ISOXAZOLINE DERIVATIVE COMPOUND AND PESTICIDAL COMPOSITION CONTAINING THE SAME

Abstract

The present invention relates to a novel isoxazoline derivative compound and an insecticide composition containing the same as an active ingredient, which can exhibit excellent insecticidal effects against various types of pests.

Description

[Technical Field]

[0001] The present invention relates to novel isoxazoline derivative compounds and insecticide compositions containing the same. [Background technology]

[0002] Pests are generally divided into sap-sucking pests such as aphids and stink bugs, and leaf-eating lepidopteran pests. These pests cause significant damage to trees and crops by extracting nutrients from the roots, stems, or leaves, or by gnawing at these parts themselves. Therefore, pest control is important for tree and crop management.

[0003] Many different types of insecticides have been developed and used to control these pests. However, despite the development of many different types of insecticides, there are limits to their effectiveness as insecticide resistance has developed. For this reason, the use of highly toxic, highly concentrated insecticides has been considered, but this not only exacerbates soil contamination, but can also cause secondary damage to humans and livestock that eat the crops due to pesticide residues on the crops.

[0004] Therefore, there is a need for new insecticide substances that are safer for humans and livestock while showing excellent pest control effects at relatively low concentrations. [Prior art documents] [Patent documents]

[0005] [Patent Document 1] Korean Patent No. 10-2267724 Summary of the Invention [Problem to be solved by the invention]

[0006] An object of the present invention is to provide a novel isoxazoline derivative compound and an insecticide composition containing the compound, which has excellent control effects against various pests.

[0007] Another object of the present invention is to provide a method for controlling pests using isoxazoline derivative compounds. [Means for solving the problem]

[0008] In order to solve the above problems, the present invention provides a compound represented by the following formula (1): [ka] [In formula 1, R 1 are each independently hydrogen, halogen, cyano (CN), C 1-5 Alkyl or C 1-5 is haloalkyl, R 2 is hydrogen, halogen, C 1-5 Alkyl or C 1-5 is haloalkyl, R 3 is hydrogen, C 1-5 Alkyl, C 3-10 Cycloalkyl, -C(=O)-C 3-10 Cycloalkyl; C 1-5 Alkyl, C 1-5 Haloalkyl and C 3-10 -C substituted with one or more cycloalkyl 1-5 Alkylene-OC(=O)H; or halogen, C 1-5 Alkyl, C 1-5 Haloalkyl and C 3-10 C substituted with one or more selected from the group consisting of cycloalkyl 1-10 is alkyl, R 4 is C 1-5 Alkyl, C 1-5 Haloalkyl, C 3-10 Cycloalkyl, C 5-12 Spiroalkyl, 3-10 membered heterocycloalkyl, 3-0 membered heterocycloalkylene-C(=O)-OC 1-5 Alkyl, C 2-10 Alkenyl, C 6-20 Aryl, 3-10 membered heteroaryl; C3-10 Cycloalkyl-substituted C 1-5 Alkyl; Cyano (CN), Halogen, C 1-5 Alkyl, C 1-5 Haloalkyl and C 3-10 C substituted with one or more selected from the group consisting of cycloalkyl 3-10 Cycloalkyl; halogen, C 1-5 Alkyl, C 1-5 Haloalkyl and C 3-10 3-10 membered heterocycloalkyl substituted with one or more cycloalkyls; C 1-5 Alkyl and C 6-20 C substituted with one or more selected from the group consisting of aryl 2-10 Alkenyl; Cyano (CN), Halogen, C 1-5 Alkyl and C 1-5 C substituted with one or more selected from the group consisting of haloalkyl 6-20 aryl; or halogen, C 1-5 Alkyl, C 1-5 Haloalkyl and C 3-10 cycloalkyl; Q is C 6-20 Arylene, 3-10 membered heteroarylene or halogen and C 1-5 C substituted with one or more selected from the group consisting of alkyl 6-20 is an arylene, a is an integer from 1 to 5, wherein said heterocycloalkyl, heteroaryl, heterocycloalkylene and heteroarylene each contain at least one heteroatom selected from the group consisting of N, O and S. The present invention provides a compound represented by the formula:

[0009] The present invention also provides an insecticide composition comprising, as an active ingredient, one or more compounds selected from the group consisting of the above compound, its stereoisomers, its hydrates and salts thereof.

[0010] The present invention also provides a method for controlling pests, which comprises treating a crop or its habitat with the pesticide composition. [Effects of the Invention]

[0011] Advantageous Effects of the Invention The insecticide composition containing the novel isoxazoline derivative compound according to the present invention can exhibit excellent control (insecticidal) effects against various pests, particularly pests of the order Thrips (e.g., western flower thrips (Frankliniella occidentalis) and onion thrips (Thrips tabaci Lindeman)) or the order Lepidoptera (e.g., bean diet moth (Maruca vitrta), common cutworm (Spodoptera litura), gypsy moth (Lymantria dispar), cotton bollworm (Helicoverpa armigera), and diamondback moth (Plutella xylostella)).

[0012] Best Mode for Carrying Out the Invention The present invention will be described in detail below. The present invention in this specification is not limited to the disclosure content shown below, and can be modified in various forms as long as the gist of the present invention is not changed.

[0013] As used herein, the term "comprising" is intended to specify certain features, regions, steps, processes, elements and / or components, and does not exclude the presence or addition of other features, regions, steps, processes, elements and / or components, unless specifically stated to the contrary.

[0014] As used herein, the term "substituted" includes not only cases in which each hydrogen or functional group is replaced by one or more substituents, but also cases in which the substituents are further replaced by one or more substituents.

[0015] In this specification, "*" or [ka] The expression indicates the position (site) where the functional group is attached.

[0016] Isoxazoline derivative compounds The present invention provides novel isoxazoline derivative compounds. Specifically, one embodiment of the present invention is a compound represented by the following formula 1: [ka] [In formula 1, R 1 are each independently hydrogen, halogen, cyano (CN), C 1-5 Alkyl or C 1-5 is haloalkyl, R 2 is hydrogen, halogen, C 1-5 Alkyl or C 1-5 is haloalkyl, R 3 is hydrogen, C 1-5 Alkyl, C 3-10 Cycloalkyl, -C(=O)-C 3-10 Cycloalkyl; C 1-5 Alkyl, C 1-5 Haloalkyl and C 3-10 -C substituted with one or more cycloalkyl 1-5 Alkylene-OC(=O)H; or halogen, C 1-5 Alkyl, C 1-5 Haloalkyl and C 3-10 C substituted with one or more selected from the group consisting of cycloalkyl 1-10 is alkyl, R 4 is C 1-5 Alkyl, C 1-5 Haloalkyl, C 3-10 Cycloalkyl, C 5-12 Spiroalkyl, 3-10 membered heterocycloalkyl, 3-10 membered heterocycloalkylene-C(=O)-OC 1-5 Alkyl, C2-10 Alkenyl, C 6-20 Aryl, 3-10 membered heteroaryl; C 3-10 C substituted by cycloalkyl 1-5 Alkyl; Cyano (CN), Halogen, C 1-5 Alkyl, C 1-5 Haloalkyl and C 3-10 C substituted with one or more selected from the group consisting of cycloalkyl 3-10 Cycloalkyl; halogen, C 1-5 Alkyl, C 1-5 Haloalkyl and C 3-10 3-10 membered heterocycloalkyl substituted with one or more cycloalkyls; C 1-5 Alkyl and C 6-20 C substituted with one or more selected from the group consisting of aryl 2-10 Alkenyl; Cyano (CN), Halogen, C 1-5 Alkyl and C 1-5 C substituted with one or more selected from the group consisting of haloalkyl 6-20 aryl; or halogen, C 1-5 Alkyl, C 1-5 Haloalkyl and C 3-10 cycloalkyl; Q is C 6-20 Arylene, 3-10 membered heteroarylene or halogen and C 1-5 C substituted with one or more selected from the group consisting of alkyl 6-20 is an arylene, a is an integer from 1 to 5, wherein said heterocycloalkyl, heteroaryl, heterocycloalkylene and heteroarylene each contain at least one heteroatom selected from the group consisting of N, O and S. The present invention provides a compound represented by the formula: embedded image or a stereoisomer thereof, a hydrate thereof, or a salt thereof. As used herein, the term "alkyl" can refer to a straight or branched chain functional group that does not contain a double or triple bond. Specifically, examples of alkyl include, but are not limited to, methyl, ethyl, propyl, isopropyl, n-butyl, isobutyl, sec-butyl, t-butyl, pentyl, etc.

[0017] As used herein, the term "haloalkyl" can refer to a functional group in which 1 to 5 (specifically, 1 to 3, or 1 to 2) halogens are replaced by alkyl. Specific examples of haloalkyl include, but are not limited to, trifluoromethyl, trichloromethyl, difluoroethyl, dichloroethyl, etc.

[0018] As used herein, the term "cycloalkyl" may refer to a cyclic functional group that does not contain double or triple bonds. Specifically, examples of cycloalkyl include, but are not limited to, cyclopropane, cyclobutane, cyclopentane, cyclohexane, and the like.

[0019] As used herein, the term "spiroalkyl" may refer to a functional group in the form of two rings that do not contain a double or triple bond and are connected by sharing one atom.

[0020] As used herein, the term "heterocycloalkyl" can refer to a cyclic functional group that does not contain a double or triple bond and has one or more heteroatoms.Specific examples of heterocycloalkyl include, but are not limited to, azetidine, pyrrolidine, tetrahydrofuran, tetrahydrothiophene, tetrahydropyran, piperidine, perhydroazepine, oxacycloheptane, etc.

[0021] As used herein, the term "alkenyl" can refer to a straight or branched chain functional group having one or more double bonds. Specific examples of alkenyl include, but are not limited to, vinyl, butenyl, pentenyl, hexenyl, etc.

[0022] As used herein, the term "aryl" may refer to a cyclic functional group containing one or more double bonds. Specific examples of aryl include, but are not limited to, phenyl, naphthyl, biphenyl, anthryl, phenanthryl, etc.

[0023] As used herein, the term "heteroaryl" can refer to a cyclic functional group having one or more heteroatoms and containing one or more double bonds. Specific examples of heteroaryl include, but are not limited to, pyrrole, thiophene, furan, pyrazole, isoxazole, thiazole, pyridine, quinoline, etc.

[0024] As used herein, the term "heterocycloalkylene" may refer to a cyclic divalent functional group containing no double or triple bonds and having one or more heteroatoms.

[0025] As used herein, the term "arylene" may refer to a cyclic divalent functional group containing one or more double bonds. Specific examples of arylene include, but are not limited to, phenylene, naphthalene, biphenylene, anthracene, etc.

[0026] As used herein, the term "heteroarylene" may refer to a cyclic divalent functional group containing one or more double bonds and having one or more heteroatoms.

[0027] As used herein, the term "heteroatom" may refer to an atom that is not carbon or hydrogen. Specifically, heteroatoms include, but are not limited to, N, O, S, etc.

[0028] According to an embodiment of the present invention, in the following formula 1, Q is [ka] [where: R 5 is hydrogen, halogen or C 1-5 It can be alkyl, X can be N, O or S. The compound may have the structure shown in

[0029] According to an embodiment of the present invention, the above formula 1 can be defined as the following formulas 1A to 1E, but is not limited thereto. Specifically, according to one embodiment of the present invention, the above formula 1 can be defined as the following formulas 1A to 1E: [ka] [ka] [ka] [ka] [ka] [In formulas 1A to 1E, R 1' are each independently halogen, cyano (CN), C 1-5 Alkyl or C 1-5 is haloalkyl, R 2 ~R 4 The definition of is the same as above, R 5 is hydrogen, halogen or C 1-5 alkyl] The compound may be any one of the following:

[0030] More specifically, according to one embodiment of the present invention, in the above formulas 1A to 1E, R 1'are each independently cyano (CN), chlorine (Cl), fluorine (F) or C 1-3 haloalkyl (e.g., trifluoromethyl (CF3)), and R 2 is C 1-3 It can be haloalkyl (e.g., trifluoromethyl (CF3)).

[0031] According to an embodiment of the present invention, in the above formula 1 (specifically, formulas 1A to 1E), R 3 Specifically, hydrogen, methyl, ethyl, [ka] It could be.

