc, etc., and acid is reduced to prepare 2-3 , followed by diazotization cyclization.

Scenario 3

In one embodiment, compound 3-1 yields compound 3-2 by a conventional method, but is not limited to this method.

Scenario 4

In one embodiment, under standard reaction conditions, including but not limited to, using a suitable base, such as potassium carbonate, DIEA, etc., to obtain compound 4-2.

Scenario 5

In one embodiment, compound 5-2 is obtained from compound 5-1 by Mitsunobu reaction using reagents including but not limited to catalysts for Mitsunobu reaction.

Option 6

In one embodiment, compound 6-2 should be obtained through Suzuki reaction (suzuki reaction), the catalyst used is a conventional catalyst for Suzuki reaction, but is not limited to this type of catalyst, and the reactant of Suzuki reaction is boronic acid or boron corresponding to the substituted part G acid esters, but not limited to boronic acids or boronic acid esters.

Option 7

In one embodiment, compound 7-2 is obtained by reacting compound 7-1 in morpholine, wherein the leaving group on the benzene ring is not limited to F.

Preferably, in the solution, the content of the intermediate product is 10-99.99 wt %; preferably 20-90 wt %; more preferably 50-80 wt %.

Therefore, the inventors can purify the intermediate product before proceeding to the next reaction; of course, the reaction mixture containing the compound can also be directly subjected to the next reaction.

The present invention will be further described below in conjunction with specific embodiments. It should be understood that these examples are only used to illustrate the present invention and not to limit the scope of the present invention. In the following examples, the experimental methods without specific conditions are usually in accordance with conventional conditions, or in accordance with the conditions suggested by the manufacturer. Percentages and parts are by weight unless otherwise indicated.

Example 1: 3-(2-(4-benzoylpiperazin-1-yl)ethyl)benzo[d][1,2,3]triazin-4(3H)-one, compound I -3.

1.1 Preparation of benzo[d][1,2,3]triazin-4(3H)-one

Dissolve _3.450g (50mmol) NaNO in 200ml 0.5M dilute hydrochloric acid, cool down to -5°C, control the temperature to -5～0°C, slowly add 3.4g (25mmol) 15ml DMF solution of 2-aminobenzamide dropwise, After the addition was completed, the reaction was placed at room temperature, and the progress of the reaction was tracked by TLC. After the reaction was completed, the pH was adjusted to 9 with ammonia and stirred for 15 minutes, suction filtered, the filter cake was washed with a large amount of water, and dried to obtain 3.124 g of a white solid with a yield of 85%. ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 14.98 (s, 1H), 8.23 (dd, J=7.6, 0.8 Hz, 1H), 8.19 (d, J=8.0 Hz, 1H), 8.14-8.05 ( m, 1H), 7.98–7.87 (m, 1H). ¹³ C NMR (101MHz, DMSO-d ₆ )δ155.50, 144.10, 135.37, 132.45, 127.77, 124.19, 120.12.

1.2 Preparation of 3-(2-bromoethyl)-benzo[d][1,2,3]triazin-4(3H)-one

5.88g (40mmol) of benzo[d][1,2,3]triazin-4(3H)-one was added to 200ml of acetone, followed by 22.44g (120mmol) of 1,2-dibromoethane and 5.520g (40mmol) potassium carbonate, stirred to make a suspension, heated to reflux reaction, TLC tracked the reaction progress. After the reaction was completed, the solvent was evaporated under reduced pressure, 200 ml of water was added to the residue, extracted with dichloromethane (150 ml × 3), the organic phase was dried over anhydrous sodium sulfate, concentrated, and separated by column to obtain 5.283 g of white solid. rate 52%. ¹ H NMR (400 MHz, CDCl ₃ ) δ 8.37 (d, J=8.0 Hz, 1H), 8.18 (d, J=8.0 Hz, 1H), 7.98 (t, J=8.4 Hz, 1H), 7.83 (t , J=7.2Hz, 1H), 4.88 (t, J=6.78Hz, 2H), 3.84 (t, J=6.4Hz, 2H).; ¹³ C NMR (100MHz, CDCl ₃ )δ155.51, 144.17, 135.11, 132.65 ,128.52,125.17,119.72,50.74,28.01.

1.3 Preparation of compound 3-(2-(piperazin-1-yl)ethyl)benzo[D]1,2,3-triazin-4(3H)-one.

2.54g (10mmol) of 3-(2-bromoethyl)-benzo[d][1,2,3]triazin-4(3H)-one was added to 50ml of tetrahydrofuran, and 2.58g of anhydrous piperazine ( 30 mmol) was dissolved by ultrasonic, the temperature was raised to reflux, and the reaction progress was tracked by TLC. After the reaction, the solvent was evaporated under reduced pressure, 100 ml of saturated sodium bicarbonate was added to the residue, extracted with dichloromethane (60 ml×4), the organic phase was dried over anhydrous sodium sulfate, concentrated, and separated by column chromatography to obtain a white Solid 1.62g, yield 62%.

¹ H NMR (400MHz, DMSO-d ₆ ) δ 8.26 (d, J=7.8 Hz, 1H), 8.20 (d, J=8.1 Hz, 1H), 8.09 (t, J=7.6 Hz, 1H), 7.94 (t, J=7.5Hz, 1H), 4.50 (t, J=6.6Hz, 2H), 2.74 (t, J=6.6Hz, 2H), 2.62 (s, 4H), 2.39 (s, 4H). ¹³ C NMR (101 MHz, DMSO-d ₆ ) δ 154.69, 143.58, 135.35, 132.86, 127.91, 124.53, 119.09, 56.31, 53.68, 46.16, 45.35.

1.4 Preparation of 3-(2-(4-benzoylpiperazin-1-yl)ethyl)benzo[D][1,2,3-triazine]-4(3H)one

Add 0.259 g (1 mmol) of 3-(2-(piperazin-1-yl)ethyl)benzo[D]1,2,3-triazin-4(3H)-one into 15 ml of tetrahydrofuran, dissolve by ultrasonic, 0.276g (2mmol) of potassium carbonate was added, and a solution of 0.21g (1.5mmol) of benzoyl chloride in 5ml of THF was added dropwise at 0°C. After the reaction, the solvent was evaporated under reduced pressure, 50 ml of saturated sodium chloride was added to the residue, extracted with dichloromethane (40 ml × 2), the organic phase was dried over anhydrous sodium sulfate, concentrated, and separated by column chromatography to obtain a white Solid 0.29g, yield 80%. ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 8.27 (dd, J=7.9, 0.9 Hz, 1H), 8.21 (dd, J=8.1, 0.5 Hz, 1H), 8.14-8.06 (m, 1H), 8.01–7.89 (m, 1H), 7.48–7.41 (m, 3H), 7.40–7.33 (m, 2H), 4.54 (t, J=6.5Hz, 2H), 3.56 (s, 2H), 3.26 (s, 2H), 2.83(t, J=6.5Hz, 2H), 2.52(s, 2H), 2.47(s, 2H). ¹³ C NMR(101MHz, DMSO-d ₆ )δ168.82,154.75,143.60,135.89,135.38, 132.89, 129.41, 128.35, 127.94, 126.83, 124.55, 119.11, 55.44, 46.18. HRMS (EI) C ₂₀ H ₂₁ N ₅ O ₂ (M), calculated: 363.1695 found: 363.1693.

Example 2: 3-(2-(4-(2,6-Dichloro-4-picolinoyl)piperazin-1-yl)ethyl)benzo[D]1,2,3-triazine- 4(3H)-ketone, namely compound I-4.

2.1 Preparation of 2,6-dichloropyridine-4-carbonyl chloride

0.38g (2mmol) of 2,6-dichloroisonicotinic acid was added to 10ml of dichloromethane, and a solution of 0.63g (5mmol) of oxalyl chloride in 5ml of dichloromethane was added dropwise with stirring in an ice-salt bath, and the reaction progress was followed by TLC. After the reaction, the solvent and the remaining oxalyl chloride were evaporated under reduced pressure, and the next step was directly added to the reaction.

2.2 Preparation of 3-(2-(4-(2,6-dichloro-4-picolinoyl)piperazin-1-yl)ethyl)benzo[D]1,2,3-triazine-4( 3H)-keto

0.259g (1mmol) 3-(2-(piperazin-1-yl)ethyl)benzo[D]1,2,3-triazin-4(3H)-one was added to 15ml acetonitrile, dissolved by ultrasonic, 0.552 g (4 mmol) of potassium carbonate was added, and a solution of 2 mmol of 2,6-dichloropyridine-4-carbonyl chloride in 5 ml of acetonitrile was added dropwise at 0°C. After the reaction, the solvent was evaporated under reduced pressure, 50ml of water was added to the residue, extracted with dichloromethane (80ml×2), the organic phase was dried over anhydrous sodium sulfate, concentrated, and separated by column chromatography to obtain 0.65g of white solid , the yield is 75%. ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 8.27 (dd, J=7.9, 0.7 Hz, 1H), 8.21 (d, J=8.0 Hz, 1H), 8.15–8.06 (m, 1H), 8.00– 7.90(m, 1H), 7.63(s, 2H), 4.55(t, J=6.4Hz, 2H), 3.55(s, 2H), 3.22(s, 2H), 2.85(t, J=6.4Hz, 2H) _The ^_ 52.26, ^51.74 , 46.66, _46.13 , _41.41 ^. HRMS (EI) ^{C19H1835Cl35ClN6O2} (M), _calcd : _{432.0868 found 432.0850} , ^{C19H1837Cl35ClN6O2} ( _{M )} ) calcd: _434.0839 found _434.0848 , ^{C19H1837Cl37ClN6O2} (M) _calcd : ^436.0809 found: _436.0814 .

Example 3: 3-(2-(4-(Cyclopropylmethylene)piperazin-1-yl)ethyl)benzo[D]1,2,3-triazin-4(3H)-one, Namely compound I-14.

0.259g (1mmol) 3-(2-(piperazin-1-yl)ethyl)benzo[D]1,2,3-triazin-4(3H)-one was added to 15ml DMF, dissolved by sonication, 0.552 g (4 mmol) of potassium carbonate was added, and a solution of 0.27 g (2 mmol) of bromomethylcyclopropane in 5 ml of DMF was added dropwise at 0°C. After the reaction, the solvent was evaporated under reduced pressure, 50ml of water was added to the residue, extracted with dichloromethane (50ml×2), the organic phase was dried over anhydrous sodium sulfate, concentrated, and separated by column chromatography to obtain 0.44g of white solid , the yield is 70%.

¹ H NMR (400 MHz, DMSO-d ₆ ) δ 8.22 (d, J=7.8 Hz, 1H), 8.16 (d, J=8.1 Hz, 1H), 8.05 (t, J=7.5 Hz, 1H), 7.89 (t, J＝7.5Hz, 1H), 4.46(t, J＝6.4Hz, 2H), 3.32(s, 4H), 2.73(t, J＝6.4Hz, 2H), 2.36(s, 4H), 2.10 (d, J=5.3Hz, 2H), 1.18 (s, 1H), 0.38 (d, J=7.5Hz, 2H), -0.01 (d, J=4.2Hz, 2H). ¹³ C NMR (101MHz, DMSO) -d ₆ )δ154.70,143.59,135.37,132.88,127.92,124.54,119.09,62.61,55.63,52.55,52.39,46.29,8.07,3.64.HRMS(EI)C ₁₇ H ₂₃ N ₅ O(M), calculated value: 313.1903 Found: 313.1904.

Example 4: 3-((3-phenylisoxazole)-5-methyl)benzo[D]1,2,3-triazin-4(3H)-one, compound I-113.

4.1 Preparation of 3-(3-propynyl)yl-benzo[d][1,2,3]triazin-4(3H)-one

Add 1.47g (10mmol) of benzo[d][1,2,3]triazin-4(3H)-one to 30ml of acetone, dissolve by ultrasonic, add 2.76g (20mmol) of potassium carbonate, and dropwise add 1.19g ( 10mmol) 5ml acetone solution of 3-bromopropyne, the dropwise addition was completed, and the temperature was raised to reflux TLC to track the reaction progress. After the reaction was completed, the solvent was evaporated under reduced pressure, 100 ml of water was added to the residue, extracted with dichloromethane (80 ml×2), the organic phase was dried over anhydrous sodium sulfate, concentrated, and separated by column chromatography to obtain a light white solid 1.39 g, yield 75%.

¹ H NMR (400 MHz, CDCl ₃ ) δ 8.39 (d, J=7.9 Hz, 1H), 8.18 (d, J=8.1 Hz, 1H), 7.98 (t, J=7.7 Hz, 1H), 7.83 (t , J=7.6Hz, 1H), 5.24(s, 2H), 2.40(s, 1H). ¹³ C NMR (101MHz, CDCl ₃ )δ154.89, 144.30, 135.13, 132.69, 128.56, 125.21, 119.94, 76.93, 73.29, 39.38.

4.2 Preparation of (E)-2-chlorobenzaldehyde oxime

Add 1.21 g (10 mmol) of (E)-2-benzaldehyde oxime to 30 ml of DMF, dissolve by ultrasonic, add 1.46 g (11 mmol) of N-chlorosuccinimide in three batches, react at room temperature, and follow the reaction progress by TLC. After the reaction, 100 ml of saturated ammonium chloride was added, extracted with ether (50 ml × 3), the organic phase was dried over anhydrous sodium sulfate, and concentrated to obtain 0.86 g of white solid with a yield of 56%.

