Pyridine compound, preparation method therefor, composition thereof and use thereof

Abstract

The present invention relates to the field of pesticides and insecticides, particularly to a compound of formula (I), comprising all geometric isomers and stereoisomers, N-oxides, and salts thereof, wherein R1, R2, R3, J and Z are as defined herein. The present invention further relates to a composition containing the compound of formula (I), and a method for controlling invertebrate pests, which method comprises bringing the invertebrate pests or the environment thereof into contact with a biologically effective amount of the compound or composition of the present invention.

Description

A pyridine compound, its preparation method, composition and application Technical Field

[0001] This invention relates to the field of insecticides, and more specifically to a compound of formula (I), its stereoisomer, its N-oxide, its agriculturally acceptable salt, its preparation method, an insecticidal composition and its use in controlling pests. Background Technology

[0002] CN114853748A discloses a class of trifluoromethane isoxazoline derivatives as shown in the figure below, along with their preparation methods and applications in the preparation of insecticides:

[0003] The specification specifically discloses compounds 4 and 9 (hereinafter referred to as CK-4 and CK-9, respectively).

[0004] CN117800929A discloses a class of isoxazoline-substituted benzamide compounds as shown in the figure below, and their applications:

[0005] Compounds 154 to 177 are specifically disclosed in Table 1 of the specification, for example:

[0006] WO2007026965A1 discloses compounds of general formula [1]-43 in Table 2 of the specification and discloses a series of isoxazoline-substituted benzamide compounds in the table.

[0007] WO2011067272A1 discloses compounds H4 and H17 (hereinafter referred to as CK-H4 and CK-H17, respectively) in Table H of the specification.

[0008] WO2013050302A1 discloses compounds B1 and B2 in Table C of the specification.

[0009] WO2022256284A1 discloses a class of pyridines and cyclohexanes for controlling invertebrate pests, as shown in the figure below:

[0010] A series of compounds are specifically disclosed in Tables 129 to 136 of the specification, for example:

[0011] These known compounds in the prior art exhibit narrow applicability or lack satisfactory insecticidal or acaricidal activity. In particular, their insecticidal or acaricidal activity at low application rates and / or their safety to non-target organisms still require improvement. Summary of the Invention

[0012] Therefore, the object of the present invention is to provide a compound that has strong insecticidal activity, particularly at low application rates, sufficiently low toxicity to humans and non-target organisms, and / or high compatibility with crops, and also exhibits a broad activity spectrum against a wide range of harmful organisms.

[0013] The compounds of formula (I), their stereoisomers, and their agriculturally acceptable salts provided by this invention offer advantages over the prior art, examples of which include better biological or environmental properties, wider application methods, better insecticidal or acaricidal effects, and good compatibility with beneficial plants. The compounds of formula (I), their stereoisomers, and their agriculturally acceptable salts can be used in combination with other compositions to improve efficacy, particularly against resistant insects.

[0014] In all formulas specified herein, unless otherwise defined, substituents and symbols have the same meaning as described in formula (I). Wavy lines around chemical groups indicate sites attached to the remainder of the molecule.

[0015] The "-" at the beginning of a fragment definition indicates the attachment point between the fragment and the rest of the molecule: for example, "-CH(CH3)2" indicates the isopropyl segment.

[0016] Cyclic segments are represented by two "-": for example, the cyclopropyl segment is represented by "-CH2CH2-".

[0017] This invention provides a compound of formula (I), its N-oxide, stereoisomer, and agriculturally acceptable salt thereof:

[0018] in,

[0019] R 1、 R3 is selected from chlorine or C1-C4 haloalkyl; R2 is selected from hydrogen, halogen, -CN, -NO2, C1-C4 alkyl, C1-C4 haloalkyl, C 1- When R2 is selected from hydrogen, R4 alkoxy or C1-C4 haloalkoxy; 1、 R3 is not simultaneously chlorine;

[0020] When J is selected from -CR4R5C(=Z1)NHR6, -C(R7)=NOR6, -Q1 or -CH2Q1, R4 and R5 are each independently selected from hydrogen or C1-C3 alkyl; or R4 and R5 together with the carbon atoms to which they are attached form a 3- to 6-membered carbon ring.

[0021] Or, when J is selected from -CR4R5C(=Z1)OR6, R4 and R5, together with the carbon atoms attached to them, form 3- to 6-membered carbon rings; or, when J is selected from -CR4R5C(=Z1)OR6, and R... 1、 When R3 is chlorine and R2 is F; R4 and R5 are each independently selected from hydrogen or C1-C3 alkyl groups;

[0022] Each Z or Z1 is independently selected from O or S;

[0023] Q1 is a 4- to 11-membered saturated or unsaturated ring or ring system, each optionally containing up to three heteroatoms selected from up to one O, up to one S and up to three N, wherein up to two carbon ring members are independently selected from C(=O) and C(=S) and the S ring member is selected from S, S(=O) and S(=O)2, and each ring or ring system is optionally substituted by one or more substituents independently selected from R8;

[0024] R6 is hydrogen, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, C1-C3 alkyl C3-C6 cycloalkyl, C3-C6 cycloalkyl C1-C3 alkyl, C1-C6 haloalkyl, C3-C6 halocycloalkyl, C1-C3 haloalkyl C3-C6 cycloalkyl, C3-C6 halocycloalkyl C1-C3 alkyl, C3-C6 cycloalkyl-cyano or -N=C(C1-C3 alkyl)2;

[0025] R7 is hydrogen or a C1-C3 alkyl group;

[0026] Each R8 is independently selected from halogens, C1-C6 alkyl groups, and C1-C6 haloalkyl groups.

[0027] Preferably,

[0028] This invention provides a compound of formula (I), its N-oxide, stereoisomer, and agriculturally acceptable salt thereof:

[0029] in:

[0030] R 1、 R3 is selected from chlorine or CF3, and R2 is selected from hydrogen, halogen, or C1-C3 haloalkyl; and when R2 is selected from hydrogen, R 1、 R3 is not simultaneously chlorine;

[0031] When J is selected from -CR4R5C(=Z1)NHR6, -C(R7)=NOR6, -Q1 or -CH2Q1, R4 and R5 are each independently hydrogen or C1-C2 alkyl; or R4 and R5 together with the carbon atoms to which they are attached form a 3-membered carbon ring.

[0032] When J is selected from -CR4R5C(=Z1)OR6, R4 and R5 together with the carbon atoms attached to them form a 3-membered carbon ring;

[0033] Q1 is a 6-membered aromatic ring or a 5-membered saturated or unsaturated ring or ring system, each optionally containing up to three heteroatoms selected from up to one O, up to one S and up to three N, wherein up to two carbon atom ring members are independently selected from C(=O) and C(=S) and the S atom ring member is selected from S, S(=O) and S(=O)2, and each ring or ring system is optionally substituted by one or more substituents independently selected from R8;

[0034] R6 is hydrogen, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, C1-C3 alkyl C3-C6 cycloalkyl, C3-C6 cycloalkyl C1-C3 alkyl, C1-C6 haloalkyl, C3-C6 halocycloalkyl, C1-C3 haloalkyl C3-C6 cycloalkyl, C3-C6 halocycloalkyl C1-C3 alkyl, C3-C6 cycloalkyl-cyano or -N=C(C1-C3 alkyl)2;

[0035] R7 is hydrogen or a C1-C3 alkyl group;

[0036] Each R8 is independently selected from halogens, C1-C3 alkyl groups, and C1-C3 haloalkyl groups.

[0037] More preferably,

[0038] This invention provides a compound of formula (I), its N-oxide, stereoisomer, and agriculturally acceptable salt thereof:

[0039] in:

[0040] Q1 is a pyridine ring or a 5-membered saturated or unsaturated ring or ring system, each optionally containing up to three heteroatoms selected from up to one O, up to one S and up to one N, wherein up to two carbon ring members are independently selected from C (=O), and each ring or ring system is optionally substituted by one or more substituents independently selected from R8.

[0041] Each R8 is independently selected from halogens, C1-C3 alkyl groups, and C1-C3 haloalkyl groups.

[0042] More preferably,

[0043] This invention provides a compound of formula (I), its N-oxide, stereoisomer, and agriculturally acceptable salt thereof:

[0044] in,

[0045] R 1、 R3 is selected from chlorine or CF3, and R2 is selected from hydrogen, F, Cl, or Br; and when R2 is selected from hydrogen, R 1、 R3 is not simultaneously chlorine;

[0046] When J is selected from -CR4R5C(=Z1)NHR6, -C(R7)=NOR6, -Q1 or -CH2Q1, R4 and R5 are each independently hydrogen, -CH3 or -CH2CH3; or R4 and R5 together with the carbon atoms to which they are attached form a 3-membered carbon ring.

[0047] When J is selected from -CR4R5C(=Z1)OR6, R4 and R5 together with the carbon atoms attached to them form a 3-membered carbon ring;

[0048] Q1 is selected from

[0049] R6 is selected from hydrogen, -CH3, -CH2CH3, -CH2CH2CH3, -CH(CH3)2, -CH2CH2CH2CH3, -CH(CH3)CH2CH3, -CH2CH(CH3)2, -C(CH3)3, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cyclopropylmethyl, -CH2CF3, -CF2CF3, -CH2CH2Cl, -CH2CFH2, -CH2CF2H, -CH2CH2CF3, -CH2CF2CF3, -CF2CF2CF3, -CH2CH2CF2H, -CH2C H2CFH2, -CF2CFHCF3, -CH(CH3)CF3, (R)-CH(CH3)CF3, (S)-CH(CH3)CF3, -CH2CF2CH3, -CH2CF2CF2CF3, -CH2CH=CH2, -CH(CH3 )CH=CH2, (E)-CH2CH=CHCH3, (Z)-CH2CH=CHCH3, -CH2CH=C(CH3)2, -CH2C≡CH, -CH2C(CH3)=CH2, -C=CH2CH2CH3, -N=C(CH3)2,

[0050] R7 is selected from hydrogen or -CH3;

[0051] Each R8 is independently selected from -CH3, -CH2CH3, -CH2CF3, -CH2CF2H, -CH2CFH2.

[0052] More preferably,

[0053] This invention provides a compound of formula (I), its N-oxide, stereoisomer, and agriculturally acceptable salt thereof:

[0054] in,

[0055] R1 is chlorine, R2 is selected from fluorine, hydrogen, or chlorine, and R3 is selected from chlorine or trifluoromethyl; and when R2 is selected from hydrogen, R 1、 R3 is not simultaneously chlorine;

[0056] When J is selected from -CR4R5C(=Z1)NHR6, -C(R7)=NOR6, -Q1 or -CH2Q1, R4 and R5 are each independently hydrogen, -CH3 or -CH2CH3; or R4 and R5 together with the carbon atoms to which they are attached form a 3-membered carbon ring.

[0057] When J is selected from -CR4R5C(=Z1)OR6, R4 and R5 together with the carbon atoms attached to them form a 3-membered carbon ring;

[0058] Q1 is selected from

[0059] R6 is selected from hydrogen, -CH3, -CH2CH3, -CH2CH2CH3, -CH(CH3)2, cyclopropyl, cyclopropylmethyl, -CH2CF3, -CF2CF3, -CH2CH2Cl, -CH2CFH2, -CH2CF2H, -CH2CH2CF3, -CH2CF2CF3, -CF2CF2CF3, -CH2CH2CF2H, -CH2CH2CFH2, -CF2CFHCF3, -CH(CH3)CF3, (R)-CH(CH3)CF3, (S)-CH(CH3)CF3, -CH2CF2CH3, -CH2CF2CF2CF3, -CH2CH=CH2, -CH2C≡CH, -N=C(CH3)2.

[0060] R7 is hydrogen;

[0061] Each R8 is independently selected from -CH2CH3, -CH2CF3, -CH2CF2H, and -CH2CFH2.

[0062] More preferably,

[0063] This invention provides a compound of formula (I), its N-oxide, stereoisomer, and agriculturally acceptable salt thereof:

[0064] in,

[0065] R1 and R3 are chlorine, and R2 is fluorine;

[0066] Or R1 and R3 are selected from chlorine or trifluoromethyl, and R1 and R3 are not the same, and R2 is selected from chlorine, hydrogen or fluorine;

[0067] J is selected from -CR4R5C(=O)OR6, -CR4R5C(=O)NHR6, -CH=NOR6 or Q1;

[0068] When J is selected from -CR4R5C(=O)NHR6, -CH=NOR6 or Q1, R4 and R5 are each independently hydrogen, -CH3 or -CH2CH3; or R4 and R5 together with the carbon atoms attached to them form a 3-membered carbon ring.

[0069] When J is selected from -CR4R5C(=Z1)OR6, R4 and R5 together with the carbon atoms attached to them form a 3-membered carbon ring;

[0070] Q1 is

[0071] R6 is hydrogen, -CH3, -CH2CH3, -CH2CH2CH3, -CH(CH3)2, cyclopropyl, cyclopropylmethyl, -CH2CF3, -CF2CF3, -CH2CFH2, -CH2CF2H, -CH2CH2CF3, -CH2CF2CF3, -CF2CF2CF3, -CH2CH2CF2H, -CH2CH2CFH2, -CF2CFHCF3, -CH(CH3)CF3, (R)-CH(CH3)CF3, (S)-CH(CH3)CF3, -CH2CF2CH3, -CH2CF2CF2CF3, -CH2CH=CH2, -CH2C≡CH, -N=C(CH3)2.

[0072] The inventors were surprised to find that when the general formula compound was selected from the S configuration, its activity was significantly improved compared to the R configuration.

[0073] Specifically, when the general formula compound is selected from the S configuration, the general formula is as shown in I':

[0074] The definitions of each substituent in the aforementioned general formula I also apply to I'.

[0075] The compounds of formula (I) of the present invention can be described by the specific compounds listed in the table below, but the present invention is not limited to these compounds.

