Amide derivative and preparation and application thereof

Abstract

The invention relates to an amide derivative as well as preparation and application thereof. Specifically, the invention relates to a compound as shown in a formula (I) as an amide derivative or an isotope labeled compound thereof, or an optical isomer, a geometric isomer, a tautomer or an isomer mixture thereof, or an acceptable salt, and application of the compound in preparation of a pesticide for pest control, the invention also relates to the use thereof for the control of insects, arachnids and nematodes in agriculture, and for the control of ectoparasites in non-agriculture. # imgabs0 #

Description

Technical Field

[0001] The present invention relates to the field of medicinal chemistry, and particularly to an amide derivative and its preparation and application. Background Art

[0002] Although there are various control measures for invertebrate pests, new and more effective and reasonable insecticidal compounds are still being continuously explored and discovered. The present invention provides a new type of compound that can be further studied. Pyrazole compounds have excellent biological and physiological activities. In the fields of healthcare and plant and animal protection, pyrazole compounds have shown extensive applications and development prospects. Especially in the field of plant and animal protection, this type of compound has a different mechanism of action from most of the agents used in the field of pest control, and can solve the increasingly serious resistance problem. Just because of this, pyrazole compounds have opened up new horizons for the development of medicinal chemistry and provided a new way to search for new invertebrate pest control agents with high efficiency and low toxicity. Summary of the Invention

[0003] The present invention relates to an amide derivative, which has a novel structure and is applicable to agricultural and non-agricultural uses. It can be used to control invertebrate pests, parasites, and sanitary pests, etc. Especially, it has excellent control effects on pests such as insects, arachnids, and nematodes in agriculture, and ectoparasites in non-agriculture.

[0004] Specifically:

[0005] On the one hand, the present invention relates to a compound, which is a compound represented by formula (I) or a stereoisomer, N-oxide or salt thereof of the compound represented by formula (I):

[0006]

[0007] Wherein,

[0008] X1, X2, X3, X4 are each independently selected from hydrogen, halogen, hydroxyl, nitro, amino, cyano, carboxyl, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-12 cycloalkyl, C 1-6 haloalkyl, C 1-6 alkoxy or C 1-6 haloalkoxy;

[0009] R1 is selected from C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-12 cycloalkyl, C 3-6 heterocyclic group, C 6-12 aryl, C 5-12 heteroaryl, C1-6 Alkoxy C 1-6 Alkyl, C 1-6 Alkylthio C 1-6 Alkyl, C 1-6 Alkylamino C 1-6 Alkyl, C 3-12 Cycloalkyl C 1-6 Alkyl, C 3-6 Heterocyclic C 1-6 Alkyl, C 6-12 Aryl C 1-6 Alkyl, C 5-12 Heteroaryl C 1-6 Alkyl, C 6-12 Aryloxy C 1-6 Alkyl, C 5-12 Heteroaryloxy C 1-6 Alkyl,

[0010] or R1 is selected from -C(=O)-R2, where R2 is selected from C 1-6 Alkyl, C 2-6 Alkenyl, C 2-6 Alkynyl, C 1-6 Alkoxy, C 1-6 Alkylthio, C 1-6 Alkylamino, C 3-12 Cycloalkyl, C 3-8 Heterocyclic, C 6-12 Aryl, C 6-12 Aryloxy, C 5-12 Heteroaryl, C 5-12 Heteroaryloxy, C 1-6 Alkoxy C 1-6 Alkyl, C 1-6 Alkylthio C 1-6 Alkyl, C 1-6 Alkylamino C 1-6 Alkyl, C 3-12 Cycloalkyl C 1-6 Alkyl, C 3-6 Heterocyclic C 1-6 Alkyl, C 6-12 Aryl C 1-6 Alkyl, C 5-12 Heteroaryl C 1-6 Alkyl, C 6-12 Aryloxy C 1-6 Alkyl, C 5-12 Heteroaryloxy C 1-6 Alkyl;

[0011] and R1, R2 may be mono - substituted or poly - substituted by one or more identical or different substituents selected from: halogen, cyano, nitro, C 1-6 Alkyl, C 1-6 Alkoxy, C 1-6 Halogenated alkyl, C1-6 alkoxycarbonyl, C 1-6 alkylamino, C 6-12 aryl;

[0012] W is selected from nitrogen or carbon;

[0013] Q is selected from C 4-12 cycloalkyl, C 4-12 heterocycloalkyl, which may be mono - substituted or poly - substituted by one or more identical or different substituents selected from: fluorine, chlorine, bromine, cyano, C 1-3 alkyl.

[0014] In some embodiments, X1, X2, X3, X4 are each independently selected from hydrogen, halogen, hydroxy, nitro, amino, cyano,, carboxy, C 1-3 alkyl, C 2-4 alkenyl, C 2-4 alkynyl, C 3-6 cycloalkyl, C 1-3 haloalkyl, C 1-3 alkoxy or C 1-3 haloalkoxy;

[0015] R1 is selected from C 1-3 alkyl, C 2-4 alkenyl, C 2-4 alkynyl, C 3-6 cycloalkyl, C 3-6 heterocyclic group, C 6-12 aryl, C 5-12 heteroaryl, C 1-3 alkoxyC 1-3 alkyl, C 1-3 alkylthioC 1-3 alkyl, C 1-3 alkylaminoC 1-3 alkyl, C 3-12 cycloalkylC 1-3 alkyl, C 3-6 heterocyclic groupC 1-3 alkyl, arylC 1-3 alkyl, C 5-12 heteroarylC 1-3 alkyl, C 6-12 aryloxyC 1-3 alkyl, C 5-12 heteroaryloxyC 1-3 alkyl,

[0016] or R1 is selected from - C(=O)-R2, where R2 is selected from C 1-3 alkyl, C 2-4 alkenyl, C 2-4 alkynyl, C 1-3 alkoxy, C 1-3 alkylthio, C 1-3Alkylamino, C 3-8 Cycloalkyl, C 3-8 Heterocyclic group, C 6-12 Aryl, C 6-12 Aryloxy, C 5-12 Heteroaryl, C 5-12 Heteroaryloxy, C 1-3 Alkoxy C 1-3 Alkyl, C 1-3 Alkylthio C 1-3 Alkyl, C 1-3 Alkylamino C 1-3 Alkyl, C 3-8 Cycloalkyl C 1-3 Alkyl, C 3-6 Heterocyclic group C 1-3 Alkyl, C 6-12 Aryl C 1-3 Alkyl, C 5-12 Heteroaryl C 1-3 Alkyl, C 6-12 Aryloxy C 1-3 Alkyl, C 5-12 Heteroaryloxy C 1-3 Alkyl;

[0017] And R1, R2 can be mono - substituted or multi - substituted by one or more identical or different substituents, and the substituents are selected from: fluorine, chlorine, bromine, cyano, nitro, C 1-3 Alkyl, C 1-3 Alkoxy, C 1-3 Halogenated alkyl, C 1-3 Alkoxycarbonyl, C 1-3 Alkylamino, C 6-12 Aryl;

[0018] W is selected from nitrogen or carbon;

[0019] Q is selected from C 4-8 Cycloalkyl, C 4-8 Heterocycloalkyl, which can be mono - substituted or multi - substituted by one or more identical or different substituents, and the substituents are selected from: fluorine, chlorine, bromine, cyano, C 1-3 Alkyl.

[0020] In some other embodiments, X1, X2, X3, X4 are each independently selected from hydrogen, fluorine, chlorine, bromine, iodine, hydroxyl, cyano, nitro, amino, carboxyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, C 1-3 Alkyl, C 1-3 Halogenated alkyl, C 1-3 Alkoxy or C 1-3 Halogenated alkoxy;

[0021] R1 is selected from C 1-3 Alkyl, C 2-4 Alkenyl, C2-4 Alkynyl, C 3-6 Cycloalkyl, C 3-6 Heterocyclic group, C 6-9 Aryl, C 5-9 Heteroaryl, C 1-3 Alkoxy C 1-3 Alkyl, C 1-3 Alkylthio C 1-3 Alkyl, C 1-3 Alkylamino C 1-3 Alkyl, C 3-6 Cycloalkyl C 1-3 Alkyl, C 3-6 Heterocyclic group C 1-3 Alkyl, C 6-9 Aryl C 1-3 Alkyl, C 5-6 Heteroaryl C 1-3 Alkyl,

[0022] or R1 is selected from -C(=O)-R2, where R2 is selected from C 1-3 Alkyl, C 2-4 Alkenyl, C 2-4 Alkynyl, C 1-3 Alkoxy, C 1-3 Alkylthio, C 1-3 Alkylamino, C 3-8 Cycloalkyl, C 3-8 Heterocyclic group, C 6-12 Aryl, C 5-12 Heteroaryl, C 1-3 Alkoxy C 1-3 Alkyl, C 1-3 Alkylthio C 1-3 Alkyl, C 3-8 Cycloalkyl C 1-3 Alkyl, C 3-6 Heterocyclic group C 1-3 Alkyl, C 6-12 Aryl C 1-3 Alkyl, C 5-12 Heteroaryl C 1-3 Alkyl;

[0023] and R1, R2 may be mono - substituted or poly - substituted by one or more identical or different substituents, and the substituents are selected from: fluorine, chlorine, bromine, cyano, nitro, C 1-3 Alkyl, C 1-3 Alkoxy, C 1-3 Halogenated alkyl, C 1-3 Alkoxycarbonyl;

[0024] W is selected from nitrogen or carbon;

[0025] Q is selected from C 4-6 Cycloalkyl, C 4-6Heterocycloalkyl, which may be mono- or polysubstituted by one or more identical or different substituents selected from: fluorine, chlorine, bromine, cyano, C 1-3 alkyl.