4.3 Preparation of 3-((3-phenylisoxazole)-5-methyl)benzo[D]1,2,3-triazin-4(3H)-one

将0.407g(2.2mmol)3-(3-丙炔)基-苯并[d][1,2,3]三嗪-4(3H)-酮与0.31g(2.0mmol)(E)-2-苯甲醛肟加入20ml乙酸乙酯中，室温滴加三乙胺0.404g(4.0mmol)，室温反应，TLC跟踪反应进程。反应结束后，向残留物中加入50ml水，用乙酸乙酯萃取(50ml×2)，有机相用无水硫酸钠干燥，浓缩，柱层析分离，得浅白色固体0.41g，收率68％。¹H NMR(400MHz,DMSO-d₆)δ8.29(t,J＝7.8Hz,2H),8.15(t,J＝7.7Hz,1H),7.99(t,J＝7.6Hz,1H),7.85(d,J＝3.4Hz,2H),7.49(s,3H),7.15(s,1H),5.84(s,2H).¹³C NMR(101MHz,DMSO-d₆)δ167.79,162.09,154.59,143.68,135.72,133.30,130.30,129.06,128.29,128.19,126.58,124.68,119.42,101.60,44.79.HRMS(ES+)C₁₇H₁₂N₄NaO₂(M+Na)⁺，计算值：327.0858,实测值：327.0858。

0.407 g (2.2 mmol) of 3-(3-propyn)yl-benzo[d][1,2,3]triazin-4(3H)-one was combined with 0.31 g (2.0 mmol) of (E)-2 - Benzaldoxime was added to 20 ml of ethyl acetate, 0.404 g (4.0 mmol) of triethylamine was added dropwise at room temperature, the reaction was carried out at room temperature, and the reaction progress was tracked by TLC. After the reaction, 50ml of water was added to the residue, extracted with ethyl acetate (50ml×2), the organic phase was dried over anhydrous sodium sulfate, concentrated, and separated by column chromatography to obtain 0.41g of a light white solid with a yield of 68% . ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 8.29 (t, J=7.8 Hz, 2H), 8.15 (t, J=7.7 Hz, 1H), 7.99 (t, J=7.6 Hz, 1H), 7.85 (d, J=3.4Hz, 2H), 7.49 (s, 3H), 7.15 (s, 1H), 5.84 (s, 2H). ¹³ C NMR (101 MHz, DMSO-d ₆ ) δ 167.79, 162.09, 154.59, 143.68 ,135.72,133.30,130.30,129.06,128.29,128.19,126.58,124.68,119.42,101.60,44.79.HRMS(ES+)C ₁₇ H ₁₂ N ₄ NaO ₂ (M+Na) ⁺ , calculated: 327.0858, found: 327.0858.

Example 5: Preparation of 3-(2-(5-phenyl-1,2,4-oxadiazole)ethyl)benzo[D]1,2,3-triazin-4(3H)-one, Namely compound I-23.

5.1 Preparation of 3-(2-cyanoethyl)-benzo[d][1,2,3]triazin-4(3H)-one

Add 2.94g (20.0mmol) benzo[d][1,2,3]triazin-4(3H)-one and 2.68g (20.0mmol) 3-bromopropionitrile to 50ml acetone, add 5.52g potassium carbonate (40.0 mmol), the temperature was raised to reflux, and the progress of the reaction was followed by TLC. After the reaction, the solvent was removed under reduced pressure, 100 ml of saturated sodium chloride was added to the residue, extracted with dichloromethane (100 ml × 2), the organic phase was dried over anhydrous sodium sulfate, concentrated, and separated by column chromatography to obtain a white solid 2.92g, yield 73%. ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 8.29 (dd, J=7.9, 1.1 Hz, 1H), 8.25 (d, J=7.9 Hz, 1H), 8.16–8.10 (m, 1H), 8.00– 7.94 (m, 1H), 4.65 (t, J=6.4Hz, 2H), 3.15 (t, J=6.4Hz, 2H).

5.2 Preparation of 3-(2-(5-phenyl-1,2,4-oxadiazole)ethyl)benzo[D]1,2,3-triazin-4(3H)-one

Combine 2.0 g (10.0 mmol) 3-(2-cyanoethyl)-benzo[d][1,2,3]triazin-4(3H)-one with 0.69 g (10.0 mmol) hydroxylamine hydrochloride, 50ml of absolute ethanol was added, potassium carbonate 2.76 (20.0 mmol) was added under stirring, the temperature was raised to reflux, and the reaction progress was followed by TLC. After the reaction was completed, the solvent was removed under reduced pressure, and it was directly used in the next reaction without purification.

40 ml of dichloromethane was added to the system after the previous reaction was completed, and a solution of 1.4 g (10 mmol) of benzoyl chloride in 10 ml of dichloromethane was added dropwise at room temperature, and the reaction progress was followed by TLC. After the reaction was completed, the solvent was removed under reduced pressure, 40 ml of toluene was added to the residue, the temperature was raised to reflux, the reaction progress was tracked by TLC, the solvent was evaporated under reduced pressure after the reaction was completed, 100 ml of saturated sodium chloride solution was added to the residue, and dichloromethane was used. Methane extraction (100ml×2), the organic phase was dried with anhydrous sodium sulfate, concentrated, and separated by column chromatography to obtain 0.67g of white solid with a yield of 21%. ¹ H NMR (400 MHz, CDCl ₃ ) δ 8.37 (dd, J=7.9, 0.7 Hz, 1H), 8.15 (d, J=8.0 Hz, 1H), 8.10-8.02 (m, 2H), 7.99-7.92 ( m,1H),7.82(dd,J=11.1,3.9Hz,1H),7.58(dd,J=8.4,6.4Hz,1H),7.50(t,J=7.5Hz,2H),4.96(t,J = 7.1Hz, 2H), 3.47 (t, J = 7.1Hz, 2H). ¹³ C NMR (101MHz, CDCl ₃ )δ175.78, 168.17, 155.57, 144.27, 134.89, 132.76, 132.45, 129.06, 128.39, 128.11, 125.16, 124.09, 119.84, 47.18, 25.57. HRMS (ES+) _C17H13N5NaO2 (M+Na) ⁺ , _calcd : _342.0969 , found: _342.0968 .

Example 6: 3-(2-(3-Phenyl-1,2,4-oxadiazole)ethyl)-benzo[D]1,2,3-triazin-4(3H)-one, Namely compound I-115.

6.1 Preparation of 5-(2-chloroethyl)-3-phenyl-1,2,4-oxadiazole

1.36g (10.0mmol) benzamide oxime and 2.03g (20.0mmol) triethylamine were added in 50ml toluene, 1.27g (10.0mmol) trichloropropionyl chloride was added dropwise at room temperature, and the reaction was carried out at room temperature. TLC tracked the reaction process, and the reaction ended. After that, the temperature was raised to reflux, and the reaction progress was followed by TLC. After the reaction was completed, the solvent was removed under reduced pressure, 100 ml of saturated sodium chloride was added to the residue, extracted with dichloromethane (80 ml × 2), the organic phase was dried over anhydrous sodium sulfate, concentrated, and separated by column chromatography to obtain a light Color oily liquid 0.79g, yield 38%. ¹ H NMR (400 MHz, CDCl ₃ ) δ 8.08 (dd, J=7.7, 1.7 Hz, 2H), 7.53-7.43 (m, 3H), 3.99 (t, J=6.9 Hz, 2H), 3.43 (t, J=6.9Hz, 2H).

6.2 Preparation of 3-(2-(3-phenyl-1,2,4-oxadiazole)ethyl)-benzo[D]1,2,3-triazin-4(3H)-one

0.294g (2.0mmol) benzo[d][1,2,3]triazin-4(3H)-one, 0.418g (2.0mmol) 5-(2-chloroethyl)-3-phenyl- 1,2,4-oxadiazole, 0.276g (2.0mmol) potassium carbonate was added to 20ml of acetone, the temperature was raised to reflux, and the reaction progress was followed by TLC. After the reaction, the solvent was evaporated under reduced pressure, 50ml of saturated sodium chloride was added to the residue, extracted with dichloromethane (50ml×2), the organic phase was dried over anhydrous sodium sulfate, concentrated, and separated by column chromatography to obtain a white Solid 0.49g, yield 77%. ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 8.27 (dd, J=7.9, 1.1 Hz, 1H), 8.22 (d, J=8.1 Hz, 1H), 8.15–8.07 (m, 1H), 7.99– 7.93(m,1H),7.93–7.87(m,2H),7.55(ddd,J=18.8,7.8,6.2Hz,3H),4.88(t,J=6.8Hz,2H),3.65(t,J= 6.8Hz, 2H). ¹³ C NMR (101MHz, DMSO-d ₆ )δ177.51,167.46,154.87,143.59,135.53,133.07,131.51,129.19,128.05,126.86,126.03,124.56,119.18,46.10 ) _C17H13N5O2 (M), _calcd : _319.1069 found: _319.1070 .

Example 7: 3-(3-(5-Isopropyl-2-methylphenoxy)propyl)-7-morpholinobenzo[d][1,2,3]triazine-4( 3H)-ketone, compound I-99.

7.1 Preparation of 2-(3-bromopropyl)-4-isopropyl-1-toluene

0.901 g (6 mmol) of carvacrol, 3.633 g (18 mmol) of 1,3-dibromopropane, 2.484 g (18 mmol) of potassium carbonate and 0.100 g (0.6 mmol) of potassium iodide were added to acetonitrile (50 mL) and stirred to make it As a suspension, the reaction was heated to reflux and the progress of the reaction was followed by TLC. It was cooled to room temperature, the solvent was evaporated under reduced pressure, the residue was saturated with sodium chloride solution (100 mL), extracted with dichloromethane (60 mL×2), the organic phases were combined, dried over anhydrous sodium sulfate, concentrated, and subjected to column chromatography, 0.98 g of colorless liquid was obtained, and the yield was 60%.

7.2 Preparation of 7-morpholinobenzo[d][1,2,3]triazin-4(3H)-one

Add 0.826g (5mmol) of 7-fluorobenzo[d][1,2,3]triazin-4(3H)-one to 20ml morpholine, react at 120℃, follow the reaction progress by TLC, after the reaction, cool down At 50°C, the precipitated product was filtered off with suction, the precipitate was washed with water, and dried in vacuo to obtain 0.81 g with a yield of 70%.

¹ H NMR (400 MHz, DMSO-d ₆ ) δ=13.65 (s, 1H), 8.00 (d, J=9.1 Hz, 1H), 7.70 (dd, J=9.2, 2.3 Hz, 1H), 7.38 (d, J=2.1Hz, 1H), 3.81–3.73 (m, 4H), 3.43–3.39 (m, 4H). ¹³ C NMR (100 MHz, DMSO-d ₆ ) δ=154.18, 150.99, 146.92, 135.44, 120.08, 119.54 , 111.87, 66.14, 52.44.

7.3 Preparation of 3-(3-(5-isopropyl-2-methylphenoxy)propyl)-7-morpholinobenzo[d][1,2,3]triazine-4(3H) -ketone

7-morpholinobenzo[d][1,2,3]triazin-4(3H)-one 1.393g (6mmol), 2-(3-bromopropyl)-4-isopropyl-1 -Toluene 1.953g (7.2mmol), potassium carbonate 1.656g (12mmol) and potassium iodide 0.100g (0.6mmol) were added to DMF (20mL), heated to 80°C to react, TLC tracked the reaction progress, after the reaction was completed, cooled to At room temperature, the solvent was evaporated under reduced pressure, water (100 mL) was added to the residue, extracted with dichloromethane (60 mL×2), the organic phases were combined, dried over anhydrous sodium sulfate, concentrated, and subjected to column chromatography to obtain 1.59 g of a white solid product , the yield is 63%. ¹ H NMR (400MHz, DMSO-d ₆ ) δH: 8.03 (d, J=9.2Hz, 1H), 7.54 (dd, J=9.2, 2.5Hz, 1H), 7.41 (d, J=2.4Hz, 1H) ,6.99(d,J＝7.6Hz,1H),6.74(s,1H),6.68(dd,J＝7.6,1.3Hz,1H),4.54(t,J＝6.8Hz,2H),4.07(t, J=6.0Hz, 2H), 3.85–3.73 (m, 4H), 3.50–3.39 (m, 4H), 2.80 (p, J=6.8Hz, 1H), 2.28 (p, J=6.4Hz, 2H), 2.00(s, 3H), 1.16(d, J=6.8Hz, 6H). ¹³ C NMR (100MHz, DMSO-d ₆ )δC: 156.33, 155.21, 154.34, 147.35, 145.92, 130.03, 125.59, 122.94, 119.68, 117.71,109.59,109.51,108.32,65.72,64.97,46.71,46.58,33.37,28.32,23.92,15.28.HRMS(EI)C ₂₄ H ₃₀ N ₄ O ₃ (M), Calculated: 422.2315; Found: 422.2318

Example 8: Compound I-2

Compound I-2 was prepared by ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 8.58 (ddd, J=4.8, 1.5, 0.9 Hz using a similar procedure as described for compound I-1 using appropriate starting materials ,1H),8.27(dd,J＝7.9,1.0Hz,1H),8.21(d,J＝7.8Hz,1H),8.14–8.07(m,1H),7.93(ddd,J＝15.6,8.0,1.4 Hz, 2H), 7.56 (d, J=7.8Hz, 1H), 7.47 (ddd, J=7.6, 4.9, 1.1Hz, 1H), 4.54 (t, J=6.5Hz, 2H), 3.69–3.52 (m , 2H), 3.34(s, 2H), 2.84(t, J＝6.6Hz, 2H), 2.64–2.55(m, 2H), 2.50–2.44(m, 2H). ¹³ C NMR(101MHz, DMSO-d ₆ ) δ166.54, 154.74, 153.96, 148.32, 143.59, _137.30 , 135.37, _132.88 , 127.94, 124.55, 124.49, 123.07, 119.11, 55.46, 52.79, 52.13, 46.48, _406.7.RMS O ₂ (M), calcd: 364.1648 found: 364.1646.

Example 9: Compound I-5

Using appropriate starting materials, Compound I-4 was prepared using similar procedures as described for Compound I-1. ¹ HNMR (400MHz, DMSO-d ₆ )δ8.98(s,1H),8.62(s,1H),8.26(d,J=7.6Hz,1H),8.21(d,J=8.0Hz,1H), 8.10(t,J＝7.2Hz,1H),7.94(t,J＝7.3Hz,1H),4.54(t,J＝6.3Hz,2H),3.62(s,2H),3.09(s,2H), 2.86(t, J=6.3Hz, 2H), 2.61(s, 2H), 2.46(s, 2H). ¹⁹ F NMR(376MHz, DMSO-d ₆ )δ-60.88(s).HRMS(EI)C _{20 H18ClF3N6O2} ( _{M ) calcd} for _{C20H1835ClF3N6O2} ^: _{466.1132 Found} : _{466.1131 ,} ^{C20H1837ClF3N6O2} _{calcd : 468.1102 Found} : _468.1099 .