[0032] Furthermore, according to an embodiment of the present invention, in the above formula 1 (specifically, formulas 1A to 1E), R 4 Specifically, C 3-6 Cycloalkyl; C 5-8 Spiroalkyl; 3-6-membered heterocycloalkyl; 3-6-membered heterocycloalkylene-C(=O)-OC 1-3 Alkyl; C 2-5 Alkenyl; C 6-10 Aryl, 3-6 membered heteroaryl; C 3-6 C substituted by cycloalkyl 1-3 Alkyl; Cyano (CN), halogen and C 1-3 C substituted with one or more selected from the group consisting of alkyl 3-6 Cycloalkyl; C 6-10 C substituted by aryl 2-5 Alkenyl; C substituted by cyano (CN) 6-10 aryl; or halogen, C 1-3 Alkyl, C 1-3 Haloalkyl and C 3-6 It may be a 3-6 membered heteroaryl substituted with one or more selected from the group consisting of cycloalkyl.

[0033] More specifically, in the above formula 1 (specifically, formulas 1A to 1E), R 4 teeth, [ka] The substituent may be represented by the formula:

[0034] According to one embodiment of the present invention, the above formula 1 has a structure in which an aromatic or heteroaromatic moiety and two carbonyls (C=O) are bonded by an amine in the molecule, and thus can exhibit excellent insecticidal effects against pests. In particular, the R 4 Due to the (e.g., cyclopropane) and isoxazoline moieties, they exhibit excellent insecticidal activity against insects of the order Thrips (e.g., western flower thrips, Thrips tabaci Lindeman) or the order Lepidoptera (e.g., maruca pod borer, tobacco cutworm, gypsy moth, cotton bollworm, and diamondback moth).

[0035] According to an embodiment of the present invention, the above formula 1 may be defined as having the following structure, but is not limited thereto. Specifically, an embodiment of the present invention may provide a compound represented by any one of the following compounds 1001 to 1085, a stereoisomer thereof, a hydrate thereof, or a salt thereof.

[0036] [ka] [ka] [ka] [ka] [ka] [ka] [ka] [ka] [ka]

[0037] According to one embodiment of the present invention, the salt of the compound represented by Formula 1 may be a salt of an agriculturally or horticulturally acceptable inorganic or organic acid. Specific examples of the salt include, but are not limited to, salts of inorganic acids such as bromic acid, hydrochloric acid, and sulfuric acid; salts of organic acids such as acetic acid, butyric acid, lactic acid, maleic acid, malonic acid, oxalic acid, propionic acid, and tartaric acid; salts of alkali metals such as lithium, sodium, and potassium; salts of alkaline earth metals such as calcium and magnesium; salts of transition metals such as iron and copper; and salts of organic bases such as ammonia, triethylamine, tributylamine, pyridine, and hydrazine. These salts can be prepared by commonly known methods.

[0038] According to one embodiment of the present invention, the hydrate of the compound represented by the above formula 1 may contain stoichiometric or non-stoichiometric water bound by non-covalent intermolecular forces, the compound represented by the above formula 1, its stereoisomer, or a salt thereof. Such a hydrate can be prepared by a commonly known method.

[0039] Insecticide composition The present invention provides an insecticide composition comprising, as an active ingredient, one or more compounds selected from the group consisting of the compound represented by the above formula 1, its stereoisomers, its hydrates, and salts thereof.

[0040] According to one embodiment of the present invention, the pesticide composition may further comprise additives commonly known in the pesticide field, including, but not limited to, surfactants, solid diluents, liquid diluents, dispersants, wetting agents, adhesives, solvents, or other active ingredients that exhibit pesticidal activity.

[0041] According to one embodiment of the present invention, the insecticide composition may be a spray composition, a bait composition or a trap composition.

[0042] According to one embodiment of the present invention, the insecticide composition may be formulated in the form of a spray liquid, concentrate, wettable powder, flowable material, granule, aerosol, smoking, sheet, and the like.

[0043] The insecticide composition according to one embodiment of the present invention may exhibit insecticidal activity against pests or parasites, specifically, cockroaches, ants, termites, mosquitoes, black flies, stable flies, deer flies, horse botflies, wasps, yellow jacket hornets, bumblebees, ticks, spiders, moths, etc.

[0044] In particular, the insecticide composition according to one embodiment of the present invention may exhibit excellent insecticidal activity against pests of the order Thrips and / or Lepidoptera. Specifically, the insecticide composition according to the present invention may be used to control pests of the order Thrips or Lepidoptera.

[0045] For example, the insecticide composition may be effective against Frankliniella occidentalis, Frankliniella tenuicornis, Frankliniella intonsa, Frankliniella lilivora, Thrips palmi Karny, Thrips tabaci Lindeman, Phaedon brassicae, Myzus persicae, Riptortus clavatus, Lymantria dispar, Helicoverpa armigera, Manulea degenerella, Rhopobota japonica ... naevana), pear fruit moth (Grapholita molesta), diamondback moth (Plutella xylostella), common cutworm (Spodoptera litura), beet armyworm (Spodoptera exigua), fall armyworm (Spodoptera frugiperda), bean diet moth (Maruca vitrta). In particular, the insecticide composition according to one embodiment of the present invention may exhibit significantly excellent insecticidal activity against pests such as western flower thrips (Frankliniella occidentalis), onion thrips (Thrips tabaci Lindeman), common cutworm (Spodoptera litura), gypsy moth (Lymantria dispar), tobacco budworm (Helicoverpa armigera), diamondback moth (Plutella xylostella), or bean leaf moth (Maruca vitrta).

[0046] When the insecticide composition according to one embodiment of the present invention is used to control the above-mentioned pests, it may contain, as an active ingredient, one or more compounds selected from the group consisting of the compound represented by formula (1) above, its stereoisomers, hydrates thereof, and salts thereof in an amount of 0.0001 wt% to 95 wt%, 0.001 wt% to 90 wt%, 0.01 wt% to 85 wt%, 0.1 wt% to 70 wt%, 1 wt% to 60 wt%, 3 wt% to 50 wt%, or 5 wt% to 45 wt%, based on the total weight of the insecticide composition. Specifically, the concentration of one or more compounds selected from the group consisting of the compound represented by the above formula (1), its stereoisomers, hydrates thereof, and salts thereof, as active ingredient(s), may be, but is not limited to, 0.01 ppm to 1,000 ppm, 0.03 ppm to 500 ppm, 0.05 ppm to 300 ppm, 0.1 ppm to 200 ppm, 0.1 ppm to 100 ppm, 0.1 ppm to 50 ppm, 0.1 ppm to 10 ppm, 0.1 ppm to 5 ppm, or 1 ppm to 5 ppm.

[0047] Furthermore, the compound represented by the above formula 1 contained in the insecticide composition according to one embodiment of the present invention can be used for pest control at a rate of 0.1 g to 10 kg, 1 g to 6 kg, or 1 g to 1 kg per hectare (Ha).

[0048] The insecticide composition according to one embodiment of the present invention not only exhibits excellent insecticidal activity against the above-mentioned pests, but also exhibits the insecticidal activity in a short period of time (for example, 24 hours), thereby enabling more efficient pest control.

[0049] Furthermore, when applied to a plant, the insecticide composition according to one embodiment of the present invention can effectively reduce the feeding area on the plant, thereby preventing pests from feeding on the plant while controlling the pests.

[0050] How to control pests The present invention provides a method for controlling pests using the above-described pesticide composition, specifically, the method comprises treating a crop or its habitat with the pesticide composition.

[0051] According to one embodiment of the present invention, treating a crop or its habitat with the insecticide composition may specifically include spraying the insecticide composition, contacting the insecticide composition, or immersing the insecticide composition.

[0052] The method for controlling pests according to the present invention can efficiently control pests.

[0053] Aspects of the present invention The present invention will be described in more detail below with reference to the following examples, although the scope of the present invention is not limited to these examples.

[0054] The abbreviations used in the following preparative and synthetic examples are as follows:

[0055] THF: tetrahydrofuran TLC: Thin Layer Chromatography NCS: N-chlorosuccinimide EA: Ethyl acetate DMF: dimethylformamide MC: methylene chloride DMAP: dimethylaminopyridine DIPEA: Diisopropylethylamine EDC: 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide

[0056] Preparation example 1 1) Synthesis of methyl (Z)-4-((hydroxyimino)methyl)-2-methylbenzoate [ka] Hydroxylamine hydrochloride (NHOH·HCl, 101.60 g, 1347.00 mmol) and sodium acetate (NaOAc, 120.00 g, 1347.00 mmol) were dissolved in THF (1,104 mL) and HO (1,104 mL). Methyl 4-formyl-2-methylbenzoate (120.00 g, 673.00 mmol) and THF (1,104 mL) were then slowly added thereto at 0 °C. The mixture was stirred at room temperature for about 1 hour. Completion of the reaction was confirmed by TLC, and the reaction product was extracted with HO / EA. The organic phase was then concentrated and purified with EA / hexane to give methyl (Z)-4-((hydroxyimino)methyl)-2-methylbenzoate (110 g).

[0057] 1 H NMR (500 MHz, DMSO-d6): δ 11.52 (s, 1H), 8.15 (s, 1H), 7.84 (d, J = 8.4 Hz, 1H), 7.54 - 7.51 (m, 2H), 3.82 (s, 3H), 2.52 (s, 3H).

[0058] 2) Synthesis of methyl 4-(5-(3-chloro-5-(trifluoromethyl)phenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)-2-methylbenzoate [ka] Methyl (Z)-4-((hydroxyimino)methyl)-2-methylbenzoate (220.00 g, 1,138.00 mmol) synthesized in step 1 above was dissolved in DMF (7,966 mL). Next, NCS (167.00 g, 1,252.00 mmol) was added, the temperature was raised to 55 °C, and the mixture was stirred for approximately 1 hour. Next, 1-chloro-3-(trifluoromethyl)-5-(3,3,3-trifluoroprop-1-en-2-yl)benzene (328.10 g, 1,195.00 mmol) was added, and the mixture was stirred at room temperature for approximately 12 hours. After that, completion of the reaction was confirmed by TLC, and the reaction product was extracted with HO / EA. The organic phase was then dried over anhydrous sodium sulfate (NaSO) and the solvent was removed under reduced pressure, thereby yielding methyl 4-(5-(3-chloro-5-(trifluoromethyl)phenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)-2-methylbenzoate (429 g).

[0059] 1 H NMR (500 MHz, DMSO-d6): δ 8.09 (s, 1H), 7.97 (s, 1H), 7.90 (d, J = 7.9 Hz, 1H), 7.85 (s, 1H), 7.71 - 7.66 (m, 2H), 4.51 - 4.34 (m, 2H), 3.85 (s, 3H), 2.55 (s, 3H).

[0060] 3) Synthesis of 4-(5-(3-chloro-5-(trifluoromethyl)phenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)-2-methylbenzoic acid [ka] Methyl 4-(5-(3-chloro-5-(trifluoromethyl)phenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)-2-methylbenzoate (429.00 g, 922.00 mmol) synthesized in step 2) above and THF (4,611 mL) were mixed, and then potassium hydroxide (KOH, 134.50 g, 2,398.00 mmol) in HO (4,611 mL) was slowly added. The mixture was stirred at reflux for 1 hour, after which completion of the reaction was confirmed by TLC, and the reaction product was extracted with HO / EA. The organic phase was then dried over anhydrous sodium sulfate (NaSO), and the solvent was removed under reduced pressure. The reaction product was then recrystallized from hexane and then dehydrated to give 4-(5-(3-chloro-5-(trifluoromethyl)phenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)-2-methylbenzoic acid (229.1 g).

[0061] 1 H NMR (500 MHz, DMSO-d6): δ 13.13 (s, 1H), 8.09 (t, J = 2.1 Hz, 1H), 7.98 (t, J = 1.9 Hz, 1H), 7.91 - 7.87 (m, 1H), 7.85 (s, 1H), 7.65 (dd, J = 8.5, 1.4 Hz, 2H), 4.49 - 4.35 (m, 2H), 2.55 (s, 3H).

[0062] 4) Synthesis of 4-(5-(3-chloro-5-(trifluoromethyl)phenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)-2-methylbenzamide (SM2) [ka] 4-(5-(3-chloro-5-(trifluoromethyl)phenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)-2-methylbenzoic acid (25.00 g, 55.34 mmol) synthesized in step 3 above and SOCl (65.80 g, 553.40 mmol) were mixed, and the mixture was refluxed for approximately 2 hours and then concentrated. The reaction product was then diluted with MC (50 mL), and aqueous ammonia (NHOH, 100 mL) was slowly added at 0 °C. After confirming the formation of a solid, the reaction product was purified with HO / hexane to give 4-(5-(3-chloro-5-(trifluoromethyl)phenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)-2-methylbenzamide (23 g).