[0026] In some other embodiments, X1, X2, X3, X4 are each independently selected from hydrogen, fluorine, chlorine, bromine, iodine, cyano, cyclopropyl, C 1-3 alkyl or C 1-3 haloalkyl;

[0027] R1 is selected from C 1-3 alkyl, C 2-4 alkenyl, C 2-4 alkynyl, C 3-6 cycloalkyl, C 3-6 heterocyclic group, C 6-9 aryl, C 5-9 heteroaryl, C 1-3 alkoxyC 1-3 alkyl, C 1-3 alkylthioC 1-3 alkyl, C 1-3 alkylaminoC 1-3 alkyl, C 3-6 cycloalkylC 1-3 alkyl, C 3-6 heterocyclic groupC 1-3 alkyl, C 6-9 arylC 1-3 alkyl, C 5-9 heteroarylC 1-3 alkyl,

[0028] or R1 is selected from -C(=O)-R2, where R2 is selected from C 1-3 alkyl, C 2-4 alkenyl, C 2-4 alkynyl, C 1-3 alkoxy, C 1-3 alkylthio, C 1-3 alkylamino, C 3-8 cycloalkyl, C 3-8 heterocyclic group, C 6-12 aryl, C 5-12 heteroaryl;

[0029] and R1 and R2 may be mono- or polysubstituted by one or more identical or different substituents selected from: fluorine, chlorine, bromine, cyano, nitro, C 1-3 alkyl, C 1-3 alkoxy, C 1-3 haloalkyl;

[0030] W is selected from nitrogen or carbon;

[0031] Q is selected from the following groups:

[0032]

[0033] In some other embodiments, X1, X2, X3, and X4 are each independently selected from hydrogen, fluorine, chlorine, bromine, iodine, cyano, cyclopropyl, C 1-3 alkyl or C 1-3 haloalkyl;

[0034] R1 is selected from methyl, ethyl, n-propyl, isopropyl, allyl, propargyl, cyclopropylmethyl, glycidylmethyl,

[0035] or R1 is selected from -C(=O)-R2, where R2 is selected from methyl, ethyl, n-propyl, isopropyl, allyl, propargyl, methoxy, ethoxy, n-propoxy, isopropoxy, N,N-dimethylamino, cyclopropyl, glycidyl, furyl, phenyl,

[0036] and R1 and R2 may be mono- or poly-substituted by one or more identical or different substituents selected from: fluorine, chlorine, bromine, cyano, nitro, C 1-3 alkyl, C 1-3 alkoxy, C 1-3 haloalkyl;

[0037] W is selected from nitrogen or carbon;

[0038] Q is selected from the following groups:

[0039]

[0040] In some other embodiments, the exemplary compound structures are as follows:

[0041]

[0042] In some other embodiments, R1 is selected from -C(=O)-R2, and the exemplary compound structures are as follows:

[0043]

[0044]

[0045] To avoid ambiguity, the terms used herein are defined below. Unless otherwise specified, the meanings of the terms used herein are as follows.

[0046] The term "alkyl", used alone or in compound words such as "alkylthio" or "haloalkyl", includes straight-chain or branched alkyl groups, such as methyl, ethyl, n-propyl, isopropyl, or the different butyl, pentyl, or hexyl isomers. "Alkenyl" includes straight-chain or branched alkenes, such as vinyl, 1-propenyl, 2-propenyl, and the different butenyl, pentenyl, and hexenyl isomers. "Alkenyl" also includes polyenes, such as 1,2-propadienyl and 2,4-hexadienyl. "Alkynyl" includes straight-chain or branched alkynes, such as ethynyl, 1-propynyl, 2-propynyl, and the different butynyl, pentynyl, and hexynyl isomers. "Alkynyl" may also include moieties composed of multiple triple bonds, such as 2,5-hexadiynyl. "Alkylene" represents a straight-chain or branched alkanediyl. The "alkyl", "alkenyl", and "alkynyl" groups may optionally be substituted with one or more (e.g., 1 to 5) suitable substituents.

[0047] The term "haloalkyl" refers to an alkyl group having one or more halogen substituents (up to perhaloalkyl, i.e., each hydrogen atom of the alkyl group is replaced by a halogen atom). For example, the term "C1-C6 haloalkyl" refers to a C1-C6 alkyl group having one or more halogen substituents (up to perhaloalkyl, i.e., each hydrogen atom of the alkyl group is replaced by a halogen atom). The term "C1 haloalkyl" refers to a methyl group having 1, 2, or 3 halogen substituents. Examples of haloalkyl groups include: CF3, C2F5, CHF2, CH2F, CH2CF3, CH2Cl, etc.

[0048] The term "alkoxy" includes, for example, methoxy, ethoxy, n-propoxy, isopropoxy, and the different butoxy, pentoxy, and hexoxy isomers. "Alkoxyalkyl" represents an alkoxy substitution on an alkyl group. Examples of "alkoxyalkyl" include CH3OCH2, CH3OCH2CH2, CH3CH2OCH2, CH3CH2CH2OCH2, and CH3CH2OCH2CH2.

[0049] The term "alkylthio" includes branched or straight-chain alkylthio moieties, such as methylthio, ethylthio, and the different propylthio, butylthio, pentylthio, and hexylthio isomers. "Alkylthioalkyl" represents an alkylthio substitution on an alkyl group, and examples include CH3SCH2, CH3SCH2CH2, CH3CH2SCH2, CH3CH2CH2CH2SCH2, and CH3CH2SCH2CH2.

[0050] The term "alkylcarbonyl" denotes a straight-chain or branched alkyl moiety bonded to a C(=O) moiety. Examples of "alkylcarbonyl" include CH3C(=O)-, CH3CH2CH2C(=O)-, and (CH3)2CHC(=O)-. Examples of "alkoxycarbonyl" include CH3OC(=O)-, CH3CH2OC(=O)-, CH3CH2CH2OC(=O)-, (CH3)2CHOC(=O), and the different butoxycarbonyl, pentyloxycarbonyl, and hexyloxycarbonyl isomers.

[0051] The term "cycloalkyl" includes, for example, cyclopropyl, cyclobutyl, cyclopentyl, and cyclohexyl. The term "alkylcycloalkyl" denotes an alkyl substitution on a cycloalkyl moiety and includes, for example, ethylcyclopropyl, isopropylcyclobutyl, 3-methylcyclopentyl, and 4-methylcyclohexyl. The term "cycloalkylalkyl" denotes a cycloalkyl substitution on an alkyl moiety. Examples of "cycloalkylalkyl" include cyclopropylmethyl, cyclopentylethyl, cyclohexylmethyl, and other cycloalkyl moieties bonded to a straight-chain or branched alkyl.

[0052] The term "halogen", either alone or in a compound word such as "haloalkyl", or when used in a description such as "alkyl substituted by halogen", includes fluorine, chlorine, bromine, or iodine. Further, when used in a compound word such as "haloalkyl", or when used in a description such as "alkyl substituted by halogen", the alkyl may be partially or completely substituted by halogen atoms, which may be the same or different. Examples of "haloalkoxy" include CF3O-, CCl3CH2O-, HCF2CH2CH2O-, and CF3CH2O-. Examples of "haloalkylthio" include CCl3S-, CF3S-, CCl3CH2S-, and ClCH2CH2CH2S-.

[0053] The total number of carbon atoms in a substituent is denoted by the "C i -C j " prefix, where i and j are numbers from 1 to 9. For example, C1-C4 alkyl denotes methyl to butyl.