Example 10: Namely Compound I-6

Compound I-6 was prepared using similar procedures as described for compound I-1 using appropriate starting materials. ¹ HNMR (400MHz, DMSO-d ₆ ) δ 8.26 (dd, J=7.9, 0.9 Hz, 1H), 8.23-8.17 (m, 1H), 8.14-8.06 (m, 1H), 7.99-7.90 (m, 1H), 7.81(d, J＝7.8Hz, 1H), 7.74(t, J＝7.4Hz, 1H), 7.65(t, J＝7.7Hz, 1H), 7.45(d, J＝7.6Hz, 1H) ,4.53(t,J＝6.5Hz,2H),4.07-3.98(m,1H),3.70-3.48(m,2H),3.14-2.91(m,2H),2.83(t,J＝6.5Hz,2H ), 2.67–2.57(m, 1H), 2.52–2.41(m, 2H), 2.33(dd, J=9.2, 5.8Hz, 1H). ¹⁹ F NMR(376MHz, DMSO)δ-58.56(s).HRMS (EI) Calculated for _{C21H20F3N5O2 ( M} ): _431.1569 Found: _431.1568 .

Example 11: Namely Compound I-7

Compound I-7 was prepared using similar procedures as described for compound I-1 using appropriate starting materials. ¹ HNMR (400MHz, DMSO-d ₆ ) δ 8.26 (dd, J=7.9, 1.0 Hz, 1H), 8.21 (d, J=7.8 Hz, 1H), 8.14-8.05 (m, 1H), 7.98-7.91 (m, 1H), 4.54(t, J＝6.5Hz, 2H), 3.60(s, 2H), 3.16(s, 2H), 2.85(t, J＝6.5Hz, 2H), 2.62(s, 3H) , 2.59(s, 2H), 2.47(s, 2H). ¹³ C NMR(101MHz, DMSO-d ₆ )δ159.16,156.37,154.74,143.58,143.37,135.37,132.88,127.93,124.55,119.09,55.25,52.49, 51.77, 46.69, 46.15, 41.89, 12.40. HRMS (EI) _calcd for _C17H19N7O2S (M): _385.1321 , found: _385.1319 .

Example 12: Namely Compound I-8

Compound I-8 was prepared using similar procedures as described for compound I-1 using appropriate starting materials. ¹ HNMR (400MHz, DMSO-d ₆ ) δ 8.27 (dd, J=7.9, 0.9 Hz, 1H), 8.23-8.17 (m, 1H), 8.14-8.05 (m, 2H), 8.00-7.88 (m, 1H), 4.54(t, J＝6.5Hz, 2H), 3.93(s, 3H), 3.52(s, 2H), 3.29(s, 2H), 2.83(t, J＝6.5Hz, 2H), 2.47( s, 4H). ¹⁹ F NMR (376 MHz, DMSO-d ₆ ) δ-59.55 (s). HRMS (EI) calcd for C ₁₉ H ₂₀ F ₃ N ₇ O ₂ (M): 435.1631 Found: 435.1624

Example 13: Namely Compound I-9

Compound I-9 was prepared using similar procedures as described for compound I-1 using appropriate starting materials. ¹ HNMR (400MHz, DMSO-d ₆ ) δ 8.27 (dd, J=7.9, 1.0 Hz, 1H), 8.21 (d, J=7.7 Hz, 1H), 8.15-8.04 (m, 1H), 7.98-7.91 (m,1H),7.83(dd,J=1.7,0.8Hz,1H),6.97(dd,J=3.5,0.8Hz,1H),6.61(dd,J=3.4,1.8Hz,1H),4.55( t, J=6.5Hz, 2H), 3.59 (s, 4H), 2.84 (t, J=6.5Hz, 2H), 2.58–2.52 (m, 4H). ¹³ C NMR (101MHz, DMSO-d ₆ )δ158 _{.17,154.75,146.94,144.61,143.60,135.38,132.90,127.95,124.56,119.11,115.45,111.21,55.44,52.65,52.58,52.54,52.51,46.17.HRMS _ _ _} Calculated: 353.1488 Found: 353.1485.

Example 14: Namely Compound I-10

Compound I-10 was prepared using similar procedures as described for compound I-1 using appropriate starting materials. ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 8.27 (dd, J=7.9, 0.8 Hz, 1H), 8.21 (d, J=8.0 Hz, 1H), 8.15–8.04 (m, 1H), 8.01– 7.89(m,1H),7.75(dd,J＝5.0,0.9Hz,1H),7.39(dd,J＝3.6,0.9Hz,1H),7.12(dd,J＝4.9,3.7Hz,1H),4.55 (t, J=6.5Hz, 2H), 2.84 (t, J=6.5Hz, 2H). ¹³ C NMR (101MHz, DMSO-d ₆ ) δ 162.13, 154.75, 143.60, 137.10, 135.38, 132.89, 129.35, 128.98, 127.94, 127.02, 124.56, 119.11, 55.42, 52.49, 46.18. HRMS (EI) _C18H19N5O2S (M) _calcd : _369.1259 found: _369.1252 .

Example 14: Namely Compound I-11

Compound I-11 was prepared using similar procedures as described for compound I-14 using appropriate starting materials. ¹ HNMR (400MHz, DMSO-d ₆ )δ8.26(d,J=7.8Hz,1H),8.20(d,J=8.0Hz,1H),8.10(t,J=7.5Hz,1H),7.94( t, J＝7.4Hz, 1H), 7.52(s, 1H), 4.51(t, J＝6.1Hz, 2H), 3.64(s, 2H), 2.78(t, J＝6.1Hz, 2H), 2.42( d, J=49.1Hz, 8H). ¹³ C NMR(101MHz, DMSO) δ154.69, 149.69, 143.58, 140.26, 139.29, 135.35, 132.86, 127.91, 124.53, 119.08, 55.49, 53.34, 52.39, 52.22, 46.27 HRMS( EI) _C17H19ClN6OS (M) _calcd for _{C17H1935ClN6OS} : _390.1310 found: _390.1028 , _{C17H1937ClN6OS calcd} : ^392.1000 _found : _392.0999 ^.

Example: 15 is compound I-12

Compound I-12 was prepared using similar procedures as described for compound I-1 using appropriate starting materials. ¹ H NMR (400MHz, DMSO-d ₆ ) δ 8.85 (d, J=8.1 Hz, 1H), 8.27 (d, J=7.7 Hz, 1H), 8.21 (d, J=7.9 Hz, 1H), 8.10 (t,J＝7.3Hz,1H),7.96(dd,J＝18.7,7.3Hz,2H),7.85(t,J＝7.7Hz,1H),4.56(t,J＝6.1Hz,2H),3.60 (s, 4H), 2.86 (t, J=6.1 Hz, 2H), 2.58 (s, 4H). ¹³ C NMR (101 MHz, DMSO-d ₆ ) δ 166.65, 158.35, 154.70, 143.61, 139.88, 135.37, 132.86, 128.68, 127.92, 127.60, 126.39, 125.52, 124.49, 119.06, 59.72, 55.37, 54.88, 52.48, 52.40, 46.16. HRMS(EI) C20H19N7O2S(M) Calculated: 421.1321 Found: 421.13.

Example 16: Namely Compound I-13

Compound I-13 was prepared using similar procedures as described for compound I-3 using appropriate starting materials. ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 8.26 (dd, J=7.9, 1.0 Hz, 1H), 8.21 (d, J=7.7 Hz, 1H), 8.14–8.06 (m, 1H), 8.00– 7.89(m, 1H), 4.51(t, J=6.6Hz, 2H), 3.39(s, 4H), 2.77(t, J=6.6Hz, 2H), 2.48(s, 2H), 2.27(s, 2H _The ^_ _{_} Calcd. for _H19N5O (M): _421.1321 Found: 421.1322.

Example 17: Namely Compound I-15

Compound I-15 was prepared using similar procedures as described for compound I-1 using appropriate starting materials. ¹ H NMR (400MHz, DMSO-d ₆ ) δ 8.28 (d, J=8.3Hz, 3H), 8.21 (d, J=8.1Hz, 1H), 8.10 (t, J=7.4Hz, 1H), 7.95 (t, J=7.3Hz, 1H), 7.66(d, J=8.3Hz, 2H), 4.54(t, J=6.1Hz, 2H), 3.59(s, 2H), 3.20(s, 2H), 2.84 (t, J=6.1Hz, 2H), 2.59(s, 2H), 2.46(s, 2H). ¹³ C NMR (101 MHz, DMSO-d ₆ ) δ 166.92, 154.76, 147.72, 143.60, 142.20, 135.40, 132.91, 128.20, 127.95, 124.56, 123.72, 119.11, 55.38, 46.16. HRMS (EI) Calculated for _C20H20N6O4 ( _M ): _408.1546 Found: _408.1544 .

Example 18: Namely Compound I-16

Compound I-16 was prepared using similar procedures as described for compound I-1 using appropriate starting materials. ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 8.27 (dd, J=7.9, 1.0 Hz, 1H), 8.21 (d, J=7.8 Hz, 1H), 8.14–8.04 (m, 1H), 7.98– 7.88(m, 1H), 7.40–7.27(m, 3H), 4.54(t, J=6.5Hz, 2H), 3.58(s, 2H), 3.17(t, J=4.8Hz, 2H), 2.84(t , J＝6.5Hz, 2H), 2.57(s, 2H), 2.46(s, 2H). ¹⁹ F NMR(376MHz, DMSO-d ₆ )δ-117.57–-117.82(m),-122.03–-122.31( m). _HRMS (EI) _calcd for _C20H19F2N5O2 (M): _399.1507 Found: _399.1508 .

Example 19: Namely Compound I-17

Compound I-17 was prepared using similar procedures as described for compound I-1 using appropriate starting materials. ¹ H NMR (400 MHz, DMSO-d ₆ ) ¹ H NMR (400 MHz, DMSO) δ 8.25 (dd, J=15.6, 6.7 Hz, 1H), 8.19 (d, J=9.2 Hz, 1H), 8.14-8.02 (m, 1H), 8.01–7.86 (m, 1H), 4.68–4.32 (m, 2H), 3.54 (s, 2H), 3.22 (s, 2H), 2.90–2.70 (m, 2H), 2.49 (d , J=5.8Hz, 4H). ¹³ C NMR (101MHz, DMSO-d ₆ )δ157.74,156.26,154.76,146.38,143.60,135.39,132.91,127.95,124.56,119.10,118.72,55.26,46.16.HRMS( _calcd for _{C17H1635Cl35ClN6O2S} (M): _{438.0433 found} : ^438.0436 , ^{C17H1635Cl37ClN6O2S} ₍ ^M ) _calcd : _440.0403 ^found : _440.0405 , C ^Calcd for _{17H1637Cl37ClN6O2S (} M): _{442.0374 found} : ^442.0372

Example 20: Namely Compound I-18

Compound I-18 was prepared using similar procedures as described for compound I-3 using appropriate starting materials. ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 8.27 (dd, J=7.9, 1.0 Hz, 1H), 8.21 (d, J=7.7 Hz, 1H), 8.14–8.06 (m, 1H), 7.98– 7.90(m,1H),7.19(dd,J=8.7,7.3Hz,2H),6.90(d,J=7.9Hz,2H),6.75(t,J=7.3Hz,1H),4.57(t,J ＝6.6Hz, 2H), 3.09-3.02(m, 3H), 2.85(t, J＝6.6Hz, 2H), 2.66-2.56(m, 4H). ¹³ C NMR (101MHz, DMSO-d ₆ )δ154. 75, 150.94, 143.61, 135.39, 132.91, 128.85, 127.95, 124.56, 119.12, 118.73, 115.29, 55.62, 52.49, 48.13, 46.28. HRMS(EI) C ₁₉ H ₂₁ N ₅ O(M) Calculated: 334 Found: 5.1728 .

Example 21: Namely Compound I-19

Using appropriate starting materials, Compound I-19 was prepared using similar procedures as described for Compound I-1. ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 8.27 (d, J=7.8 Hz, 1H), 8.21 (d, J=8.1 Hz, 1H), 8.11 (dd, J=11.2, 4.1 Hz, 1H) ,7.94(t,J＝7.5Hz,1H),7.35(d,J＝8.6Hz,2H),6.97(d,J＝8.6Hz,2H),4.54(t,J＝6.4Hz,2H),3.79 (s, 3H), 3.43 (s, 4H), 2.83 (t, J=6.4Hz, 2H), 2.51 (d, J=1.6Hz, 4H). ¹³ C NMR (101MHz, DMSO-d ₆ )δ168. _{77,160.10,154.74,143.59,135.37,132.89,128.95,127.93,127.76,124.55,119.10,113.57,55.46,55.19,52.54,52.49,52.46,52.39,46.123} N O _{(3 HEIC )} M) Calculated: 393.1801 Found: 393.1794.

Example 22: Namely Compound I-20

Compound I-20 was prepared using similar procedures as described for compound I-1 using appropriate starting materials. ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 8.26 (dd, J=7.9, 1.0 Hz, 1H), 8.21 (d, J=7.9 Hz, 1H), 8.14–8.06 (m, 1H), 7.97– 7.91(m, 1H), 7.78(s, 2H), 4.53(t, J=6.4Hz, 2H), 3.64-3.48(m, 2H), 3.16-2.99(m, 2H), 2.85(t, J= 6.4Hz, 2H), 2.64–2.54 (m, 2H), 2.49–2.39 (m, 2H). ¹³ C NMR (101MHz, DMSO-d ₆ )δ161.61, 154.76, 143.59, 135.40, 134.57, 133.67, 132.92, 131.40 ,128.27,127.96,124.56,119.10,55.29,52.58,51.80,46.17,45.67,41.06.HRMS ESI+C ₂₀ H ₁₉ ³⁵ Cl ³⁵ Cl ³⁵ ClN ₅ O ₂ (M+H) ⁺ calcd: 466.0604 found: ^466.0606 , _calcd for _{C20H1935Cl35Cl37ClN5O2} ( _M + ^H ) ⁺ _calcd : _468.0575 , ^found : ^468.0569 , ^{C20H1935Cl37Cl37ClN5O2} _{( M +} ^H ) ⁺ Calcd: _470.0545 , Found: ^470.0548 , Calcd for _{C20H1937Cl37Cl37ClN5O} ( _{M +} H) ⁺² : ^472.0516 Found: ^472.0511 .