[0076] J = -CR4R5C(=Z1)OR6, Z, Z1 = 0, Table 1 shows the corresponding general formula.

[0077] Table 1

[0078] J = -CR4R5C(=Z1)NHR6, Z, Z1 = 0, corresponding to the general formula in Table 2.

[0079] Table 2

[0080] J = -CR4R5C(=Z1)NHR6, Z = O, Z1 = S, the general formula corresponding to Table 3.

[0081] Table 3

[0082] J = -C(R7) = NOR6, Z = 0, Table 4 corresponds to the general formula

[0083] Table 4

[0084] J = Q1, Z = O (corresponding general formula in Table 5)

[0085] Table 5

[0086] The compound of formula (I) of the present invention may exist in the form of one or more stereoisomers. Stereoisomers are isomers with the same composition but different atomic spatial arrangements, including enantiomers, diastereomers, cis-trans isomers (also called geometric isomers), and trans-isomers. Trans-isomers arise from restricted rotation around a single bond, where the rotational energy barrier is high enough to allow the separation of isomeric substances. Those skilled in the art will understand that when a stereoisomer is enriched relative to other stereoisomers, or when it is separated from other stereoisomers, it may be more active and / or may exhibit beneficial effects. Furthermore, those skilled in the art know how to separate, enrich, and / or selectively prepare said stereoisomers.

[0087] "Stereoisomer" or "stereoisomeric form" refers to a stereoisomer of a compound that is substantially free of other stereoisomers of the compound. For example, a stereoisomerically pure compound having one chiral center will substantially be free of its opposite enantiomers. A stereoisomerically pure compound having two chiral centers will substantially be free of its other diastereomers. A typical stereoisomerically pure compound contains more than about 60% by weight of one stereoisomer and less than about 40% by weight of other stereoisomers of the compound, more than about 80% by weight of one stereoisomer and less than about 20% by weight of other stereoisomers of the compound, more than about 90% by weight of one stereoisomer and less than about 10% by weight of other stereoisomers of the compound, more than about 95% by weight of one stereoisomer and less than about 5% by weight of other stereoisomers of the compound, or more than about 97% by weight of one stereoisomer and less than about 3% by weight of other stereoisomers of the compound. The compounds may have a chiral center and may exist as racemic, enantiomers alone, or diastereomers and mixtures thereof. All such isomeric forms (including mixtures thereof) are included in the examples disclosed herein. The use of the stereoisomeric pure forms of such compounds and the use of mixtures of those forms are included in the examples disclosed herein. For example, mixtures comprising equal or unequal amounts of enantiomers of a particular compound may be used in the methods and compositions disclosed herein. These isomers may be asymmetrically synthesized or resolved using standard techniques such as chiral columns or chiral resolving agents.

[0088] The compounds of formula (I) of the present invention generally exist in more than one form, and therefore all crystalline and amorphous forms of the compounds of formula (I). Amorphous forms include embodiments as solids, such as waxes and gums, and embodiments as liquids, such as solutions and melts. Crystalline forms include embodiments that substantially represent a single crystal type and embodiments that represent mixtures of polymorphs (i.e., different crystal types). The term "polymorph" refers to a specific crystalline form of a compound that can crystallize in different crystalline forms, having different arrangements and / or conformations of molecules in the crystal lattice. Although polymorphs may have the same chemical composition, their compositions may also differ due to the presence or absence of co-crystallization water or other molecules that can be weakly or strongly bound in the crystal lattice. The chemical, physical, and biological properties of polymorphs may differ, such as crystal shape, density, hardness, color, chemical stability, melting point, hygroscopicity, suspension, dissolution rate, and bioavailability. Those skilled in the art will understand that, relative to another polymorph or mixture of polymorphs of the same compound represented by formula (I), a polymorph of the compound represented by formula (I) may exhibit beneficial effects (e.g., suitability for preparing useful formulations, improved biological properties). The preparation and isolation of specific polymorphs of the compound represented by formula (I) can be achieved by methods known to those skilled in the art, including, for example, crystallization using selected solvents and temperatures. The compounds of the present invention can exist as one or more crystalline polymorphs. The present invention includes individual polymorphs and mixtures of polymorphs, including mixtures enriched in one polymorph relative to other polymorphs.

[0089] The present invention also provides a method for preparing the compound of formula (I) described above, its N-oxide, its stereoisomers, and its agriculturally acceptable salts.

[0090] J-NH2 reacts with a compound of formula (II) in an organic solvent in the presence of a base, in the presence of a dehydrating coupling agent, to prepare a compound of formula (I), wherein the organic solvent is selected from pentane, n-hexane, cyclohexane, heptane, octane, dichloromethane, 1,2-dichloroethane, chloroform, carbon tetrachloride, petroleum ether, diethyl ether, methyl tert-butyl ether, ethylene glycol dimethyl ether, tetrahydrofuran, 2-methyltetrahydrofuran, 1,4-dioxane, ethyl acetate, butyl acetate, benzene, toluene, o-xylene, m-xylene, p-xylene, xylene, chlorobenzene, acetone, butanone, 4-methyl-2-pentanone, cyclohexanone, N-methylpyrrolidone, acetonitrile, N,N-dimethyl... At least one of formamide, N,N-dimethylacetamide, or dimethyl sulfoxide; the base is selected from at least one of 4-dimethylaminopyridine (DMAP), trimethylamine, triethylamine, diisopropylethylamine, pyridine, 2-methylpyridine, 3-methylpyridine, 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU), or 2,6-dimethylpyridine; the dehydrating coupling agent is selected from propylphosphonic anhydride, butylphosphonic anhydride, dicyclohexylcarbodiimide, N-(3-dimethylaminopropyl)-N'ethylcarbodiimide, N,N'-carbonyldiimidazole, 2-chloro-1,3-dimethylimidazolium chloride, or 2-chloro-1-methylpyridinium iodide. Polymer-supported agents, such as polymer-supported cyclohexylcarbodiimide, are also suitable. These reactions are typically carried out at temperatures ranging from 0°C to 60°C; for coupling conditions using butylphosphonic anhydride, see Organic Process Research & Development, 2009, 13, 900-906; R1, R2, R3 and J are as defined above.

[0091] This invention also provides another method for preparing the compound of formula (I) described above, its N-oxide, its stereoisomers, and its agriculturally acceptable salts.

[0092] J-NH2 reacts with a compound of formula (II-A) in an organic solvent in the presence of a base to prepare a compound of formula (I), wherein the organic solvent is selected from pentane, n-hexane, cyclohexane, heptane, octane, dichloromethane, 1,2-dichloroethane, chloroform, carbon tetrachloride, petroleum ether, diethyl ether, methyl tert-butyl ether, ethylene glycol dimethyl ether, tetrahydrofuran, 2-methyltetrahydrofuran, 1,4-dioxane, ethyl acetate, butyl acetate, benzene, toluene, o-xylene, m-xylene, p-xylene, xylene, chlorobenzene, acetone, butane, etc. The base is selected from at least one of the following: ketone, 4-methyl-2-pentanone, cyclohexanone, N-methylpyrrolidone, acetonitrile, N,N-dimethylformamide, N,N-dimethylacetamide, or dimethyl sulfoxide; the base is selected from at least one of 4-dimethylaminopyridine (DMAP), trimethylamine, triethylamine, diisopropylethylamine, pyridine, 2-methylpyridine, 3-methylpyridine, 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU), or 2,6-dimethylpyridine; R1, R2, R3, and J are as defined above.

[0093] Specifically, the compounds of formula (II-A) of the present invention can be prepared by the various methods listed below:

[0094] Option 1:

[0095] As shown in Scheme 1, acyl chlorides having formula (II-A) can be readily prepared from carboxylic acids having formula (II) by many well-known methods. For example, reacting the carboxylic acid in a solvent such as dichloromethane or toluene, and optionally in the presence of a catalytic amount of N,N-dimethylformamide, with a chlorinating agent (such as thionyl chloride, oxalyl chloride, or phosphorus oxychloride) can provide the corresponding acyl chloride having formula (II-A).

[0096] Option 2:

[0097] As shown in Scheme 2, carboxylic acids having formula (II) can be prepared, preferably in a slightly excess of a base hydroxide (e.g., lithium hydroxide), at a temperature between about 0°C and 45°C, by a well-known method of basic or acidic hydrolysis of the corresponding compound having formula (III), in an aqueous cosolvent such as methanol, ethanol, or tetrahydrofuran. The product can be separated by acidification, followed by filtration or extraction (optionally after removal of the organic solvent by evaporation). Ak represents a lower alkane, such as methyl or ethyl.

[0098] Option 3:

[0099] As outlined in Scheme 3, esters having formula (III) can also be prepared from ketones having formula (V) via a two-step procedure. In the first step, the ketone having formula (V) is condensed with a trifluoromethyl ketone having formula (VI) to provide a compound having formula (IV). This reaction is typically carried out in the presence of a base such as calcium hydroxide, potassium carbonate, or cesium carbonate, in a solvent or mixture of solvents such as toluene, N,N-dimethylformamide, 2-methoxy-2-methylpropane (MTBE), (trifluoromethyl)benzene, 1,2-dichloroethane, or acetonitrile. Ak represents a lower alkane, such as methyl or ethyl.

[0100] In the second step, the condensation product having formula (IV) is treated with a hydroxylamine or a hydroxylamine salt to produce an isoxazoline compound having formula (III). This reaction is typically carried out under basic conditions. Typical bases include sodium hydroxide, lithium hydroxide, or 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU). The reaction can be carried out in solvents or mixtures of solvents such as toluene, N,N-dimethylformamide, 2-methoxy-2-methylpropane (MTBE), (trifluoromethyl)benzene, 1,2-dichloroethane, or acetonitrile. The general procedure for the method of Scheme 3 is described in detail in the chemical literature, see, for example, WO2009126668A.

[0101] Option 4:

[0102] As outlined in Scheme 4, esters having formula (V) can also be prepared from pyridine halides having formula (VIII) via a two-step procedure. In the first step, the halide of formula (VIII) is converted to an organomaglenite in the presence of a Grignard reagent, which is then reacted with acetamide to give an acetyl-functionalized ketone of formula (VII). The Grignard reagent is selected from isopropyl magnesium chloride, isopropyl magnesium chloride-lithium chloride complex, cyclohexyl magnesium chloride, or n-butyl magnesium chloride. The acylating agent is selected from N,N-dimethylacetamide, N-methyl-N-methoxyacetamide, acetyl chloride, acetic anhydride, N-methyl-N-methoxy-2-chloroacetamide, or N-methyl-N-methoxy-2-bromoacetamide. The reaction solvent is tetrahydrofuran, toluene, 2-methyltetrahydrofuran, or dichloromethane. The reaction temperature is generally between -75 and 80 °C.

[0103] In the second step, the ketone having formula (VII) is reacted in the presence of a palladium catalyst under a CO atmosphere to produce an ester compound having formula (V). The palladium catalyst used in the method of the present invention typically comprises palladium in the form of an oxidation state of 0 (i.e., Pd(0)) or 2 (i.e., Pd(II)). A variety of such palladium-containing compounds and complexes can be used as catalysts in the method of the present invention. The palladium catalysts include PdCl2(PPh3)2 (i.e., bis(triphenylphosphine)palladium(II)), Pd2(dba)3 (i.e., tris(dibenzylacetone)palladium(0)), Pd(PPh3)4 (i.e., tetra(triphenylphosphine)palladium(0)), Pd(C5H7O2)2 (i.e., palladium(II) acetylacetone), dichloro-[1,1'-bis(diphenylphosphine)ferrocene]palladium(II), and complexes of palladium acetate with 1,1'-bis(diphenylphosphine)ferrocene. The reaction is typically carried out under alkaline conditions. Typical bases include sodium hydroxide, lithium hydroxide, or 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU), triethylamine, and isopropylethylamine. The reaction can be carried out in solvents or mixtures of solvents such as methanol, ethanol, isopropanol, and n-butanol. Ak represents a lower alkane, such as methyl, ethyl, isopropyl, or n-butyl.

[0104] In the definitions of compounds of formula (I) given above, the terms used in the compilation are generally defined as follows:

[0105] "alkyl" includes, in each case, a saturated straight-chain or branched hydrocarbon group having a specified number of carbon atoms, such as C1-C6-alkyl groups, including methyl, ethyl, propyl, 1-methylethyl, butyl, 1-methylpropyl, 2-methylpropyl, 1,1-dimethylethyl, pentyl, 1-methylbutyl, 2-methylbutyl, 3-methylbutyl, 2,2-dimethylpropyl, 1-ethylpropyl, hexyl, 1,1-dimethylpropyl, 1,2-dimethylpropyl 1-Methylpentyl, 2-Methylpentyl, 3-Methylpentyl, 4-Methylpentyl, 1,1-Dimethylbutyl, 1,2-Dimethylbutyl, 1,3-Dimethylbutyl, 2,2-Dimethylbutyl, 2,3-Dimethylbutyl, 3,3-Dimethylbutyl, 1-Ethylbutyl, 2-Ethylbutyl, 1,1,2-Trimethylpropyl, 1,2,2-Trimethylpropyl, 1-Ethyl-1-Methylpropyl, and 1-Ethyl-2-Methylpropyl.

[0106] "Alkenyl" includes straight-chain or branched alkenes, such as vinyl, 1-propenyl, 2-propenyl, and various butenyl, pentenyl, and hexenyl isomers. "Alkenyl" also includes polyenes, such as 1,2-propadienyl and 2,4-hexadienyl.

[0107] "Alynyl" includes straight-chain or branched alkynes, such as ethynyl, 1-propynyl, 2-propynyl, and various butynyl, pentynyl, and hexynyl isomers. "Alynyl" may also include a part consisting of multiple triple bonds, such as 2,5-hexadiynyl.