[0054] The following abbreviations may be used herein: Me is methyl, Et is ethyl, Pr is propyl, cPr is cyclopropyl, nPr is n-propyl, iPr is isopropyl, Bu is butyl, nBu is n-butyl, iBu is isobutyl, sBu is sec-butyl, tBu is tert-butyl, cBu is cyclobutyl, Pn is pentyl, cPn is cyclopentyl, cHx is cyclohexyl, cHp is cycloheptyl, Oct is octyl, Ph is phenyl, Bn is benzyl, Thi is thien-2-yl, Pyrr is pyrrol-1-yl, 2-Py is pyridin-2-yl, 3-Py is pyridin-3-yl, 4-Py is pyridin-4-yl. In substituents represented by multiple abbreviations, the substituents are composed of the substituents represented by the abbreviations bonded to each other. For example, 2-Me-Ph represents a 2-methyl-substituted phenyl, and cPr-CH2 represents a cyclopropyl-substituted methyl.

[0055] A variety of synthetic methods are known in the art for preparing aromatic and non-aromatic heterocycles and ring systems; for a comprehensive review, see the eight-volume collection of Comprehensive Heterocyclic Chemistry, edited by A. R. Katritzky and C. W., Pergamon Press, Oxford, 1984 and the twelve-volume collection of Comprehensive Heterocyclic Chemistry II, edited by A. R. Katritzky, C. W. Rees and E. F. V. Scriven, Pergamon Press, Oxford, 1996.

[0056] The compounds of the present invention may exist as one or more stereoisomers. Stereoisomers are isomers that have the same constitution but differ in the arrangement of their atoms in space, and include enantiomers, diastereomers, cis-trans isomers (also known as geometric isomers) and atropisomers. Atropisomers result from restricted rotation about a single bond, where the rotational barrier is high enough to allow separation of the isomeric species. Those skilled in the art will understand that a stereoisomer may be more active and / or may exhibit beneficial effects when enriched relative to one or more other stereoisomers or when separated from one or more other stereoisomers. Additionally, those skilled in the art know how to separate, enrich and / or selectively prepare the stereoisomers. For a comprehensive discussion of all aspects of stereochemistry, see Ernest L. Eliel and Samuel H. Wilen, Stereochemistry of Organic Compounds, John Wiley & Sons, 1994.

[0057] The present invention provides a method for preparing a compound of formula (I) as an amide derivative:

[0058] Synthesis scheme:

[0059]

[0060] The target compound I can be prepared by the above synthesis scheme. The specific steps include: dissolving raw material A in a suitable solvent, obtaining product B under the action of an acyl chlorination reagent, performing an amide condensation reaction between product B and the corresponding amine or amine salt to obtain product C, obtaining a boric acid intermediate from product C under the action of a boron donor and a catalyst, and then performing a Suzuki coupling with compound E to obtain product F. Product F undergoes a substitution reaction with G under basic conditions at a temperature of 0 - 120 °C for 1 - 24 hours to obtain the target compound I. Among them, Y is selected from fluorine, chlorine or bromine, and Z is selected from bromine or iodine. The remaining substituents are as described above.

[0061] In addition, the present invention also lists multiple synthesized exemplary compounds, and the specific group selections are shown in Table 1 below. It should be understood that the scope of the present invention is not limited to the exemplary compounds listed in the following table, and the group selections of the compounds in Table 1 below can be combined arbitrarily without particular limitation.

[0062] In general formula I - 1 of Table 1, W = N, and X1, X2, X3, X4, R1, Q are specifically shown in the following table.

[0063]

[0064]

[0065] In general formula I - 1 of Table 2, W = C, and the remaining substituents X1, X2, X3, X4, R1, Q are the same as those in Table 1.

[0066] In general formula I - 2 of Table 3, W = N, R1 = C(=O)R2, and X1, X2, X3, X4, R2, Q are specifically shown in the following table.

[0067]

[0068]

[0069] In general formula I - 2 of Table 4, W = C, and the remaining substituents X1, X2, X3, X4, R2, Q are the same as those in Table 3.

[0070] In a second aspect, the present invention provides an insecticide composition comprising a compound of formula (I) or its isotope - labeled compound, or its optical isomer, geometric isomer, tautomer or isomer mixture, or an acceptable salt, and an acceptable carrier.

[0071] An acceptable carrier for the composition can be an organic or inorganic inert carrier material. For example, suitable carriers include water, gelatin, gum arabic, magnesium stearate, talc, vegetable oils, polyalkylene glycols, petrolatum, mannitol, cellulose, cellulose derivatives, sodium saccharin, magnesium carbonate, brine, glycerol, ethanol, etc. In addition, the pesticidal composition may further contain other additives, such as preservatives, stabilizers, emulsifiers, buffering agents, diluents, binders, wetting agents, lubricants, glidants, etc.

[0072] The dosage form of the pesticidal composition of the present invention can be a liquid dosage form, a solid dosage form or a semi-solid dosage form, without particular limitation. In some embodiments, the dosage form of the pesticidal composition is selected from powders, granules, liquids, suspensions or sprays, preferably wettable powders, wettable liquids, soluble powders, dispersible liquids, aqueous solutions, microemulsions, emulsifiable concentrates, emulsions in water, sprayable solutions, dispersible oil suspensions, microcapsule suspensions, water-dispersible granules, water-soluble granules, macrogranules, granules for broadcasting and soil application, aerosols, ultra-low volume agents and wax products.

[0073] The content of the compound of the present invention in its pesticidal composition can be adjusted according to actual needs (such as dosage form, application method, application object, etc.), including but not limited to 0.001 mg / L - 10 mg / L, for example 0.001 mg / L, 0.01 mg / L, 0.1 mg / L, 0.5 mg / L, 1 mg / L, 2.5 mg / L, 5 mg / L or 10 mg / L.

[0074] The specific application frequency can be determined by those skilled in the relevant art, such as once a day, once every two days, once every three days, once every four days, once every five days, once every six days, twice a day, three times a day, etc.

[0075] In a third aspect, the present invention provides the use of a compound of formula (I) or its isotope-labeled compound, or its optical isomer, geometric isomer, tautomer or isomer mixture, or an acceptable salt thereof in the preparation of a pesticide for pest control.

[0076] The compounds of the present invention are suitable for controlling pests or mites, that is, controlling pests or mites. The pests or mites refer to harmful or unwanted insects or mites, especially harmful or unwanted insects or mites encountered in the fields of agriculture, forestry, storage protection, material protection, as well as the fields of hygiene and animal protection. The compounds of the present invention are active against both generally sensitive and resistant species and are effective at all stages of the development of pests or mites.

[0077] The present invention also relates to a method for controlling pests or acarids, which method comprises applying a controlling effective amount of a compound of formula (I) to the location of insects, insect habitats, pest habitats, areas to be protected, or directly to the insects to be controlled. The compounds of the present invention can also be used to control other invertebrate pests or organisms.

[0078] Specifically, the insect habitats, pest habitats or acarid habitats refer to the environments where insects, pests or acarids live or their eggs exist, including the surrounding air, the food they eat or the objects they contact. For example, by applying the active compound to the seeds of plants (before planting), to seedlings, or planted cuttings, leaves, stems, fruits, grains and / or roots, or to the soil or other growth media (before or after crop planting), insects or acarids that eat, damage or contact edible agricultural products, ornamental plants, turf, forage plants or other economically valuable plants can be controlled. It is also possible to protect these plants against diseases caused by viruses, fungi or bacteria by controlling sap-sucking pests such as whiteflies, planthoppers, aphids, etc. or acarids such as Tetranychus urticae, Tetranychus cinnabarinus, etc.; the plants include plants obtained by conventional breeding methods and also plants with insect or acarid resistance, herbicide resistance, high yield and / or other beneficial characteristics obtained by genetic modification using modern biotechnology. It is expected that these compounds can be applied to protect articles and / or places such as fabrics, paper, stored grains, seeds and other foods, houses, buildings, etc., by applying the compounds of the present invention to or near these objects.