Example 23: Namely Compound I-21

Compound I-21 was prepared using similar procedures as described for compound I-14 using appropriate starting materials. ¹ HNMR (400MHz, DMSO-d ₆ ) δ 8.15 (d, J=7.9Hz, 1H), 8.12-8.03 (m, 2H), 7.98-7.88 (m, 1H), 7.67-7.44 (m, 10H) , 4.74(s, 4H), 4.49(t, J=6.3Hz, 2H), 3.20(s, 4H), 3.09(s, 4H), 2.92(t, J=6.3Hz, 2H). ¹³ C NMR( 101MHz,DMSO-d ₆ ) _{δ154.78,143.43,135.34,133.59,132.93,130.33,128.93,127.88,127.30,124.47,118.90,54.38,54.33,45.85,44.96.HRMS} (ES+) N ₅ O M-C ₂₇ Br) ⁺ Calculated: 440.2448 Found: 440.2450.

Example 24: Namely Compound I-22

Compound I-22 was prepared using similar procedures as described for compound I-14 using appropriate starting materials. ¹ H NMR (400 MHz, CDCl ₃ ) δ 8.36 (dd, J=8.0, 1.0 Hz, 1H), 8.17 (dd, J=8.1, 0.4 Hz, 1H), 8.02-7.93 (m, 1H), 7.87-7.79 ^13C NMR (101MHz, DMSO-d ₆ ) δ 165.02, 158.54, 150.39, 139.00, 129.63, 127.17, 123.07, 119.83, 114.50, 50.62, 47.12, 41.25, _38.85.HRMS (ES+)C ₁₆ H ₁₇ O ³⁵ Cl ³⁵ (M+H) ⁺ _calcd : _407.0902 , found: _407.0901 , ^{C16H1737Cl35ClN8O} ( ^M +H) ⁺ calculated: ^409.0873 , ^found : _409.0879 , _C16H1737Cl37 calcd for _ClN8O (M+H) ⁺ : 411.0843 found: 411.0851.

Example 25: Phenyl 4-(2-(benzo[d][1,2,3]triazin-4(3H)-one-ethyl)piperazinecarboxylate, compound I-24.

0.518 g (2.0 mmol) of 3-(2-(piperazin-1-yl)ethyl)benzo[D]1,2,3-triazin-4(3H)-one and 0.303 g (3.0 mmol) Triethylamine was added to 30 ml of dichloromethane, 0.238 g (2.0 mmol) of phenyl isocyanate was added dropwise at room temperature, and the reaction progress was followed by TLC. After the reaction, 50ml of saturated sodium chloride was added to the residue, extracted with dichloromethane (50ml×2), the organic phase was dried over anhydrous sodium sulfate, concentrated, and separated by column chromatography to obtain a white solid 0.57g in a yield of 0.57g. 75%. ¹ H NMR (400 MHz, CDCl ₃ ) δ 8.37 (dd, J=7.9, 1.0 Hz, 1H), 8.17 (d, J=8.1 Hz, 1H), 8.01-7.91 (m, 1H), 7.85-7.78 ( m, 1H), 7.35 (t, J=7.9Hz, 2H), 7.18 (t, J=7.4Hz, 1H), 7.13–7.05 (m, 2H), 4.65 (t, J=6.5Hz, 2H), 3.58(d, J=40.3Hz, 4H), 2.97(t, J=6.5Hz, 2H), 2.63(s, 4H). ¹³ C NMR (101 MHz, CDCl ₃ ) δ 155.65, 153.63, 151.35, 144.28, 134.84, 132.38,129.25,128.32,125.26,125.09,121.71,119.79,56.10,52.69,46.57,44.42,43.87.HRMS(EI)C ₂₀ H ₂₁ N ₅ O ₃ (M), Calculated: 379.1644, Measured: 379.164.4

Example 26: Compound I-26

Compound I-26 was prepared using similar procedures as described for compound I-24 using appropriate starting materials. ¹ HNMR (400MHz, DMSO-d ₆ ) δ 9.29 (s, 1H), 8.28 (dd, J=7.9, 1.0 Hz, 1H), 8.22 (d, J=7.8 Hz, 1H), 8.15-8.05 (m , 1H), 7.99–7.91 (m, 1H), 7.32–7.25 (m, 4H), 7.09 (ddd, J=8.5, 5.8, 2.6Hz, 1H), 4.57 (t, J=6.5Hz, 2H), 3.91–3.71 (m, 4H), 2.85 (t, J=6.5Hz, 2H), 2.63–2.53 (m, 4H). ¹³ C NMR (101 MHz, DMSO-d ₆ ) δ 181.31, 154.76, 143.61, 140.96, 135.40 ,132.91,127.96,127.94,125.15,124.57,124.20,119.12,55.99,55.30,52.19,47.91,46.23,18.53.HRMS(EI)C ₂₀ H ₂₂ N ₆ O ₂ (M), Calculated: 378.1804, Measured : 378.1802.

Example 27, Compound I-27

Compound I-27 was prepared using similar procedures as described for compound I-1 using appropriate starting materials. ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 8.27 (d, J=7.3 Hz, 1H), 8.22 (d, J=8.1 Hz, 1H), 8.11 (t, J=7.2 Hz, 1H), 7.95 (t,J＝7.4Hz,1H),7.40(d,J＝6.8Hz,1H),7.18(s,1H),7.08(d,J＝8.2Hz,1H),7.00(t,J＝7.1Hz , 1H), 4.56(s, 2H), 3.79(s, 4H), 3.49(s, 4H), 3.06(s, 2H), 2.51(s, 3H). ¹³ C NMR (101MHz, DMSO-d ₆ ) δ166.33, 154.85, 143.61, 135.43, 132.98, 128.01, 124.55, 120.62, 111.35, 55.44. HRMS (EI) C ₂₁ H ₂₃ N ₅ O ₃ (M), calculated: 393.1801 Found: 393.1797.

Example 28: Namely Compound I-28.

Using appropriate starting materials, Compound I-28 was prepared using similar procedures as described for Compound I-1. ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 8.27 (d, J=7.8 Hz, 1H), 8.21 (d, J=8.0 Hz, 1H), 8.10 (t, J=7.5 Hz, 1H), 7.94 (t, J=7.4Hz, 1H), 7.52 (d, J=7.4Hz, 1H), 7.48–7.38 (m, 2H), 7.34 (d, J=6.9Hz, 1H), 4.53 (t, J= 5.9Hz, 2H), 3.58(s, 2H), 3.34(s, 3H), 3.05(s, 2H), 2.83(t, J=5.9Hz, 2H), 2.57(s, 2H), 2.44(s, 2H). HRMS (EI ₎ C21H23N5O3 ( _M ), calcd: _393.1801 Found: _393.1797 .

Example 29: Compound I-29.

Compound I-29 was prepared using similar procedures as described for compound I-1 using appropriate starting materials. ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 8.51 (dd, J=4.7, 1.4 Hz, 1H), 8.27 (d, J=7.6 Hz, 1H), 8.25–8.18 (m, 2H), 8.16– 8.04(m, 1H), 7.95(t, J=7.5Hz, 1H), 7.61(dd, J=8.1, 4.7Hz, 1H), 6.99(s, 1H), 4.54(t, J=6.4Hz, 2H) ), 3.46(d, J=32.0Hz, 4H), 2.84(t, J=6.4Hz, 2H), 2.49(d, J=14.5Hz, 4H). ¹³ C NMR(101MHz, DMSO-d ₆ )δ157 .90,154.76,147.15,146.97,143.59,140.29,139.47,135.40,132.91,127.95,126.89,126.29,126.16,124.56,119.10,110.16,55.37,52.34,51.79,46.89,46.15,41.54.HRMS(EI),C ₂₂ Calcd for _{H2079Br35ClN8O2} ( _M ): ^542.0581 _Found : ^542.0576 , _{C22H2081Br35ClN8O2 ( M} ) _calcd : _{544.0561 Found} : ^{544.0557 , C22H2079Br} Calcd. for ^37ClN8O2 (M): _544.0552 Found: _544.0557 , _Calcd . for _{C22H2081Br37ClN8O2 ( M} ): ^546.0531 Found: ^546.0538 .

Example 30: Compound I-30.

Using appropriate starting materials, Compound I-30 was prepared using procedures similar to those described for Compound I-1. ¹ H NMR (400MHz, DMSO-d ₆ )δ8.32-8.24(m,2H),8.24-8.16(m,2H),8.14-8.06(m,1H),8.00-7.90(m,1H),7.85 (dt, J=7.6, 1.2Hz, 1H), 7.74(t, J=7.9Hz, 1H), 4.54(t, J=6.5Hz, 2H), 3.59(s, 2H), 3.26(s, 2H) , 2.85(t, J=6.5Hz, 2H), 2.59(s, 2H), 2.47(s, 2H). ¹³ C NMR(101MHz, DMSO-d ₆ )δ166.57,154.75,147.63,143.59,137.36,135.38, 133.32,132.89,130.19,127.94,124.55,124.18,121.79,119.10,55.37,52.52,51.93,47.09,46.15,41.62.HRMS(EI),C ₂₀ H ₂₀ N ₆ O ₄ (M) Calculated value: 408.154 : 408.1545.

Example 31: Compound I-31

Using appropriate starting materials, Compound I-31 was prepared using procedures similar to those described for Compound I-1. ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 8.27 (dd, J=7.9, 0.9 Hz, 1H), 8.20 (dt, J=8.4, 4.3 Hz, 2H), 8.13-8.06 (m, 1H), 8.00–7.90 (m, 1H), 7.84 (td, J=7.5, 1.0Hz, 1H), 7.76–7.64 (m, 1H), 7.52 (dd, J=7.6, 1.2Hz, 1H), 4.54 (t, ^13C NMR(101MHz,DMSO-d ₆ )δ165.18,154.75,145.29,143.59,135.38,134.81,132.89,132.29,130.21,128.02,127.94,124.67,124.55,119.10,55.42,52.16,51.73,46.44,46.17,41.19.HRMS (EI) calcd for _C20H20N6O4 ( _M ): _408.1546 , found: _408.1548 .

Example 32: Compound I-32

Compound I-32 was prepared using similar procedures as described for compound I-119 using appropriate starting materials. ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 8.27 (dd, J=7.9, 0.9 Hz, 1H), 8.22 (d, J=8.1 Hz, 1H), 8.15–8.08 (m, 1H), 7.99– 7.92(m,1H),7.92–7.89(m,1H),7.79(d,J=8.1Hz,2H),7.33(d,J=8.0Hz,2H),4.88(t,J=6.8Hz,2H) _The ^_ 126.79, 124.55, 123.26, 119.17, 46.08, 25.31, 21.01. _HRMS (EI) Calculated for _C18H15N5O2 (M): _333.1226 , found: _333.1227 .

Example 33: Compound I-33

Using appropriate starting materials, Compound I-33 was prepared using procedures similar to those described for Compound I-1. ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 9.59 (s, 1H), 9.04 (d, J=5.2 Hz, 1H), 8.13 (d, J=5.2 Hz, 1H), 7.51-7.41 (m, 3H), 7.41–7.31(m, 2H), 4.55(t, J=6.5Hz, 2H), 3.56(s, 2H), 3.26(s, 2H), 2.83(t, J=6.4Hz, 2H), 2.50(d, J=32.5Hz, 4H). ¹³ C NMR (101MHz, DMSO-d ₆ )δ168.82,153.88,151.59,151.27,138.18,135.87,129.42,128.36,126.83,124.47,116.93,55.24,46. (EI), _calcd for _C19H20N6O2 ( _M ): _364.1648 , found: 364.1651.

Example 34: (4-(2-(1,1-dioxo-2H-benzo[e][1,2,3,4]thitriazin-2-yl)ethyl)piperazine-1 - base) (phenyl) ketone, namely compound I-34.

34.1 Preparation of N-(2-bromoethyl)-2-nitrobenzenesulfonamide

Add 3.82g (20.0mmol) o-nitrobenzenesulfonyl chloride, 4.10g (20.0mmol) dibromoethylamine hydrobromide to 300ml acetonitrile, slowly add 2.76g (20.0mmol) of potassium carbonate, react at room temperature for 2h, heat up to 60°C, TLC followed the progress of the reaction. After the reaction was completed, the solvent was evaporated under reduced pressure, 100 ml of saturated sodium chloride was added to the residue, extracted with dichloromethane (80 ml × 3), the organic phase was dried over anhydrous sodium sulfate, concentrated, and separated by column chromatography to obtain a white Solid 4.07g, yield 73%. ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 8.46 (t, J=5.3 Hz, 1H), 8.08-7.96 (m, 2H), 7.92-7.84 (m, 2H), 3.48 (t, J=6.3 Hz, 2H), 3.34 (t, J=6.1Hz, 2H). ¹³ C NMR (101MHz, DMSO-d ₆ )δ147.55, 134.15, 132.75, 129.47, 124.44, 44.44, 31.85.

34.2 Preparation of N-(2-(4-benzoylpiperazin-1-yl)ethyl)-2-nitrosulfonamide

3.09 (10.0 mmol) of N-(2-bromoethyl)-2-nitrobenzenesulfonamide, 1.90 g (10.0 mmol) of benzoylpiperazine and 2.76 g (20.0 mmol) of potassium carbonate were added to 150 ml of tetrahydrofuran, The reaction was carried out at room temperature for 2 h, and the temperature was raised to reflux, and the reaction progress was followed by TLC. After the reaction, the solvent was evaporated under reduced pressure, 100 ml of saturated sodium bicarbonate solution was added to the residue, extracted with dichloromethane (60 ml × 5), the organic phase was dried over anhydrous sodium sulfate, concentrated, and separated by column chromatography to obtain 2.59 g of white solid, yield 62%. ¹ H NMR (400MHz, DMSO-d ₆ )δ8.10-8.03(m,1H),8.02-7.96(m,1H),7.92(s,1H),7.89-7.83(m,2H),7.48-7.39 (m, 3H), 7.35(dd, J=6.5, 3.1Hz, 2H), 3.50(s, 2H), 3.20(s, 2H), 3.07(d, J=4.9Hz, 2H), 2.38(t, J=6.4Hz, 2H), 2.37–2.14 (m, 4H). ¹³ C NMR (101MHz, DMSO-d ₆ )δ168.78, 147.57, 135.84, 133.89, 133.07, 132.64, 129.50, 129.43, 128.36, 126.81, 124.42, 59.72, 56.37, 52.49, 52.14, 46.86, 41.24.