[0108] "Cycloalkyl" includes, for example, cyclopropyl, cyclobutyl, cyclopentyl, and cyclohexyl. The term "alkylcycloalkyl" indicates alkyl substitution on the cycloalkyl moiety and includes, for example, ethylcyclopropyl, isopropylcyclobutyl, 3-methylcyclopentyl, and 4-methylcyclohexyl. The term "cycloalkylalkyl" indicates cycloalkyl substitution on the alkyl moiety. Examples of "cycloalkylalkyl" include cyclopropylmethyl, cyclopentylethyl, and other cycloalkyl moiety bonded to straight-chain or branched alkyl groups.

[0109] Halogen-substituted alkyl groups (halogenated alkyl groups) refer to the following straight-chain or branched alkyl groups in which some or all of the hydrogen atoms are replaced by halogen atoms, such as C1-C2 haloalkyl groups, including chloromethyl, bromomethyl, dichloromethyl, trichloromethyl, fluoromethyl, difluoromethyl, trifluoromethyl, chlorofluoromethyl, dichlorofluoromethyl, chlorodifluoromethyl, 1-chloroethyl, 1-bromoethyl, 1-fluoroethyl, 2-fluoroethyl, 2,2-difluoroethyl, 2,2,2-trifluoroethyl, 2-chloro-2-fluoroethyl, 2-chloro-2,2-difluoroethyl, 2,2,2-dichloro-2-fluoroethyl, 2,2,2-trichloroethyl, pentafluoroethyl, and 1,1,1-trifluoropropyl-2-yl. The term "halogenated cycloalkyl" is defined similarly to the term "halogenated alkyl". Examples of "halogenated cycloalkyl" include chlorocyclopropyl, fluorocyclobutyl, and chlorocyclohexyl.

[0110] The term "halogen" refers to fluorine, chlorine, bromine, or iodine. If the term is used with a group, then "halogen" or "halogen atom" refers to a fluorine, chlorine, bromine, or iodine atom.

[0111] As used in this article, the chemical abbreviations S(O) and S(=O) represent the sulfinyl group. The chemical abbreviations SO2, S(O)2, and S(=O)2 represent the sulfonyl group. The chemical abbreviations C(O) and C(=O) represent the carbonyl group. The chemical abbreviations CO2, C(O)O, and C(=O)O represent the oxycarbonyl group. "CHO" means acyl group.

[0112] The terms "carbocyclic ring," "carbocycle," or "carbocyclic system" indicate a ring or ring system in which the atoms forming the ring skeleton are selected only from carbon. The terms "heterocyclic ring," "heterocycle," or "heterocyclic system" indicate a ring or ring system in which at least one atom forming the ring skeleton is not carbon (e.g., nitrogen, oxygen, or sulfur). Typically, a heterocyclic ring contains no more than four nitrogen atoms, no more than two oxygen atoms, and no more than two sulfur atoms. Unless otherwise specified, a carbon ring or heterocyclic ring can be saturated or unsaturated. "Saturated" means a ring having a skeleton consisting of atoms connected to each other by single bonds; unless otherwise specified, the remaining atoms are occupied by hydrogen atoms. Unless otherwise stated, an "unsaturated ring" can be partially unsaturated or completely unsaturated. The term "fully unsaturated ring" refers to a ring of atoms in which the bonds between atoms are either single or double bonds according to valence bond theory, and furthermore, the bonds between atoms in the ring include as many double bonds as possible, but no cumulative double bonds (i.e., no C=C=C or C=C=N). The term "partially unsaturated ring" indicates a ring containing at least one ring member bonded to a neighboring ring member by a double bond, and conceptually may accommodate more than the number of non-cumulative double bonds (i.e., their fully unsaturated counterparts) between adjacent ring members.

[0113] Unless otherwise specified, heterocyclic and cyclic systems can be attached by any available carbon or nitrogen in place of hydrogen on said carbon or nitrogen.

[0114] The term "aromatic" indicates that each ring atom of a fully unsaturated ring is substantially in the same plane and has p-orbitals perpendicular to the ring plane, and that (4n+2) π electrons (where n is a positive integer) are associated with the ring to conform to Hückel's rule.

[0115] The term "aromatic ring system" refers to a ring system in which at least one ring is an aromatic carbon ring or heterocyclic system. When the fully unsaturated carbon ring satisfies Hückel's rule, the ring is also called an "aromatic ring" or "aromatic carbon ring." The term "aromatic carbon ring system" refers to a ring system in which at least one ring is an aromatic carbon ring. When the fully unsaturated heterocyclic ring satisfies Hückel's rule, the ring is also called a "heteroaromatic ring" or "aromatic heterocyclic ring." The term "aromatic heterocyclic system" refers to a ring system in which at least one ring is an aromatic heterocyclic system.

[0116] The term "non-aromatic ring system" refers to a carbon ring or heterocyclic system that can be fully saturated, partially or fully unsaturated, provided that none of the rings in the system are aromatic. The term "non-aromatic carbon ring system" refers to a system in which no ring is an aromatic carbon ring. The term "non-aromatic heterocyclic system" refers to a heterocyclic system in which no ring is an aromatic ring.

[0117] The term "optionally substituted" in relation to heterocycles refers to a group that is unsubstituted or has at least one non-hydrogen substituent that does not eliminate the biological activity possessed by the unsubstituted analogue. As used herein, unless otherwise specified, the following definitions shall apply. The term "optionally substituted" is used interchangeably with the phrase "substituted or unsubstituted" or the term "(un)substituted." Unless otherwise specified, an optionally substituted group may have substituents at each substituted position of the group, and each substitution is independent of the others.

[0118] When Q1 is a 5- or 6-membered nitrogen-containing heterocycle, it can be attached to the remainder of formula (I) by any available carbon or nitrogen ring atom unless otherwise described.

[0119] The compounds of the present invention can exist as mixtures of stereoisomers or as individual stereoisomers. For example, two possible enantiomers having formula (I) are described as formula I' and II' involving the isoxazoline chiral center identified by an asterisk (*). Similarly, other chiral centers may exist, for example, at J.

[0120] The molecular descriptions in this paper follow standard conventions for depicting stereochemistry. To indicate stereochemistry, bonds extending from the drawing plane toward the viewer are represented by solid wedges, with the wide end of the wedge connected to an atom extending from the drawing plane toward the viewer. Bonds extending below the drawing plane and away from the viewer are represented by dashed wedges, with the wide end of the wedge connected to an atom further away from the viewer.

[0121] Since chiral carbon atoms may be present in formula (I), the invented compound can exist as stereoisomers. Therefore, the invented compound includes individual stereoisomers of the compound having formula (I), as well as mixtures of stereoisomers of the compound having formula (I).

[0122] The present invention includes racemic mixtures, such as equal amounts of enantiomers having formula I' and I". Furthermore, the invention includes compounds enriched compared to racemic mixtures of enantiomers having formula (I). It also includes substantially pure enantiomers of compounds having formula (I) (e.g., formulas I' and I").

[0123] When enantiomers are enriched, one enantiomer is present in a larger amount than the other, and the degree of enrichment can be defined as an enantiomer excess of (2x-1)·100% (“ee”), where x is the mole fraction of the dominant enantiomer in the mixture (e.g., 20% ee corresponds to a 60:40 ratio of enantiomers). Preferably, the invented composition has an enantiomer excess of at least 50% of the more active isomer; more preferably at least 75%; even more preferably at least 90%; and most preferably at least 94%. Particularly noteworthy are examples of enantiomer purity of the more active isomer.

[0124] Compounds having formula (I) may contain additional chiral centers. For example, substituents and other molecular components such as J itself may contain chiral centers. The invention includes racemic mixtures and substantially pure stereoconfigurations enriched at these additional chiral centers.

[0125] The invented compounds can exist as one or more conformational isomers due to rotational restriction around the amide bond (e.g., C(=O)-N) in formula (I). The invention includes mixtures of conformational isomers. Furthermore, the invention includes compounds in which one conformational isomer is enriched relative to other conformational isomers.

[0126] The invention includes all stereoisomers, conformational isomers and mixtures thereof in all proportions, as well as isotopic forms such as deuterated compounds.

[0127] Those skilled in the art will understand that not all nitrogen-containing heterocycles can form N-oxides, because nitrogen requires a lone pair of electrons to be oxidized into an oxide; those skilled in the art will recognize which nitrogen-containing heterocycles can form N-oxides. Those skilled in the art will also recognize that tertiary amines can form N-oxides. Synthetic methods for preparing N-oxides of heterocycles and tertiary amines are well known to those skilled in the art, including the oxidation of heterocycles and tertiary amines using peroxyacids such as peracetic acid and 3-chloroperoxybenzoic acid (MCPBA), hydrogen peroxide, alkyl hydroperoxides such as tert-butyl hydroperoxide, sodium perborate, and diethylene oxides such as dimethyldiethylene oxide. These methods for preparing N-oxides have been extensively described and reviewed in the literature.

[0128] Based on the properties of the substituents defined above, compounds of formula (I) are acidic and can form salts, and, if suitable, can form internal salts, or form adducts with inorganic or organic bases or with metal ions. If compounds of formula (I) contain a hydroxyl group, a carboxyl group, or other groups that cause acidity, these compounds can react with bases to form salts. Suitable bases are, for example, hydroxides, carbonates, and bicarbonates of alkali metals and alkaline earth metals, particularly sodium, potassium, magnesium, and calcium; and ammonia; primary, secondary, and tertiary amines having C1-C4-alkyl groups; monoalkylolamines, dialkylolamines, and trialkylolamines of C1-C4-alkanols; choline and choline chloride; and organic amines such as trialkylamines, morpholine, piperidine, or pyridine. These salts are compounds in which the acidic hydrogen is replaced by an agriculturally suitable cation, for example, metal salts, especially alkali metal salts or alkaline earth metal salts, particularly sodium and potassium salts; or ammonium salts, organic amine salts, or quaternary ammonium salts, such as salts of cations having the formula [NRR′R″R″′]+ (where R to R″′ each independently represents an organic group, particularly alkyl, aryl, aralkyl, or alkylaryl). Also suitable are alkyl sulfonium salts and alkyl oxide sulfonium salts, such as C1-C4-trialkyl sulfonium salts and C1-C4-trialkyl oxide sulfonium salts.

[0129] Compounds of formula (I) can form salts by adding a suitable inorganic or organic acid to a basic group; the inorganic acid being, for example, HCl, HBr, H₂SO₄, H₃PO₄, or HNO₃, the organic acid being, for example, a carboxylic acid (e.g., formic acid, acetic acid, propionic acid, oxalic acid, lactic acid, or salicylic acid) or a sulfonic acid (e.g., p-toluenesulfonic acid), and the basic group being, for example, an amino, alkylamino, dialkylamino, piperidinyl, morpholinyl, or pyridinyl group. In this case, the salts contain the conjugate base of the acid as an anion.

[0130] Suitable substituents (e.g., sulfonic acids or carboxylic acids) in deprotonated form can form internal salts with groups that are themselves protonable (e.g., amino groups).

[0131] A composition is also provided, characterized in that it comprises at least one of the compound of formula (I) described above, its stereoisomer or salt thereof, wherein the compound of formula (I) is used as the active component, and the weight percentage of the active component in the composition is 0.1-99.9%.

[0132] Common dosage forms include: water-soluble liquids (SL), emulsion concentrates (EC), water-in-oil emulsions (EW), suspension concentrates (SC, SE, FS, OD), water-dispersible granules (WG), granules (GR), and capsule concentrates (CS).

[0133] Preferred formulations or application forms include at least one adjuvant, such as a extender, solvent, spontaneous growth promoter, carrier, emulsifier, dispersant, antifreeze, biocide, thickener; and / or other adjuvants, such as adjuvants. In the context of this invention, an adjuvant is a component that enhances the biological efficacy of the formulation, while the component itself does not possess any biological efficacy. Examples of adjuvants are agents that promote retention, spreading, adhesion to leaf surfaces, or penetration. Suitable extenders are, for example, water, polar and nonpolar organic chemical liquids.

[0134] The formulation preferably comprises 0.00000001% by weight to 98% by weight of a compound of formula (I), more preferably 0.01% by weight to 95% by weight of a compound of formula (I), and most preferably 0.5% by weight to 90% by weight of a compound of formula (I), based on the weight of the formulation.

[0135] Compounds of formula (I) may also be used in combination with one or more suitable of the following substances: fungicides, bactericides, acaricides, molluscicides, nematicides, insecticides, microbial agents, beneficial organisms, herbicides, fertilizers, bird repellents, phytotonics, phytotoxicants, safety agents, chemical pheromones and / or plant growth regulators, thereby, for example, broadening the spectrum of action, prolonging the duration of action, increasing the rate of action, preventing rejection or the development of resistance.

[0136] Compounds of formula (I) can also be combined with biological pesticides. Biological pesticides include, in particular, bacteria, fungi, yeasts, plant extracts, and products formed by microorganisms, including proteins and secondary metabolites.

[0137] The present invention also provides a method for controlling pests, characterized in that the compound of formula (I) described above, its stereoisomers and agriculturally acceptable salts thereof, or the composition described above are applied to the pest or its growth environment.

[0138] The treatment of plants and plant parts using compounds of formula (I) in this invention is carried out directly by conventional treatment methods or by applying the compound to its environment, habitat, or storage space, for example by impregnation, spraying, evaporation, atomization, broadcasting, application, injection, and, in the case of propagation materials, especially seeds, by applying one or more layers of coating. As described above, all plants and their parts can be treated according to this invention.

[0139] The present invention also provides the use of a compound of formula (I) as described above, its stereoisomers, and agriculturally acceptable salts thereof, or the composition described above, in the control of pests.

[0140] In particular, the present invention also relates to a method for protecting seeds and germinating plants from pests by treating seeds with one of the compounds of formula (I).

[0141] The present invention also relates to the use of the compound of formula (I) for treating seeds to protect the seeds and the resulting plants from animal pests.