[0079] The inventors of the present invention have found that even when the compounds of the present invention are applied at a lower dose, they can also control animal pests encountered in the agricultural and non-agricultural as well as sanitary fields and the animal protection field, especially insects, arachnids, worms, nematodes and mollusks. These compounds are preferably used as insecticides. They are effective against both normally sensitive and resistant species and can resist all or part of the developmental stages. The above pests include:

[0080] Pests from the phylum Arthropoda, especially from the class Arachnida, such as the orders Acari, Metastigmata and Mesostigmata, the families Tetranychidae, Eupodidae, Eriophyidae, Phytoseiidae, Acaridae, and the genera Acarus (such as Acarus siro, Aceria kuko, Aceria sheldoni), Aculops spp., Aculus spp. (such as Aculus fockeui, Aculus schlechtendali), Amblyomma spp., Amphitetranychus viennensis, Argas spp., Boophilus spp., Brevipalpus spp. (such as Brevipalpus phoenicis), Bryobia graminum, Bryobia praetiosa, Centruroides spp., Chorioptes spp., Dermanyssus gallinae, Dermatophagoides pteronyssinus, Dermatophagoides farinae, Dermacentor spp., Eotetranychus spp., Ornithodorus spp., Otobius spp., Ixodes spp., Haemophysalis spp., Hyalomma spp., Rhipicephalus spp. (the original genus of heteroxenous mites), Ornithonyssus spp., Pneumonyssus spp., Raillietia spp., Sternostoma spp., Varroa spp., Acarapis spp., etc.;

[0081] Pests from the order Coleoptera, such as Acalymma vittatum, Acanthoscelides obtectus, Adoretus spp., Agelastica alni, Agriotes spp. (such as Agriotes linneatus, Agriotes mancus), Alphitobius diaperinus, Amphimallon solstitialis, Anobium punctatum, Anoplophora spp., Anthonomus spp. (such as Anthonomus grandis), Anthrenus spp., Apion spp., Apogonia spp., Atomaria spp. (such as Atomaria linearis), Attagenus spp., Baris caerulescens, Bruchidius obtectus, Bruchus spp. (such as Bruchus pisorum, Bruchus rufimanus), Cassida spp., Cerotoma trifurcata, Ceuthorhynchus spp. (such as Ceutorrhynchus assimilis, Ceutorrhynchus quadridens, Ceutorrhynchus rapae), Chaetocnema spp. (such as Chaetocnema confinis, Chaetocnema denticulata, Chaetocnema ectypa), Cleonus mendicus, Conoderus spp., Cosmopolites spp. (such as Cosmopolites sordidus), etc.;

[0082] Pests from the order Diptera, such as, Aedes spp. (e.g., Aedes aegypti, Aedes albopictus, Aedes sticticus, Aedes vexans), Agromyza spp. (e.g., Agromyza frontella, Agromyza parvicornis), Anastrepha spp., Anopheles spp. (e.g., Anopheles quadrimaculatus, Anopheles gambiae), Asphondylia spp., Bactrocera spp. (e.g., Bactrocera cucurbitae, Bactrocera dorsalis, Bactrocera oleae), Bibio hortulanus, Calliphora erythrocephala, Calliphora vicina, Ceratitis capitata, Chironomus spp., Chrysomyia spp., Chrysops spp., Chrysozona pluvialis, Cochliomyia spp., Contarinia spp. (e.g., Contarinia johnsoni, Contarinia nasturtii, Contarinia pyrivora, etc.;

[0083] Pests from the order Heteroptera, such as, Anasa tristis, Antestiopsis spp., Boisea spp., Blissus spp., Calocoris spp., Campylomma livida, Cavelerius spp., Cimex spp. (such as Cimex adjunctus, Cimex hemipterus, Cimex lectularius, Cimex pilosellus), Collaria spp., Creontiades dilutus, Dasynus piperis, Dichelops furcatus, Diconocoris hewetti, Dysdercus spp., Euschistus spp., etc.;

[0084] Pests from the order Homoptera, such as Acizzia acaciaebaileyanae, Acizziadodonaeae, Acizzia uncatoides, Acrida turrita, Acyrthosipon spp. (such as Acyrthosiphon pisum), Acrogonia spp., Aeneolamia spp., Agonoscena spp., Aleyrodes proletella, Aleurolobus barodensis, Aleurothrixus floccosus, Allocaridara malayensis, Amrasca spp. (such as Amrasca bigutulla, Amrasca devastans), Anuraphis cardui, Aonidiella spp. (such as Aonidiella aurantii, Aonidiella citrina, Aonidiella inornata), Aphanostigma piri, Aphis spp (such as Aphis craccivora, Aphis fabae, Aphis forbesi, Aphis glycines, Aphis gossypii, Aphis hederae, Aphis illinoisensis, Aphis middletoni, Aphis nasturtii, Aphis nerii, etc.);

[0085] Pests from the order Hymenoptera, such as Acromyrmex spp., Athalia spp. (such as Athalia rosae), Atta spp., Diprion spp. (such as Diprion similis), Hoplocampa spp. (such as Hoplocampa cookei, Hoplocampa testudinea), Lasius spp., etc.;

[0086] Pests from the order Isoptera, such as Coptotermes spp. (such as Coptotermes formosanus), Cornitermes cumulans, Cryptotermes spp., Incisitermes spp., Microtermes obesi, Odontotermes spp., Reticulitermes spp. (such as Reticulitermes flavipes, Reticulitermes hesperus), etc.;

[0087] Pests from the order Lepidoptera, such as Argyroploce spp., Anarsia spp., Choristoneura spp., Cnephasia spp., Conopomorpha spp., as well as Heliothis spp., Helicoverpa spp., Spodoptera spp., Mythimna unipuncta, Agrotis spp. (such as Agrotis segetum, Agrotis ipsilon), Earias spp., Trichoplusia ni, Anticarsia gemmatalis, Rachiplusia nu, Plutella xylostella, Chilo spp, Scirpophaga incertulas, Sesamia inferens, Cnaphalocrocis medinalis, Ostrinia nubilalis, Cydia pomonella, Carposina niponensis, Cacoecia spp., Adoxophyes orana, Archips argyrospilus, Pandemis heparana, Carpocapsa pomonella, Epinotia aporema, Eupoecilia ambiguella, Lobesia botrana, Polychrosis biteana, Pectinophora gossypiella, Pieris rapae, Phyllonorycter spp., Leucoptera malifoliella, Phyllocnisitis citrella, Podoptera exigua Hübner, etc.;

[0088] Pests from the order Orthoptera or Saltatoria, such as Acheta domesticus, Dichroplus spp., Gryllotalpa spp. (such as Gryllotalpa gryllotalpa), Hieroglyphus spp., Locusta spp. (such as Locusta migratoria, Locusta migratoria manilensis), Melanoplus spp. (such as Melanoplus devastator), Schistocerca gregaria, Gryllotalpidae (mole crickets), etc.;

[0089] Pests from the order Phthiraptera, such as Damalinia spp., Haematopinus spp., Linognathus spp., Pediculus spp., Phylloxera vastatrix, Ptirus pubis, Trichodectes spp., sucking lice, Pthirus pubis, etc.;

[0090] Pests from the order Siphonapterida, such as Pulex spp., Ctenocephalides spp., Tunga spp., Xenopsylla spp., Ceratophyllus spp.; In particular, representative examples are Ctenocephalides canis, Ctenocephalides felis, Pulex irritans, Tunga penetrans, Xenopsylla cheopis, etc.;

[0091] Pests from the order Blattarida, such as, in the order Blattarida: cockroaches, Blatta orientalis, Blattella germanica, Periplaneta americana, Supella longipalpa, Periplaneta australasiae, Periplaneta brunnea, Parcoblatta pennsylvanica, Periplaneta fuliginosa, Pycnoscelus surinamensis, Supella spp. (e.g., Suppella longipalpa), etc.;

[0092] Pests from the order Thysanoptera, such as, Anaphothrips obscurus, Baliothrips biformis, Drepanothris reuteri, Enneothrips flavens, Frankliniella spp. (e.g., Frankliniella fusca, Frankliniella occidentalis, Frankliniella schultzei, Frankliniella tritici, Frankliniella vaccinii, Frankliniella williamsi), Heliothrips spp., Hercinothrips femoralis, Rhipiphorothrips cruentatus, Scirtothrips spp., Taeniothrips cardamoni, Thrips spp. (e.g., Thrips palmi, Thrips tabaci), etc.;

[0093] Plant pests from the phylum Nematoda, namely plant-parasitic nematodes, especially Aglenchus spp. (such as Aglenchus agricola), Anguina spp. (such as Anguina tritici), Aphelenchoides spp. (such as Aphelenchoides arachidis, Aphelenchoides fragariae), Belonolaimus spp. (such as Belonolaimus gracilis, Belonolaimus longicaudatus, Belonolaimus nortoni), Bursaphelenchus spp. (such as Bursaphelenchus cocophilus, Bursaphelenchus eremus, Bursaphelenchus xylophilus), Dirofilaria immitis, Meloidogyne spp., Heterodera spp., Hoplolaimus columbus, Belonolaimus spp., Pratylenchus spp., Rotylenchus reniformis, Criconemella ornata, Ditylenchus spp., Aphelenchoides besseyi, Hirschmanniella spp., etc.

[0094] In another preferred embodiment of the present invention, the pests that can be prevented and / or controlled by the compounds or compositions described in the present invention can be selected from Plutella xylostella, Spodoptera exigua, Chilo suppressalis, Conopomorpha sinensis, Frankliniella occidentalis, Phyllotreta striolata, Sitophilus spp., Agrotis ypsilon, Bradysia odoriphaga, Aedes albopictus, Boophilus microplus, Ctenocephalides felis, termites, Solenopsis invicta, etc.