34.3 Preparation of N-(2-(4-benzoylpiperazin-1-yl)ethyl)-2-aminosulfonamide

Add 2.09 (5.0 mmol) N-(2-(4-benzoylpiperazin-1-yl)ethyl)-2-nitrosulfonamide, 0.56 g (10.0 mmol) iron powder to 50 ml of saturated ammonium chloride , add 2 drops of concentrated hydrochloric acid, add 10 ml of ethanol, react at 60 °C, and follow the reaction process by TLC. After the reaction, the iron powder was filtered off with celite, 50 ml of water was added to the residue, extracted with dichloromethane (60 ml × 3), the organic phase was dried over anhydrous sodium sulfate, concentrated, and separated by column chromatography to obtain pale 1.67 g of yellow oily liquid, yield 86%. ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 7.50 (dd, J=8.0, 1.5 Hz, 1H), 7.47-7.41 (m, 3H), 7.40-7.31 (m, 3H), 7.26 (ddd, J =8.5,7.2,1.6Hz,1H),6.81(dd,J=8.3,0.9Hz,1H),6.67–6.55(m,1H),5.93(s,2H),3.55(s,2H),3.25( s, 2H), 2.84 (q, J=6.4Hz, 2H), 2.40–2.09 (m, 6H).

34.4 Preparation of (4-(2-(1,1-dioxo-2H-benzo[e][1,2,3,4]thitriazin-2-yl)ethyl)piperazin-1-yl ) (phenyl) ketone

1.94g (5mmol) of N-(2-(4-benzoylpiperazin-1-yl)ethyl)-2-aminosulfonamide was added to 2mol/L of 10ml of dilute hydrochloric acid at 0-5°C, A solution of 1.035 g (15 mmol) of sodium nitrite in 5 ml of aqueous solution was added dropwise, and the dropwise addition was completed at 0-5° C. The reaction was followed by TLC. After the reaction, the pH was adjusted to 7-8 with sodium hydroxide solution, and a brown precipitate was precipitated, which was left to stand, suction filtered, the solid was washed with water, and dried to obtain 1.25 g of a brown solid with a yield of 63%. ¹ H NMR (400 MHz, CDCl ₃ ) δ 8.02 (t, J=7.5 Hz, 2H), 7.93-7.84 (m, 1H), 7.84-7.73 (m, 1H), 7.39 (s, 5H), 4.37 ( ^13C NMR( _101MHz , CDCl ₃ ) _{δ170.26,141.59,135.80,134.07,132.66,129.67,129.30,128.47,127.04,125.79,120.24,57.04,53.18,52.89,47.64,451EI.51,42.0} Calcd for _N5O3S ( _M ): 399.1365 Found: 399.1370.

Example 35: 3-(3-(5-Isopropyl-2-methylphenoxy)propyl)-8-benzobenzo[d][1,2,3]triazine-4(3H )-ketone, namely compound I-94.

35.1 Preparation of 8-benzobenzo[d][1,2,3]triazin-4(3H)-one

To a solution of 8-bromobenzotriazinone (1.130 g, 5.0 mmol) and phenylboronic acid (0.914 g, 7.5 mmol) in DMF (30 ml) was added K ₂ CO ₃ (2.073 g, 15.0 mmol) and H ₂ O ( 3ml). The reaction mixture was stirred for 5 min under an atmosphere of dry N ₂ , PdCl 2 (dppf) (146 mg, 0.2 mmol) was added, and the resulting mixture was heated at 90 °C until the disappearance of compound 2-A was detected by TLC. Cooled to room temperature, evaporated the solvent under reduced pressure, added water (100 mL) to the residue, extracted with dichloromethane (60 mL×2), combined the organic phases, dried over anhydrous sodium sulfate, filtered with suction, concentrated the filtrate, separated by column, 0.932 g of white solid product was obtained with a yield of 80%. ¹ H NMR (400 MHz, DMSO-d ₆ ) δ _H : 14.98 (s, 1H), 8.44 (d, J=1.6 Hz, 1H), 8.29 (d, J=8.4 Hz, 1H), 8.23 (dd, J =8.4,1.7Hz,1H),7.91(d,J=7.2Hz,2H),7.57(t,J=7.2Hz,2H),7.51(t,J=7.2Hz,1H).

35.2 Preparation of 3-(3-(5-isopropyl-2-methylphenoxy)propyl)-8-benzobenzo[d][1,2,3]triazine-4(3H)- ketone

7-Benzobenzo[d][1,2,3]triazin-4(3H)-one (1.340 g, 6 mmol), 2-(3-bromopropyl)-4-isopropyl-1 - Toluene (1.953 g, 7.2 mmol), K ₂ CO ₃ (1.656 g, 12 mmol) and KI (0.100 g, 0.6 mmol) were added to DMF (20 mL), stirred to make a mixture, the resulting mixture was placed in Heating at 80°C until the disappearance of compound 7-benzobenzo[d][1,2,3]triazin-4(3H)-one detected by TLC. Cooled to room temperature, evaporated the solvent under reduced pressure, added water (100 mL) to the residue, extracted with dichloromethane (60 mL×2), combined the organic phases, dried over anhydrous sodium sulfate, filtered with suction, concentrated the filtrate, separated by column, 1.56 g of white solid product was obtained, with a yield of 63%. ¹ H NMR (400 MHz, CDCl ₃ ) δ: 8.39 (dd, J=7.8, 1.5 Hz, 1H), 7.95 (dd, J=7.6, 1.6 Hz, 1H), 7.85 (t, J=7.6 Hz, 1H) ,7.63(d,J＝6.6Hz,2H),7.53–7.43(m,3H),7.02(d,J＝7.6Hz,1H),6.72(d,J＝7.6Hz,1H),6.67(s, 1H), 4.73(t, J＝7.2Hz, 2H), 4.13(t, J＝5.8Hz, 2H), 2.84(p, J＝6.8Hz, 1H), 2.46(p, J＝6.2Hz, 2H) , 2.14(s, 3H), 1.22(d, J=6.8Hz, 6H). ¹³ C NMR (101MHz, CDCl ₃ )δ: 156.68, 155.65, 147.85, 141.30, 141.07, 136.65, 135.80, 132.14, 130.64, 130.42 ,128.28,124.31,124.12,120.27,118.15,109.39,65.06,47.51,34.13,28.84,24.13,15.72.HRMS(EI)C ₂₆ H ₂₇ N ₃ O ₂ (M), Calculated: 413.2103; Found: 413.2104 .

Example 36: 2-(2-(4-Benzoylpiperazin-1-yl)ethyl)naphthalen-1(2H)-one, Compound I-54.

36.1 Preparation of 2-(2-Bromoethyl)naphthalen-1(2H)-one

Add 1.00 g (6.84 mmol) of 1-(2H)-phthalazinone and 1.79 g (6.84 mmol) of triphenylphosphine to 25 ml of tetrahydrofuran, and add 0.85 g (6.84 mmol) of 2-bromoethanol dropwise to the ice bath, and the dropwise addition is completed. Then, 1.22 g (7.00 mmol) of diethyl azodicarboxylate was added dropwise in the ice bath. After stirring in the ice bath for 1 hour, the reaction was carried out at room temperature until TLC followed the reaction progress. After the reaction was completed, the solvent was evaporated under reduced pressure, and the residue was added with Saturated sodium chloride solution (100 mL), extracted with dichloromethane (80 mL×2), combined the organic phases, dried over anhydrous sodium sulfate, concentrated, and separated by column to obtain 1.01 g of a reddish-brown solid product with a yield of 58%.

36.2 Preparation of 2-(2-(4-benzoylpiperazin-1-yl)ethyl)naphthalen-1(2H)-one

2-(2-Bromoethyl)naphthalene-1(2H)-one 0.89g (3.5mmol), benzoylpiperazine 0.67g (3.5mmol) and N,N-diisopropylethylamine 0.68g (5.25mmol) was added to 25ml of tetrahydrofuran, the temperature was raised to reflux reaction, the reaction progress was followed by TLC, after the reaction was completed, the solvent was evaporated under reduced pressure, saturated sodium chloride solution (100mL) was added to the residue, and the mixture was extracted with dichloromethane ( 80 mL×2), the organic phases were combined, dried over anhydrous sodium sulfate, concentrated, and separated by column to obtain 0.85 g of a white solid product with a yield of 67%. ¹ H NMR (400MHz, DMSO-d ₆ ) δ 8.45 (s, 1H), 8.28 (d, J=7.8Hz, 1H), 7.94 (dd, J=5.9, 3.5Hz, 2H), 7.87 (ddd, J=8.3, 5.6, 2.9Hz, 1H), 7.50–7.34(m, 5H), 5.77(s, 1H), 4.29(t, J=6.7Hz, 2H), 3.60(s, 2H), 3.29(s , 2H), 2.77(t, J=6.7Hz, 2H), 2.47(s, 4H). ¹³ C NMR (101MHz, DMSO-d ₆ )δ168.82,158.35,137.84,135.90,133.39,131.93,129.38,129.26, 128.33, 126.95, 126.82, 126.73, 125.72, 55.47, 52.71, 52.30, 47.31, 47.10, 41.46.HRMS(ES+)C21H23N4O2(M+H) ⁺ Calculated: 363.1821 Measured: 363.1820.

Example 37: 3-(2-(4-Benzoylpiperazin-1-yl)ethyl)quinazoline-2,4(1H,3H)-dione, namely compound I-43.

37.1 Preparation of 2-amino-N-(2-bromoethyl)benzamide

Add 2.54 g (15 mmol) of isatoic anhydride to 30 ml of tetrahydrofuran, stir at room temperature, add 3.10 g (15 mmol) of 2-bromoethylamine hydrobromide and 2.07 g (15 mmol) of potassium carbonate, stir at room temperature for 2 hours, and heat up to Reflux reaction, follow the reaction progress by TLC, after the reaction, evaporate the solvent under reduced pressure, add saturated sodium chloride solution (100 mL) to the residue, extract with dichloromethane (80 mL×2), combine the organic phases, use anhydrous sulfuric acid It was dried over sodium, concentrated, and separated by column to obtain 2.99 g of a white solid product with a yield of 82%. ¹ H NMR (400 MHz, CDCl ₃ ) δ 7.69 (dd, J=7.9, 1.5 Hz, 1H), 7.19 (ddd, J=8.5, 7.2, 1.6 Hz, 1H), 6.73-6.61 (m, 2H), 6.05(s, 2H), 4.35-4.23(m, 2H), 4.08(dd, J=14.2, 5.1Hz, 2H). ¹³ CNMR(101MHz, CDCl ₃ )δ164.85,148.50,131.98,129.64,116.04,115.67, 109.19, 65.76, 54.98.

37.2 Preparation of 3-(2-Bromoethyl)quinazoline-2,4(1H,3H)-dione

1.514g (6.2mmol) of 2-amino-N-(2-bromoethyl)benzamide and 4.28g (31.0mmol) of potassium carbonate were added to 20ml of tetrahydrofuran, and 1.85g of trichloromethyl carbonate was added dropwise at room temperature ( 6.2 mmol) in 10 ml of tetrahydrofuran solution, react at room temperature, follow the reaction progress by TLC, after the reaction is completed, quench with 100 ml of saturated ammonium chloride, extract with ethyl acetate (100 mL × 2), combine the organic phases, wash the organic phase with water, use It was dried over sodium sulfate, concentrated, and separated by column to obtain a white solid product 1.32 with a yield of 79%. ¹ H NMR (400MHz, DMSO-d ₆ ) δ 8.03 (dd, J=7.9, 1.3 Hz, 1H), 7.71 (ddd, J=8.6, 7.2, 1.6 Hz, 1H), 7.43 (dd, J=8.2 , 0.5Hz, 1H), 7.38–7.29 (m, 1H), 4.72 (dd, J=9.4, 7.0Hz, 2H), 4.25 (dd, J=9.8, 6.6Hz, 2H). ¹³ C NMR (101MHz, DMSO-d ₆ )δ160.07,156.07,149.07,134.45,125.93,125.64,124.11,118.27,66.34,42.18.

37.3 Preparation of 3-(2-(4-benzoylpiperazin-1-yl)ethyl)quinazoline-2,4(1H,3H)-dione

3-(2-Bromoethyl)quinazoline-2,4(1H,3H)-dione 0.54g (2mmol), benzoylpiperazine 0.38g (2mmol), potassium carbonate 0.55g (4mmol) and Potassium iodide 0.03g (0.2mmol) was added to 15ml of acetonitrile, the temperature was raised to reflux reaction, the reaction progress was followed by TLC, after the reaction was completed, the solvent was evaporated under reduced pressure, saturated sodium chloride solution (60mL) was added to the residue, and dichloromethane was extracted. (50 mL×2), the organic phases were combined, dried over anhydrous sodium sulfate, concentrated, and separated by column to obtain 0.514 g of a white solid product with a yield of 68%. ¹ H NMR (400 MHz, CDCl ₃ ) δ 10.31-9.37 (m, 1H), 8.12-8.04 (m, 2H), 7.52 (d, J=4.1 Hz, 2H), 7.20-7.04 (m, 5H), 4.44(s, 2H), 4.23–4.15(m, 2H), 3.74(s, 2H), 3.39(s, 2H), 2.64(s, 2H), 1.90(s, 2H). ¹³ C NMR(101MHz, DMSO-d ₆ )δ168.81,162.21,161.12,150.25,139.50,135.89,135.31,129.39,128.34,127.99,126.81,122.81,122.43.HRMS(EI)C ₂₁ H ₂₂ N ₄ O 29 ( _M ) Calculated: 378.16 Measured value: 378.1689.

Example 38: 3-(2-(1-Benzoylpiperidin-4-yl)ethyl)benzo[D][1,2,3]-triazin-4(3H)-one, the compound I-48.