[0142] Typically, compounds of formula (I) are applied to seeds in a suitable formulation. Suitable formulations and methods for seed treatment are known to those skilled in the art.

[0143] Compounds of formula (I) can be converted into conventional seed coating formulations, such as solutions, emulsions, suspensions, powders, foams, slurries, or other seed coating compositions, as well as ULV formulations.

[0144] The application rate of the seed dressing formulation that can be used according to the present invention can vary over a wide range. This is determined by the specific content of the compound of formula (I) in the formulation and the seed. The application rate of the compound of formula (I) is typically from 0.001 to 50 g / kg of seed, preferably from 0.01 to 15 g / kg of seed.

[0145] The compounds of formula (I) provided by this invention can also be applied in the field of animal health. In the field of animal health, i.e., veterinary medicine, the compounds of formula (I) are active against animal parasites, particularly ectoparasites or endoparasites. The term "endoparasites" specifically includes worms and protozoa, such as coccidia. Ectoparasites are generally and preferably arthropods, especially insects or mites.

[0146] In veterinary medicine and animal husbandry, compounds of formula (I) are administered in suitable formulations via methods commonly known in the art, such as intravenous, parenteral, dermal, or nasal routes. Administration may be prophylactic, metaphylactically, or therapeutically.

[0147] According to one specific embodiment, the compound of formula (I) is applied to a mammal.

[0148] According to another specific embodiment, the compound of formula (I) is applied to poultry, i.e., caged birds or, in particular, domestic poultry.

[0149] By using compounds of formula (I) to control animal parasites, the aim is to reduce or prevent disease, mortality, and performance decline (in the case of meat, milk, wool, hides, eggs, honey, etc.), thereby making animal husbandry more economical and simpler, and achieving better animal health.

[0150] The compound of formula (I) provided by this invention can also be applied to the field of vector control. The vectors are arthropods, especially insects or arachnids, capable of transmitting pathogens such as viruses, worms, single-celled organisms, and bacteria from a host (plant, animal, human, etc.) to a host. Pathogens can be mechanically transmitted to the host (e.g., trachoma transmitted via non-stinging flies) or through injection (e.g., malaria parasites transmitted via mosquitoes).

[0151] The compound of formula (I) provided by this invention can also be applied to the protection of industrial materials.

[0152] Compounds of formula (I) are suitable for protecting industrial materials from insects that may infest or damage them, such as those from the orders Coleoptera, Hymenoptera, Isoptera, Lepidoptera, Psittacosae, and Zygentoma.

[0153] In the context of this invention, industrial materials should be understood to mean inanimate materials, such as, preferably, plastics, adhesives, pastes, paper and cards, leather, wood, processed wood products, and coating compositions. The use of this invention for the protection of wood is particularly preferred.

[0154] The compound of formula (I) provided by this invention can also be used in the field of hygiene for the prevention and control of animal pests.

[0155] Compounds of Formula (I) are suitable for controlling animal pests in the sanitation field. In particular, the present invention can be used for the protection of indoor, sanitation, and stored products, especially for controlling insects, arachnids, ticks, and mites encountered in enclosed spaces such as dwellings, factory lobbies, offices, vehicle cabins, and livestock farms. For controlling animal pests, compounds of Formula (I) can be used alone or in combination with other active compounds and / or adjuvants. They are preferably used in indoor insecticide products. Compounds of Formula (I) are effective against susceptible and resistant species, as well as their entire developmental stages.

[0156] In this invention, if there is a conflict between the naming of compounds and their structural formulas, the structural formula shall prevail, unless the structural formula is obviously incorrect. Detailed Implementation

[0157] The following examples are for illustrative purposes only and should not be construed as limiting the invention in any way. The scope of protection of this invention is defined by the claims. Simple substitutions or modifications made to this invention by those skilled in the art are all within the scope of the technical solutions protected by this invention.

[0158] Several methods for preparing the compounds of the present invention are described in detail in the following schemes and examples. The raw materials can be commercially available or prepared by methods known in the literature or as detailed in the description. Those skilled in the art will understand that other synthetic routes can also be used to synthesize the compounds of the present invention. Although specific raw materials and conditions in the synthetic routes have been described below, they can be easily replaced with other similar raw materials and conditions. Such variations or modifications to the preparation methods of the present invention, such as various isomers of the compounds, are all included within the scope of the present invention. Furthermore, the preparation methods described below can be further modified according to the disclosure of the present invention using conventional chemical methods well known to those skilled in the art. For example, protecting appropriate groups during the reaction process, etc.

[0159] The following method examples are provided to further illustrate the preparation methods of the present invention. The specific substances, types, and conditions used are intended to further explain the invention and are not intended to limit its reasonable scope. The reagents used in the synthetic compounds described below are either commercially available or can be easily prepared by those skilled in the art.

[0160] The analytical instruments described in the examples are as follows:

[0161] I. High Performance Liquid Chromatography (hereinafter referred to as HPLC): Using an Agilent Technologies 1260 Infinity II instrument.

[0162] Column: Agilent Eclipse Plus C 18 3.5μm, 4.6*100mm

[0163] Mobile phase: A: water + 0.1% phosphoric acid; B: acetonitrile; Temperature: 30℃

[0164] Gradient: 10%B to 95%B over 15 minutes; 95%B over 3 minutes

[0165] Flow rate: 1 mL / min

[0166] II. Ultra-high performance liquid chromatography-tandem mass spectrometry (hereinafter referred to as LC-MS): Using a Waters, ACQUITY H-Class UPLC-SQ Detector 2 instrument.

[0167] column: BEH C 18 1.7μm, 2.1*50mm Column

[0168] Mobile phase: A: Water + 0.2% formic acid; B: Acetonitrile; Temperature: 30℃

[0169] Gradient: 10%B to 95%B over 5 minutes; 95%B over 1 minute

[0170] Flow rate: 0.5 mL / min

[0171] MS method: ESI positive, negative, quality range (m / z): 100-800

[0172] III. Gas Chromatography-Tandem Mass Spectrometry (hereinafter referred to as GC-MS): Using Agilent Technologies, 7890B GC System-5977A MSD equipment.

[0173] Column: Agilent Technologies, HP-5MS UI 0.25μm, 30m*0.250mm

[0174] Injector temperature: 250℃

[0175] Column flow rate: Helium 1 mL / min

[0176] Method: Hold at 40℃ for 2 min, increase temperature to 280℃ at 20℃ / min, hold at 280℃ for 5 min, total time 19 min.

[0177] MSD transmission line temperature: 280℃

[0178] EI ion source temperature: 230℃, MS quadrupole temperature: 150℃, scan range: 30.00-400.00

[0179] In addition, the proton nuclear magnetic resonance spectra described below (hereinafter referred to as...) 1 The chemical shift values ​​of H-NMR were measured at 400 MHz (Bruker, AVANCE III HD 400M) in deuterated chloroform (CDCl3) using Me4Si (tetramethylsilane) as the reference material. When measured in deuterated dimethyl sulfoxide, the chemical shift values ​​are shown as "(DMSO-d6)" in the data. It should be noted that... 1 The symbols in the chemical shift values ​​of H-NMR represent the following meanings:

[0180] s: singlet, d: doublet, dd: doublett, dt: doublettuplet, td: triplettuplet, ddd: doublettuplet, t: triplet, q: quartet, sep: septet, m: multiplet, brs: broad singlet. Furthermore, in cases where two or more stereoisomers are present, the chemical shift values ​​for the resolvable signal are marked with "and".

[0181] Examples of representative compounds are given below. The synthesis methods of other compounds are similar and will not be described in detail here.

[0182] Preparation Example 1

[0183] Preparation of compound I-1.29:

[0184] Step 1: Preparation of Compound VII

[0185] At 0 °C under a nitrogen atmosphere, 1.3 M isopropyl magnesium chloride-lithium chloride complex (242 mL, 315 mmol) was added dropwise to 2-chloro-3-methyl-5-bromopyridine (50.0 g, 242 mmol) in tetrahydrofuran (100 mL) over 30 minutes. After 90 minutes, N-methoxy-N-methylacetamide (32.4 g, 314.6 mmol) was added dropwise. The reaction mixture was stirred at room temperature for 12 hours. After the reaction was complete, it was quenched by adding 20 mL of saturated ammonium chloride aqueous solution. The reaction mixture was extracted with ethyl acetate (3 x 100 mL). The combined organic layers were washed with water, dried over sodium sulfate, and concentrated under reduced pressure to give 39.0 g of yellow solid. LCMS (ESI): m / z 170 [M+H] + .

[0186] Step 2: Preparation of compound V

[0187] VII (13.0 g, 77 mmol), methanol (40 mL), triethylamine (15.5 g, 153 mmol), palladium acetate (86.5 mg, 0.38 mmol), and 1,1'-bis(diphenylphosphine)ferrocene (426 mg, 0.76 mmol) were added to a 100 mL pressure reactor. CO (g) was introduced at a pressure of 3 atm. The resulting reaction mixture was stirred at 110 °C for 12 hours. After the reaction was complete, the mixture was cooled to room temperature, concentrated under reduced pressure, and purified by column chromatography to give 12.5 g of a yellow solid. LCMS (ESI): m / z 194 [M+H] + .

[0188] Step 3: Preparation of compound IV-1

[0189] Under a nitrogen atmosphere, 25.0 g (129 mmol) of V was added to 130 mL of dichloroethane, along with 3,5-dichloro-4-fluorotrifluoroacetylbenzene VI-1 (33.7 g (129 mmol), potassium carbonate (23.2 g (167 mmol), and triethylamine (16.9 g (167 mmol)). The resulting reaction mixture was refluxed for 12 hours. After the reaction was complete, it was cooled to room temperature and extracted with dichloromethane (3 x 50 mL) by adding 50 mL of aqueous solution. The combined organic layers were washed with a saturated sodium chloride solution, dried over sodium sulfate, concentrated under reduced pressure, and purified by column chromatography to give 27.0 g of a white solid. LCMS (ESI): m / z 436 [M+H] + .

[0190] Step 4: Preparation of Compound III-1

[0191] IV-1 (21.4 g, 49 mmol) was added to dichloromethane (200 mL) along with a chiral quinine catalyst (1.45 g, 1.47 mmol) (prepared according to method WO2016023787 A1). The resulting reaction mixture was cooled to -20 °C, and 10 M potassium carbonate solution (16.2 mL, 161 mmol) was added. The reaction mixture was stirred at this temperature for 30 minutes, followed by slow dropwise addition of hydroxylamine solution (50% in H2O, 8.92 mL, 147 mmol). The mixture was stirred at this temperature for 2 days. After the reaction was complete, the mixture was brought to room temperature, diluted with water, and extracted with dichloromethane (3 x 50 mL). The combined organic layers were washed with a saturated sodium chloride solution, dried over sodium sulfate, and concentrated under reduced pressure to give 22 g of a colorless solid. LCMS (ESI): m / z 451 [M+H] + Analysis by chiral HPLC (method: column: AD-H column, wavelength (nm): 254nm, temperature (°C): 30°C, mobile phase: n-hexane:isopropanol = 95:5, injection volume: 1uL, flow rate: 1mL / min): The product contained a leading peak (10.53min) as the major product (77%) and a trailing peak (12.18min) as the minor product (23%). (Based on the preparation method in patent WO2016023787 A1, the major product in this preparation method is confirmed to be of the S-configuration.)

[0192] Step 5: Preparation of Compound II-1

[0193] To III-1 (22.0 g, 49 mmol), sodium hydroxide (4.5 g, 112.5 mmol) and deionized water (40 mL) were added to methanol (80 mL), and the resulting reaction mixture was stirred at room temperature for 2 hours. After the reaction was complete, the mixture was concentrated under reduced pressure to remove most of the methanol, and the pH was adjusted to acidic with 10 N hydrochloric acid. The reaction mixture was extracted with dichloromethane (3 x 50 mL). The combined organic layers were washed with a saturated sodium chloride solution, dried over sodium sulfate, concentrated under reduced pressure, and purified by column chromatography to give 21.0 g of a pale yellow solid. 1 H NMR(400MHz,Chloroform-d)δ8.76(d,J=1.9Hz,1H),8.01(d,J=1.9Hz,1H),7.79(s,1H ), 7.59 (d, J = 5.9Hz, 2H), 4.14 (d, J = 17.2Hz, 1H), 3.76 (d, J = 17.3Hz, 1H), 2.82 (s, 3H). LCMS(ESI):m / z 435[MH] + Chiral HPLC analysis (method: column: AD-H column, wavelength (nm): 254nm, temperature (°C): 30°C, mobile phase: n-hexane:ethanol:trifluoroacetic acid = 70:30:0.05, injection volume: 5uL, flow rate: 1mL / min) showed that the product contained a leading peak (4.2min) as the major product (75%) and a trailing peak (6.9min) as the minor product (25%). (By comparing the optical rotation with that reported in reference patent WO2011104089(A1), the major product of this method was confirmed to be the S configuration). Chiral separation of the enantiomers of the above product was performed on a preparative SFC column to obtain S-configuration II-1 with 100% optical purity. After separation by chiral HPLC (Column: CHIRALPAK AD-H; Column Size: 3cm x 25cm, 5µm; Injection: 3.0mL; Mobile phase: Hex (0.05% TFA): EtOH = 65:35; Flow rate: 28mL / min; Wavelength: UV 254nm; Temperature: 25℃; Sample solution: 300mg / mL in EtOH / Hex; Run time = 14min), the light yellow solids II-1-S (Rt = 5.7min, 100% ee, purity 98%) and II-1-R (Rt = 9.6min, 99% ee, purity 98%) were obtained and concentrated.

[0194] The following compounds II-2, II-3, II-4, and II-5 can all be synthesized using a similar procedure to that of II-1.