[0063] 1 H NMR (500 MHz, DMSO-d6): δ 8.09 (s, 1H), 7.98 (s, 1H), 7.86 (s, 1H), 7.82 (s, 1H), 7.62 - 7.56 (m, 2H), 7.49 (s, 1H), 7.46 (d, J = 7.9 Hz, 1H), 4.48 - 4.32 (m, 2H), 2.40 (s, 3H).

[0064] Preparation 2~11 Steps 1) to 4) of Preparative Example 1 were carried out in the same manner, but the reactants in each step were changed to synthesize the following compounds SM1 and SM3 to SM11, respectively.

[0065] [ka]

[0066] Synthesis Example 1 - Synthesis of Compound 1001 1) Synthesis of Compound 1001 (R / S) [ka] SM1 (0.50 g, 1.19 mmol) synthesized in the above preparative example was dissolved in THF (10 mL), and then sodium hydride (NaH, 0.09 g, 2.35 mmol) was added at 0 °C. The mixture was then stirred at room temperature for 2 hours, and then cyclopropanecarbonyl chloride (0.13 g, 1.08 mmol) was added and reacted at room temperature for 4 hours. After the completion of the reaction was confirmed by TLC, ammonium chloride (NH4Cl) was added at 0 °C, and the mixture was then extracted with EA. The organic phase was then dried over anhydrous Na2SO4, and the solvent was removed under reduced pressure. The reaction product was then purified by silica gel column chromatography to obtain compound 1001 (0.3 g).

[0067] 1 H NMR (500 MHz, DMSO-d6): δ 11.34 (s, 1H), 7.82 (t, J = 1.9 Hz, 1H), 7.68 - 7.58 (m, 4H), 7.49 (d, J = 8.0 Hz, 1H), 4.37 (s, 1H), 4.32 (s, 1H), 2.36 (s, 3H), 2.20 (tt, J = 7.8, 4.5 Hz, 1H), 0.94 - 0.86 (m, 2H), 0.85 (dt, J = 4.4, 2.9 Hz, 2H).

[0068] 2) Synthesis of Compound 1001(S) [ka] Compound 1001(S) was obtained using (S)-4-(5-(3,5-dichlorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)-2-methylbenzoic acid via the same process as in step 1).

[0069] 1H NMR (500 MHz, DMSO-d6): δ 11.34 (s, 1H), 7.82 (t, J = 1.9 Hz, 1H), 7.68 - 7.58 (m, 4H), 7.49 (d, J = 8.0 Hz, 1H), 4.37 (s, 1H), 4.32 (s, 1H), 2.36 (s, 3H), 2.20 (tt, J = 7.8, 4.5 Hz, 1H), 0.94 - 0.86 (m, 2H), 0.85 (dt, J = 4.4, 2.9 Hz, 2H).

[0070] 3) Synthesis of Compound 1001(R) [ka] Compound 1001(R) was obtained using (R)-4-(5-(3,5-dichlorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)-2-methylbenzoic acid via the same process as in step 1).

[0071] 1 H NMR (500 MHz, DMSO-d6): δ 11.34 (s, 1H), 7.82 (t, J = 1.9 Hz, 1H), 7.68 - 7.58 (m, 4H), 7.49 (d, J = 8.0 Hz, 1H), 4.37 (s, 1H), 4.32 (s, 1H), 2.36 (s, 3H), 2.20 (tt, J = 7.8, 4.5 Hz, 1H), 0.94 - 0.86 (m, 2H), 0.85 (dt, J = 4.4, 2.9 Hz, 2H).

[0072] Synthesis Example 2 - Synthesis of Compound 1002 1) Synthesis of Compound 1002 (R / S) [ka] SM2 (10.00 g, 22.13 mmol) synthesized in the above Preparative Example was dissolved in THF (200 mL), and then NaH (1.77 g, 44.26 mmol) was added and mixed. The mixture was then stirred at room temperature for 2 hours, and cyclopropanecarbonyl chloride (2.10 g, 20.12 mmol) was added and reacted at room temperature for 4 hours. After confirming the completion of the reaction by TLC, NH4Cl was added at 0 °C, and the mixture was extracted with EA. The organic phase was then dried over anhydrous Na2SO4, and the solvent was removed under reduced pressure. The reaction product was then purified by silica gel column chromatography to obtain compound 1002 (6 g).

[0073] 1 H NMR (500 MHz, DMSO-d6): δ 11.35 (s, 1H), 8.09 (td, J = 1.7, 0.8 Hz, 1H), 7.98 (d, J = 1.9 Hz, 1H), 7.86 (s, 1H), 7.66 - 7.59 (m, 2H), 7.50 (d, J = 7.9 Hz, 1H), 4.43 (s, 1H), 4.39 (s, 1H), 2.36 (s, 3H), 2.20 (tt, J = 7.2, 4.6 Hz, 1H), 0.94 - 0.86 (m, 2H), 0.88 - 0.80 (m, 2H).

[0074] 2) Synthesis of Compound 1002(S) [ka] Compound 1002(S) was obtained using (S)-4-(5-(3-chloro-5-(trifluoromethyl)phenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)-2-methylbenzoic acid via the same process as in step 1).

[0075] 1H NMR (500 MHz, DMSO-d6): δ 11.35 (s, 1H), 8.09 (td, J = 1.7, 0.8 Hz, 1H), 7.98 (d, J = 1.9 Hz, 1H), 7.86 (s, 1H), 7.66 - 7.59 (m, 2H), 7.50 (d, J = 7.9 Hz, 1H), 4.43 (s, 1H), 4.39 (s, 1H), 2.36 (s, 3H), 2.20 (tt, J = 7.2, 4.6 Hz, 1H), 0.94 - 0.86 (m, 2H), 0.88 - 0.80 (m, 2H).

[0076] 3) Synthesis of Compound 1002(R) [ka] Compound 1002(R) was obtained using (R)-4-(5-(3-chloro-5-(trifluoromethyl)phenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)-2-methylbenzoic acid via the same process as in step 1).

[0077] 1 H NMR (500 MHz, DMSO-d6): δ 11.35 (s, 1H), 8.09 (td, J = 1.7, 0.8 Hz, 1H), 7.98 (d, J = 1.9 Hz, 1H), 7.86 (s, 1H), 7.66 - 7.59 (m, 2H), 7.50 (d, J = 7.9 Hz, 1H), 4.43 (s, 1H), 4.39 (s, 1H), 2.36 (s, 3H), 2.20 (tt, J = 7.2, 4.6 Hz, 1H), 0.94 - 0.86 (m, 2H), 0.88 - 0.80 (m, 2H).

[0078] Synthesis Example 3 - Synthesis of Compound 1003 1) Synthesis of Compound 1003 (R / S) [ka] Compound 1003 (R / S) was obtained through the same process as in Synthesis Example 1, except that SM4 was used instead of SM1.

[0079] 1 H NMR (500 MHz, DMSO-d6): δ 11.35 (s, 1H), 7.81 (d, J = 6.1 Hz, 2H), 7.65 - 7.58 (m, 2H), 7.50 (d, J = 8.0 Hz, 1H), 4.40 - 4.28 (m, 2H), 2.36 (s, 3H), 2.20 (tt, J = 7.6, 4.5 Hz, 1H), 0.91 (ddt, J = 7.5, 5.6, 2.3 Hz, 2H), 0.85 (dt, J = 4.5, 2.9 Hz, 2H).

[0080] 2) Synthesis of Compound 1003(S) [ka] Compound 1003(S) was obtained using (S)-4-(5-(3,5-dichloro-4-fluorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)-2-methylbenzoic acid via the same process as in step 1).

[0081] 1 H NMR (500 MHz, DMSO-d6): δ 11.35 (s, 1H), 7.81 (d, J = 6.1 Hz, 2H), 7.65 - 7.58 (m, 2H), 7.50 (d, J = 8.0 Hz, 1H), 4.40 - 4.28 (m, 2H), 2.36 (s, 3H), 2.20 (tt, J = 7.6, 4.5 Hz, 1H), 0.91 (ddt, J = 7.5, 5.6, 2.3 Hz, 2H), 0.85 (dt, J = 4.5, 2.9 Hz, 2H).

[0082] 3) Synthesis of Compound 1003(R) [ka] Compound 1003(R) was obtained using (R)-4-(5-(3,5-dichloro-4-fluorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)-2-methylbenzoic acid via the same process as in step 1).

[0083] 1 H NMR (500 MHz, DMSO-d6): δ 11.35 (s, 1H), 7.81 (d, J = 6.1 Hz, 2H), 7.65 - 7.58 (m, 2H), 7.50 (d, J = 8.0 Hz, 1H), 4.40 - 4.28 (m, 2H), 2.36 (s, 3H), 2.20 (tt, J = 7.6, 4.5 Hz, 1H), 0.91 (ddt, J = 7.5, 5.6, 2.3 Hz, 2H), 0.85 (dt, J = 4.5, 2.9 Hz, 2H).

[0084] Synthesis Example 4 - Synthesis of Compound 1004 [ka] Compound 1004 was obtained through the same process as in Synthesis Example 1, except that SM5 was used instead of SM1.

[0085] 1H NMR (500 MHz, DMSO-d6): δ 11.36 (s, 1H), 8.08 - 8.03 (m, 1H), 8.00 (dt, J = 7.8, 1.4 Hz, 1H), 7.96 (d, J = 8.4 Hz, 1H), 7.76 (t, J = 7.9 Hz, 1H), 7.66 - 7.60 (m, 2H), 7.49 (d, J = 8.1 Hz, 1H), 4.42 (d, J = 18.3 Hz, 1H), 4.31 (d, J = 18.3 Hz, 1H), 2.35 (s, 3H), 2.20 (ddd, J = 12.4, 7.8, 4.7Hz, 1H), 0.90 (dq, J = 7.8, 2.5 Hz, 2H), 0.85 (dq, J = 5.8, 2.7 Hz, 2H).

[0086] Synthesis Example 5 - Synthesis of Compound 1005 [ka] Compound 1005 was obtained through the same process as in Synthesis Example 1, except that SM11 was used instead of SM1.

[0087] 1 H NMR (500 MHz, DMSO-d6): δ 11.36 (s, 1H), 8.35 (s, 1H), 8.21 (d, J = 1.2 Hz, 2H), 7.64 (d, J = 2.1 Hz, 1H), 7.64 - 7.60 (m, 1H), 7.50 (d, J = 7.9 Hz, 1H), 4.48 (q, J = 18.4 Hz, 2H), 2.36 (s, 3H), 2.20 (tt, J = 7.8, 4.6 Hz, 1H), 0.90 (dt, J = 7.6, 3.0 Hz, 2H), 0.85 (dt, J = 4.4, 2.9 Hz, 2H).

[0088] Synthesis Example 6 - Synthesis of Compound 1006 [ka] Compound 1006 was obtained through the same process as in Synthesis Example 1, except that SM3 was used instead of SM1.

[0089] 1 H NMR (500 MHz, DMSO-d6): δ 11.63 (s, 1H), 8.84 - 8.76 (m, 1H), 8.11 (d, J = 1.8 Hz, 1H), 8.09 - 8.03 (m, 2H), 7.95 - 7.85 (m, 2H), 7.83 - 7.64 (m, 3H), 4.62 (s, 2H), 2.29 - 2.18 (m, 1H), 0.93 (ddt, J = 7.7, 6.0, 2.8 Hz, 2H), 0.87 - 0.83 (m, 2H).

[0090] Synthesis Example 7 - Synthesis of Compound 1007 [ka] Compound 1007 was obtained through the same process as in Synthesis Example 1, except that SM6 was used instead of SM1.

[0091] 1 H NMR (500 MHz, DMSO-d6): δ 11.26 (s, 1H), 8.01 (d, J = 1.9 Hz, 1H), 7.99 (d, J = 1.7 Hz, 1H), 7.87 (d, J = 3.8 Hz, 1H), 7.85 (d, J = 1.7 Hz, 1H), 7.82 (q, J = 1.9 Hz, 1H), 7.64 (d, J = 1.9 Hz, 2H), 4.44 (d, J = 18.3 Hz, 1H), 4.38 - 4.30 (m, 1H), 2.48 - 2.45 (m, 1H), 0.93 - 0.92 (m, 2H), 0.87 - 0.84 (m, 2H).

[0092] Synthesis Example 8 - Synthesis of Compound 1008 [ka] Compound 1008 was obtained through the same process as in Synthesis Example 1, except that SM7 was used instead of SM1.