[0095] Those skilled in the art will understand that the definitions and preferences described in one aspect of the present invention are equally applicable to other aspects. Those skilled in the art will appreciate that the embodiments of the various aspects of the present invention can be combined in various ways without departing from the subject matter and spirit of the present invention, and such combinations are also within the scope of the present invention. Detailed Description

[0096] As used in this disclosure, the term "invertebrate pest" includes arthropods, gastropods, nematodes, and worms that are of economic importance as pests. The term "arthropod" includes insects, mites, spiders, scorpions, centipedes, millipedes, pill bugs, and symphylans. The term "gastropod" includes snails, slugs, and other Stylommatophora. The term "nematode" includes members of the phylum Nematoda, such as phytophagous nematodes and vermiform nematodes parasitic on animals. The term "worm" includes all parasites, such as roundworms (phylum Nematoda), heartworms (phylum Nematoda, class Secernentea), flukes (phylum Platyhelminthes, class Tematoda), acanthocephalans (phylum Acanthocephala), and tapeworms (phylum Platyhelminthes, class Cestoda).

[0097] In the context of this disclosure, "invertebrate pest control" means inhibiting the development of invertebrate pests (including death, reduced feeding, and / or mating disruption), and related expressions are similarly defined.

[0098] The term "agronomy" refers to the production of field crops such as for food and fiber, and includes the growth of maize or corn, soybeans and other legumes, rice, grains (e.g., wheat, oats, barley, rye, and rice), leafy vegetables (e.g., lettuce, cabbage, and other brassica crops), fruit vegetables (e.g., tomatoes, peppers, eggplants, cruciferous plants, and cucurbit crops), potatoes, other tuberous vegetables, onions, garlic, sweet potatoes, grapes, cotton, tree fruits (e.g., pome, stone, and citrus), small fruits (e.g., berries and cherries), and other specialty crops (e.g., canola, sunflowers, and olives).

[0099] The term "non-agronomic" refers to applications different from field crops, such as horticultural crops (e.g., greenhouse, nursery, or ornamental plants not grown in the field), residential, agricultural, commercial, and industrial structures, turf (e.g., sod farm, pasture, golf course, lawn, sports field, etc.), wood products, stored products, agroforestry and vegetation management, public health (i.e., human) and animal health (e.g., domestic animals such as pets, livestock, and poultry, non-domestic animals such as wild animals).

[0100] Non-agronomic applications include protecting animals from invertebrate parasitic pests by administering to the animal to be protected a parasitically effective (i.e., biologically effective) amount of a compound of the present disclosure, typically in the form of a composition formulated for veterinary use. As used in the present disclosure and the claims, the terms "parasiticidal" and "parasitically" refer to the observable effects on invertebrate parasitic pests to protect the animal from the pests. The parasiticidal effect is typically associated with a reduction in the occurrence or activity of the target invertebrate parasitic pests. Such effects on the pests include necrosis, death, growth retardation, reduced mobility, or reduced ability to remain on or in the host animal, reduced feeding, and reproductive inhibition. These effects on invertebrate parasitic pests prevent (including preventing, reducing, or eliminating) parasitic infestation or infection of the animal.

[0101] The compounds of formula (I) of the present invention can be synthesized by a variety of methods familiar to those skilled in the art of organic synthesis. Some exemplary methods for synthesizing compounds of formula (I) are given in the following specific examples, which are well known in the field of synthetic chemistry. Obviously, referring to the exemplary schemes in this patent, those skilled in the art can easily design other synthetic routes for compounds of formula (I) by appropriately adjusting the reactants, reaction conditions, and protecting groups.

[0102] The present invention will be further illustrated below in conjunction with examples; however, these examples do not limit the scope of the present invention. Unless otherwise stated, all reactants used in the examples are obtained commercially; the instruments and equipment used in the synthetic experiments and product analysis and detection are all conventional instruments and equipment commonly used in organic synthesis.

[0103] Example 1: Synthesis of Compound I-1

[0104]

[0105] First step: Synthesis of intermediate 5-bromo-2-chloro-N-cyclobutylnicotinamide

[0106] 5-Bromo-2-chloronicotinic acid (2.35 g, 10 mmol) and 20 ml of dichloromethane were placed in a 100 ml reaction flask. Under ice bath conditions, oxalyl chloride (3.82 g, 30 mmol) was slowly added with stirring, and 2 drops of DMF were added as a catalyst. Then the temperature was raised to 40 °C and the reaction was carried out for 2 h. After the reaction was completed, it was cooled to room temperature, and the solvent and unreacted substances were removed by rotary evaporation under reduced pressure to obtain the acyl chloride for standby.

[0107] Cyclobutylamine hydrochloride (1.61 g, 15 mmol) and 40 ml of dichloromethane were placed in a 100 ml reaction flask, and triethylamine (1.52 g, 15 mmol) was added. Under ice bath conditions, the acyl chloride obtained in the above step was slowly added dropwise with stirring, and the reaction was stirred overnight at room temperature. After the reaction was completed, the solvent and unreacted substances were removed by rotary evaporation, washed with water, and air-dried to obtain a white solid (2.65 g, yield: 92%). LC-MS: (M + 1) m / z = 289.1.

[0108] Step 2: Synthesis of 2-chloro-N-cyclobutyl-5-(1-(2,6-dichloro-4-(2,2,2-trifluoro-1,1,1-trifluoroethyl)phenyl)-1H-pyrazol-4-yl)nicotinamide

[0109] 5-Bromo-2-chloro-N-cyclobutylnicotinamide (0.58 g, 2 mmol) and 30 ml of isopropanol were placed in a 100 ml reaction flask. Tetrahydroxydiboron (0.89 g, 2 mmol), N,N-diisopropylethylamine (0.52 g, 4 mmol), and tetrakis(triphenylphosphine)palladium(II) (10% mmol) were added in sequence. The mixture was evacuated and replaced with nitrogen 3 times, and the reaction was carried out at 65 °C for 6 h. After monitoring the reaction to completion by TLC, it was cooled to room temperature.

[0110] To the above reaction flask was added a solution of 1-(2,6-dichloro-4-(2,2,2-trifluoro-1,1,1-trifluoroethyl)phenyl)-4-iodo-1H-pyrazole (1.01 g, 2 mmol), potassium carbonate (0.83 g, 6 mmol), and 10 ml of H2O, and then tetrakis(triphenylphosphine)palladium (10% mmol) was added. Under nitrogen protection, the temperature was controlled at 80 °C and the reaction was carried out overnight. After 12 h, the reaction was terminated, cooled to room temperature, extracted, dried, filtered, concentrated under reduced pressure, and purified by flash column chromatography to obtain a pale yellow solid (0.68 g, yield: 58%).

[0111] 11H NMR (400 MHz, Chloroform-d) δ 8.66 (d, J = 2.5 Hz, 1H), 8.29 (d, J = 2.5 Hz, 1H), 8.16 (s, 1H), 7.94 (s, 1H), 7.75 (s, 2H), 6.74 (d, J = 7.7 Hz, 1H), 4.62 (q, J = 8.2 Hz, 1H), 2.60–2.35 (m, 2H), 2.07–1.98 (m, 2H), 1.88–1.71 (m, 2H).

[0112] LC-MS: (M+1) m / z = 589.0。

[0113] Example 2: Synthesis of Compound I-2

[0114]

[0115] The compound of Example 1 (0.59 g, 1 mmol) and 20 ml of THF were placed in a 50 ml reaction flask. Under ice bath conditions, 60% NaH (0.06 g, 2 mmol) was added with stirring, and then methyl iodide was slowly added. After completion, the reaction was stirred at 50 °C overnight. After the reaction was completed, it was cooled to room temperature, quenched with water, the aqueous layer was extracted, the organic phases were combined, concentrated under reduced pressure, and column chromatography was performed to obtain a white solid (0.50 g, yield: 83%).

[0116] 1 1H NMR (400 MHz, DMSO-d6) δ 8.74 (d, J = 0.7 Hz, 1H), 8.45 (s, 1H), 8.10 (s, 2H), 7.71 (dd, J = 4.5, 2.2 Hz, 1H), 7.54 (d, J = 9.0 Hz, 1H), 3.54 (s, 3H), 2.79 (d, J = 5.8 Hz, 1H), 0.90–0.73 (m, 2H), 0.83–0.79 (m, 2H), 0.54–0.33 (m, 2H).

[0117] LC-MS: (M+1) m / z = 603.2。

[0118] Example 3: Synthesis of Compound I-4

[0119]

[0120] Referring to the synthesis method of Example 2, the corresponding halide was replaced with bromomethyl cyclopropane, and the rest of the synthesis method was the same to prepare the target compound. White solid, yield 83%.