[0195] Step 6: Preparation of compound I-1.29

[0196] To II-1 (104.5 mg, 0.25 mmol), D-alanine methyl ester hydrochloride (41.8 mg, 0.3 mmol) and triethylamine (75.9 mg, 0.75 mmol) were added to dichloromethane (4 mL), and the resulting reaction mixture was stirred at room temperature for 15 minutes. Then, 50% butylphosphonic anhydride (713.3 mg, 0.99 mmol) in ethyl acetate was added, and the resulting reaction mixture was stirred at room temperature for 2 hours. After the reaction was complete, the solvent was removed by concentration under reduced pressure, and the compound was purified by column chromatography to give compound I-1.29 (104 mg). 1 H NMR(400MHz,Chloroform-d)δ8.68(d,J=2.0Hz,1H),8.51(d,J=7.8Hz,1H),7.86(dd,J=2.1,0.8Hz,1H),7.59(d,J=6.0 Hz, 2H), 4.74 (p, J = 7.3Hz, 1H), 4.11 (d, J = 17.2Hz, 1H), 3.79 (s, 3H), 3.72 (d, J = 17.3Hz, 1H), 2.77 (s, 3H), 1.57 (s, 3H). LCMS(ESI):m / z 522[M+H] + .

[0197] Preparation Example 2

[0198] Preparation of compound I-1.32:

[0199] Step 1: Preparation of compound I-1.29-a

[0200] I-1.25 (156.0 mg, 0.3 mmol) was added to methanol (10 mL) along with 2 M sodium hydroxide solution (3 mL), and the resulting reaction mixture was stirred at room temperature for 1 hour. After the reaction was complete, the mixture was concentrated under reduced pressure to remove most of the methanol, and the pH was adjusted to acidic with 10 N hydrochloric acid. The reaction mixture was extracted with dichloromethane (3 x 10 mL). The combined organic layers were washed with a saturated sodium chloride solution, dried over sodium sulfate, and concentrated under reduced pressure to give crude I-1.29-a. LCMS (ESI): m / z 508 [MH] + .

[0201] Step 2: Preparation of compound I-1.32

[0202] I-1.29-a was added to dichloromethane (10 mL) along with acetone oxime (21.9 mg, 0.3 mmol), 4-dimethylaminopyridine (3.6 mg, 0.03 mmol), and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (69.0 mg, 0.36 mmol). The resulting reaction mixture was stirred at room temperature for 12 hours. After the reaction was complete, the solvent was removed by concentration under reduced pressure, and the compound was purified by column chromatography to give compound I-1.32 (118 mg). 1 H NMR(400MHz,Chloroform-d)δ8.67(d,J=2.0Hz,1H),8.55(d,J=8.0Hz,1H),7.88(d,J=2.2Hz,1H),7.60(d,J=5.9Hz,2H), 4.88 (p, J = 7.3Hz, 1H), 4.12 (d, J = 17.2Hz, 1H), 3.73 (d, J = 17.3Hz, 1H), 2.76 (s, 3H), 2.05 (d, J = 17.5Hz, 6H), 1.60 (s, 3H). LCMS(ESI):m / z 584[M+H] + .

[0203] Preparation Example 3

[0204] Preparation of compound I-2.20:

[0205] Step 1: Preparation of compound A-1

[0206] N-Boc-glycine (175.0 mg, 1 mmol) was added to dichloromethane (4 mL) along with 2,2,2-trifluoroethylamine hydrochloride (162.6 mg, 1.2 mmol) and triethylamine (303.6 mg, 0.75 mmol). The resulting reaction mixture was stirred at room temperature for 15 minutes. Then, 50% butylphosphonic anhydride (2.8 g, 4.40 mmol) in ethyl acetate was added, and the reaction mixture was stirred at room temperature for 2 hours. After the reaction was complete, the solvent was removed by concentration under reduced pressure, and the compound was purified by column chromatography to give compound A-1 (204 mg). LCMS (ESI): m / z 257 [M+H] + .

[0207] Step 2: Preparation of compound B-1

[0208] To A-1 (128.0 mg, 0.5 mmol), 1 mL of 4 M dioxane chloride solution was added to 4 mL of dioxane, and the resulting reaction mixture was stirred at room temperature for 2 hours. After the reaction was complete, the solvent was removed by concentration under reduced pressure to give a white solid compound B-1. LCMS (ESI): m / z 157 [M+H] + .

[0209] Step 3: Preparation of compound I-2.20

[0210] To a solution of II-1 (104.5 mg, 0.25 mmol) in dichloromethane (4 mL), B-1 (57.6 mg, 0.3 mmol) and triethylamine (75.9 mg, 0.75 mmol) were added, and the resulting reaction mixture was stirred at room temperature for 15 minutes. Then, 50% butylphosphonic anhydride (713.3 mg, 0.99 mmol) in ethyl acetate was added, and the reaction mixture was stirred at room temperature for 2 hours. After the reaction was complete, the solvent was removed by concentration under reduced pressure, and the compound was purified by column chromatography to give compound I-2.20 (116 mg). 1 H NMR(400MHz,Chloroform-d)δ8.82–8.54(m,2H),7.90(d,J=2.0Hz,1H),7.59(d,J=6.0Hz,2H),6.64(s,1H ), 4.17 (d, J = 6.1Hz, 2H), 4.11 (d, J = 17.2Hz, 1H), 4.01–3.88 (m, 2H), 3.72 (d, J = 17.2Hz, 1H), 2.78 (s, 3H). LCMS(ESI):m / z 575[M+H] + .

[0211] Preparation Example 4

[0212] Preparation of compound I-2.134:

[0213] Step 1: Preparation of compound A-2

[0214] BOC-D-alanine (189.0 mg, 1 mmol) was added to dichloromethane (4 mL) along with 2,2,2-trifluoroethylamine hydrochloride (162.6 mg, 1.2 mmol) and triethylamine (303.6 mg, 0.75 mmol). The resulting reaction mixture was stirred at room temperature for 15 minutes. Then, 50% butylphosphonic anhydride (2.8 g, 4.40 mmol) in ethyl acetate was added, and the reaction mixture was stirred at room temperature for 2 hours. After the reaction was complete, the solvent was removed by concentration under reduced pressure, and the compound was purified by column chromatography to give compound A-2 (202 mg). LCMS (ESI): m / z 271 [M+H] + .

[0215] Step 2: Preparation of compound B-2

[0216] To A-2 (135 mg, 0.5 mmol), 1 mL of 4 M dioxane chloride solution was added to 4 mL of dioxane, and the resulting reaction mixture was stirred at room temperature for 2 hours. After the reaction was complete, the solvent was removed by concentration under reduced pressure to give a white solid compound B-2. LCMS (ESI): m / z 171 [M+H] + .

[0217] Step 3: Preparation of compound I-2.134

[0218] To a solution of II-1 (104.5 mg, 0.25 mmol), B-2 (61.8 mg, 0.3 mmol) and triethylamine (75.9 mg, 0.75 mmol) were added to dichloromethane (4 mL), and the reaction mixture was stirred at room temperature for 15 minutes. Then, 50% butylphosphonic anhydride (713.3 mg, 0.99 mmol) in ethyl acetate was added, and the reaction mixture was stirred at room temperature for 2 hours. After the reaction was complete, the solvent was removed by concentration under reduced pressure, and the compound was purified by column chromatography to give compound I-2.134 (119 mg). 1H NMR(400MHz,Chloroform-d)δ8.66(d,J=2.0Hz,1H),8.41(d,J=7.6Hz,1H),7.89(d,J=2.0Hz,1H),7.60(s,1H),7.59(s,1H),7.00(t,J =6.5Hz,1H),4.72–4.58(m,1H),4.11(d,J=17.2Hz,1H),4.01–3.86(m,2H),3.73(d,J=17.2Hz,1H),2.76(s,3H),1.55(d,J=7.0Hz,3H). LCMS(ESI):m / z 589[M+H] + .

[0219] Preparation Example 5

[0220] Preparation of compound I-2.362:

[0221] Step 1: Preparation of compound A-3

[0222] 2-((tert-butoxycarbonyl)amino)-2-methylpropionic acid (203.0 mg, 1 mmol) was added to dichloromethane (4 mL), along with 2,2,2-trifluoroethylamine hydrochloride (162.6 mg, 1.2 mmol) and triethylamine (303.6 mg, 0.75 mmol). The resulting reaction mixture was stirred at room temperature for 15 minutes. Then, 50% butylphosphonic anhydride (2.8 g, 4.40 mmol) in ethyl acetate was added, and the reaction mixture was stirred at room temperature for 2 hours. After the reaction was complete, the solvent was removed by concentration under reduced pressure, and the compound was purified by column chromatography to give compound A-3 (207 mg). LCMS (ESI): m / z 285 [M+H] + .

[0223] Step 2: Preparation of compound B-3

[0224] To A-3 (142.0 mg, 0.5 mmol), 1 mL of 4 M dioxane chloride solution was added to 4 mL of dioxane, and the resulting reaction mixture was stirred at room temperature for 2 hours. After the reaction was complete, the solvent was removed by concentration under reduced pressure to give a white solid compound B-3. LCMS (ESI): m / z 185 [M+H] + .

[0225] Step 3: Preparation of compound I-2.362

[0226] To a solution of II-1 (104.5 mg, 0.25 mmol), B-3 (66.0 mg, 0.3 mmol) and triethylamine (75.9 mg, 0.75 mmol) were added to dichloromethane (4 mL), and the resulting reaction mixture was stirred at room temperature for 15 minutes. Then, 50% butylphosphonic anhydride (713.3 mg, 0.99 mmol) in ethyl acetate was added, and the reaction mixture was stirred at room temperature for 2 hours. After the reaction was complete, the solvent was removed by concentration under reduced pressure, and the compound was purified by column chromatography to give compound I-2.362 (112 mg). 1 H NMR(400MHz,Chloroform-d)δ8.67(d,J=2.0Hz,1H),8.38(s,1H),7.85(d,J=2.0Hz,1H),7.59(s,1H),7.58(s,1H), 7.41(t,J=6.4Hz,1H),4.10(d,J=17.3Hz,1H),4.00–3.86(m,2H),3.71(d,J=17.3Hz,1H),2.74(s,3H),1.68(s,6H). LCMS(ESI):m / z 603[M+H] + .

[0227] Preparation Example 6

[0228] Preparation of compound I-2.476:

[0229] Step 1: Preparation of compound A-4

[0230] Boc-1-aminocyclopropylcarboxylic acid (201.0 mg, 1 mmol) was added to dichloromethane (4 mL), along with 2,2,2-trifluoroethylamine hydrochloride (162.6 mg, 1.2 mmol) and triethylamine (303.6 mg, 0.75 mmol). The resulting reaction mixture was stirred at room temperature for 15 minutes. Then, 50% butylphosphonic anhydride (2.8 g, 4.40 mmol) in ethyl acetate was added, and the reaction mixture was stirred at room temperature for 2 hours. After the reaction was complete, the solvent was removed by concentration under reduced pressure, and the compound was purified by column chromatography to give compound A-4 (205 mg). LCMS (ESI): m / z 283 [M+H] + .

[0231] Step 2: Preparation of compound B-4

[0232] To A-4 (141 mg, 0.5 mmol), 1 mL of 4 M dioxane chloride solution was added to 4 mL of dioxane, and the resulting reaction mixture was stirred at room temperature for 2 hours. After the reaction was complete, the solvent was removed by concentration under reduced pressure to give a white solid compound B-4. LCMS (ESI): m / z 183 [M+H] + .

[0233] Step 3: Preparation of compound I-2.476

[0234] To II-1 (104.5 mg, 0.25 mmol), B-4 (65.4 mg, 0.3 mmol) and triethylamine (75.9 mg, 0.75 mmol) were added to dichloromethane (4 mL), and the resulting reaction mixture was stirred at room temperature for 15 minutes. Then, 50% butylphosphonic anhydride (713.3 mg, 0.99 mmol) in ethyl acetate was added, and the resulting reaction mixture was stirred at room temperature for 2 hours. After the reaction was complete, the solvent was removed by concentration under reduced pressure, and the compound was purified by column chromatography to give compound I-2.476 (124 mg). 1 H NMR (400MHz, Chloroform-d) δ8.68(d,J=2.0Hz,1H),8.59(s,1H),7.88(d,J=2.0Hz,1H),7.59(s,1H),7.58(s,1H),6.85(t,J=6.5Hz ,1H),4.11(d,J=17.2Hz,1H),4.00–3.86(m,2H),3.72(d,J=17.2Hz,1H),2.78(s,3H),1.72(q,J=4.8Hz,2H),1.18(q,J=4.8Hz,2H). LCMS(ESI):m / z 601[M+H] + .

[0235] Preparation Example 7

[0236] Preparation of compound I-3.20:

[0237] Step 1: Preparation of compound C-1

[0238] Lawson's reagent (525.8 mg, 1.3 mmol) was added to toluene (10 mL) to A-1 (512.0 mg, 2 mmol). The reaction mixture was refluxed for 12 hours. After the reaction was complete, the mixture was cooled to room temperature, concentrated under reduced pressure to remove the solvent, and purified by column chromatography to give compound C-1 (190 mg). LCMS (ESI): m / z 273 [M+H] + .

[0239] Step 2: Preparation of compound D-1

[0240] C-1 (136.0 mg, 0.5 mmol) was added to dioxane (4 mL) along with 1 mL of 4 M dioxane hydrochloride solution. The resulting reaction mixture was stirred at room temperature for 2 hours. After the reaction was complete, the solvent was removed by concentration under reduced pressure to give a white solid compound D-1. LCMS (ESI): m / z 173 [M+H] + .