[0093] 1 H NMR (500 MHz, CDCl3): δ 8.42 (s, 1H), 7.97 - 7.91 (m, 1H), 7.79 - 7.71 (m, 1H), 7.57 (d, J = 8.0 Hz, 1H), 7.52 (d, J = 1.8 Hz, 2H), 7.47 (t, J = 1.9 Hz, 1H), 4.13 - 4.05 (m, 1H), 3.71 (dd, J = 17.3, 3.8 Hz, 1H), 2.51 (s, 1H), 1.21 (dt, J = 4.5, 3.3 Hz, 2H), 1.10 - 1.07 (m, 2H).

[0094] Synthesis Example 9 - Synthesis of Compound 1009 [ka] Compound 1009 was obtained through the same process as in Synthesis Example 1, except that SM8 was used instead of SM1.

[0095] 1 H NMR (500 MHz, CDCl3): δ 8.52 (s, 1H), 7.66 (d, J = 1.5 Hz, 1H), 7.65 - 7.51 (m, 2H), 7.43 (d, J = 1.8 Hz, 2H), 7.37 (t, J = 1.8 Hz, 1H), 3.99 (d, J = 17.2 Hz, 1H), 3.62 (d, J = 17.2 Hz, 1H), 2.46 (s, 1H), 1.12 (dd, J = 4.4, 3.2 Hz, 2H), 1.00 - 0.97 (m, 2H).

[0096] Synthesis Example 10 - Synthesis of Compound 1010 [ka] Compound 1010 was obtained through the same process as in Synthesis Example 1, except that SM9 was used instead of SM1.

[0097] 1 H NMR (500 MHz, CDCl3): δ 10.37 (s, 1H), 8.86 (dd, J = 2.1, 0.9 Hz, 1H), 8.35 (dd, J = 8.2, 0.8 Hz, 1H), 8.22 (dd, J = 8.2, 2.1 Hz, 1H), 7.80 (s, 1H), 7.74 (s, 1H), 7.70 (s, 1H), 4.17 (d, J = 17.2 Hz, 1H), 3.76 (d, J = 17.2 Hz, 1H), 2.99 (tt, J = 7.9, 4.6 Hz, 1H), 1.22 (dd, J = 4.6, 3.2Hz, 2H), 1.05 (dt, J = 8.1, 3.3 Hz, 2H).

[0098] Synthesis Example 11 - Synthesis of Compound 1011 [ka] 4-(5-(3-chloro-5-(trifluoromethyl)phenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)-2-methylbenzoic acid (0.50 g, 1.20 mmol) was diluted in MC (10 mL), EDC (0.46 g, 2.40 mmol) and DMAP (0.03 g, 0.24 mmol) were added, and methylamine (0.06 g, 1.80 mmol) was added. The mixture was then stirred at room temperature for 12 hours. After completion of the reaction was confirmed by TLC, the reaction product was extracted with MC / sodium bicarbonate (NaHCO). The organic phase was then dried over anhydrous NaSO, and the solvent was removed under reduced pressure. The reaction product was then purified by silica gel column chromatography to obtain compound (0.4 g).

[0099] The resulting compound (0.05 g) was diluted with MC (0.11 mL), and then DIPEA (0.03 mL, 0.16 mmol) and cyclopropanecarbonyl chloride (0.02 mL, 0.16 mmol) were added at 0 °C, followed by reaction at room temperature for 12 hours. After confirming the completion of the reaction by TLC, the reaction product was extracted with MC / NaHCO. The organic phase was then dried over anhydrous NaSO, and the solvent was removed under reduced pressure. The reaction product was then purified by silica gel column chromatography to obtain compound 1011 (0.03 g).

[0100] 1 H NMR (500 MHz, CDCl3): δ 7.80 (s, 1H), 7.74 (s, 1H), 7.67 (s, 1H), 7.54 (dt, J = 1.5, 0.7 Hz, 1H), 7.54 - 7.50 (m, 1H), 7.31 (d, J = 7.9 Hz, 1H), 4.12 (d, J = 17.2 Hz, 1H), 3.70 (d, J = 17.2 Hz, 1H), 3.27 (s, 3H), 2.39 (s, 3H), 1.91 (tt, J = 7.8, 4.6 Hz, 1H), 1.04 (dq, J = 4.6, 3.7 Hz, 2H), 0.80 - 0.76 (m, 2H).

[0101] Synthesis Example 12 - Synthesis of Compound 1012 [ka] Compound 1012 was obtained through the same process as in Synthesis example 11, except that 4-(5-(3-chloro-5-(trifluoromethyl)phenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)-1-naphthoic acid was used instead of 4-(5-(3-chloro-5-(trifluoromethyl)phenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)-2-methylbenzoic acid.

[0102] 1H NMR (500 MHz, CDCl3): δ 8.91 - 8.88 (m, 1H), 8.05 - 8.01 (m, 1H), 7.85 (s, 1H), 7.79 (s, 1H), 7.72 - 7.69 (m, 1H), 7.69 - 7.62 (m, 2H), 7.54 (d, J = 7.5 Hz, 1H), 7.50 (d, J = 7.5 Hz, 1H), 4.32 (d, J = 17.2 Hz, 1H), 3.92 (d, J = 17.2 Hz, 1H), 3.31 (s, 3H), 1.95 (tt, J = 7.9, 4.7 Hz, 1H), 0.99 - 0.96 (m, 2H), 0.67 (dd, J = 7.5, 3.7 Hz, 2H).

[0103] Synthesis Example 13 - Synthesis of Compound 1013 [ka] Compound 1013 was obtained through the same process as in Synthesis example 11, except that 4-(5-(3,5-dichlorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)-2-methylbenzoic acid was used instead of 4-(5-(3-chloro-5-(trifluoromethyl)phenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)-2-methylbenzoic acid.

[0104] 1 H NMR (500 MHz, CDCl3): δ 7.55 - 7.47 (m, 4H), 7.41 (t, J = 1.8 Hz, 1H), 7.31 (d, J = 7.9 Hz, 1H), 4.06 (d, J = 17.1 Hz, 1H), 3.67 (d, J = 17.2 Hz, 1H), 3.27 (s, 3H), 2.39 (s, 3H), 1.90 (tt, J = 7.8, 4.6 Hz, 1H), 1.06 - 1.02 (m, 2H), 0.80 - 0.74 (m, 2H).

[0105] Synthesis Example 14 - Synthesis of Compound 1014 [ka] Compound 1014 was obtained through the same process as in Synthesis example 11, except that SM10 was used instead of 4-(5-(3-chloro-5-(trifluoromethyl)phenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)-2-methylbenzoic acid.

[0106] 1 H NMR (500 MHz, CDCl3): δ 8.89 (dt, J = 8.9, 1.0 Hz, 1H), 8.05 - 8.01 (m, 1H), 7.66 (dddd, J = 19.5, 8.2, 6.9, 1.4 Hz, 2H), 7.56 - 7.47 (m, 4H), 7.44 (t, J = 1.9 Hz, 1H), 4.26 (d, J = 17.2 Hz, 1H), 3.89 (d, J = 17.2 Hz, 1H), 3.31 (s, 3H), 1.94 (tt, J = 7.8, 4.6 Hz, 1H), 0.97 (dd, J = 4.6, 3.4 Hz, 2H), 0.68 - 0.63 (m, 2H).

[0107] Synthesis Example 15 - Synthesis of Compound 1015 [ka] 4-(5-(3,5-Dichlorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)-1-naphthoic acid (0.25 g, 0.50 mmol) was diluted with MC (5 mL), DIPEA (0.13 mL, 0.75 mmol) was added at 0 °C, and then cyclopropanecarbonyl chloride (0.07 mL, 0.75 mmol) was added. The mixture was stirred at room temperature for 12 hours. After completion of the reaction was confirmed by TLC, the reaction product was extracted with MC / HO. The organic phase was then dried over anhydrous NaSO, and the solvent was removed under reduced pressure. The reaction product was then purified by silica gel column chromatography to obtain compound 1015 (0.012 g).

[0108] 1 H NMR (500 MHz, CDCl3): δ 8.88 (dd, J = 7.7, 2.4 Hz, 1H), 8.21 - 8.15 (m, 1H), 7.72 - 7.64 (m, 2H), 7.63 - 7.59 (m, 1H), 7.56 - 7.50 (m, 3H), 7.44 (q, J = 2.0 Hz, 1H), 4.27 (d, J = 6.0 Hz, 2H), 4.24 (d, J = 5.2 Hz, 1H), 3.89 (d, J = 17.4 Hz, 1H), 3.84 (t, J = 6.1 Hz, 2H), 1.28 (d, J = 6.7 Hz, 3H), 1.10 (d, J = 6.9 Hz, 2H).

[0109] Synthesis Example 16 - Synthesis of Compound 1016 [ka] Compound 1016 was obtained through the same process as in Synthesis example 15, except that 4-(5-(3-chloro-5-(trifluoromethyl)phenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)-2-methylbenzoic acid was used instead of 4-(5-(3,5-dichlorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)-1-naphthoic acid.

[0110] 1 H NMR (500 MHz, CDCl3): δ 7.99 (s, 1H), 7.57 - 7.46 (m, 4H), 7.41 (t, J = 1.8 Hz, 1H), 7.31 (d, J = 7.9 Hz, 1H), 5.44 - 5.36 (m, 1H), 4.13 - 4.03 (m, 2H), 3.95 (dd, J = 14.3, 3.1 Hz, 1H), 3.67 (d, J = 17.2 Hz, 1H), 3.37 (q, J = 7.2 Hz, 1H), 2.42 (s, 3H), 1.70 - 1.62 (m, 2H), 1.62 - 1.47 (m, 2H), 1.30 (d, J = 6.4 Hz, 3H).

[0111] Synthesis Example 17 - Synthesis of Compound 1017 [ka] Compound 1017 was obtained through the same process as in Synthesis example 15, except that 4-(5-(3-chloro-5-(trifluoromethyl)phenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)-1-naphthoic acid was used instead of 4-(5-(3,5-dichlorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)-1-naphthoic acid.

[0112] 1H NMR (500 MHz, CDCl3): δ 8.90 - 8.86 (m, 1H), 8.16 - 8.12 (m, 1H), 7.85 (t, J = 2.0 Hz, 1H), 7.79 (s, 1H), 7.70 (q, J = 1.3 Hz, 1H), 7.69 - 7.63 (m, 2H), 7.58 - 7.51 (m, 2H), 4.68 (dt, J = 47.3, 4.9 Hz, 2H), 4.31 (d, J = 17.2 Hz, 1H), 4.21 (dt, J = 24.7, 4.8 Hz, 2H), 3.96 - 3.87 (m, 1H), 3.26 (q, J = 6.8 Hz, 1H), 1.76 - 1.55 (m, 4H).

[0113] Synthesis Example 18 - Synthesis of Compound 1018 [ka] Compound 1018 was obtained through the same process as in Synthesis Example 1, except that 5-methyl-2-furancarbonyl chloride was used instead of cyclopropanecarbonyl chloride and SM2 was used instead of SM1.

[0114] 1 H NMR (500 MHz, DMSO-d6): δ 11.31 (s, 1H), 8.09 (s, 1H), 7.98 (s, 1H), 7.86 (s, 1H), 7.65 (d, J = 2.0 Hz, 1H), 7.62 (dd, J = 8.0, 2.1 Hz, 1H), 7.52 (d, J = 3.5 Hz, 1H), 7.49 (d, J = 8.1 Hz, 1H), 6.36 (dd, J = 3.5, 1.1 Hz, 1H), 4.49 - 4.35 (m, 2H), 2.36 (s, 3H), 2.35 (s, 3H).

[0115] Synthesis Example 19 - Synthesis of Compound 1019 [ka] Compound 1019 was obtained through the same process as in Synthesis example 15, except that 4-(5-(3-chloro-5-(trifluoromethyl)phenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)-2-methylbenzoic acid was used instead of 4-(5-(3,5-dichlorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)-1-naphthoic acid.

[0116] 1 H NMR (500 MHz, CDCl3): δ 7.80 (s, 1H), 7.73 (s, 1H), 7.67 (s, 1H), 7.53 (s, 1H), 7.52 - 7.49 (m, 1H), 7.29 (d, J = 7.9 Hz, 1H), 4.11 (d, J = 17.2 Hz, 1H), 3.88 (q, J = 7.0 Hz, 2H), 3.69 (d, J = 17.2 Hz, 1H), 2.40 (s, 3H), 1.74 - 1.66 (m, 2H), 1.16 - 1.14 (m, 1H), 1.02 - 0.99 (m, 3H), 0.72 (dd, J = 7.8, 3.4 Hz, 2H).