[0121] 11H NMR (400 MHz, Chloroform-d) δ 8.66 (d, J = 2.6 Hz, 1H), 8.46 (d, J = 2.5 Hz, 1H), 8.12 (s, 1H), 7.88 (s, 1H), 7.74 (s, 2H), 4.59 (d, J = 7.2 Hz, 1H), 2.71–2.37 (m, 2H), 1.95 (dd, J = 8.9, 2.7 Hz, 2H), 1.88–1.76 (m, 2H), 1.55 (t, J = 7.1 Hz, 2H), 1.23 (d, J = 15.9 Hz, 2H), 1.16 (s, 1H), 0.96–0.81 (m, 2H).

[0122] LC-MS: (M+1) m / z = 643.1。

[0123] Example 4: Synthesis of Compound I-8

[0124]

[0125] Referring to the synthesis method of Reference Example 1, replace the amine corresponding to Step 1 with cyclopentylamine hydrochloride, and keep the rest of the synthesis method the same to prepare the target compound. White solid, yield 41%.

[0126] 1 1H NMR (400 MHz, Chloroform-d) δ 8.93 (t, J = 2.3 Hz, 1H), 8.85–8.73 (m, 1H), 8.36 (d, J = 10.6 Hz, 1H), 8.33–8.27 (m, 1H), 8.12 (d, J = 8.5 Hz, 1H), 7.97–7.80 (m, 1H), 6.20 (s, 1H), 4.45 (q, J = 7.0 Hz, 1H), 2.28–2.02 (m, 2H), 1.85–1.64 (m, 4H), 1.58–1.38 (m, 2H).

[0127] LC-MS: (M+1) m / z = 603.1。

[0128] Example 5: Synthesis of Compound I-15

[0129]

[0130] Referring to the synthesis method of Reference Example 1, replace the amine corresponding to Step 1 with cyclohexylamine hydrochloride, and keep the rest of the synthesis method the same to prepare the target compound. White solid, yield 46%.

[0131] 11H NMR (400 MHz, Chloroform-d) δ 8.93 (t, J = 2.4 Hz, 1H), 8.80 (t, J = 1.9 Hz, 1H), 8.36 (d, J = 10.5 Hz, 1H), 8.29 (q, J = 2.1 Hz, 1H), 8.12 (d, J = 8.4 Hz, 1H), 7.95–7.80 (m, 1H), 6.08 (d, J = 7.9 Hz, 1H), 4.03 (d, J = 10.2 Hz, 1H), 2.32–2.02 (m, 2H), 1.92–1.65 (m, 2H), 1.44 (t, J = 12.4 Hz, 2H), 1.32–1.05 (m, 4H).

[0132] LC-MS: (M+1) m / z = 617.3。

[0133] Example 6: Synthesis of Compound I-22

[0134]

[0135] Referring to the synthesis method of Reference Example 1, replace the amine corresponding to Step 1 with 3-oxetanamine hydrochloride, and keep the rest of the synthesis method the same to prepare the target compound. White solid, yield 32%.

[0136] 1 1H NMR (400 MHz, Chloroform-d) δ 8.70 (d, J = 2.5 Hz, 1H), 8.31 (d, J = 2.5 Hz, 1H), 8.17 (s, 1H), 7.96 (s, 1H), 7.75 (s, 2H), 7.24 (s, 1H), 5.40–5.17 (m, 1H), 5.05 (t, J = 7.1 Hz, 2H), 4.66 (t, J = 6.5 Hz, 2H).

[0137] LC-MS: (M+1) m / z = 591.2。

[0138] Example 7: Synthesis of Compound I-29

[0139]

[0140] Referring to the synthesis method of Reference Example 1, replace the amine corresponding to Step 1 with 1-(methyl)cyclobutanamine hydrochloride, and keep the rest of the synthesis method the same to prepare the target compound. White solid, yield 28%.

[0141] 11H NMR (400 MHz, Chloroform-d) δ 8.65 (d, J = 2.5 Hz, 1H), 8.27 (d, J = 2.5 Hz, 1H), 8.16 (s, 1H), 7.95 (s, 1H), 7.75 (s, 2H), 6.65 (s, 1H), 2.61–2.29 (m, 2H), 2.17 (ddt, J = 12.5, 8.5, 3.2 Hz, 2H), 2.06–1.76 (m, 2H), 1.62 (s, 3H).

[0142] LC-MS: (M+1) m / z = 603.2。

[0143] Example 8: Synthesis of Compound I-36

[0144]

[0145] Referring to the synthesis method of Reference Example 1, replace the amine corresponding to Step 1 with 3,3-difluorocyclobutylamine hydrochloride, and keep the rest of the synthesis method the same to prepare the target compound. White solid, yield 63%.

[0146] 1 1H NMR (400 MHz, Chloroform-d) δ 8.69 (d, J = 2.5 Hz, 1H), 8.31 (d, J = 2.5 Hz, 1H), 8.17 (s, 1H), 7.96 (s, 1H), 7.75 (s, 2H), 6.94 (d, J = 6.8 Hz, 1H), 4.71–4.42 (m, 1H), 3.15 (td, J = 11.7, 3.4 Hz, 2H), 2.65 (ddd, J = 13.4, 6.4, 1.5 Hz, 2H).

[0147] LC-MS: (M+1) m / z = 625.1。

[0148] Example 9: Synthesis of Compound II-36

[0149]

[0150] Referring to the synthesis method of Reference Example 1, replace the starting material with 5-bromo-2-chlorobenzoic acid, and replace the amine corresponding to Step 1 with 3,3-difluorocyclobutylamine hydrochloride, and keep the rest of the synthesis method the same to prepare the target compound. White solid, yield 41%.

[0151] 11H NMR (400 MHz, Chloroform-d) δ 8.16 (s, 1H), 8.03–7.97 (m, 1H), 7.92 (s, 1H), 7.75 (d, J = 3.8 Hz, 2H), 7.62 (d, J = 7.7 Hz, 1H), 7.50 (d, J = 7.8 Hz, 1H), 6.42 (s, 1H), 4.50 (s, 1H), 3.12 (dtd, J = 15.2, 7.5, 3.6 Hz, 2H), 2.69–2.52 (m, 2H).

[0152] LC-MS: (M+1) m / z = 624.0。

[0153] Example 10: Synthesis of Compound III-1

[0154]

[0155] Referring to the synthesis method of Reference Example 2, replace the corresponding halide with acetyl chloride, and the rest of the synthesis method is the same to prepare the target compound. White solid, yield 58%.

[0156] 1 1H NMR (400 MHz, DMSO-d6) δ 8.90 (d, J = 7.6 Hz, 1H), 8.85 (s, 1H), 8.57 (s, 1H), 8.20 (d, J = 2.4 Hz, 1H), 8.12 (s, 2H), 4.38 (q, J = 8.0 Hz, 1H), 2.27 (s, 3H), 2.25–2.18 (m, 2H), 2.07–1.96 (m, 2H), 1.76–1.63 (m, 2H).

[0157] LC-MS: (M+1) m / z = 631.1。

[0158] Example 11: Synthesis of Compound III-13

[0159]

[0160] Referring to the synthesis method of Reference Example 7, replace the corresponding halide with acetyl chloride, and the rest of the synthesis method is the same to prepare the target compound. White solid, yield 52%.

[0161] 11H NMR (400 MHz, DMSO-d6) δ 8.87 (d, J = 2.4 Hz, 1H), 8.84 (s, 1H), 8.53 (s, 1H), 8.33 (d, J = 2.4 Hz, 1H), 8.13 (s, 2H), 4.45 (dt, J = 8.4, 4.1 Hz, 1H), 3.19 (q, J = 9.2, 8.4 Hz, 2H), 2.96 (t, J = 11.7 Hz, 2H), 2.31 (s, 3H).

[0162] LC-MS: (M+1) m / z = 667.2。

[0163] Example 12: Synthesis of Compound III-14

[0164]

[0165] Referring to the synthesis method of Reference Example 7, replace the corresponding halide with propionyl chloride, and the rest of the synthesis methods are the same to prepare the target compound. White solid, yield 44%.

[0166] 1 1H NMR (400 MHz, DMSO-d6) δ 8.86 (d, J = 2.5 Hz, 1H), 8.84 (s, 1H), 8.53 (s, 1H), 8.31 (d, J = 2.4 Hz, 1H), 8.13 (s, 2H), 4.47 (dt, J = 8.3, 4.2 Hz, 1H), 3.29–3.06 (m, 2H), 3.03–2.85 (m, 2H), 2.68 (q, J = 7.1 Hz, 2H), 0.98 (t, J = 7.1 Hz, 3H).

[0167] LC-MS: (M+1) m / z = 681.0。

[0168] Example 13: Synthesis of Compound III-24

[0169]

[0170] Referring to the synthesis method of Reference Example 7, replace the corresponding halide with 2-methylbenzoyl chloride, and the rest of the synthesis methods are the same to prepare the target compound. White solid, yield 56%.