Example 38.1 Preparation of (4-(2-hydroxyethyl)piperidin-1-yl)-phenyl-methanone

1.65 g (10 mmol) of 4-piperidine ethanol hydrochloride was added to 40 ml of acetonitrile, 2.53 g (25 mmol) of triethylamine was added dropwise to the ice bath, and the reaction was performed at room temperature for 10 min. Formyl chloride, after the dropwise addition, reacted at room temperature, followed the reaction progress by TLC, after the reaction, evaporated the solvent under reduced pressure, added saturated sodium chloride solution (60 mL) to the residue, extracted with dichloromethane (100 mL×2), The organic phases were combined, dried over anhydrous sodium sulfate, concentrated, and separated by column to obtain 2.0 g of an oily product with a yield of 86%. ¹ H NMR(400MHz,DMSO-d ₆ )δ7.44-7.42(m,3H),7.37-7.34(m,2H),4.45(s,1H),3.54(s,1H),3.45(t,J =6.5Hz,3H),2.98(s,1H),2.73(s,1H),1.66(tdd,J=14.3,6.9,3.3Hz,3H),1.39(q,J=6.5Hz,2H),1.08 (s,2H).

38.2 Preparation of (4-(2-Chloroethyl)piperidin-1-yl)-phenyl-methanone

(4-(2-hydroxyethyl)piperidin-1-yl)-phenyl-methanone 1.40g (6mmol) was added to 20ml of dichloromethane, and thionyl chloride (20mmol) was added dropwise to the ice bath. After the reaction was performed at room temperature for 10 min, 2.38 (10 mmol) of benzoyl chloride was added dropwise to the ice bath. After the dropwise addition, the reaction was performed at room temperature. The reaction progress was followed by TLC. After the reaction was completed, the solvent was evaporated under reduced pressure, and saturated sodium chloride was added to the residue. The solution (60 mL) was extracted with dichloromethane (100 mL×2), the organic phases were combined, dried over anhydrous sodium sulfate, concentrated, and separated by column to obtain 1.0 g of a white solid with a yield of 67%. ¹ H NMR (400MHz, DMSO-d ₆ )δ7.46-7.40(m,3H),7.39-7.33(m,2H),4.46(s,1H),3.68(t,J=6.6Hz,2H), 3.54(s, 1H), 3.00(s, 1H), 2.75(s, 1H), 1.80–1.66(m, 4H), 1.62(s, 1H), 1.11(s, 2H).

38.3 Preparation of 3-(2-(1-benzoylpiperidin-4-yl)ethyl)benzo[D][1,2,3]-triazin-4(3H)-one

(4-(2-Chloroethyl)piperidin-1-yl)-phenyl-methanone 0.5g (2mmol), benzo[d][1,2,3]triazine-4(3H)- Ketone 0.29g (2mmol) and potassium carbonate 0.414g (3mmol) were added in 20ml of acetonitrile, reacted at 60 degrees Celsius, TLC tracked the reaction progress, after the reaction was completed, the solvent was evaporated under reduced pressure, and a saturated sodium chloride solution was added to the residue ( 60 mL), extracted with dichloromethane (100 mL×2), the organic phases were combined, dried over anhydrous sodium sulfate, concentrated, and separated by column to obtain 0.36 g of white solid with a yield of 50%. ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 8.36 (dd, J=7.9, 0.9 Hz, 1H), 8.16 (d, J=7.9 Hz, 1H), 8.04–7.90 (m, 1H), 7.86– 7.75(m, 1H), 7.44–7.34(m, 5H), 4.71(s, 1H), 4.54(t, J=7.3Hz, 2H), 3.80(s, 1H), 2.88(s, 2H), 1.92 (m, J=14.3, 7.0Hz, 4H), 1.73–1.60 (m, 1H), 1.42–1.13 (m, 2H).

¹³ C NMR (101MHz, CDCl ₃ ) δ 170.33, 155.49, 144.31, 136.25, 134.86, 132.43, 129.51, 128.44, 128.30, 126.84, _125.06 , _119.77 , 47.33, 35.28, 33.65, 32.13 N. HRMS (EI) Calcd for _4O2 (M): _362.1743 , found: 362.1744.

Example 39: 2-(2-Fluorophenyl)-4-(2-(4-oxobenzo[D][1,2,3]triazin-3(4H)-yl)ethyl)- 4H-1,3,4-oxadiazin-5(6H)-one, namely compound I-62.

39.1 Preparation of 2-(2-Fluorophenyl)-4H-1,3,4-oxadiazin-5(6H)-one

Add 3.08 g (20 mmol) of difluorobenzoic hydrazide and 4.14 g (30 mmol) of potassium carbonate to 30 ml of N,N-dimethylformamide, and dropwise add 2.35 g (21 mmol) of chloroacetyl chloride in 10 ml of N at 0-5°C. , N-dimethylformamide solution, the room temperature reaction was completed dropwise, TLC tracked the reaction progress, after the reaction was completed, the temperature was raised to 80 ° C, TLC tracked the reaction progress, after the reaction was completed, the solvent was evaporated under reduced pressure, and added to the residue. Saturated ammonium chloride solution (100 mL), extracted with dichloromethane (100 mL×2), combined organic phases, dried over anhydrous sodium sulfate, concentrated, and separated by column to obtain 1.75 g of white solid product with a yield of 45%. ¹ H NMR (400MHz, DMSO-d ₆ ) δ 10.19 (s, 1H), 8.20 (d, J=2.1 Hz, 1H), 7.68 (d, J=7.9 Hz, 2H), 7.42 (t, J= 7.8Hz, 2H), 7.18 (t, J=7.3Hz, 1H), 5.81 (d, J=2.3Hz, 1H). ¹³ C NMR (101MHz, DMSO-d ₆ )δ162.65, 139.81, 129.31, 128.35, 124.55 ,116.72,94.32.

39.2 Preparation of 4-(2-Bromoethyl)-2-(2-fluorophenyl)-4H-1,3,4-oxadiazin-5(6H)-one

2-(2-Fluorophenyl)-4H-1,3,4-oxadiazin-5(6H)-one 0.97g (5mmol) was added to anhydrous N,N-dimethylformamide, ice bath Add sodium hydrogen 0.22g (greater than 5mmol, content is more than 60%), react in ice bath for 2 hours, add 1,2-dibromoethane 1.50g (8mmol) dropwise in ice bath, complete the dropwise addition, react at room temperature, and then heat up to 80 ℃, TLC followed the progress of the reaction, after the reaction was completed, the solvent was evaporated under reduced pressure, saturated ammonium chloride solution (100 mL) was added to the residue, extracted with dichloromethane (100 mL×2), the organic phases were combined, and anhydrous sodium sulfate After drying, concentration and column separation, 0.72 g of a white solid product was obtained with a yield of 48%. ¹ H NMR (400MHz, DMSO-d ₆ )δ7.82-7.73(m,1H),7.62-7.54(m,1H),7.37-7.27(m,2H),4.90(s,2H),4.08(t , J=6.1Hz, 2H), 3.74(t, J=6.1Hz, 2H).

39.3 Preparation of 2-(2-Fluorophenyl)-4-(2-(4-oxobenzo[D][1,2,3]triazin-3(4H)-yl)ethyl)-4H- 1,3,4-Oxadiazin-5(6H)-one

Benzo[d][1,2,3]triazin-4(3H)-one 0.29 g (2.0 mmol), 4-(2-bromoethyl)-2-(2-fluorophenyl)-4H -1,3,4-oxadiazin-5(6H)-one 0.60g (2.0mmol), potassium carbonate 0.28g (2.0mmol) and potassium iodide 0.03g (0.2mmol) were added to 15ml of acetone, and the temperature was raised to reflux for reaction , TLC tracked the reaction progress, after the reaction was completed, the solvent was evaporated under reduced pressure, saturated sodium chloride solution (60 mL) was added to the residue, extracted with dichloromethane (50 mL×2), the organic phases were combined and dried with anhydrous sodium sulfate , concentrated, and column separation to obtain 0.55 g of white solid product with a yield of 75%. ¹ H NMR (400MHz, DMSO-d ₆ ) δ 8.85 (t, J=5.5Hz, 1H), 8.50 (dd, J=4.6, 1.2Hz, 1H), 8.25 (d, J=7.4Hz, 1H) ,8.23–8.14(m,2H),8.09(dd,J=11.2,4.1Hz,1H),7.93(t,J=7.5Hz,1H),7.62(dd,J=8.1,4.7Hz,1H), 7.16(s, 1H), 4.41(t, J=7.2Hz, 2H), 3.26(q, J=6.6Hz, 2H), 2.03(m, 2H). ¹³ C NMR (101MHz, DMSO-d ₆ )δ156 _{.79,154.71,14.57,147.01,143.65,139.64,139.19,135.30} , _{132.83,127.91,127.85,126.49} , _119.22 , _{109.7.15,36.48.04.04.04.04.04.04.04.04.04.04.04.04.04.04.04.04.04} . M) Calculated: 367.1081 Found: 367.1080.

Example 40: 3-(2-(4-Benzoylpiperazin-1-yl)ethyl)quinazolin-4(3H)-one, compound I-51.

40.1 Preparation of 3-(2-hydroxyethyl)quinazolin-4(3H)-one

2.92g (20mmol) of 4-hydroxyquinazoline, 3.13g (25mmol) of 3-bromopropanol, 3.45g (25mmol) of potassium carbonate were added to 40ml of acetonitrile, and the reaction was carried out at 70°C. The solvent was evaporated under reduced pressure, saturated sodium chloride solution (60 mL) was added to the residue, extracted with dichloromethane (50 mL×2), the organic phases were combined, dried over anhydrous sodium sulfate, concentrated, and separated by column to obtain a white solid product 3.04g, yield 80%. ¹ H NMR (400MHz, DMSO-d ₆ ) δ 8.27 (s, 1H), 8.17 (dd, J=8.0, 1.2Hz, 1H), 7.83 (ddd, J=8.6, 7.2, 1.6Hz, 1H), 7.68 (d, J=7.7Hz, 1H), 7.59–7.51 (m, 1H), 4.96 (t, J=5.6Hz, 1H), 4.05 (dd, J=6.7, 4.0Hz, 2H), 3.73–3.62 (m,2H).

40.2 Preparation of 3-(2-Chloroethyl)quinazolin-4(3H)-one

1.50g (8mmol) of 3-(2-hydroxyethyl)quinazolin-4(3H)-one was added to 30ml of tetrahydrofuran, and 4.76g (40mmol) of thionyl chloride was added dropwise in an ice-salt bath, and the dropwise addition was completed. After the reaction at room temperature, the reaction progress was followed by TLC. After the reaction was completed, the solvent was evaporated under reduced pressure, saturated sodium chloride solution (60 mL) was added to the residue, extracted with dichloromethane (50 mL×2), the organic phases were combined, and anhydrous It was dried over sodium sulfate, concentrated, and separated by column to obtain white solid product 0.79g, yield 47%, ¹ H NMR (400MHz, DMSO-d ₆ )δ8.41(s, 1H), 8.19(dd, J=8.0, 1.2 Hz, 1H), 7.86 (ddd, J=8.4, 7.2, 1.5Hz, 1H), 7.74–7.68 (m, 1H), 7.61–7.54 (m, 1H), 4.36 (t, J=6.0Hz, 2H) ,4.01(t,J=6.0Hz,2H).

40.3 Preparation of 3-(2-(4-benzoylpiperazin-1-yl)ethyl)quinazolin-4(3H)-one

3-(2-Chloroethyl)quinazolin-4(3H)-one 0.42g (2mmol), benzoylpiperazine 0.38g (2mmol), potassium carbonate 0.276g (2mmol) were added to 15ml of acetonitrile, The temperature was raised to reflux reaction, and the reaction progress was followed by TLC. After the reaction was completed, dichloromethane extraction (50 mL×2) was performed, and the organic phases were combined, dried with anhydrous sodium sulfate, concentrated, and separated by column to obtain a white solid product 0.55g, yield 76 %. ¹ H NMR (400 MHz, CDCl ₃ ) δ 7.83 (d, J=8.1 Hz, 1H), 7.72 (dd, J=8.0, 0.4 Hz, 1H), 7.44-7.35 (m, 1H), 7.34-7.24 ( m, 1H), 4.05 (dd, J=7.0, 4.0 Hz, 2H), 3.54–3.45 (m, 2H). HRMS(EI) Calculated for C ₂₁ H ₂₂ N ₄ O ₂ (M): 326.1743 Found: 326.1744.

Example 41: 2-(2-(4-Benzoylpiperazin-1-yl)ethyl)-2H-benzo[e][1,2,4]desen-3(4H)-one 1 , 1-dioxide, namely compound I-119.

1.55 g (4 mmol) of N-(2-(4-benzoylpiperazin-1-yl)ethyl)-2-aminosulfonamide was added to 20 ml of tetrahydrofuran, and 1.19 g (4 mmol) of triphosgene was added dropwise at room temperature. 10ml of tetrahydrofuran solution was added dropwise, the reaction was carried out at room temperature, and the reaction progress was followed by TLC. After the reaction was completed, the solvent was evaporated under reduced pressure, and saturated sodium chloride solution (60mL) was added to the residue, and extracted with dichloromethane (50mL×3). The organic phases were combined, dried over anhydrous sodium sulfate, concentrated, and separated by column to obtain 0.86 g of a white solid product with a yield of 52%. ¹ H NMR (400MHz, DMSO-d ₆ ) δ 11.44 (s, 1H), 7.84 (dd, J=7.9, 1.1 Hz, 1H), 7.75-7.66 (m, 1H), 7.48-7.41 (m, 3H) ), 7.39–7.27(m, 4H), 3.90(t, J=6.7Hz, 2H), 3.54(s, 2H), 3.23(s, 2H), 2.58(t, J=6.8Hz, 2H), 2.42 (d, J=32.9 Hz, _4H ). HRMS (EI) calcd for _C20H22N4O4S (M): _414.1362 Found: _414.1360 .

Example 42: N-(4-oxo-3-propyl-3,4-dihydrobenzo[d][1,2,3]triazin-7-yl)benzamide, i.e. compound I- 137.