[0117] Synthesis Example 20 - Synthesis of Compound 1020 [ka] Compound 1020 was obtained through the same process as in Synthesis example 15, except that 4-(5-(3-chloro-5-(trifluoromethyl)phenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)-2-methylbenzoic acid was used instead of 4-(5-(3,5-dichlorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)-1-naphthoic acid.

[0118] 1H NMR (500 MHz, CDCl3): δ 7.80 (s, 1H), 7.74 (s, 1H), 7.68 (s, 1H), 7.58 (s, 1H), 7.54 (dd, J = 7.9, 1.8 Hz, 1H), 7.37 (d, J = 8.1 Hz, 1H), 4.58 (q, J = 8.5 Hz, 2H), 4.12 (d, J = 17.2 Hz, 1H), 3.70 (d, J = 17.4 Hz, 1H), 2.46 (s, 3H), 0.93 (dt, J = 4.9, 3.2 Hz, 1H), 0.88 - 0.84 (m, 2H), 0.68 (ddd, J = 7.9, 4.5, 1.7 Hz, 2H).

[0119] Synthesis Example 21 - Synthesis of Compound 1021 [ka] Compound 1021 was obtained through the same process as in Synthesis example 15, except that 4-(5-(3-chloro-5-(trifluoromethyl)phenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)-2-methylbenzoic acid was used instead of 4-(5-(3,5-dichlorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)-1-naphthoic acid.

[0120] 1H NMR (500 MHz, CDCl3): δ 7.80 (s, 1H), 7.74 (s, 1H), 7.67 (s, 1H), 7.53 (s, 1H), 7.53 - 7.50 (m, 1H), 7.36 (d, J = 7.9 Hz, 1H), 4.12 (d, J = 17.2 Hz, 1H), 3.74 (d, J = 7.0 Hz, 2H), 3.70 (d, J = 17.4 Hz, 1H), 2.43 (s, 3H), 1.71 - 1.65 (m, 1H), 1.65 - 1.59 (m, 1H), 1.15 (dd, J = 4.6, 3.1 Hz, 2H), 0.68 (h, J = 4.2 Hz, 2H), 0.52 - 0.47 (m, 2H), 0.32 - 0.27 (m, 2H).

[0121] Synthesis Example 22 - Synthesis of Compound 1022 [ka] Compound 1022 was obtained through the same process as in Synthesis Example 15, except that 4-(5-(3-chloro-5-(trifluoromethyl)phenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)-2-methylbenzoic acid was used instead of 4-(5-(3,5-dichlorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)-1-naphthoic acid.

[0122] 1H NMR (500 MHz, CDCl3): δ 7.80 (s, 1H), 7.73 (s, 1H), 7.68 (t, J = 1.8 Hz, 1H), 7.63 - 7.56 (m, 2H), 7.52 (d, J = 2.0 Hz, 1H), 4.12 (d, J = 17.2 Hz, 1H), 3.70 (d, J = 17.2 Hz, 1H), 2.55 (s, 3H), 2.03 (ddd, J = 7.8, 4.7, 3.2 Hz, 2H), 1.14 (td, J = 4.4, 2.5 Hz, 4H), 1.02 (dq, J = 7.2, 3.7 Hz, 4H).

[0123] Synthesis Example 23 - Synthesis of Compound 1023 [ka] Compound 1023 was obtained through the same process as in Synthesis example 15, except that 4-(5-(3-chloro-5-(trifluoromethyl)phenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)-2-methylbenzoic acid was used instead of 4-(5-(3,5-dichlorophenyl)-5-(trifluoromethyl)-4,5-dihydroisoxazol-3-yl)-1-naphthoic acid.

[0124] 1 H NMR (500 MHz, CDCl3): δ 7.79 (s, 1H), 7.73 (s, 1H), 7.66 (s, 1H), 7.50 - 7.46 (m, 2H), 7.21 (d, J = 8.5 Hz, 1H), 4.10 (d, J = 17.2 Hz, 1H), 3.68 (d, J = 17.1 Hz, 1H), 2.83 (tt, J = 6.9, 3.8 Hz, 1H), 2.35 (d, J = 2.0 Hz, 3H), 1.59 (tt, J = 8.1, 4.6 Hz, 1H), 1.05 - 1.00 (m, 4H), 0.92 (ddt, J = 8.1, 6.9, 3.3 Hz, 4H).

[0125] Synthesis Example 24 - Synthesis of Compound 1024 [ka] Compound 1024 was obtained through the same process as in Synthesis Example 1, except that 1-methylcyclopropanecarbonyl chloride was used instead of cyclopropanecarbonyl chloride.

[0126] 1 H NMR (500 MHz, CDCl3): δ 8.45 (s, 1H), 7.55 - 7.46 (m, 4H), 7.41 (q, J = 2.1 Hz, 1H), 7.33 (s, 1H), 4.05 (d, J = 17.1 Hz, 1H), 3.66 (d, J = 17.2 Hz, 1H), 2.39 (s, 3H), 1.42 (s, 3H), 1.27 (s, 2H), 0.76 (s, 1H), 0.74 - 0.71 (m, 1H).

[0127] Synthesis Example 25 - Synthesis of Compound 1025 [ka] Compound 1025 was obtained through the same process as in Synthesis Example 1, except that 1-methylcyclopropanecarbonyl chloride was used instead of cyclopropanecarbonyl chloride and SM2 was used instead of SM1.

[0128] 1 H NMR (500 MHz, CDCl3): δ 8.46 (s, 1H), 7.79 (s, 1H), 7.73 (s, 1H), 7.67 (s, 1H), 7.54 - 7.49 (m, 2H), 7.32 (d, J = 8.4 Hz, 1H), 4.10 (d, J = 17.1 Hz, 1H), 3.68 (d, J = 17.0 Hz, 1H), 2.39 (s, 3H), 1.41 (s, 3H), 1.25 (q, J = 4.0 Hz, 2H), 0.78 - 0.74 (m, 2H).

[0129] Synthesis Example 26 - Synthesis of Compound 1026 [ka] Compound 1026 was obtained through the same process as in Synthesis Example 1, except that 1-cyanocyclopropanecarbonyl chloride was used instead of cyclopropanecarbonyl chloride.

[0130] 1 H NMR (500 MHz, CDCl3): δ 8.96 (s, 1H), 7.56 (dd, J = 7.6, 0.7 Hz, 2H), 7.50 - 7.45 (m, 3H), 7.41 (t, J = 1.8 Hz, 1H), 4.06 (d, J = 17.1 Hz, 1H), 3.68 (d, J = 17.2 Hz, 1H), 2.48 (s, 3H), 1.81 - 1.76 (m, 2H), 1.72 - 1.67 (m, 2H).

[0131] Synthesis Example 27 - Synthesis of Compound 1027 [ka] Compound 1027 was obtained through the same process as in Synthesis Example 1, except that 1-cyanocyclopropanecarbonyl chloride was used instead of cyclopropanecarbonyl chloride and SM2 was used instead of SM1.

[0132] 1 H NMR (500 MHz, DMSO-d6): δ 11.43 (s, 1H), 8.08 (s, 1H), 7.98 (s, 1H), 7.85 (s, 1H), 7.69 - 7.61 (m, 2H), 7.56 (d, J = 8.1 Hz, 1H), 4.46 (d, J = 18.3 Hz, 1H), 4.37 (d, J = 18.3 Hz, 1H), 2.40 (s, 3H), 1.73 (dd, J = 3.8, 1.7 Hz, 4H).

[0133] Synthesis Example 28 - Synthesis of Compound 1028 [ka] Compound 1028 was obtained through the same process as in Synthesis Example 1, except that 1-(trifluoromethyl)cyclopropanecarbonyl chloride was used instead of cyclopropanecarbonyl chloride.

[0134] 1 H NMR (500 MHz, CDCl3): δ 8.66 (s, 1H), 7.57 - 7.53 (m, 2H), 7.48 (d, J = 1.8 Hz, 2H), 7.42 - 7.38 (m, 2H), 4.06 (d, J = 17.1 Hz, 1H), 3.67 (d, J = 17.2 Hz, 1H), 2.45 (s, 3H), 1.54 - 1.49 (m, 2H), 1.39 - 1.36 (m, 2H).

[0135] Synthesis Example 29 - Synthesis of Compound 1029 [ka] Compound 1029 was obtained through the same process as in Synthesis example 1, except that 1-(trifluoromethyl)cyclopropanecarbonyl chloride was used instead of cyclopropanecarbonyl chloride and SM2 was used instead of SM1.

[0136] 1 H NMR (500 MHz, DMSO-d6): δ 10.95 (s, 1H), 8.08 (s, 1H), 7.97 (s, 1H), 7.85 (s, 1H), 7.66 - 7.58 (m, 2H), 7.44 (d, J = 8.1 Hz, 1H), 4.45 (d, J = 18.5 Hz, 1H), 4.36 (d, J = 18.3 Hz, 1H), 2.33 (s, 3H), 1.61 (d, J = 1.7 Hz, 2H), 1.37 - 1.33 (m, 2H).

[0137] Synthesis Example 30 - Synthesis of Compound 1030 [ka] Compound 1030 was obtained through the same process as in Synthesis Example 1, except that 2,2-difluoro-1-methylcyclopropanecarbonyl chloride was used instead of cyclopropanecarbonyl chloride.

[0138] 1 H NMR (500 MHz, CDCl3): δ 8.26 (s, 1H), 7.56 - 7.52 (m, 2H), 7.49 (d, J = 2.0 Hz, 2H), 7.44 - 7.39 (m, 2H), 4.06 (dd, J = 17.1, 0.8 Hz, 1H), 3.68 (d, J = 17.2 Hz, 1H), 2.46 (s, 3H), 2.16 - 2.08 (m, 1H), 1.58 (dd, J = 2.8, 1.6 Hz, 3H), 1.36 (ddd, J = 11.1, 8.4, 5.3 Hz, 1H).

[0139] Synthesis Example 31 - Synthesis of Compound 1031 [ka] Compound 1031 was obtained through the same process as in Synthesis Example 1, except that 2,2-difluoro-1-methylcyclopropanecarbonyl chloride was used instead of cyclopropanecarbonyl chloride and SM2 was used instead of SM1.

[0140] 1H NMR (500 MHz, CDCl3): δ 8.22 (s, 1H), 7.80 (s, 1H), 7.73 (s, 1H), 7.68 (s, 1H), 7.59 - 7.54 (m, 2H), 7.42 (d, J = 8.5 Hz, 1H), 4.12 (dd, J = 17.2, 0.9 Hz, 1H), 3.70 (d, J = 17.2 Hz, 1H), 2.46 (s, 3H), 1.58 (dd, J = 2.8, 1.6 Hz, 3H), 1.45 (dd, J = 2.9, 2.0 Hz, 1H), 1.38 - 1.34 (m, 1H).

[0141] Synthesis Example 32 - Synthesis of Compound 1032 [ka] Compound 1032 was obtained through the same process as in Synthesis Example 1, except that cyclobutanecarbonyl chloride was used instead of cyclopropanecarbonyl chloride.

[0142] 1 H NMR (500 MHz, CDCl3): δ 8.28 (s, 1H), 7.56 - 7.51 (m, 2H), 7.49 (d, J = 2.0 Hz, 2H), 7.45 (d, J = 7.9 Hz, 1H), 7.41 (t, J = 1.9 Hz, 1H), 4.06 (d, J = 17.1 Hz, 1H), 3.68 (d, J = 17.2 Hz, 1H), 3.16 (pd, J = 8.5, 1.1 Hz, 1H), 2.46 (s, 3H), 2.24 - 2.19 (m, 2H), 2.06 - 1.95 (m, 2H), 1.94 - 1.87 (m, 2H).

[0143] Synthesis Example 33 - Synthesis of Compound 1033 [ka] Compound 1033 was obtained through the same process as in Synthesis Example 1, except that cyclobutanecarbonyl chloride was used instead of cyclopropanecarbonyl chloride and SM2 was used instead of SM1.

[0144] 1 H NMR (500 MHz, CDCl3): δ 8.05 (s, 1H), 7.80 (s, 1H), 7.73 (s, 1H), 7.67 (s, 1H), 7.58 - 7.52 (m, 2H), 7.44 (d, J = 7.9 Hz, 1H), 4.12 (d, J = 17.2 Hz, 1H), 3.87 (pd, J = 8.5, 1.2 Hz, 1H), 3.70 (d, J = 17.2 Hz, 1H), 2.46 (s, 3H), 2.39 - 2.27 (m, 4H), 2.10 - 1.96 (m, 1H), 1.95 - 1.83 (m, 1H).