[0241] Step 3: Preparation of compound I-3.20

[0242] To a solution of II-1 (104.5 mg, 0.25 mmol) in dichloromethane (4 mL), D-1 (62.4 mg, 0.3 mmol) and triethylamine (75.9 mg, 0.75 mmol) were added, and the resulting reaction mixture was stirred at room temperature for 15 minutes. Then, 50% butylphosphonic anhydride (713.3 mg, 0.99 mmol) in ethyl acetate was added, and the reaction mixture was stirred at room temperature for 2 hours. After the reaction was complete, the solvent was removed by concentration under reduced pressure, and the compound was purified by column chromatography to give compound I-3.20 (122 mg). 1 H NMR(400MHz,Chloroform-d)δ8.98(s,1H),8.83(t,J=6.3Hz,1H),8.69(d,J=2.0Hz,1H),7.97–7.87(m,1H),7.59(s,1H ),7.58(s,1H),4.55(d,J=6.4Hz,2H),4.48–4.35(m,2H),4.11(d,J=17.2Hz,1H),3.72(d,J=17.3Hz,1H),2.77(s,3H). LCMS(ESI):m / z 591[M+H] + .

[0243] Preparation Example 8

[0244] Preparation of compound I-4.4:

[0245] Step 1: Preparation of compound E-1

[0246] Under a nitrogen atmosphere, 2 drops of N,N-dimethylformamide were added to II-1 (209.0 mg, 0.5 mmol) in anhydrous dichloromethane (10 mL), followed by the addition of oxaloyl chloride (82.5 mg, 0.65 mmol). The resulting reaction mixture was stirred at room temperature for 2 hours. After the reaction was complete, the solvent was removed by concentration under reduced pressure to obtain a brown crude product. Under a nitrogen atmosphere, the above crude product was added to tetrahydrofuran (5 mL) with ammonia (25% by mass, 5 mL), and the resulting reaction mixture was stirred at room temperature for 2 hours. After the reaction was complete, the reaction mixture was extracted with dichloromethane (3 x 20 mL) by adding 10 mL of aqueous solution. The combined organic layers were washed with a saturated sodium chloride solution, dried over sodium sulfate, and concentrated under reduced pressure to obtain crude product E-1. LCMS (ESI): m / z 436 [M+H] + .

[0247] Step 2: Preparation of compound I-4.4

[0248] To the crude product E-1, triethyl orthoformate (96.3 mg, 0.65 mmol) and methoxyamine hydrochloride (125.2 mg, 1.5 mmol) were added to toluene (10 mL), and the resulting reaction mixture was stirred at room temperature for 12 hours. After the reaction was complete, the solvent was removed by concentration under reduced pressure, and the compound was purified by column chromatography to give compound I-4.4 (123 mg). 1 H NMR(400MHz,Chloroform-d)δ10.65(d,J=10.4Hz,1H),8.76(d,J=2.0Hz,1H),7.94–7.86(m,1H),7.73(d,J=1 0.3Hz, 1H), 7.59 (d, J = 6.0Hz, 2H), 4.11 (d, J = 17.2Hz, 1H), 3.96 (s, 3H), 3.72 (d, J = 17.2Hz, 1H), 2.80 (s, 3H). LCMS(ESI):m / z 493[M+H] + .

[0249] Preparation Example 9

[0250] Preparation of compound I-5.4:

[0251] Step 1: Preparation of compound F-1

[0252] To (R)-4-aminoisoxazolidine-3-one (1.0 g, 10 mmol), triethylamine (1.5 g, 15 mmol) was added to tetrahydrofuran (10 mL) and deionized water (10 mL). Then, a solution of di-tert-butyl dicarbonate (2.6 g, 12 mmol) was slowly added dropwise to tetrahydrofuran (10 mL). The resulting reaction mixture was stirred at room temperature for 12 hours. After the reaction was complete, the mixture was concentrated under reduced pressure, extracted with dichloromethane (3 x 20 mL), and the combined organic layers were washed with a saturated sodium chloride solution and dried over sodium sulfate. The mixture was then concentrated under reduced pressure, and the compound was purified by column chromatography to give compound F-1 (1 g). LCMS (ESI): m / z 203 [M+H] + .

[0253] Step 2: Preparation of compound G-1

[0254] F-1 (1.0 g, 5 mmol) was added to N,N-dimethylformamide (15 mL) along with potassium carbonate (1.4 g, 10 mmol). The reaction mixture was stirred at 0 °C for 30 min, followed by the slow addition of iodoethane (1.2 g, 7.5 mmol). The reaction mixture was stirred at room temperature for 12 h. After the reaction was complete, the reaction mixture was diluted with water and extracted with dichloromethane (3 x 20 mL). The combined organic layers were washed with a saturated sodium chloride solution, dried over sodium sulfate, and concentrated under reduced pressure. The compound was purified by column chromatography to give compound G-1 (575 mg). LCMS (ESI): m / z 231 [M+H] + .

[0255] Step 3: Preparation of compound H-1

[0256] G-1 (115.0 mg, 0.5 mmol) was added to dioxane (4 mL) along with 1 mL of 4 M dioxane hydrochloride solution. The resulting reaction mixture was stirred at room temperature for 2 hours. After the reaction was complete, the solvent was removed by concentration under reduced pressure to give a white solid compound H-1. LCMS (ESI): m / z 131 [M+H] + .

[0257] Step 4: Preparation of compound I-5.4

[0258] To a solution of II-1 (104.5 mg, 0.25 mmol), H-1 (49.8 mg, 0.3 mmol) and triethylamine (75.9 mg, 0.75 mmol) were added to dichloromethane (4 mL), and the reaction mixture was stirred at room temperature for 15 minutes. Then, 50% butylphosphonic anhydride (713.3 mg, 0.99 mmol) in ethyl acetate was added, and the reaction mixture was stirred at room temperature for 2 hours. After the reaction was complete, the solvent was removed by concentration under reduced pressure, and the compound was purified by column chromatography to give compound I-5.4 (109 mg). 1 H NMR(400MHz,Chloroform-d)δ8.64(d,J=2.0Hz,1H),8.59(d,J=4.8Hz,1H),7.89(d,J=2.0Hz,1H),7.59(d, J=6.0Hz,2H),5.00–4.81(m,2H),4.18–4.01(m,2H),3.82–3.58(m,3H),2.76(s,3H),1.27(t,J=7.1Hz,3H). LCMS(ESI):m / z 549[M+H] + .

[0259] Preparation Example 10

[0260] Preparation of compound I-5.7:

[0261] To II-1 (104.5 mg, 0.25 mmol), 2-pyridinemethylamine (32.4 mg, 0.3 mmol) and triethylamine (75.9 mg, 0.75 mmol) were added to dichloromethane (4 mL), and the resulting reaction mixture was stirred at room temperature for 15 minutes. Then, 50% butylphosphonic anhydride (713.3 mg, 0.99 mmol) in ethyl acetate was added, and the resulting reaction mixture was stirred at room temperature for 2 hours. After the reaction was complete, the solvent was removed by concentration under reduced pressure, and the compound was purified by column chromatography to give compound I-2.32 (105 mg). 1H NMR (400MHz, Chloroform-d) δ8.95(t,J=5.6Hz,1H),8.70(d,J=2.0Hz,1H),8.64–8.50(m,1H),7.87(d,J=2.0Hz,1H),7.68(td,J=7.7,1.8Hz,1H),7.59( d,J=6.0Hz,2H),7.35(d,J=7.8Hz,1H),7.22(dd,J=7.5,5.0Hz,1H),4.76(d ,J=5.6Hz,2H),4.11(d,J=17.3Hz,1H),3.72(d,J=17.2Hz,1H),2.80(s,3H). LCMS(ESI):m / z 527[M+H] + .

[0262] Table 6

[0263] The compound of formula (I) of this invention was tested for its control activity against various agricultural pests, including cotton aphids, peach aphids, diamondback moths, rice stem borers, rice leaf rollers, beet armyworms, fall armyworms, cotton bollworms, whiteflies, thrips, brown planthoppers, gray planthoppers, flea beetles, and root-knot nematodes. The tested compound of formula (I) showed superior control efficacy, achieving unexpected technical results compared to existing technologies. Furthermore, the compound of formula (I) of this invention was tested for toxicity against environmental organisms such as bees, large daphnia, zebrafish, and earthworms. The tested compound of formula (I) showed low toxicity.

[0264] Biological Example 1

[0265] Cotton aphid (Aphis gossypii (Glover))

[0266] The activity of cotton aphids was tested using the immersion method. The test unit consisted of a 9cm plastic petri dish containing cucumber leaves that had grown for one month, and was kept moist with absorbent cotton. Healthy adult aphids were inoculated onto the cucumber leaves, and after 24 hours, the adult aphids were removed, and the total number of nymphs on each plate was recorded.

[0267] Prepare the test compound, add an appropriate amount of organic solvent (solvent content not exceeding 2%), and then dilute it to different concentrations with 0.1% Tween-80 aqueous solution. Soak cucumber leaves with 2-day-old aphid nymphs in the solution for 5 seconds, and allow the residual solution to dry completely. Perform three parallel treatments. Place all test units at 25±1℃ and a photoperiod of 16h:8h (L:D) for rearing and observation. Record the number of dead insects 72 hours after treatment and calculate the mortality rate.

[0268] Compounds of formula (I) of the present invention I-1.29, I-1.33, I-1.37, I-2.20, I-2.21, I-2.24, I-2.25, I-2.26 , I-2.27, I-2.28, I-2.30, I-2.32, I-2.33, I-2.34, I-2.39, I-2.40, I-2.41, I-2 .43, I-2.44, I-2.45, I-2.46, I-2.47, I-2.58, I-2.59, I-2.60, I-2.62, I-2.63 , I-2.64, I-2.65, I-2.66, I-2.135, I-2.136, I-2.138, I-2.139, I-2.141, I-2.1 42. I-2.146, I-2.148, I-2.153, I-2.154, I-2.155, I-2.157, I-2.158, I-2.160 , I-2.161, I-2.172, I-2.173, I-2.174, I-2.176, I-2.177, I-2.179, I-2.180, I- At a concentration of 50 ppm, pesticides I-2.249, I-2.250, I-2.268, I-2.287, I-2.481, I-2.500, I-2.502, I-2.519, I-4.4, I-4.7, I-4.10, I-5.1, I-5.4, I-5.8, and I-5.11 showed a mortality rate of ≥80% against cotton aphids 3 days after application.

[0269] Biological Example 2

[0270] Diamondback moth (Plutella xylostella (Linnaeus))

[0271] The activity of diamondback moth was tested by leaf immersion feeding. The test unit consisted of a 9cm plastic petri dish containing three fresh cabbage leaves of equal area.

[0272] Prepare the test compound by adding an appropriate amount of organic solvent (solvent content not exceeding 2%), then dilute it to different concentrations with 0.5% Triton X-100 aqueous solution. Soak fresh cabbage leaves in the solution for 10 seconds, and after the residual solution is fully dried, place them in petri dishes. Then, pick 10 third-instar larvae of diamondback moths into each petri dish, and perform three parallel treatments. Place all test units at 25±1℃ and a photoperiod of 16h:8h (L:D) for rearing and observation. Record the number of dead insects 3–5 days after treatment and calculate the mortality rate.

[0273] Compounds of formula (I) of the present invention I-2.9, I-2.20, I-2.21, I-2.22, I-2.24, I-2.25, I-2.26, I-2.27, I-2.28, I-2.29, I-2.30, I- 2.31, I-2.32, I-2.33, I-2.34, I-2.39, I-2.40, I-2.41, I-2.43, I-2.44, I-2.45, I-2.46, I-2.47, I-2.58, I -2.59, I-2.60, I-2.62, I-2.63, I-2.64, I-2.65, I-2.66, I-2.134, I-2.135, I-2136, I-2.138, I-2.139, I-2 .41, I-2.142, I-2.43, I-2.146, I-2.147, I-2.148, I-2.153, I-2.154, I-2.155, I-2.157, I-2.158, I-2.159 , I-2.160, I-2.161, I-2.172, I-2.173, I-2.174, I-2.176, I-2.177, I-2.178, I-2.179, I-2.180, I-2.249, I-2.287, I-2.376, I-2.476, I-2.480, I-2.481, I-2.483, I-2.484, I-2.485, I-2.489, I-2.490, I-2.495, I- 2.496, I-2.499, I-2.500, I-2.502, I-2.503, I-2.514, I-2.515, I-2.518, I-2.519, I-2.521, I-2.522, I-3. 20. When the concentration of I-3.134, I-3.476, I-4.4, I-4.10, I-5.1, I-5.4, I-5.6, I-5.8 and I-5.11 is 1ppm, the death rate of diamondback moth is ≥80% 3 days after treatment.

[0274] Parallel comparative experiments were conducted on the insecticidal activity of some of the compounds of this invention against the diamondback moth, using control compounds CK-H4 and CK-H17. Treatments were assessed by counting the number of live and dead larvae and by visually evaluating the percentage of feeding on plant material using a 0-10 rating scale. An increase of 10% in feeding from 0-100% was considered. Efficacy grading criteria:

[0275] A indicates that the insect mortality rate is greater than or equal to 80% to 100%;

[0276] B indicates that the insect mortality rate is greater than or equal to 60% and less than 80%;

[0277] C indicates that the insect mortality rate is greater than or equal to 40% and less than 60%;

[0278] D indicates that the insect mortality rate is greater than or equal to 20% and less than 40%;

[0279] E indicates that the insect mortality rate is less than 20%.

[0280] The results are as follows:

[0281] Biological Example 3

[0282] Rice stem borer (Chilo suppressalis (Walker))

[0283] The activity test of rice stem borer was conducted by leaf-immersion feeding method. The test unit was a 9cm plastic petri dish containing 15 6cm long 1-month-old rice stems.