[0171] 11H NMR (400 MHz, DMSO-d6) δ 8.70 (s, 1H), 8.61 (d, J = 2.4 Hz, 1H), 8.41 (s, 1H), 8.14 (s, 2H), 7.92 (s, 1H), 7.48–7.37 (m, 1H), 7.22–7.11 (m, 2H), 6.99 (d, J = 7.5 Hz, 1H), 4.82 (q, J = 4.2 Hz, 1H), 3.34–3.20 (m, 2H), 3.08 (t, J = 11.2 Hz, 2H), 2.71 (s, 3H),.

[0172] LC-MS: (M+1) m / z = 743.1。

[0173] Example 14: Synthesis of Compound IV-13

[0174]

[0175] Referring to the synthesis method of Reference Example 13, the corresponding halide was replaced with acetyl chloride, and the rest of the synthesis method was the same to prepare the target compound. White solid, yield 48%.

[0176] 1 1H NMR (400 MHz, Chloroform-d) δ 8.65 (d, J = 2.6 Hz, 1H), 8.29 (d, J = 2.5 Hz, 2H), 8.16 (s, 1H), 7.95 (s, 1H), 7.75 (s, 2H), 4.55–4.46 (m, 1H), 4.16–4.05 (m, 2H), 3.29–3.04 (m, 2H), 2.31 (s, 3H).

[0177] LC-MS: (M+1) m / z = 666.1。

[0178] The structural formula, physical and chemical properties, NMR and mass spectrometry data of the exemplary compounds of the present invention are as follows:

[0179]

[0180]

[0181] Indoor Activity Determination Method

[0182] 2.1 Determination of Activity against Plutella xylostella

[0183] Soak an appropriate amount of radish / corn leaves in the prepared liquid medicine for 30 s, then place them in a plastic petri dish lined with filter paper to air dry naturally. Place 8 diamondback moth larvae at the 2nd - 3rd instar in each dish and put them in an observation room with a temperature of 22 °C and a light cycle of 16 / 8 h. Observe after 48 h. Gently touch the insect body with a writing brush, and those with no response are regarded as dead insects. Repeat each treatment 3 times and set a solvent control. The test concentration is 10 mg / L.

[0184] Test results: Among some of the tested compounds, the compounds of Example I - 1, I - 2, I - 29, I - 36, I - 37, I - 41, II - 36, III - 1, III - 13, III - 14, III - 15, III - 20, III - 21, III - 24, III - 27, III - 42, III - 44 showed significant control effects against diamondback moths at a dose of 10 mg / L, and the mortality rates were all 100%.

[0185] 2.2 Determination of activity against Spodoptera exigua

[0186] Pour the prepared artificial diet into 12 - well plates while it is still hot, adding 2.5 ml of artificial diet to each well. Wait for the diet to cool completely before use. For each concentration gradient of each agent, make 3 12 - well plates, with each 12 - well plate being 1 replicate, for a total of 3 replicates. Add 50 μL of the corresponding concentration gradient agent to each well and let it dry. Place 1 Spodoptera litura larva in each well. For the control, 3 12 - well plates, with a total of 3 replicates, add 50 μL of the solvent control to each well. Place them in an insect - rearing room with a temperature of 26 ± 2 °C, a light cycle of 16 h∶8 h (L∶D), and a humidity of 50 - 70%. Investigate the death of the test insects 48 h after the experiment and calculate the mortality rate of the test insects. The test concentration is 10 mg / L.

[0187] Test results: Among some of the tested compounds, the compounds of Example I - 1, I - 2, I - 29, I - 36, I - 37, I - 41, II - 36, III - 1, III - 13, III - 14, III - 15, III - 20, III - 21, III - 24, III - 27, III - 42, III - 44 showed significant control effects against Spodoptera exigua at a dose of 10 mg / L, and the mortality rates were all 100%.

[0188] In addition, the compounds of the present invention can also effectively control other Lepidoptera pests, such as the severely harmful Spodoptera litura, Spodoptera frugiperda, Mythimna separata, Conopomorpha sinensis Bradley, Chilo suppressalis, Tryporyza incertulas, etc.

[0189] The compounds of the present invention have excellent control effects against Thysanoptera thrips and Coleoptera weevils.

[0190] The compounds of the present invention have unexpectedly excellent effects against underground pests such as Agrotis ypsilon and Bradysia odoriphaga.

[0191] The compounds of the present invention have high insecticidal activities against sanitary pests such as mosquitoes, flies and cockroaches.

[0192] The compounds of the present invention have high insecticidal activities against ectoparasites of animals such as ticks and fleas.

[0193] The compounds of the present invention also have excellent insecticidal effects against termites, red imported fire ants, etc.

[0194] In addition to the pest control properties, compared with the compounds of the prior art, the compounds according to the present invention also unexpectedly show improved degradation properties. Additionally, compared with the prior art compounds, the compounds according to the present invention also unexpectedly show lower toxicity to bees (or aquatic animals).

[0195] It should be further noted that, in the case of no conflict, the various specific technical features described in the above specific embodiments can be combined in any appropriate manner. To avoid unnecessary repetition, the present invention will not separately describe various possible combination manners.

[0196] The above are only the preferred embodiments of the present invention, and are not intended to limit the present invention. Any modifications, equivalent replacements, improvements, etc. made within the spirit and principle of the present invention shall be included within the protection scope of the present invention.

Claims

1. A compound of formula (I) as an amide derivative, or an isotopically labeled compound thereof, or an optical isomer, geometric isomer, tautomer or mixture of isomers thereof, or an acceptable salt, wherein, X1, X2, X3, X4 are each independently selected from hydrogen, halogen, hydroxy, nitro, amino, cyano, carboxy, C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-12 cycloalkyl, C 1-6 haloalkyl, C 1-6 alkoxy or C 1-6 haloalkoxy; R1 is selected from C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 3-12 cycloalkyl, C 3-6 heterocyclic group, C 6-12 aryl, C 5-12 heteroaryl, C 1-6 alkoxy C 1-6 alkyl, C 1-6 alkylthio C 1-6 alkyl, C 1-6 alkylamino C 1-6 alkyl, C 3-12 cycloalkyl C 1-6 alkyl, C 3-6 heterocyclic group C 1-6 alkyl, aryl C 1-6 alkyl, C 5-12 heteroaryl C 1-6 alkyl, C 6-12 aryloxy C 1-6 alkyl, C 5-12 heteroaryloxy C 1-6 alkyl, or R1 is selected from -C(=O)-R2, where R2 is selected from C 1-6 alkyl, C 2-6 alkenyl, C 2-6 alkynyl, C 1-6 alkoxy, C 1-6 alkylthio, C 1-6 alkylamino, C 3-12 cycloalkyl, C 3-8 heterocyclic group, C 6-12 aryl, C 6-12 aryloxy, C 5-12 heteroaryl, C 5-12 heteroaryloxy, C 1-6 alkoxyC 1-6 alkyl, C 1-6 alkylthioC 1-6 alkyl, C 1-6 alkylaminoC 1-6 alkyl, C 3-12 cycloalkylC 1-6 alkyl, C 3-6 heterocyclic groupC 1-6 alkyl, C 6-12 arylC 1-6 alkyl, C 5-12 heteroarylC 1-6 alkyl, C 6-12 aryloxyC 1-6 alkyl, C 5-12 heteroaryloxyC 1-6 alkyl; And R1 and R2 may be mono-substituted or multi-substituted by one or more identical or different substituents selected from: halogen, cyano, nitro, C 1-6 alkyl, C 1-6 alkoxy, C 1-6 haloalkyl, C 1-6 alkoxycarbonyl, C 1-6 alkylamino, C 6-12 aryl; W is selected from nitrogen or carbon; Q is selected from C 4-12 cycloalkyl, C 4-12 heterocycloalkyl, which may be mono- or polysubstituted by one or more identical or different substituents selected from: fluorine, chlorine, bromine, cyano, C 1-3 alkyl.