[0145] Synthesis Example 34 - Synthesis of Compound 1034 [ka] Compound 1034 was obtained through the same process as in Synthesis Example 1, except that 2-naphthoyl chloride was used instead of cyclopropanecarbonyl chloride.

[0146] 1H NMR (500 MHz, CDCl3): δ 9.03 (s, 1H), 8.42 (d, J = 1.8 Hz, 1H), 7.98 (dd, J = 8.3, 1.9 Hz, 2H), 7.91 (ddd, J = 20.1, 8.3, 1.6 Hz, 2H), 7.85 (d, J = 1.9 Hz, 1H), 7.79 (s, 1H), 7.75 - 7.68 (m, 1H), 7.68 - 7.64 (m, 1H), 7.64 - 7.61 (m, 2H), 7.61 (d, J = 1.1 Hz, 1H), 7.54 (d, J = 7.9 Hz, 1H), 4.22 - 4.12 (m, 1H), 3.76 (d, J = 17.2 Hz, 1H), 2.53 (s, 3H).

[0147] Synthesis Example 35 - Synthesis of Compound 1035 [ka] Compound 1035 was obtained through the same process as in Synthesis Example 1, except that 2-naphthoyl chloride was used instead of cyclopropanecarbonyl chloride and SM2 was used instead of SM1.

[0148] 1 H NMR (500 MHz, CDCl3): δ 9.03 (s, 1H), 8.42 (d, J = 1.8 Hz, 1H), 7.98 (dd, J = 8.3, 1.9 Hz, 2H), 7.91 (ddd, J = 20.1, 8.3, 1.6 Hz, 2H), 7.85 (d, J = 1.9 Hz, 1H), 7.79 (s, 1H), 7.75 - 7.68 (m, 1H), 7.68 - 7.64 (m, 1H), 7.64 - 7.61 (m, 2H), 7.61 (d, J = 1.1 Hz, 1H), 7.54 (d, J = 7.9 Hz, 1H), 4.22 - 4.12 (m, 1H), 3.76 (d, J = 17.2 Hz, 1H), 2.53 (s, 3H).

[0149] Synthesis Example 36 - Synthesis of Compound 1036 [ka] Compound 1036 was obtained through the same process as in Synthesis Example 1, except that 2-naphthoyl chloride was used instead of cyclopropanecarbonyl chloride and SM3 was used instead of SM1.

[0150] 1 H NMR (500 MHz, CDCl3): δ 9.27 (s, 1H), 8.96 - 8.91 (m, 1H), 8.44 - 8.40 (m, 1H), 8.26 (dt, J = 8.3, 1.0 Hz, 1H), 7.96 - 7.93 (m, 2H), 7.93 - 7.86 (m, 3H), 7.84 (s, 1H), 7.76 - 7.74 (m, 1H), 7.73 - 7.69 (m, 2H), 7.68 - 7.64 (m, 2H), 7.63 - 7.58 (m, 2H), 4.36 (d, J = 17.2 Hz, 1H), 3.96 (d, J = 17.2 Hz, 1H).

[0151] Synthesis Example 37 - Synthesis of Compound 1037 [ka] Compound 1037 was obtained through the same process as in Synthesis Example 1, except that benzoyl chloride was used instead of cyclopropanecarbonyl chloride.

[0152] 1 H NMR (500 MHz, DMSO-d6): δ 11.58 (s, 1H), 8.14 - 8.09 (m, 1H), 7.96 - 7.88 (m, 4H), 7.57 - 7.50 (m, 6H), 4.38 (s, 1H), 4.33 (s, 1H), 2.39 (s, 3H).

[0153] Synthesis Example 38 - Synthesis of Compound 1038 [ka] Compound 1038 was obtained through the same process as in Synthesis example 1, except that tert-butyl 3-(chlorocarbonyl)azetidine-1-carboxylate was used instead of cyclopropanecarbonyl chloride.

[0154] 1 H NMR (500 MHz, CDCl3): δ 8.35 (s, 1H), 7.58 - 7.54 (m, 2H), 7.49 (q, J = 3.1 Hz, 3H), 7.41 (t, J = 1.8 Hz, 1H), 4.26 - 4.12 (m, 4H), 4.09 - 4.04 (m, 2H), 3.69 (d, J = 17.2 Hz, 1H), 2.48 (s, 3H), 1.42 (s, 9H).

[0155] Synthesis Example 39 - Synthesis of Compound 1039 [ka] Compound 1039 was obtained through the same process as in Synthesis Example 1, except that cyclohexanecarbonyl chloride was used instead of cyclopropanecarbonyl chloride.

[0156] 1H NMR (500 MHz, CDCl3): δ 8.06 (s, 1H), 7.56 - 7.51 (m, 2H), 7.49 (d, J = 1.8 Hz, 2H), 7.45 - 7.39 (m, 2H), 4.06 (d, J = 17.2 Hz, 1H), 3.67 (d, J = 17.2 Hz, 1H), 3.03 (tt, J = 11.4, 3.5 Hz, 1H), 2.46 (s, 3H), 1.99 - 1.92 (m, 2H), 1.81 (dt, J = 13.4, 3.5 Hz, 2H), 1.70 (dtd, J = 13.0, 3.4, 1.8 Hz, 1H), 1.46 (qd, J = 12.4, 3.1 Hz, 2H), 1.35 (qt, J = 12.7, 3.1 Hz, 2H), 1.24 (tt, J = 12.2, 3.4 Hz, 1H).

[0157] Synthesis Example 40 - Synthesis of Compound 1040 [ka] Compound 1040 was obtained through the same process as in Synthesis Example 1, except that cyclohexanecarbonyl chloride was used instead of cyclopropanecarbonyl chloride and SM2 was used instead of SM1.

[0158] 1 H NMR (500 MHz, CDCl3): δ 8.13 (s, 1H), 7.75 (d, J = 1.8 Hz, 1H), 7.68 (s, 1H), 7.67 - 7.60 (m, 1H), 7.49 (d, J = 9.4 Hz, 2H), 7.38 (d, J = 7.8 Hz, 1H), 4.07 (d, J = 17.2 Hz, 1H), 3.65 (d, J = 17.2 Hz, 1H), 2.97 (s, 1H), 2.41 (s, 3H), 1.76 (dt, J = 13.4, 3.7 Hz, 2H), 1.33 - 1.11 (m, 8H).

[0159] Synthesis Example 41 - Synthesis of Compound 1041 [ka] Compound 1041 was obtained through the same process as in Synthesis Example 1, except that cyclohexanecarbonyl chloride was used instead of cyclopropanecarbonyl chloride and SM3 was used instead of SM1.

[0160] 1 H NMR (500 MHz, CDCl3): δ 8.93 - 8.87 (m, 1H), 8.67 (s, 1H), 8.28 - 8.23 (m, 1H), 7.89 (d, J = 1.9 Hz, 1H), 7.83 (s, 1H), 7.74 (t, J = 1.9 Hz, 1H), 7.74 - 7.64 (m, 3H), 7.58 (d, J = 7.5 Hz, 1H), 4.35 (d, J = 17.2 Hz, 1H), 4.04 - 3.92 (m, 1H), 3.20 (tt, J = 11.4, 3.4 Hz, 1H), 1.78 - 1.77 (m, 2H), 1.37 - 1.29 (m, 8H).

[0161] Synthesis Example 42 - Synthesis of Compound 1042 [ka] Compound 1042 was obtained through the same process as in Synthesis Example 1, except that 1-methylcyclohexanecarbonyl chloride was used instead of cyclopropanecarbonyl chloride.

[0162] 1H NMR (500 MHz, CDCl3): δ 8.44 (s, 1H), 7.52 (dt, J = 3.8, 2.1 Hz, 2H), 7.48 (d, J = 2.0 Hz, 2H), 7.41 (t, J = 1.8 Hz, 1H), 7.29 (d, J = 8.5 Hz, 1H), 4.05 (d, J = 17.1 Hz, 1H), 3.67 (d, J = 17.4 Hz, 1H), 2.39 (s, 3H), 2.05 - 1.98 (m, 4H), 1.90 (dd, J = 11.0, 7.0 Hz, 2H), 1.50 (dd, J = 6.1, 2.9 Hz, 2H), 1.37 (t, J = 1.8 Hz, 2H), 1.21 (s, 3H).

[0163] Synthesis Example 43 - Synthesis of Compound 1043 [ka] Compound 1043 was obtained through the same process as in Synthesis Example 1, except that 1-methylcyclohexanecarbonyl chloride was used instead of cyclopropanecarbonyl chloride and SM2 was used instead of SM1.

[0164] 1 H NMR (500 MHz, CDCl3): δ 8.45 (s, 1H), 7.84 (d, J = 1.9 Hz, 1H), 7.78 (s, 1H), 7.72 (q, J = 1.7, 1.2 Hz, 1H), 7.60 - 7.55 (m, 2H), 7.34 (d, J = 8.5 Hz, 1H), 4.16 (d, J = 17.2 Hz, 1H), 3.74 (d, J = 17.2 Hz, 1H), 2.43 (s, 3H), 1.95 (t, J = 5.6 Hz, 2H), 1.65 - 1.60 (m, 2H), 1.47 - 1.37 (m, 6H), 1.25 (s, 3H).

[0165] Synthesis Example 44 - Synthesis of Compound 1044 [ka] Compound 1044 was obtained through the same process as in Synthesis Example 1, except that 1-methylcyclohexanecarbonyl chloride was used instead of cyclopropanecarbonyl chloride and SM3 was used instead of SM1.

[0166] 1 H NMR (500 MHz, CDCl3): δ 8.97 - 8.91 (m, 1H), 8.56 (s, 1H), 8.09 (dt, J = 8.4, 1.0 Hz, 1H), 7.89 (d, J = 1.9 Hz, 1H), 7.83 (s, 1H), 7.76 - 7.72 (m, 1H), 7.72 - 7.67 (m, 1H), 7.67 - 7.64 (m, 1H), 7.64 - 7.57 (m, 1H), 7.54 (d, J = 7.4 Hz, 1H), 4.36 (d, J = 17.1 Hz, 1H), 3.96 (d, J = 17.1 Hz, 1H), 1.93 (dt, J = 9.1, 3.9 Hz, 2H), 1.61 (dd, J = 9.5, 3.4 Hz, 2H), 1.51 - 1.33 (m, 6H), 1.26 (s, 3H).

[0167] Synthesis Example 45 - Synthesis of Compound 1045 [ka] Compound 1045 was obtained through the same process as in Synthesis Example 1, except that 3-difluoromethyl-1-methylpyrazole-4-carbonyl chloride was used instead of cyclopropanecarbonyl chloride.

[0168] 1H NMR (500 MHz, DMSO-d6): δ 11.36 (s, 1H), 8.60 (t, J = 1.3 Hz, 1H), 7.81 (t, J = 1.9 Hz, 1H), 7.68 - 7.59 (m, 4H), 7.49 (d, J = 7.9 Hz, 1H), 7.27 - 7.02 (m, 1H), 4.40 (d, J = 18.3 Hz, 1H), 4.31 (d, J = 18.5 Hz, 1H), 3.94 (s, 3H), 2.36 (s, 3H).

[0169] Synthesis Example 46 - Synthesis of Compound 1046 [ka] Compound 1046 was obtained through the same process as in Synthesis example 1, except that 3-difluoromethyl-1-methylpyrazole-4-carbonyl chloride was used instead of cyclopropanecarbonyl chloride and SM10 was used instead of SM1.

[0170] 1 H NMR (500 MHz, DMSO-d6): δ 11.63 (s, 1H), 8.82 (ddd, J = 8.7, 1.4, 0.8 Hz, 1H), 8.62 (t, J = 1.2 Hz, 1H), 8.10 - 8.05 (m, 1H), 7.92 (d, J = 7.6 Hz, 1H), 7.83 (t, J = 1.9 Hz, 1H), 7.76 - 7.66 (m, 5H), 7.25 - 6.96 (m, 1H), 4.62 - 4.50 (m, 2H), 3.94 (s, 3H).

[0171] Synthesis Example 47 - Synthesis of Compound 1047 [ka] Compound 1047 was obtained through the same process as in Synthesis example 1, except that 1-methyl-3-(trifluoromethyl)-1H-pyrazole-4-carbonyl chloride was used instead of cyclopropanecarbonyl chloride.