[0284] Prepare the test compound by adding an appropriate amount of organic solvent (solvent content not exceeding 2%), and then dilute it to different concentrations with 0.5% Triton X-100 aqueous solution. Cut rice plants that have grown for one month at the root, clean them, and let them dry. Soak them in the drug solution for 10 seconds, and let the residual drug solution dry completely. Place them in a petri dish, and place filter paper in the petri dish to keep them moist. Then pick out 10 late second instar larvae of the rice stem borer into the petri dish, cover them with two layers of black cloth, and then cover the petri dish with the petri dish lid. Place all test units under the conditions of 28±1℃ and a photoperiod of 16h:8h (L:D) for rearing and observation. Record the number of dead insects 5 days after the drug treatment and calculate the mortality rate.

[0285] Compounds of formula (I) of the present invention I-1.25, I-1.37, I-2.9, I-2.24, I-2.25, I-2.27, I-2.31, I-2.39, I-2.40, I-2.47, I-2.58, I-2.135, I-2.1 36. When the concentration of I-2.139, I-2.141, I-2.362, I-2.364, I-2.476, I-4.6, I-5.1, I-5.6, I-5.8, and I-5.11 is 2ppm, the mortality rate for stem borer 5 days after treatment is ≥80%.

[0286] Biological Example 4

[0287] Rice leaf roller (Cnaphalocrocis medinalis Guenee)

[0288] The activity test of rice leaf roller was carried out by the leaf immersion method. The test unit consisted of a 7cm glass petri dish containing 10 wheat leaves about 5cm in length. Qualitative filter paper was placed at the bottom of the glass petri dish and moistened with water.

[0289] Prepare the test compound by adding an appropriate amount of organic solvent (solvent content not exceeding 2%), then dilute it to different concentrations with 0.1% Tween-80 aqueous solution. Cut wheat leaves to a length of about 5 cm and set aside. Immerse the wheat leaves in the prepared solutions of different concentrations for 20 seconds, then remove them and allow them to dry thoroughly on tissue paper. Transfer the wheat leaves to corresponding petri dishes, and inoculate 10 rice leaf roller larvae into each dish. Perform three parallel treatments. Place all test units in an incubator at 28±1℃ with a photoperiod of 16h:8h (L:D) for observation. Record the number of dead insects 48 hours after treatment and calculate the mortality rate.

[0290] The compound of formula (I) of this invention has excellent control efficacy against rice leaf roller.

[0291] Biological Example 5

[0292] Frankliniella occidentalis (Perganda)

[0293] The activity of western flower thrips was tested using the bean immersion drug film method. The test unit consisted of a 6cm plastic culture dish with drug attached, containing a fresh sword bean about 4cm in length.

[0294] Prepare the test compound by adding an appropriate amount of organic solvent (solvent content not exceeding 2%), then dilute it to different concentrations with 0.1% Triton X-100 aqueous solution. Cut fresh sword beans into lengths of approximately 4 cm and set aside. Immerse the sword beans in the prepared solutions of different concentrations for 30 seconds, then remove them and allow them to air dry thoroughly on tissue paper. Pour the remaining solution into 6 cm petri dishes, ensuring the plastic dishes are completely submerged. Let them stand for 30 seconds, then pour out the solution and allow them to air dry thoroughly. Transfer the dried sword beans to their respective petri dishes, and inoculate each petri dish with western flower thrips nymphs. Perform three parallel treatments. Place all test units in an incubator at 25±1℃ with a photoperiod of 16h:8h (L:D) and observe the results. Record the number of dead insects 72 hours after treatment and calculate the mortality rate.

[0295] Compounds of formula (I) of the present invention I-2.24, I-2.25, I-2.27, I-2.30, I-2.32, I-2.34, I-2.39, I-2.40, I-2.41, I-2.4 3. I-2.44, I-2.45, I-2.46, I-2.47, I-2.58, I-2.59, I-2.60, I-2.62, I-2.63, I-2.64, I-2.65, I -2.66, I-2.135, I-2.136, I-2.138, I-2.139, I-2.140, I-2.141, I-2.142, I-2.143, I-2.146, I- 2.148, I-2.153, I-2.154, I-2.155, I-2.157, I-2.158, I-2.160, I-2.161, I-2.172, I-2.173, I- 2.174, I-2.176, I-2.177, I-2.178, I-2.179, I-2.180, I-2.249, I-2.268, I-2.287, I-2.288, I -2.382, I-2.476, I-2.477, I-2.478, I-2.480, I-2.481, I-2.483, I-2.484, I-2.488, I-2.490, I At a concentration of 4 ppm, the mortality rate of western flower thrips was ≥80% 3 days after application of the pesticides I-2.495, I-2.496, I-2.497, I-2.499, I-2.500, I-2.502, I-2.503, I-2.514, I-2.515, I-2.516, I-2.518, I-2.519, I-2.521, I-2.522, I-3.134, I-5.8, and I-5.11.

[0296] Biological Example 6

[0297] Brown planthopper *Nilaparvata lugens* (Stal)

[0298] The activity test of brown planthopper was conducted using the rice seedling immersion method. The test unit consisted of a flat-bottomed glass test tube with a diameter of 3 cm and a height of 20 cm. Five rice seedlings with a height of 15 cm and a growth period of 15 days were placed inside the test tube, and 10 ml of water agar was poured into the bottom of the test tube to keep the roots of the rice seedlings moist.

[0299] Prepare the test compound by adding an appropriate amount of organic solvent (solvent content not exceeding 2%), then dilute it to different concentrations with 0.1% Triton X-100 aqueous solution. Clean and dry 15-day-old rice seedlings, immerse them in the drug for 10 seconds, and allow the residual drug solution to dry thoroughly on tissue paper. Pour agar into a glass flat-bottomed test tube, place the rice seedlings inside, and after the agar solidifies, use a suction device to inoculate brown planthopper nymphs, plugging the tube opening with cotton to prevent nymph escape. Perform three parallel treatments, placing all test units in an incubator at 28±1℃ with a photoperiod of 16h:8h (L:D) for observation. Record the number of dead insects 96 hours after drug application and calculate the mortality rate.

[0300] Compounds of formula (I) of the present invention I-1.37, I-2.20, I-2.21, I-2.25, I-2.30, I-2.39, I-2.40, I-2.44, I-2.59, I-2.60, I-2.135, I-2.136, I-2.139, I-2.141, I-2 .148, I-2.154, I-2.155, I-2.172, I-2.173, I-2.174, I-2.176, I-2.177, I-2.179, I-5.4, I-5.8 and I-5.11 have a mortality rate of ≥80% on brown planthoppers 4 days after treatment at a concentration of 50ppm.

[0301] Biological Example 7

[0302] Zebrafish (Barchydanio rerio)

[0303] Use healthy, disease-free zebrafish of uniform size. Before the experiment, they should be pre-reared under the same environmental conditions as the experimental one for 7-14 days. During the pre-rearing period, feed them 1-2 times a day, provide 12-16 hours of light per day, and clean up feces and food scraps promptly. Stop feeding 24 hours before the experiment.

[0304] The test unit was a 3L beaker, and a static test method was used. Test compounds were prepared by using organic solvents (DMSO, DMF, etc.) to create stock solutions, with a solvent content not exceeding 2%. Five to seven concentration gradients were prepared using tap water aerated for at least 24 hours. Five zebrafish were placed in each test unit, with a minimum capacity of 500mL. The poisoning symptoms and mortality rate of the fish were observed and recorded continuously for the first 6 hours of the experiment. Subsequently, the poisoning symptoms and mortality rate were observed and recorded at 24h, 48h, 72h, and 96h. The mortality rate was calculated and determined according to LC-125. 50 To determine toxicity level, the ratio of (96h) / (mg ai / L) is used. The toxicity classification standard is as follows: Extremely toxic: LC 50 ≤0.1; Highly toxic: 0.1 < LC 50 ≤1; Poisoning: 1 < LC 50 ≤10; Low toxicity: LC 50 >10.

[0305] The compound of formula (I) of the present invention exhibits low toxicity to fish.

[0306] Biological Example 8

[0307] Large Daphnia magna

[0308] Non-primate daphnia were cultured for at least three generations under laboratory conditions in a parthenogenetic state. The daphnia used in the experiment were healthy daphnia from the same maternal lineage, i.e., those that did not show any signs of stress (such as high mortality, presence of male daphnia and winter eggs, delayed primiparity, abnormal body color, etc.).

[0309] The test unit was a 50mL plastic cup. Test compounds were prepared using organic solvents (DMSO, DMF, etc.) to create a stock solution, with a solvent concentration not exceeding 0.1g / L. Five to seven concentration groups were set up. Ten juvenile Daphnia were placed in each test unit. All test units were cultured under conditions of a water temperature of 18℃~22℃ and a photoperiod of 16h:8h (L:D). The mortality rate of the large Daphnia was observed and statistically analyzed after 48 hours, based on EC... 50 To determine toxicity level, the ratio of (48h) / (mg ai / L) is as follows: Extremely toxic: EC 50 ≤0.1; Highly toxic: 0.1 < EC 50 ≤1; Poisoning: 1 < EC 50 ≤10; Low toxicity: EC 50 >10.

[0310] The compound of formula (I) of the present invention exhibits low toxicity to daphnia.

[0311] Biological Example 9

[0312] Italian worker bee (Apis mellifera L.)

[0313] Using adult Italian worker bees (Apis mellifera L.), test bees should be collected in the early morning; avoid conducting bee tests in early spring and late autumn; bees should not be used for testing within four weeks of receiving antibiotics or anti-mite drugs. Test bees should be healthy individuals of uniform size. Bees used for acute oral toxicity tests should be starved for 2 hours before the test.

[0314] 1. Acute oral toxicity

[0315] Prepare the test compound by using an organic solvent (acetone, etc.) to create a stock solution. Prepare 5-7 gradient concentrations of 50% sucrose solution, with 10 bees per concentration. Then, add 200 μL of the 50% sucrose solution containing different concentrations of the compound to the feeder. Set up a blank control group and a solvent control group. Measure the consumption of the drug solution. After the drug solution is consumed, feed the bees with the sucrose solution without the compound. Observe and record the poisoning symptoms and the number of deaths after 48 hours, calculate the mortality rate, and determine the 48-hour LD50. 50 Value and 95% confidence limit.

[0316] 2. Acute contact toxicity of bees

[0317] Prepare the test compound by using an organic solvent (acetone, etc.) to create a stock solution. Prepare 5-7 concentration gradients using a 50% sucrose solution, with 10 bees per concentration. Include a blank control group and a solvent control group. After anesthetizing the bees, apply 2 μL of the different concentrations of the test compound to the mesothorax of the bees. After the solvent evaporates, transfer the bees to test cages and feed them cotton wool soaked in sucrose water. Observe and record the poisoning symptoms and mortality rate of the bees after 48 hours, calculate the mortality rate, and determine the 48-hour LD50. 50 Value and 95% confidence limit.

[0318] According to LD 50 The toxicity level is determined by (48h) / (μg ai / bee). The toxicity levels are classified as follows: Extremely Toxic: LD 50 ≤0.001; Highly toxic: 0.001 < LD50 50 ≤2; Poisoning: 2 < LD 50 ≤11; Low toxicity: LD 50 >11.

[0319] Biological Example 10

[0320] A child loves earthworms (Eisenia foetida)

[0321] Adult Eisenia foetida earthworms, weighing between 0.3 and 0.6 g, were used in the experiment. The experimental temperature was 20℃ ± 2℃, the relative humidity was 70%–90%, and the light intensity was 400 lx–800 lx.

[0322] Prepare the test compound by using an organic solvent (acetone, etc.) to create a stock solution. Set up 5-7 concentration gradients, with the organic solvent volume generally not exceeding 0.1 mL / L. Include a blank control group and a solvent control group. Weigh 500 g of artificial soil into a specimen bottle and add the different concentrations of the drug solution, mixing thoroughly. Place 10 earthworms in each treatment, seal the bottle opening with gauze, and incubate for two weeks. Observe and record the poisoning symptoms and mortality of the earthworms on days 7 and 14, and calculate the median lethal concentration (LC50) of the drug solution for the earthworms. 50 Value and 95% confidence limit.

[0323] According to LC 50 To determine toxicity level using (14d) / (mg ai / kg dry soil), the toxicity levels are classified as follows: Extremely toxic: LD50 50 ≤0.1; Highly toxic: 0.1 < LC 50 ≤1; Poisoning: 1 < LC 50 ≤10; Low toxicity: LC 50 >10.

[0324] Biological Example 11

[0325] Chlorella vulgaris

[0326] The experiment used common Chlorella vulgaris, which was cultured under sterile conditions to achieve synchronous growth. The experimental environment temperature was 21℃~24℃ (the temperature of a single experiment was controlled within ±2℃); continuous and uniform light was provided, with the light intensity difference maintained within ±15%, and the light intensity was 4440lx~8880lx.

[0327] Prepare the test compound by using an organic solvent (acetone, etc.) to create a stock solution. Set up 5-7 concentration gradients, with the organic solvent volume generally not exceeding 0.1 mL / L. Include a blank control group and a solvent control group. Add different concentrations of the drug solution to the Chlorella solution. The experimental observation period is 72 hours, with samples taken every 24 hours. Measure the absorbance of the algae directly using a spectrophotometer. Calculate the algal growth inhibition rate according to EC. 50 To determine toxicity level using (72h) / (mg ai / L), the toxicity levels are classified as follows: Highly toxic: EC 50 ≤0.3; Poisoning: 0.3<EC 50 ≤3; Low toxicity: EC 50 >3.

[0328] Biological Example 12

[0329] North American quail (Colinus virginianus)

[0330] The test species is the North American quail (Colinus virginianus). The test birds should be in good health and without obvious deformities. A mortality rate of less than 5% within the first 7 days after introduction into the laboratory, and growth patterns consistent with the species' growth characteristics, are considered to indicate good health. The test birds should pass animal quarantine to ensure they are free of disease. The test birds should come from the same maternal parent and hatch on the same day.