42.1 Preparation of 7-nitro-3-propylbenzo[d][1,2,3]triazin-4(3H)-one

In a 100ml bottle, add 1.92g (10mmol) 7-nitrobenzo[d][1,2,3]triazin-4(3H)-one, 1.22g (10mmol) 3-bromopropane, 1.38g (10mmol) ) potassium carbonate, 40ml of acetonitrile, react at 60°C, follow the reaction progress by TLC, after the reaction, remove the solvent under reduced pressure, add saturated sodium chloride solution (60mL) to the residue, extract with dichloromethane (50mL×3), The organic phases were combined, dried over anhydrous sodium sulfate, concentrated, and separated by column to obtain 2.01 g of a white solid product with a yield of 86%.

42.2 Preparation of 7-amino-3-propylbenzo[d][1,2,3]triazin-4(3H)-one

In a 100ml bottle, add 1.17g (5mmol), 40ml of ethanol, 1g of palladium on carbon, pass hydrogen, react at 60°C, follow the reaction progress by TLC, after the reaction, filter off the palladium on carbon, evaporate the solvent under reduced pressure to obtain a pale yellow solid product 0.918g, yield 90%. ¹ HNMR (400MHz, DMSO-d ₆ ) 7.90 (d, J=8.6Hz, 1H), 7.09 (dd, J=8.7, 2.0Hz, 1H), 7.04 (d, J= 1.9Hz, 1H), 6.58(s, 2H), 4.26(t, J=7.1Hz, 2H), 1.80(h, J=7.3Hz, 2H), 0.91(t, J=7.4Hz, 3H).

42.3 Preparation of N-(4-oxo-3-propyl-3,4-dihydrobenzo[d][1,2,3]triazin-7-yl)benzamide

Into a 50ml bottle, add 0.612g (3mmol) 7-aminobenzo[d][1,2,3]triazin-4(3H)-one, 0.55g (5mmol) triethylamine, 30ml acetonitrile, drop in ice bath Add 0.42g (3mmol), after the dropwise addition, be warmed up to 60 DEG C to react, TLC tracks the reaction progress, after the reaction is finished, evaporate the solvent under reduced pressure, add saturated sodium chloride solution (60mL) to the residue, dichloromethane Extraction (50 mL×3), combined organic phases, dried over anhydrous sodium sulfate, concentrated, and column separated to obtain 0.6 g of a white solid product with a yield of 66%. ¹ H NMR (400MHz, DMSO-d ₆ )δ10.92(s,1H),8.71(s,1H),8.25-8.21(m,2H),8.04-8.01(m,2H),7.69-7.64(m ,1H),7.59(t,J＝7.4Hz,2H),4.34(t,J＝7.2Hz,2H),1.84(dt,J＝14.6,7.4Hz,2H),0.94(t,J＝7.4Hz , 3H). HRMS (EI) _calcd for _C17H16N4O2 (M): _308.1273 found: _308.1269 .

Example 43: 3-(2-(8-Chloro-6-(trifluoromethyl)imidazo[1,2-A]pyridine-2-carboxypiperazin-1-yl)ethyl)benzo[D ][1,2,3-triazine]-4(3H) ketone, namely compound I-92.

43.1 Preparation of ethyl 8-chloro-6-(trifluoromethyl)imidazo[1,2-A]pyridine-2-carboxylate

In a 250ml bottle, add 3.92g (20mmol) of 2-amino-3-chloro-5-trifluoromethylpyridine, 3.9g (20mmol) of ethyl 3-bromopyruvate, and 100ml of tetrahydrofuran, warm up to reflux reaction, and follow the reaction by TLC process, after the reaction was completed, the solvent was evaporated under reduced pressure, saturated sodium chloride solution (60 mL) was added to the residue, extracted with dichloromethane (50 mL×3), the organic phases were combined, dried with anhydrous sodium sulfate, concentrated, After separation, 4.4 g of white solid product was obtained, and the yield was 75%. ¹ H NMR (400MHz, DMSO-d ₆ ) δ 9.25(s, 1H), 8.71(s, 1H), 7.93(s, 1H), 4.37(q, J=7.1Hz, 2H), 1.36(t, J=7.1Hz, 3H).

43.2 Preparation of 8-chloro-6-(trifluoromethyl)imidazo[1,2-A]pyridine-2-carboxylic acid

Add 2.93 g (10 mmol) of ethyl 8-chloro-6-(trifluoromethyl)imidazo[1,2-A]pyridine-2-carboxylate to a 100 ml bottle, add 50 ml of ethanol, and add lithium hydroxide monohydrate 0.84g (20mmol) was refluxed for reaction, TLC tracked the reaction process, after the reaction was completed, the pH was adjusted to 3, and a light yellow precipitate was precipitated, which was washed with suction and dried to obtain 2.28g, with a yield of 86%. ¹ H NMR (400 MHz, CDCl ₃ ) δ 8.51 (s, 1H), 8.40 (s, 1H), 7.55 (s, 1H).

43.3 Preparation of 3-(2-(8-Chloro-6-(trifluoromethyl)imidazo[1,2-A]pyridine-2-carboxypiperazin-1-yl)ethyl)benzo[D][ 1,2,3-Triazin]-4(3H)one.

3-(2-(piperazin-1-yl)ethyl)benzo[D]1,2,3-triazin-4(3H)-one 0.518g (2mmol), dichloromethane 10ml, tert-butyl Alcohol 10ml, 8-chloro-6-(trifluoromethyl)imidazo[1,2-A]pyridine-2-carboxylic acid 0.53g (2mmol), 1-ethyl-(3-dimethylaminopropyl) ) carbodiimide hydrochloride 0.93g (6mmol), 4-dimethylaminopyridine 0.73g (7mmol), react at room temperature overnight, TLC tracks the reaction progress, after the reaction finishes, add dilute hydrochloric acid (1N, 100ml), extracted with dichloromethane (50mL×3), the organic phases were combined, dried over anhydrous sodium sulfate, concentrated, and separated by column to obtain 0.35g of white solid product with a yield of 35%. ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 9.25 (s, 1H), 8.71 (s, 1H), 8.27 (dd, J=7.9, 0.9 Hz, 1H), 8.21 (dd, J=8.1, 0.5 Hz, 1H), 8.14–8.06 (m, 1H), 8.01–7.89 (m, 2H), 4.54 (t, J=6.5Hz, 2H), 3.56 (s, 2H), 3.26 (s, 2H), 2.83 (t, J=6.5 Hz, 2H), 2.52 (s, 2H), 2.47 (s, 2H). HRMS (EI) C ₂₂ H ₁₉ ClF ₃ N ₇ O ₂ (M) C ₂₂ H ₁₉ ³⁵ ClF ₃ N Calcd for _7O2 : ^505.1241 _Found : _505.1240 , Calcd for _{C22H1937ClF3N7O2 : 507.1212} Found: _507.1210 .

Example 44: 3-(2-(4-(2-Cyanobenzoyl)piperazin-1-yl)ethyl)benzo[D][1,2,3-triazine]-4(3H ) ketone, namely compound I-90.

44.1 Preparation of 2-cyanobenzoyl chloride

0.29g (2mmol) of 2-cyanobenzoic acid and 20ml of dichloromethane were added to a 50ml bottle, 0.51g (4mmol) of oxalyl chloride was added dropwise, the reaction was carried out at room temperature, and the reaction progress was followed by TLC. used directly in the next reaction.

44.2 Preparation of 3-(2-(4-(2-cyanobenzoyl)piperazin-1-yl)ethyl)benzo[D][1,2,3-triazin]-4(3H)one

3-(2-(Piperazin-1-yl)ethyl)benzo[D]1,2,3-triazin-4(3H)-one 0.518g (2mmol), potassium carbonate (3mmol), added In 15ml of acetonitrile, a solution of 2-cyanobenzoyl chloride (2mmol) in 5ml of acetonitrile was added dropwise at room temperature, and after 2 hours of reaction at room temperature, the temperature was raised to 60°C, and the reaction progress was followed by TLC. After the reaction was completed, the solvent was evaporated under reduced pressure. Saturated sodium chloride solution (60 mL) was added to the residue, extracted with dichloromethane (50 mL×3), the organic phases were combined, dried over anhydrous sodium sulfate, concentrated, and separated by column to obtain 0.59 g of white solid product, yield 76% . ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 8.27 (dd, J=7.9, 1.0 Hz, 1H), 8.21 (d, J=7.7 Hz, 1H), 8.14-8.06 (m, 1H), 7.94 ( ddd, J=4.2, 3.7, 1.2Hz, 2H), 7.78 (td, J=7.7, 1.2Hz, 1H), 7.63 (td, J=7.7, 1.2Hz, 1H), 7.54 (d, J=7.2Hz) ,1H),4.53(t,J＝6.5Hz,2H),3.60(s,2H),3.18-3.06(m,2H),2.83(t,J＝6.5Hz,2H),2.66-2.55(m, 2H), 2.48-2.42 (m, 2H). HRMS (EI) _calcd for _C21H20N6O2 ( _M ): _388.1648 Found: 388.1645.

Example 45: 3-(2-(4-(2-Chloro-5-methoxysulfonyl)piperazin-1-yl)ethyl)benzo[D][1,2,3-triazine] -4(3H) ketone, compound I-91.

3-(2-(Piperazin-1-yl)ethyl)benzo[D]1,2,3-triazin-4(3H)-one 0.518g (2mmol), potassium carbonate (3mmol), added In 15ml of acetonitrile, 5ml of acetonitrile solution of 2-chloro-5-methoxybenzenesulfonyl chloride 0.482g (2mmol) was added dropwise at room temperature, and the reaction was carried out at room temperature for 2 hours. The solvent was evaporated under pressure, saturated sodium chloride solution (60 mL) was added to the residue, extracted with dichloromethane (50 mL×3), the organic phases were combined, dried over anhydrous sodium sulfate, concentrated, and separated by column to obtain a white solid product 0.78 g, the yield is 84%. ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 8.23 (dd, J=7.9, 0.9 Hz, 1H), 8.19 (d, J=7.9 Hz, 1H), 8.14–8.01 (m, 1H), 7.96– 7.89(m, 1H), 7.59(d, J=8.8Hz, 1H), 7.39(d, J=3.1Hz, 1H), 7.25(dd, J=8.8, 3.1Hz, 1H), 4.49(t, J =6.4Hz,2H),3.83(s,3H),3.17–3.03(m,4H),2.80(t,J=6.4Hz,2H),2.55–2.51(m,4H).HRMS(EI)C _{20 H22ClN5O4S ( M )} calcd for _{C20H2235ClN5O4S} : _463.1081 ^Found : _463.1081 , ^{C20H2237ClN5O4S} _calcd : _{465.1052 Found} : _465.1049 .

Example 46: Compound I-141

46.1 Preparation of N-sulfobenzo[d][1,2,3]triazin-4(3H)-one

2.21 g (15 mmol) of benzo[d][1,2,3]triazin-4(3H)-one was added to 20 ml of 1,2-dichloroethane, and 1.74 g ( 15mmol), react at room temperature, TLC tracks the reaction progress, after the reaction is completed, the solvent is evaporated under reduced pressure and used directly in the next step.

46.2 Preparation of N-sulfonyl chloride-benzo[d][1,2,3]triazin-4(3H)-one

N-sulfobenzo[d][1,2,3]triazin-4(3H)-one 3.41g (15mmol) was added to 30ml 1,2-dichloroethane, and chlorination was added dropwise in an ice bath Sulfoxide 3.57 (30 mmol), react at room temperature, follow the reaction progress by TLC, after the reaction is completed, the solvent and excess thionyl chloride are evaporated under reduced pressure, which is directly used in the next reaction.

46.3 Preparation of N-sulfonamidobenzo[d][1,2,3]triazin-4(3H)-one

Ammonia water (ammonia content greater than 40mmol) was added dropwise to the product of the previous step, reacted at room temperature, and the reaction progress was followed by TLC. After the reaction was completed, dichloromethane was extracted (50mL×3), and the organic phases were combined and dried with anhydrous sodium sulfate, Concentration and column separation gave 1.4 g of white solid product. ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 2.2 (s, 2H), 8.23 (dd, J=7.6, 0.8 Hz, 1H), 8.19 (d, J=8.0 Hz, 1H), 8.14-8.05 ( m,1H),7.98–7.87(m,1H).

46.4 Preparation of final product (I-141)

8-Chloro-6-(trifluoromethyl)imidazo[1,2-A]pyridine-2-carboxylic acid 0.53g (2mmol), 1-(3-dimethylaminopropyl)-3-ethyl 0.96g (5mmol) of carbodiimide hydrochloride and 0.61g (5mmol) of 4-dimethylaminopyridine were added to a mixed solvent of 15ml of tert-butanol and 15ml of dichloromethane, stirred at room temperature for 15 minutes, and added with N-sulfonamide Benzo[d][1,2,3]triazin-4(3H)-one 0.45 g (2 mmol), the reaction progress was followed by TLC, after the reaction was completed, 1N hydrochloric acid (200 ml) was added to extract with dichloromethane (60 mL). ×3), the organic phases were combined, dried over anhydrous sodium sulfate, concentrated, and separated by column to obtain 0.33 g of a white solid product with a yield of 35%. ¹ H NMR (400MHz, DMSO-d ₆ ) δ 14.25(s, 1H), 9.25(s, 1H), 8.71(s, 1H), 8.23(dd, J=7.9, 0.9Hz, 1H), 8.19( d, J=8.1Hz, 1H), 8.14–8.05 (m, 1H), 7.98–7.87 (m, 2H).HRMS(EI)C ₁₆ H ₈ ClF ₃ N ₆ O ₄ S(M)C ₁₆ H _{8 Calcd} ^. for ^35ClF3N6O4S _{: 471.9968} , _found for _{C16H837ClF3N6O4S : 471.9972 .} Calculated value: 473.9939 Measured value: 473.9930,

Example 47: 3-(2-(4-Benzoylpiperazin-1-yl)ethyl)-2H-benzo[e][1,3]oxazine-2,4(3H)-dione , namely compound I-105.