[0172] 1 H NMR (500 MHz, DMSO-d6): δ 11.64 (s, 1H), 8.82 (ddd, J = 8.6, 1.4, 0.7 Hz, 1H), 8.63 (d, J = 1.3 Hz, 1H), 8.08 (ddd, J = 8.3, 1.5, 0.7 Hz, 1H), 7.93 (d, J = 7.5 Hz, 1H), 7.84 (t, J = 1.9 Hz, 1H), 7.78 - 7.65 (m, 5H), 4.57 (d, J = 6.2 Hz, 2H), 3.95 (s, 3H).

[0173] Synthesis Example 48 - Synthesis of Compound 1048 [ka] Compound 1048 was obtained through the same process as in Synthesis example 1, except that 1-methyl-3-(trifluoromethyl)-1H-pyrazole-4-carbonyl chloride was used instead of cyclopropanecarbonyl chloride and SM10 was used instead of SM1.

[0174] 1 H NMR (500 MHz, DMSO-d6): δ 11.69 (s, 1H), 8.82 (dt, J = 8.6, 1.0 Hz, 1H), 8.70 (d, J = 1.1 Hz, 1H), 8.14 - 8.08 (m, 1H), 7.93 (d, J = 7.5 Hz, 1H), 7.84 (t, J = 1.9 Hz, 1H), 7.81 - 7.66 (m, 5H), 4.57 (d, J = 6.2 Hz, 2H), 3.97 (s, 3H).

[0175] Synthesis Example 49 - Synthesis of Compound 1049 [ka] Compound 1049 was obtained through the same process as in Synthesis Example 1, except that 1-fluorocyclopropanecarbonyl chloride was used instead of cyclopropanecarbonyl chloride.

[0176] 1 H NMR (300 Hz, CDCl3): δ 9.05 (d, J = 4.1 Hz, 1H), 7.55 (d, J = 5.6 Hz, 2H), 7.48 (d, J = 1.4 Hz, 2H), 7.44 (d, J = 8.5 Hz, 1H), 7.41 (t, J = 1.8 Hz, 1H), 4.06 (d, J = 15.7 Hz, 1H), 3.68 (d, J = 17.2 Hz, 1H), 2.46 (s, 3H), 1.47 (s, 2H), 1.42 (q, J = 3.3 Hz, 2H).

[0177] Synthesis Example 50 - Synthesis of Compound 1050 [ka] Compound 1050 was obtained through the same process as in Synthesis Example 1, except that 2,2-difluorocyclopropanecarbonyl chloride was used instead of cyclopropanecarbonyl chloride.

[0178] 1 H NMR (300 Hz, CDCl3): δ 8.37 (s, 1H), 7.57 (d, J = 6.8 Hz, 2H), 7.53 (s, 1H), 7.51 - 7.47 (m, 2H), 7.42 (t, J = 1.8 Hz, 1H), 4.07 (d, J = 17.3 Hz, 1H), 3.79 - 3.64 (m, 2H), 2.52 (s, 3H), 2.35 - 2.22 (m, 1H), 1.89 - 1.76 (m, 1H).

[0179] Synthesis Example 51 - Synthesis of Compound 1051 [ka] Compound 1051 was obtained through the same process as in Synthesis Example 1, except that 2-fluorocyclopropanecarbonyl chloride was used instead of cyclopropanecarbonyl chloride.

[0180] 1 H NMR (300 MHz, CDCl3): δ 8.20 (s, 1H), 7.56 (d, J = 6.7 Hz, 2H), 7.52 - 7.48 (m, 3H), 7.42 (t, J = 1.8 Hz, 1H), 5.05 - 4.78 (m, 1H), 4.07 (d, J = 17.3 Hz, 1H), 3.68 (d, J = 17.1 Hz, 1H), 3.50 - 3.36 (m, 1H), 2.52 (s, 3H), 1.68 (ddt, J = 13.6, 6.8, 3.2 Hz, 2H).

[0181] Synthesis Example 52 - Synthesis of Compound 1052 [ka] Compound 1052 was obtained through the same process as in Synthesis Example 1, except that spiro[2.3]hexane-1-carbonyl chloride was used instead of cyclopropanecarbonyl chloride.

[0182] 1 H NMR (300 Hz, CDCl3): δ 8.14 (s, 1H), 7.54 (d, J = 7.3 Hz, 2H), 7.49 (d, J = 4.2 Hz, 3H), 7.41 (t, J = 1.8 Hz, 1H), 4.07 (d, J = 17.2 Hz, 1H), 3.68 (d, J = 17.0 Hz, 1H), 2.72 (dd, J = 8.0, 5.5 Hz, 1H), 2.51 (s, 3H), 2.41 - 2.33 (m, 1H), 2.24 - 2.12 (m, 3H), 2.12 - 2.01 (m, 2H), 1.40 (t, J = 4.9 Hz, 1H), 1.19 (dd, J = 8.1, 4.4 Hz, 1H).

[0183] Synthesis Example 53 - Synthesis of Compound 1053 [ka] Compound 1053 was obtained through the same process as in Synthesis Example 1, except that [1,1'-bicyclopropyl]-2-carbonyl chloride was used instead of cyclopropanecarbonyl chloride.

[0184] 1 H NMR (300 Hz, CDCl3): δ 9.33 (s, 1H), 7.56 - 7.47 (m, 4H), 7.41 (t, J = 1.8 Hz, 1H), 7.37 (d, J = 8.5 Hz, 1H), 4.06 (d, J = 17.2 Hz, 1H), 3.66 (d, J = 17.3 Hz, 1H), 2.42 (s, 3H), 1.35 (ddd, J = 13.1, 7.9, 5.0 Hz, 1H), 1.13 (q, J = 4.0 Hz, 2H), 0.73 - 0.62 (m, 4H), 0.27 (q, J = 5.1 Hz, 2H).

[0185] Synthesis Example 54 - Synthesis of Compound 1054 [ka] Compound 1054 was obtained through the same process as in Synthesis Example 1, except that 2,2,3,3-tetramethylcyclopropanecarbonyl chloride was used instead of cyclopropanecarbonyl chloride.

[0186] 1H NMR (500 MHz, CDCl3): δ 8.40 (s, 1H), 7.54 - 7.50 (m, 2H), 7.49 (d, J = 1.8 Hz, 2H), 7.45 (d, J = 7.9 Hz, 1H), 7.41 (t, J = 1.8 Hz, 1H), 4.06 (d, J = 17.2 Hz, 1H), 3.67 (d, J = 17.4 Hz, 1H), 2.47 (s, 3H), 1.26 (d, J = 4.9 Hz, 13H).

[0187] Synthesis Example 55 - Synthesis of Compound 1055 [ka] Compound 1055 was obtained through the same process as in Synthesis Example 1, except that cyclopropaneacetyl chloride was used instead of cyclopropanecarbonyl chloride.

[0188] 1 H NMR (500 MHz, CDCl3): δ 8.23 (s, 1H), 7.57 - 7.52 (m, 2H), 7.49 (d, J = 2.0 Hz, 2H), 7.46 (d, J = 7.9 Hz, 1H), 7.41 (t, J = 1.8 Hz, 1H), 4.06 (d, J = 17.2 Hz, 1H), 3.68 (d, J = 17.4 Hz, 1H), 2.79 (d, J = 7.0 Hz, 2H), 2.48 (s, 3H), 0.86 (t, J = 7.0 Hz, 1H), 0.65 - 0.58 (m, 2H), 0.26 - 0.21 (m, 2H).

[0189] Synthesis Example 56 - Synthesis of Compound 1056 [ka] Compound 1056 was obtained through the same process as in Synthesis Example 1, except that 2,5-dimethyl-3-furancarbonyl chloride was used instead of cyclopropanecarbonyl chloride.

[0190] 1 H NMR (500 MHz, DMSO-d6): δ 11.03 (s, 1H), 7.81 (t, J = 1.8 Hz, 1H), 7.63 (t, J = 1.8 Hz, 3H), 7.60 (dd, J = 7.9, 1.8 Hz, 1H), 7.44 (d, J = 8.1 Hz, 1H), 6.66 (d, J = 1.4 Hz, 1H), 4.43 - 4.35 (m, 1H), 4.31 (d, J = 18.3 Hz, 1H), 2.41 (s, 3H), 2.34 (s, 3H), 2.23 (s, 3H).

[0191] Synthesis Example 57 - Synthesis of Compound 1057 [ka] Compound 1057 was obtained through the same process as in Synthesis Example 1, except that 2,5-dimethyl-3-furancarbonyl chloride was used instead of cyclopropanecarbonyl chloride and SM2 was used instead of SM1.

[0192] 1 H NMR (500 MHz, DMSO-d6): δ 11.03 (s, 1H), 8.09 (t, J = 2.0 Hz, 1H), 7.98 (t, J = 1.9 Hz, 1H), 7.86 (s, 1H), 7.64 (d, J = 2.0 Hz, 1H), 7.61 (dd, J = 7.9, 1.9 Hz, 1H), 7.45 (d, J = 7.9 Hz, 1H), 6.66 (d, J = 1.2 Hz, 1H), 4.45 (d, J = 18.3 Hz, 1H), 4.38 (d, J = 18.3 Hz, 1H), 2.41 (s, 3H), 2.34 (s, 3H), 2.23 (s, 3H).

[0193] Synthesis Example 58 - Synthesis of Compound 1058 [ka] Compound 1058 was obtained through the same process as in Synthesis Example 1, except that 2-furancarbonyl chloride was used instead of cyclopropanecarbonyl chloride.

[0194] 1 H NMR (500 MHz, DMSO-d6): δ 11.44 (s, 1H), 8.00 (d, J = 2.4 Hz, 1H), 7.81 (t, J = 1.9 Hz, 1H), 7.68 - 7.59 (m, 5H), 7.51 (d, J = 8.1 Hz, 1H), 6.72 (dd, J = 3.7, 1.8 Hz, 1H), 4.40 (d, J = 18.5 Hz, 1H), 4.32 (d, J = 18.5 Hz, 1H), 2.37 (s, 3H).

[0195] Synthesis Example 59 - Synthesis of Compound 1059 [ka] Compound 1059 was obtained through the same process as in Synthesis Example 1, except that 2-furancarbonyl chloride was used instead of cyclopropanecarbonyl chloride and SM2 was used instead of SM1.

[0196] 1 H NMR (500 MHz, DMSO-d6): δ 11.44 (s, 1H), 8.09 (t, J = 1.9 Hz, 1H), 7.99 (dd, J = 12.1, 2.0 Hz, 2H), 7.86 (s, 1H), 7.66 (d, J = 1.8 Hz, 1H), 7.65 - 7.59 (m, 2H), 7.51 (d, J = 8.1 Hz, 1H), 6.72 (dd, J = 3.6, 1.8 Hz, 1H), 4.46 (d, J = 18.3 Hz, 1H), 4.38 (d, J = 18.5 Hz, 1H), 2.37 (s, 3H).

[0197] Synthesis Example 60 - Synthesis of Compound 1060 [ka] Compound 1060 was obtained through the same process as in Synthesis Example 1, except that 3-methyl-2-thiophenecarbonyl chloride was used instead of cyclopropanecarbonyl chloride.

[0198] 1 H NMR (500 MHz, DMSO-d6): δ 11.31 (s, 1H), 7.83 - 7.78 (m, 2H), 7.67 - 7.59 (m, 4H), 7.51 (d, J = 8.1 Hz, 1H), 7.07 - 7.04 (m, 1H), 4.39 (d, J = 18.3 Hz, 1H), 4.31 (d, J = 18.5 Hz, 1H), 2.43 (s, 3H), 2.39 (s, 3H).

[0199] Synthesis Example 61 - Synthesis of Compound 1061 [ka] Compound 1061 was obtained through the same process as in Synthesis Example 1, except that 3-methyl-2-thiophenecarbonyl chloride was used instead of cyclopropanecarbonyl chloride and SM2 was used instead of SM1.

[0200] 1 H NMR (500 MHz, DMSO-d6): δ 11.44 - 11.23 (m, 1H), 8.08 (t, J = 2.0 Hz, 1H), 8.00 - 7.96 (m, 1H), 7.86 (s, 1H), 7.80 (dd, J = 4.7, 2.3 Hz, 1H), 7.65 (d, J = 1.8 Hz, 1H), 7.62 (dd, J = 7.9, 2.0 Hz, 1H), 7.51 (dd, J = 8.0, 2.4 Hz, 1H), 7.06 (d, J = 5.0 Hz, 1H), 4.50 - 4.42 (m, 1H), 4.37 (d, J = 18.5 Hz, 1H), 2.43 (s, 3H), 2.40 (s, 3H).