[0331] 1. Acute oral toxicity

[0332] Prepare the test compound by using an organic solvent (acetone, etc.) to form a stock solution. Set up 5-7 concentration gradients, with 10 birds (half male and half female) at each concentration. Include a blank control group and a solvent control group. Administer different doses of the test compound (I) orally at a single dose of 1 mL / 100g body weight. Observe the poisoning and mortality of the test birds for 7 consecutive days and determine the 7-day LD50. 50 Values ​​and 95% confidence limits. Based on LD... 50 To determine toxicity level using / (mg(ai) / kg body weight), the toxicity levels are classified as follows: Extremely Toxic: LD50 50 ≤10; Highly toxic: 10 < LD50 50 ≤50; Poisoning: 50<LD 50 ≤500; Low toxicity: LD 50 >500.

[0333] 2. Acute feeding toxicity

[0334] Prepare the test compound by using an organic solvent (acetone, etc.) to create a stock solution. Establish 5-7 concentration gradients, with 10 birds per concentration (half male, half female), and include a blank control group and a solvent control group. Use a sprayer to apply the different concentrations of the solution to the food, stirring constantly until evenly mixed. Feed the test birds with feed containing different concentrations of the test compound (I) for 5 days. Starting from day 6, feed them with feed without the test compound for 3 days. Record the birds' poisoning and mortality daily, and calculate the LC50 over 8 days. 50 Values ​​and 95% confidence limits. According to LC... 50 To determine toxicity level using / (mg(ai) / kg feed), the toxicity levels are classified as follows: Extremely toxic: LC 50 ≤50; Highly toxic: 50 < LC 50 ≤500; Poisoning: 500 < LC 50 ≤1000; Low toxicity: LC 50 >1000.

[0335] Parallel comparative experiments were conducted on the insecticidal activity of some of the compounds of this invention against diamondback moth and western flower thrips, using control compounds CK-9 and CK-4. Treatments were assessed by counting the number of live and dead larvae and by visually evaluating the percentage of feeding on plant material using a 0-10 rating scale. An increase of 10% in feeding from 0-100% was considered. Efficacy grading criteria:

[0336] A indicates that the insect mortality rate is greater than or equal to 80% to 100%;

[0337] B indicates that the insect mortality rate is greater than or equal to 60% and less than 80%;

[0338] C indicates that the insect mortality rate is greater than or equal to 40% and less than 60%;

[0339] D indicates that the insect mortality rate is greater than or equal to 20% and less than 40%;

[0340] E indicates that the insect mortality rate is less than 20%.

[0341] The results are as follows:

[0342] As shown in the results above, the compounds of the present invention generally exhibit good insecticidal effects, producing excellent insecticidal efficacy even at low application doses. Furthermore, they demonstrate good safety for environmental organisms.

[0343] The above description is only a preferred embodiment of the present invention. It should be noted that those skilled in the art can make several changes and improvements without departing from the inventive concept of the present invention, and these all fall within the protection scope of the present invention.

Claims

A compound of formula (I), its N-oxide, stereoisomers, and agriculturally acceptable salts: in, R 1、 R3 is selected from chlorine or C1-C4 haloalkyl; R2 is selected from hydrogen, halogen, -CN, -NO2, C1-C4 alkyl, C1-C4 haloalkyl, C 1- When R2 is selected from hydrogen, R4 alkoxy or C1-C4 haloalkoxy; 1、 R3 is not simultaneously chlorine; When J is selected from -CR4R5C(=Z1)NHR6, -C(R7)=NOR6, -Q1 or -CH2Q1, R4 and R5 are each independently selected from hydrogen or C1-C3 alkyl; or R4 and R5 together with the carbon atoms to which they are attached form a 3- to 6-membered carbon ring. Or, when J is selected from -CR4R5C(=Z1)OR6, R4 and R5, together with the carbon atoms attached to them, form 3- to 6-membered carbon rings; or, when J is selected from -CR4R5C(=Z1)OR6, and R... 1、 When R3 is chlorine and R2 is F; R4 and R5 are each independently selected from hydrogen or C1-C3 alkyl groups; Each Z or Z1 is independently selected from O or S; Q1 is a 4- to 11-membered saturated or unsaturated ring or ring system, each optionally containing up to three heteroatoms selected from up to one O, up to one S and up to three N, wherein up to two carbon ring members are independently selected from C(=O) and C(=S) and the S ring member is selected from S, S(=O) and S(=O)2, and each ring or ring system is optionally substituted by one or more substituents independently selected from R8; R6 is hydrogen, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, C1-C3 alkyl C3-C6 cycloalkyl, C3-C6 cycloalkyl C1-C3 alkyl, C1-C6 haloalkyl, C3-C6 halocycloalkyl, C1-C3 haloalkyl C3-C6 cycloalkyl, C3-C6 halocycloalkyl C1-C3 alkyl, C3-C6 cycloalkyl-cyano or -N=C(C1-C3 alkyl)2; R7 is hydrogen or a C1-C3 alkyl group; Each R8 is independently selected from halogens, C1-C6 alkyl groups, and C1-C6 haloalkyl groups. The compound as claimed in claim 1, its N-oxide, stereoisomer, and agriculturally acceptable salt thereof: in: R 1、 R3 is selected from chlorine or CF3, and R2 is selected from hydrogen, halogen, or C1-C3 haloalkyl; and when R2 is selected from hydrogen, R 1、 R3 is not simultaneously chlorine; When J is selected from -CR4R5C(=Z1)NHR6, -C(R7=NOR6, -Q1 or -CH2Q1, R4 and R5 are each independently hydrogen or C1-C2 alkyl; Or R4 and R5, together with the carbon atoms attached to them, form a ternary carbon ring; When J is selected from -CR4R5C(=Z1)OR6, R4 and R5 together with the carbon atoms attached to them form a 3-membered carbon ring; Q1 is a 6-membered aromatic ring or a 5-membered saturated or unsaturated ring or ring system, each optionally containing up to three heteroatoms selected from up to one O, up to one S and up to three N, wherein up to two carbon atom ring members are independently selected from C(=O) and C(=S) and the S atom ring member is selected from S, S(=O) and S(=O)2, and each ring or ring system is optionally substituted by one or more substituents independently selected from R8; R6 is hydrogen, C1-C6 alkyl, C2-C6 alkenyl, C2-C6 alkynyl, C3-C6 cycloalkyl, C1-C3 alkyl C3-C6 cycloalkyl, C3-C6 cycloalkyl C1-C3 alkyl, C1-C6 haloalkyl, C3-C6 halocycloalkyl, C1-C3 haloalkyl C3-C6 cycloalkyl, C3-C6 halocycloalkyl C1-C3 alkyl, C3-C6 cycloalkyl-cyano or -N=C(C1-C3 alkyl)2; R7 is hydrogen or a C1-C3 alkyl group; Each R8 is independently selected from halogens, C1-C3 alkyl groups, and C1-C3 haloalkyl groups. The compound as claimed in claim 2, its N-oxide, stereoisomer, and agriculturally acceptable salt thereof: in: Q1 is a pyridine ring or a 5-membered saturated or unsaturated ring or ring system, each optionally containing up to three heteroatoms selected from up to one O, up to one S and up to one N, wherein up to two carbon ring members are independently selected from C (=O), and each ring or ring system is optionally substituted by one or more substituents independently selected from R8. Each R8 is independently selected from halogens, C1-C3 alkyl groups, and C1-C3 haloalkyl groups. The compound as claimed in claim 3, its N-oxide, stereoisomer, and agriculturally acceptable salt thereof: in, R 1、 R3 is selected from chlorine or CF3, and R2 is selected from hydrogen, F, Cl, or Br; and when R2 is selected from hydrogen, R 1、 R3 is not simultaneously chlorine; When J is selected from -CR4R5C(=Z1)NHR6, -C(R7)=NOR6, -Q1 or -CH2Q1, R4 and R5 are each independently hydrogen, -CH3 or -CH2CH3; or R4 and R5 together with the carbon atoms to which they are attached form a 3-membered carbon ring. When J is selected from -CR4R5C(=Z1)OR6, R4 and R5 together with the carbon atoms attached to them form a 3-membered carbon ring; Q1 is selected from R6 is selected from hydrogen, -CH3, -CH2CH3, -CH2CH2CH3, -CH(CH3)2, -CH2CH2CH2CH3, -CH(CH3)CH2CH3, -CH2CH(CH3)2, -C(CH3)3, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cyclopropylmethyl, -CH2CF3, -CF2CF3, -CH2CH2Cl, -CH2CFH2, -CH2CF2H, -CH2CH2CF3, -CH2CF2CF3, -CF2CF2CF3, -CH2CH2CF2H, -CH2C H2CFH2, -CF2CFHCF3, -CH(CH3)CF3, (R)-CH(CH3)CF3, (S)-CH(CH3)CF3, -CH2CF2CH3, -CH2CF2CF2CF3, -CH2CH=CH2, -CH(CH3 )CH=CH2, (E)-CH2CH=CHCH3, (Z)-CH2CH=CHCH3, -CH2CH=C(CH3)2, -CH2C≡CH, -CH2C(CH3)=CH2, -C=CH2CH2CH3, -N=C(CH3)2, R7 is selected from hydrogen or -CH3; Each R8 is independently selected from -CH3, -CH2CH3, -CH2CF3, -CH2CF2H, -CH2CFH2. The compound as claimed in claim 4, its N-oxide, stereoisomer, and agriculturally acceptable salt thereof: in, R1 is chlorine, R2 is selected from fluorine, hydrogen, or chlorine, and R3 is selected from chlorine or trifluoromethyl; and when R2 is selected from hydrogen, R 1、 R3 is not simultaneously chlorine; When J is selected from -CR4R5C(=Z1)NHR6, -C(R7)=NOR6, -Q1 or -CH2Q1, R4 and R5 are each independently hydrogen, -CH3 or -CH2CH3; or R4 and R5 together with the carbon atoms to which they are attached form a 3-membered carbon ring. When J is selected from -CR4R5C(=Z1)OR6, R4 and R5 together with the carbon atoms attached to them form a 3-membered carbon ring; Q1 is selected from R6 is selected from hydrogen, -CH3, -CH2CH3, -CH2CH2CH3, -CH(CH3)2, cyclopropyl, cyclopropylmethyl, -CH2CF3, -CF2CF3, -CH2CH2Cl, -CH2CFH2, -CH2CF2H, -CH2CH2CF3, -CH2CF2CF3, -CF2CF2CF3, -CH2CH2CF2H, -CH2CH2CFH2, -CF2CFHCF3, -CH(CH3)CF3, (R)-CH(CH3)CF3, (S)-CH(CH3)CF3, -CH2CF2CH3, -CH2CF2CF2CF3, -CH2CH=CH2, -CH2C≡CH, -N=C(CH3)2. R7 is hydrogen; Each R8 is independently selected from -CH2CH3, -CH2CF3, -CH2CF2H, and -CH2CFH2. The compound as claimed in claim 5, its N-oxide, stereoisomer, and agriculturally acceptable salt thereof: in, R1 and R3 are chlorine, and R2 is fluorine; Or R1 and R3 are selected from chlorine or trifluoromethyl, and R1 and R3 are not the same, and R2 is selected from chlorine, hydrogen or fluorine; J is selected from -CR4R5C(=O)OR6, -CR4R5C(=O)NHR6, -CH=NOR6 or Q1; When J is selected from -CR4R5C(=O)NHR6, -CH=NOR6 or Q1, R4 and R5 are each independently hydrogen, -CH3 or -CH2CH3; or R4 and R5 together with the carbon atoms attached to them form a 3-membered carbon ring. When J is selected from -CR4R5C(=Z1)OR6, R4 and R5 together with the carbon atoms attached to them form a 3-membered carbon ring; Q1 is R6 is selected from hydrogen, -CH3, -CH2CH3, -CH2CH2CH3, -CH(CH3)2, cyclopropyl, cyclopropylmethyl, -CH2CF3, -CF2CF3, -CH2CFH2, -CH2CF2H, -CH2CH2CF3, -CH2CF2CF3, -CF2CF2CF3, -CH2CH2CF2H, -CH2CH2CFH2, -CF2CFHCF3, -CH(CH3)CF3, (R)-CH(CH3)CF3, (S)-CH(CH3)CF3, -CH2CF2CH3, -CH2CF2CF2CF3, -CH2CH=CH2, -CH2C≡CH, -N=C(CH3)2. A method for preparing the compound of formula (I) according to any one of claims 1-6, its N-oxide, stereoisomers, and agriculturally acceptable salts thereof, characterized in that: J-NH2 reacts with a compound of formula (II-A) in an organic solvent in the presence of a base to prepare a compound of formula (I), wherein the organic solvent is selected from at least one of dichloromethane, 1,2-dichloroethane, chloroform, carbon tetrachloride, tetrahydrofuran, 2-methyltetrahydrofuran, 1,4-dioxane, benzene, toluene, o-xylene, m-xylene, p-xylene, xylene, chlorobenzene, acetonitrile, N,N-dimethylformamide, N,N-dimethylacetamide, or dimethyl sulfoxide; the base is selected from at least one of 4-dimethylaminopyridine, trimethylamine, triethylamine, diisopropylethylamine, pyridine, 2-methylpyridine, 3-methylpyridine, 1,8-diazabicyclo[5.4.0]undec-7-ene, or 2,6-dimethylpyridine; and R1, R2, R3, J, and Z are as defined in any one of claims 1-6. A composition comprising a compound of formula (I) as described in any one of claims 1-6 and at least one additional component selected from the group consisting of surfactants, solid diluents and liquid diluents, wherein the weight percentage of the compound of formula (I) in the composition is 0.1-99.9%. A method for controlling pests, characterized in that, The compound of formula (I) as described in any one of claims 1-6, its stereoisomers and agriculturally acceptable salts thereof, or the composition of claim 8, is applied to the pest or its growth environment. The use of a compound of formula (I) as described in any one of claims 1-6, its stereoisomers and agriculturally acceptable salts thereof, or the composition of claim 8 in the control of pests.

Images