47.1 Preparation of N-2-bromoethyloxaquinedione

0.82g (5mmol) of oxaquinedione, 1.51g (8mmol) of 1,2-dibromoethane, 1.10g (8mmol) of potassium carbonate were added to 30ml of acetonitrile, and the reaction was carried out at 60°C. , the solvent was evaporated under reduced pressure, saturated sodium chloride solution (60 mL) was added to the residue, extracted with dichloromethane (50 mL×3), the organic phases were combined, dried over anhydrous sodium sulfate, concentrated, and separated by column to obtain a white solid The product was 0.4 g, and the yield was 75%. ¹ H NMR (400MHz, DMSO-d ₆ ) δ 7.25-7.50 (m, 1H), 7.56-7.80 (m, 1H) 7.81-8.01 (m, 2H), 4.88 (t, J=6.78Hz, 2H) ,3.84(t,J=6.4Hz,2H).

47.2 Preparation of 3-(2-(4-Benzoylpiperazin-1-yl)ethyl)-2H-benzo[e][1,3]oxazine-2,4(3H)-dione

The final product was synthesized according to method 36.2 in Example 36. ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 7.81-8.01 (m, 2H), 7.56-7.80 (m, 1H), 7.48-7.41 (m, 3H), 7.40-7.33 (m, 2H), 7.25 -7.50(m, 1H), 4.54(t, J=6.5Hz, 2H), 3.56(s, 2H), 3.26(s, 2H), 2.83(t, J=6.5Hz, 2H), 2.52(s, 2H), 2.47 (s, 2H). HRMS (EI) calcd for _C21H21N3O4 ( _M ): _379.1532 Found: _379.1536 .

Example 48: 7-Chloro-3-(3-(5-isopropyl-2-methylphenoxy)propyl)benzo[d][1,2,3]triazine-4(3H) - Ketone, ie compound I-146.

Using appropriate starting materials, compound I-146 was prepared using similar procedures as described for compound I-99. ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 8.91 (d, J=2.1 Hz, 1H ),8.59(dd,J＝8.7,2.0Hz,1H),8.47(d,J＝8.7Hz,1H),6.98(d,J＝7.6Hz,1H),6.75(s,1H),6.68(d , J=7.6Hz, 1H), 4.63 (t, J=6.8Hz, 2H), 4.11 (t, J=5.7Hz, 2H), 2.88–2.73 (m, 1H), 2.33 (p, J=6.3Hz) , 2H), 2.00(s, 3H), 1.17(d, J=6.9Hz, 6H). ¹ H NMR(400MHz, DMSO)δ8.91,8.91,8.61,8.60,8.59,8.58,8.48,8.46,6.99 ,6.97,6.75,6.69,6.67,4.65,4.63,4.61,4.13,4.11,4.10,2.86,2.84,2.82,2.80,2.79,2.77,2.75,2.37,2.35,2.33,2.32,2.30,2.00,1.18,1.16 .HRMS (EI) _calcd for _{C20H2235ClN3O2} ( _M ): _371.1401 Found: ^371.1403 , _{C20H2237ClN3O2} ( _M ) _calcd : _373.1371 Found: ^373.1369 .

Example 49: 7-Chloro-3-(3-(5-isopropyl-2-methylphenoxy)propyl)benzo[d][1,2,3]triazine-4(3H) - Ketone, ie compound I-146.

Compound I-146 was prepared using a similar procedure as described for compound I-99 using appropriate starting materials. ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 8.33 (d, J=1.9 Hz, 1H ), 8.23(dd, J＝8.6, 2.1Hz, 1H), 8.12(d, J＝8.6Hz, 1H), 6.97(d, J＝7.6Hz, 1H), 6.73(s, 1H), 6.67(d , J=7.5Hz, 1H), 4.60 (t, J=6.8Hz, 2H), 4.09 (dd, J=11.0, 5.5Hz, 2H), 2.86–2.73 (m, 1H), 2.42–2.22 (m, 2H), 1.98(s, 3H), 1.17(d, J=7.0Hz, 6H). ¹ H NMR (400MHz, DMSO) δ8.33, 8.32, 8.24, 8.24, 8.22, 8.21, 8.13, 8.11, 6.98, HRMS( EI) _calcd for _{C20H2279BrN3O2} ( _M ): _415.0895 found: ^415.0898 , _{C20H2281BrN3O2} ( _M ) _calcd : _417.0875 found: ^417.0877 .

Example 50: 5-Chloro-3-(2-(4-(2-nitrobenzyl)piperazin-1-yl)ethyl)benzo[d][1,2,3]-triazine- 4(3H)-ketone, compound I-160.

Compound I-160 was prepared using appropriate starting materials using similar procedures as described for compound I-3. ¹ H NMR (400 MHz, CDCl ₃ ) δ 8.19 (d, J=8.3 Hz, 1H), 8.06(dd,J=7.9,1.2Hz,1H),7.83(t,J=7.9Hz,1H),7.77(dd,J=7.9,1.1Hz,1H),7.73–7.67(m,1H),7.61 –7.53(m,1H),7.37(dd,J=7.6,1.1Hz,1H),4.58(t,J=6.4Hz,2H),3.84(s,1H),3.73(s,1H),3.17( t, J=4.9Hz, 2H), 2.94(t, J=6.4Hz, 2H), 2.75(s, 1H), 2.67(s, 1H), 2.52(s, 2H). ¹³ C NMR (101MHz, CDCl) ₃ ) Δ166.32,153.63,146.00,145.34,134.58,134.44,1342,1325,132.88,129.8.10, _{127.62,17.15.70} , _{52.25,46.82,41.81.81.81.81.81.81.82,41.81,5.81,5.81,5.81,5.81,5.81,5.81,5.81,5.81,5.81,5.81,5.81,5.81,5.81,5.81,5.81,5.81,5.81,5.81,5.81.81.82,41.82,41.82,41.82,41.82,41.82,41.82,41.82} . Calcd for ^35ClN6O4 (M): _442.1156 Found: ^442.1157 , Calcd for _{C20H1937ClN6O4 ( M} ): _444.1127 Found: _444.1129 .

Example 51: Example Compound I-189

Compound I-189 was prepared using a similar procedure as described for compound I-115 using appropriate starting materials. ¹ H NMR (400 MHz, DMSO) δ 8.37 (d, J=7.7 Hz, 1H), 8.22 (d, J=7.8Hz, 1H), 7.81-7.94 (m, 2H), 7.78 (td, J=7.7, 1.2Hz, 1H), 7.63 (td, J=7.7, 1.2Hz, 1H), 7.54 ( d, J=7.2Hz, 1H), 4.76 (t, J=6.9Hz, 2H), 3.44 (t, J=6.9Hz, 2H). HRMS(EI) C ₁₈ H ₁₁ BrN ₆ O ₂ (M) calculation Value: 422.0127 Found: 422.0128.

Example 52: 8-Methoxy-3-(2-(4-(2-nitrobenzyl)piperazin-1-yl)ethyl)benzo[d][1,2,3]-tris Azin-4(3H)-one, compound I-190.

Compound I-190 was prepared using appropriate starting materials using similar procedures as described for compound I-3. ¹ H NMR (400 MHz, CDCl ₃ ) δ 8.18 (d, J=8.1 Hz, 1H), 7.91–7.85 (m, 1H), 7.74 (t, J=8.1Hz, 1H), 7.72–7.66 (m, 1H), 7.61–7.53 (m, 1H), 7.36 (dd, J=5.0, 3.8Hz, 2H), 4.62(t, J=6.2Hz, 2H), 4.11(s, 3H), 3.82(s, 1H), 3.71(s, 1H), 3.15(s, 2H), 2.95(t, J=6.0 Hz, 2H), 2.73(s, 1H), 2.67(s, 1H), 2.52(s, 2H). ¹³ C NMR(101MHz, CDCl ₃ )δ166.28,155.65,155.52,145.32,134.85,134.44,133.37,132.87 ,129.80,128.09,124.79,120.97,115.94,115.08,56.62,55.83,52.33,52.22,46.79,46.41.HRMS(EI)C ₂₁ H ₂₂ N ₆ O ₅ (M) Calculated: 438.1652 Measured: 438.1654.

Example 53: Namely Compound I-194.

Using appropriate starting materials, compound I-194 was prepared using procedures similar to those described for compounds I-3 and I-54. ¹ H NMR (400 MHz, DMSO-d ₆ ) δ 8.45 (s, 1H) ,8.28(d,J＝7.8Hz,1H),7.94-7.86(m,3H)7.78(td,J＝7.7,1.2Hz,1H),7.63(td,J＝7.7,1.2Hz,1H),7.54 (d, J=7.2Hz, 1H), 5.77(s, 1H), 4.29(t, J=6.7Hz, 2H), 3.60(s, 2H), 3.29(s, 2H), 2.77(t, J =6.7Hz, 2H), 2.47(s, 4H).HRMS(EI) Calculated for C ₂₂ H ₂₁ N ₅ O ₂ (M): 387.1695 Found: 387.1699.

The remaining individual compounds can be prepared by methods similar to the above examples, using suitable starting materials.

Example 54: Nematicidal Activity Test of Compounds of the Invention

Root-knot nematodes belong to the phylum Nematoda, Tylenchida, Tylenchida, Heteroderidea, Meloidogyninae, and the genus Meloidogyninae. of plant parasitic nematodes.

Taking Meloidogyne incognita as the test object and cucumber seedlings as the test host, the test was carried out by in vitro planting method.

Operation process: prepare the test sample into a liquid medicine according to the required concentration, and prepare a sufficient amount of the second instar larvae of root knot nematodes. After planting one-week-old cucumber seedlings into test tubes, add an appropriate amount of the prepared medicinal liquid to the test tubes, and put about 2,000 larvae into each test tube. The test tube was placed at 20-25°C and cultivated under the light for 10 hours. After 45 days, the results were investigated and the number of root knots on the root system of each plant was counted. Each sample was replicated 3 times, and each sample was subjected to 4 replicates in each experiment.

Distilled water was used as blank control, distilled water plus root knot nematode was used as negative control, and fenamiphos and abamectin solution were used as positive control.

For the calculation of disease index classification, please refer to Table 1.

Table 1

Table 2 Nematicidal activity of compounds of formula (I)

其中A为V₁-(Q)_Z-V₂

where A is V ₁ -(Q) _Z -V ₂

It can be seen from the above table that the compounds of the present invention have very good nematicidal activity, and can show obvious nematicidal effect at a concentration as low as 40 ppm.

All documents mentioned herein are incorporated by reference in this application as if each document were individually incorporated by reference. In addition, it should be understood that after reading the above teaching content of the present invention, those skilled in the art can make various changes or modifications to the present invention, and these equivalent forms also fall within the scope defined by the appended claims of the present application.

Claims (7)

1. A compound having the structure shown in general formula (I) or a pesticide acceptable salt:

Wherein, the compound of general formula (I) has the following structure

In the formula, Structural units

has a structure selected from the group consisting of:

wherein, G is each independent substituent at any one or more positions of ring α, and G is selected from the group consisting of halogen, cyano, nitro, substituted or unsubstituted C _1-6 alkoxy, substituted or Unsubstituted C _1-6 alkyl, NR'R", C(O)OR', C(O)NR'R", OC(O)R'; or structural unit

for

wherein, G is a substituent at any one or more positions of ring α, and G is selected from the group consisting of halogen, cyano, nitro, substituted C _1-6 alkoxy, substituted or unsubstituted C _1-6 alkyl, NR'R", C(O)OR', C(O)NR'R", OC(O)R'; or structural unit

for

Wherein, Y is C(O); X ₂ is N(Rb); X ₃ is N(Rb); X ₁ is independently C(Ra)(Rb) or N(Rb); Ra is selected from the group consisting of H, halogen, cyano, nitro, substituted or unsubstituted C _1-6 alkoxy, substituted or unsubstituted C _1-6 alkyl; Rb is none; m is 2, 3, 4, 5, 6; each L is independently -CH ₂ -; A is

in, Q is -CH ₂ -, -COO-, -CONR'-, -CO-, -S(O) ₂ -; V ₂ is a group selected from the group consisting of substituted or unsubstituted phenyl, substituted or unsubstituted naphthyl, substituted or unsubstituted five- or six-membered ring, or substituted or unsubstituted benzo[d] [1,2,3]thiadiazole; wherein, the five- or six-membered ring contains one or more heteroatoms selected from nitrogen, oxygen or sulfur; The substitution refers to substitution by one or more groups selected from the group consisting of halogen, cyano, nitro, C _1-6 alkyl, C _1-6 alkoxy, C _1-6 haloalkyl; Wherein, R' and R" are each independently H, C _1-6 alkyl. 2. The compound of claim 1 or a pesticide acceptable salt, wherein V ₂ is a group selected from the group consisting of substituted or unsubstituted phenyl, substituted or unsubstituted pyridyl, Substituted or unsubstituted thienyl, substituted or unsubstituted thiazolyl, substituted or unsubstituted benzo[d][1,2,3]thiadiazole; said substitution refers to one or more selected from the group consisting of Substituted by one group: halogen, cyano, nitro, C _1-6 alkyl, C _1-6 alkoxy, C _1-6 haloalkyl. 3. The compound of claim 1 or a pesticide acceptable salt, wherein Q is -CO-; V ₂ is a group selected from the group consisting of substituted or unsubstituted phenyl, substituted or unsubstituted pyridyl, substituted or unsubstituted thienyl, substituted or unsubstituted thiazolyl, substituted or unsubstituted benzo [d][1,2,3]thiadiazole; The substitution refers to substitution by one or more groups selected from the group consisting of halogen, cyano, nitro, C _1-6 alkyl, C _1-6 alkoxy, C _1-6 haloalkyl. 4. A compound or a pesticide acceptable salt, wherein the compound is selected from the group consisting of:

Wherein A is V ₁ -(Q) _Z -V ₂ ;

5. An agricultural composition, characterized in that it comprises: 0.001-99.99 wt % of the compound or agrochemically acceptable salt of any one of claims 1-4, or a combination thereof; and a pesticide Scientifically acceptable carriers and/or excipients. 6. Use of the compound or agrochemically acceptable salt of claim 1 or the agricultural composition of claim 5 for the preparation of a nematicidal composition. 7. a compound as claimed in claim 1 or the preparation method of pesticide acceptable salt is characterized in that,

in an inert solvent, with

and

reaction to obtain the compound of formula I; Wherein, LG is a leaving group, and the definitions of other groups are as described in claim 1.