2. The compound of formula (I) according to claim 1, or an isotopically labeled compound thereof, or an optical isomer, geometric isomer, tautomer or mixture of isomers thereof, or an acceptable salt, wherein, X1, X2, X3, X4 are each independently selected from hydrogen, halogen, hydroxyl, nitro, amino, cyano, carboxyl, C 1-3 alkyl, C 2-4 alkenyl, C 2-4 alkynyl, C 3-6 cycloalkyl, C 1-3 haloalkyl, C 1-3 alkoxy or C 1-3 haloalkoxy; R1 is selected from C 1-3 alkyl, C 2-4 alkenyl, C 2-4 alkynyl, C 3-6 cycloalkyl, C 3-6 heterocyclic group, C 6-12 aryl, C 5-12 heteroaryl, C 1-3 alkoxy C 1-3 alkyl, C 1-3 alkylthio C 1-3 alkyl, C 1-3 alkylamino C 1-3 alkyl, C 3-12 cycloalkyl C 1-3 alkyl, C 3-6 heterocyclic group C 1-3 alkyl, C 6-12 aryl C 1-3 alkyl, C 5-12 heteroaryl C 1-3 alkyl, C 6-12 aryloxy C 1-3 alkyl, C 5-12 heteroaryloxy C 1-3 alkyl, or R1 is selected from -C(=O)-R2, where R2 is selected from C 1-3 alkyl, C 2-4 alkenyl, C 2-4 alkynyl, C 1-3 alkoxy, C 1-3 alkylthio, C 1-3 alkylamino, C 3-8 cycloalkyl, C 3-8 heterocyclic group, C 6-12 aryl, C 6-12 aryloxy, C 5-12 heteroaryl, C 5-12 heteroaryloxy, C 1-3 alkoxyC 1-3 alkyl, C 1-3 alkylthioC 1-3 alkyl, C 1-3 alkylaminoC 1-3 alkyl, C 3-8 cycloalkylC 1-3 alkyl, C 3-6 heterocyclic groupC 1-3 alkyl, C 6-12 arylC 1-3 alkyl, C 5-12 heteroarylC 1-3 alkyl, C 6-12 aryloxyC 1-3 alkyl, C 5-12 heteroaryloxyC 1-3 alkyl; and R1, R2 may be mono-substituted or multi-substituted by one or more identical or different substituents selected from: fluorine, chlorine, bromine, cyano, nitro, C 1-3 alkyl, C 1-3 alkoxy, C 1-3 haloalkyl, C 1-3 alkoxycarbonyl, C 1-3 alkylamino, C 6-12 aryl; W is selected from nitrogen or carbon; Q is selected from C 4-8 cycloalkyl, C 4-8 heterocycloalkyl, which may be mono- or polysubstituted by one or more identical or different substituents selected from: fluorine, chlorine, bromine, cyano, C 1-3 alkyl.

3. The compound of formula (I) according to claim 2, or an isotopically labeled compound thereof, or an optical isomer, geometric isomer, tautomer or mixture of isomers thereof, or an acceptable salt, wherein, X1, X2, X3, X4 are each independently selected from hydrogen, fluorine, chlorine, bromine, iodine, hydroxy, cyano, nitro, amino, carboxyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, C 1-3 alkyl, C 1-3 haloalkyl, C 1-3 alkoxy or C 1-3 haloalkoxy; R1 is selected from C 1-3 alkyl, C 2-4 alkenyl, C 2-4 alkynyl, C 3-6 cycloalkyl, C 3-6 heterocyclic group, C 6-9 aryl, C 5-9 heteroaryl, C 1-3 alkoxy C 1-3 alkyl, C 1-3 alkylthio C 1-3 alkyl, C 1-3 alkylamino C 1-3 alkyl, C 3-6 cycloalkyl C 1-3 alkyl, C 3-6 heterocyclic group C 1-3 alkyl, C 6-9 aryl C 1-3 alkyl, C 5-9 heteroaryl C 1-3 alkyl; or R1 is selected from -C(=O)-R2, where R2 is selected from C 1-3 alkyl, C 2-4 alkenyl, C 2-4 alkynyl, C 1-3 alkoxy, C 1-3 alkylthio, C 1-3 alkylamino, C 3-8 cycloalkyl, C 3-8 heterocyclic group, C 6-12 aryl, C 5-12 heteroaryl, C 1-3 alkoxyC 1-3 alkyl, C 1-3 alkylthioC 1-3 alkyl, C 3-8 cycloalkylC 1-3 alkyl, C 3-6 heterocyclic groupC 1-3 alkyl, C 6-12 arylC 1-3 alkyl, C 5-12 heteroarylC 1-3 alkyl; and R1 and R2 may be mono-substituted or multi-substituted by one or more identical or different substituents selected from: fluorine, chlorine, bromine, cyano, nitro, C 1-3 alkyl, C 1-3 alkoxy, C 1-3 haloalkyl, C 1-3 alkoxycarbonyl; W is selected from nitrogen or carbon; Q is selected from C 4-6 cycloalkyl, C 4-6 heterocycloalkyl, which may be mono- or polysubstituted by one or more identical or different substituents selected from: fluorine, chlorine, bromine, cyano, C 1-3 alkyl.

4. The compound of formula (I) according to claim 3, or an isotopically labeled compound thereof, or an optical isomer, geometric isomer, tautomer or mixture of isomers thereof, or an acceptable salt, wherein, X1, X2, X3, X4 are each independently selected from hydrogen, fluorine, chlorine, bromine, iodine, cyano, cyclopropyl, C 1-3 alkyl or C 1-3 haloalkyl; R1 is selected from C 1-3 alkyl, C 2-4 alkenyl, C 2-4 alkynyl, C 3-6 cycloalkyl, C 3-6 heterocyclic group, C 6-9 aryl, C 5-9 heteroaryl, C 1-3 alkoxy C 1-3 alkyl, C 1-3 alkylthio C 1-3 alkyl, C 1-3 alkylamino C 1-3 alkyl, C 3-6 cycloalkyl C 1-3 alkyl, C 3-6 heterocyclic group C 1-3 alkyl, C 6-9 aryl C 1-3 alkyl, C 5-9 heteroaryl C 1-3 alkyl, Or R1 is selected from -C(=O)-R2, where R2 is selected from C 1-3 alkyl, C 2-4 alkenyl, C 2-4 alkynyl, C 1-3 alkoxy, C 1-3 alkylthio, C 1-3 alkylamino, C 3-8 cycloalkyl, C 3-8 heterocyclic group, C 6-12 aryl, C 5-12 heteroaryl; and R1 and R2 may be mono-substituted or poly-substituted by one or more identical or different substituents selected from: fluorine, chlorine, bromine, cyano, nitro, C 1-3 alkyl, C 1-3 alkoxy, C 1-3 haloalkyl; W is selected from nitrogen or carbon; Q is selected from the following groups:

5. The compound of formula (I) according to claim 4, or an isotopically labeled compound thereof, or an optical isomer, geometric isomer, tautomer or mixture of isomers thereof, or an acceptable salt, wherein: X1, X2, X3, X4 are each independently selected from hydrogen, fluorine, chlorine, bromine, iodine, cyano, cyclopropyl, C 1-3 alkyl or C 1-3 haloalkyl; R1 is selected from methyl, ethyl, n-propyl, isopropyl, allyl, propargyl, cyclopropylmethyl, glycidylmethyl, or R1 is selected from -C(=O)-R2, wherein R2 is selected from methyl, ethyl, n-propyl, isopropyl, allyl, propargyl, methoxy, ethoxy, n-propoxy, isopropoxy, N,N-dimethylamino, cyclopropyl, glycidyl, furyl, phenyl, and R1, R2 may be mono- or poly-substituted by one or more identical or different substituents selected from: fluorine, chlorine, bromine, cyano, nitro, C 1-3 alkyl, C 1-3 alkoxy, C 1-3 haloalkyl; W is selected from nitrogen or carbon; Q is selected from the following groups:

6. An active composition comprising the compound of formula (I) according to any one of claims 1-5, or an isotopically labeled compound thereof, or an optical isomer, geometric isomer, tautomer or mixture of isomers thereof, or an acceptable salt, and an acceptable carrier.

7. The active composition according to claim 6, wherein the dosage form is selected from powder, bait, granule, liquid, suspension or spray, preferably wettable powder, wettable liquid, soluble powder, dispersible liquid, aqueous solution, microemulsion, emulsifiable concentrate, emulsion in water, sprayable solution, dispersible oil suspension, microcapsule suspension, water dispersible granule, water soluble granule, macrogranule, granule for broadcasting and soil application, aerosol, ultra-low volume agent and wax product.

8. Use of the compound of formula (I) according to any one of claims 1-5, or an isotopically labeled compound thereof, or an optical isomer, geometric isomer, tautomer or mixture of isomers thereof, or an acceptable salt in the preparation of an insecticide for pest control.

9. The use according to claim 8, wherein the pests are selected from pests belonging to the phylum Arthropoda, Coleoptera, Diptera, Heteroptera, Homoptera, Hymenoptera, Isoptera, Lepidoptera, Orthoptera, Phthiraptera, Thysanoptera, Nematoda.

10. Use of a compound of formula (I) or an isotopically labeled compound thereof, or an optical isomer, geometric isomer, tautomer or isomer mixture thereof, or an acceptable salt according to any one of claims 1-5 for the preparation of an agent for controlling animal parasites or a sanitizing and disinfecting agent.

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