[0201] Synthesis Example 62 - Synthesis of Compound 1062 [ka] Compound 1062 was obtained through the same process as in Synthesis Example 1, except that 2-thiophenecarbonyl chloride was used instead of cyclopropanecarbonyl chloride.

[0202] 1 H NMR (500 MHz, DMSO-d6): δ 11.62 (s, 1H), 8.16 (dd, J = 3.9, 1.3 Hz, 1H), 7.99 (dd, J = 5.0, 1.4 Hz, 1H), 7.81 (t, J = 1.8 Hz, 1H), 7.67 - 7.58 (m, 4H), 7.51 (d, J = 7.9 Hz, 1H), 7.23 (dd, J = 5.0, 3.8 Hz, 1H), 4.40 (d, J = 18.5 Hz, 1H), 4.32 (d, J = 18.5 Hz, 1H), 2.37 (s, 3H).

[0203] Synthesis Example 63 - Synthesis of Compound 1063 [ka] Compound 1063 was obtained through the same process as in Synthesis Example 1, except that 2-thiophenecarbonyl chloride was used instead of cyclopropanecarbonyl chloride and SM2 was used instead of SM1.

[0204] 1H NMR (500 MHz, DMSO-d6): δ 11.62 (s, 1H), 8.16 (dt, J = 3.2, 1.5 Hz, 1H), 8.09 (t, J = 1.8 Hz, 1H), 7.99 (h, J = 2.4, 1.9 Hz, 2H), 7.86 (s, 1H), 7.68 - 7.61 (m, 2H), 7.52 (d, J = 7.9 Hz, 1H), 7.24 (dd, J = 5.1, 3.7 Hz, 1H), 4.46 (d, J = 18.3 Hz, 1H), 4.38 (d, J = 18.5 Hz, 1H), 2.37 (s, 3H).

[0205] Synthesis Example 64 - Synthesis of Compound 1064 [ka] Compound 1064 was obtained through the same process as in Synthesis Example 1, except that tetrahydro-2H-pyran-4-carbonyl chloride was used instead of cyclopropanecarbonyl chloride.

[0206] 1 H NMR (500 MHz, DMSO-d6): δ 11.10 (s, 1H), 7.81 (t, J = 1.9 Hz, 1H), 7.63 (dd, J = 5.4, 1.9 Hz, 4H), 7.47 (d, J = 7.9 Hz, 1H), 4.42 - 4.36 (m, 1H), 4.31 (d, J = 18.5 Hz, 1H), 3.87 (ddd, J = 11.3, 4.3, 2.3 Hz, 2H), 3.35 - 3.33 (m, 1H), 3.29 (ddt, J = 4.3, 2.7, 1.7 Hz, 1H), 2.89 (t, J = 11.4 Hz, 1H), 2.35 (s, 3H), 1.73 (ddd, J = 13.0, 4.0, 1.9 Hz, 2H), 1.56 (dtd, J = 13.4, 11.7, 4.4 Hz, 2H).

[0207] Synthesis Example 65 - Synthesis of Compound 1065 [ka] Compound 1065 was obtained through the same process as in Synthesis Example 1, except that tetrahydro-2H-pyran-4-carbonyl chloride was used instead of cyclopropanecarbonyl chloride and SM2 was used instead of SM1.

[0208] 1 H NMR (500 MHz, DMSO-d6): δ 11.11 (s, 1H), 8.09 (td, J = 1.8, 0.8 Hz, 1H), 7.98 (t, J = 1.9 Hz, 1H), 7.86 (s, 1H), 7.65 - 7.60 (m, 2H), 7.47 (d, J = 7.9 Hz, 1H), 4.45 (d, J = 18.3 Hz, 1H), 4.37 (d, J = 18.6 Hz, 1H), 3.87 (ddd, J = 11.3, 4.2, 2.3 Hz, 2H), 3.85 - 3.73 (m, 1H), 3.36 - 3.33 (m, 1H), 2.89 (tt, J = 11.3, 3.7 Hz, 1H), 2.35 (s, 3H), 1.77 - 1.71 (m, 2H), 1.56 (dtd, J = 13.4, 11.7, 4.3 Hz, 2H).

[0209] Synthesis Example 66 - Synthesis of Compound 1066 [ka] Compound 1066 was obtained through the same process as in Synthesis Example 1, except that 1-piperidinecarbonyl chloride was used instead of cyclopropanecarbonyl chloride.

[0210] 1H NMR (500 MHz, DMSO-d6): δ 10.28 (s, 1H), 7.81 (t, J = 1.8 Hz, 1H), 7.64 - 7.57 (m, 4H), 7.43 (d, J = 7.9 Hz, 1H), 4.38 (d, J = 18.3 Hz, 1H), 4.30 (d, J = 18.3 Hz, 1H), 3.43 - 3.34 (m, 4H), 2.37 (s, 3H), 1.62 - 1.44 (m, 6H).

[0211] Synthesis Example 67 - Synthesis of Compound 1067 [ka] Compound 1067 was obtained through the same process as in Synthesis Example 1, except that 1-piperidinecarbonyl chloride was used instead of cyclopropanecarbonyl chloride and SM2 was used instead of SM1.

[0212] 1 H NMR (500 MHz, DMSO-d6): δ 10.29 (s, 1H), 8.09 (td, J = 1.8, 0.7 Hz, 1H), 7.98 (t, J = 1.8 Hz, 1H), 7.86 (s, 1H), 7.63 - 7.58 (m, 2H), 7.43 (d, J = 7.9 Hz, 1H), 4.44 (d, J = 18.5 Hz, 1H), 4.36 (d, J = 18.5 Hz, 1H), 3.38 (t, J = 5.6 Hz, 4H), 2.37 (s, 3H), 1.61 - 1.54 (m, 2H), 1.49 (d, J = 3.7 Hz, 4H).

[0213] Synthesis Example 68 - Synthesis of Compound 1068 [ka] Compound 1068 was obtained through the same process as in Synthesis Example 1, except that cyclopentanecarbonyl chloride was used instead of cyclopropanecarbonyl chloride.

[0214] 1 H NMR (500 MHz, DMSO-d6): δ 11.06 (s, 1H), 7.82 (t, J = 1.9 Hz, 1H), 7.65 - 7.59 (m, 4H), 7.45 (d, J = 7.9 Hz, 1H), 4.42 - 4.27 (m, 2H), 3.12 - 3.03 (m, 1H), 2.34 (s, 3H), 1.88 - 1.80 (m, 2H), 1.68 (dtd, J = 12.5, 5.2, 2.7 Hz, 2H), 1.63 - 1.58 (m, 2H), 1.53 (ddt, J = 9.3, 4.4, 2.4 Hz, 2H).

[0215] Synthesis Example 69 - Synthesis of Compound 1069 [ka] Compound 1069 was obtained through the same process as in Synthesis Example 1, except that cyclopentanecarbonyl chloride was used instead of cyclopropanecarbonyl chloride and SM2 was used instead of SM1.

[0216] 1 H NMR (500 MHz, DMSO-d6): δ 12.01 (s, 1H), 8.09 (s, 1H), 7.98 (s, 1H), 7.86 (s, 1H), 7.61 - 7.57 (m, 2H), 7.46 (d, J = 7.8 Hz, 1H), 4.48 - 4.32 (m, 2H), 2.65 - 2.60 (m, 1H), 2.40 (s, 3H), 1.80 - 1.76 (m, 2H), 1.67 (ddd, J = 9.8, 6.1, 2.1 Hz, 2H), 1.59 - 1.56 (m, 2H), 1.53 - 1.49 (m, 2H).

[0217] Synthesis Example 70 - Synthesis of Compound 1070 [ka] Compound 1070 was obtained through the same process as in Synthesis Example 1, except that 3-methyl-2-butenoyl chloride was used instead of cyclopropanecarbonyl chloride and SM2 was used instead of SM1.

[0218] 1 H NMR (500 MHz, DMSO-d6): δ 10.97 (s, 1H), 8.09 (s, 1H), 7.98 (s, 1H), 7.86 (s, 1H), 7.64 - 7.62 (m, 1H), 7.60 - 7.57 (m, 1H), 7.45 (d, J = 7.9 Hz, 1H), 6.18 - 6.14 (m, 1H), 4.45 (d, J = 18.5 Hz, 1H), 4.40 (d, J = 10.1 Hz, 1H), 2.34 (s, 3H), 2.08 (d, J = 1.4 Hz, 3H), 1.89 - 1.87 (m, 3H).

[0219] Synthesis Example 71 - Synthesis of Compound 1071 [ka] Compound 1071 was obtained through the same process as in Synthesis Example 1, except that 2-butenoyl chloride was used instead of cyclopropanecarbonyl chloride and SM2 was used instead of SM1.

[0220] 1H NMR (500 MHz, DMSO-d6): δ 11.12 (s, 1H), 8.09 (d, J = 1.8 Hz, 1H), 7.98 (d, J = 1.8 Hz, 1H), 7.86 (s, 1H), 7.68 - 7.59 (m, 2H), 7.49 (d, J = 7.9 Hz, 1H), 6.92 (dq, J = 15.3, 6.9 Hz, 1H), 6.44 - 6.38 (m, 1H), 4.49 - 4.42 (m, 1H), 4.38 (d, J = 18.5 Hz, 1H), 2.41 - 2.33 (m, 3H), 1.87 (ddd, J = 6.7, 5.0, 1.7 Hz, 3H).

[0221] Synthesis Example 72 - Synthesis of Compound 1072 [ka] Compound 1072 was obtained through the same process as in Synthesis Example 1, except that 2,4-hexadienoyl chloride was used instead of cyclopropanecarbonyl chloride and SM2 was used instead of SM1.

[0222] 1 H NMR (500 Hz, CDCl3): δ 8.18 (s, 1H), 7.80 (s, 1H), 7.74 (s, 1H), 7.67 (s, 1H), 7.58 - 7.53 (m, 2H), 7.50 - 7.43 (m, 2H), 6.87 (d, J = 14.6 Hz, 1H), 6.36 - 6.21 (m, 2H), 4.12 (d, J = 17.2 Hz, 1H), 3.71 (d, J = 17.9 Hz, 1H), 2.49 (s, 3H), 1.89 - 1.86 (m, 3H).

[0223] Synthesis Example 73 - Synthesis of Compound 1073 [ka] Compound 1073 was obtained through the same process as in Synthesis Example 1, except that methacryloyl chloride was used instead of cyclopropanecarbonyl chloride and SM2 was used instead of SM1.

[0224] 1 H NMR (500 MHz, DMSO-d6): δ 11.14 (s, 1H), 8.09 (t, J = 2.1 Hz, 1H), 7.98 (t, J = 1.9 Hz, 1H), 7.86 (s, 1H), 7.65 - 7.62 (m, 1H), 7.60 (dd, J = 7.9, 2.0 Hz, 1H), 7.46 (d, J = 7.9 Hz, 1H), 5.99 (d, J = 1.1 Hz, 1H), 5.71 (d, J = 1.5 Hz, 1H), 4.45 (d, J = 18.5 Hz, 1H), 4.37 (d, J = 18.3 Hz, 1H), 2.34 (s, 3H), 1.85 (t, J = 1.3 Hz, 3H).

[0225] Synthesis Example 74 - Synthesis of Compound 1074 [ka] Compound 1074 was obtained through the same process as in Synthesis Example 1, except that cinnamoyl chloride was used instead of cyclopropanecarbonyl chloride and SM2 was used instead of SM1.

[0226] 1 H NMR (500 Hz, CDCl3): δ 8.22 (s, 1H), 7.89 (d, J = 15.7 Hz, 1H), 7.81 (t, J = 2.0 Hz, 1H), 7.74 (s, 1H), 7.70 - 7.66 (m, 1H), 7.64 - 7.52 (m, 6H), 7.40 (dd, J = 5.1, 1.9 Hz, 3H), 4.13 (d, J = 17.2 Hz, 1H), 3.72 (d, J = 17.4 Hz, 1H), 2.53 (s, 3H).

[0227] Synthesis Example 75 - Synthesis of Compound 1075 [ka] Compound 1075 was obtained through the same process as in Synthesis Example 1, except that cyclopropaneacetyl chloride was used instead of cyclopropanecarbonyl chloride and SM2 was used instead of SM1.

[0228] 1 H NMR (500 Hz, CDCl3): δ 8.26 (s, 1H), 7.80 (s, 1H), 7.73 (s, 1H), 7.67 (s, 1H), 7.58 - 7.53 (m, 2H), 7.47 (d, J = 8.2 Hz, 1H), 4.12 (d, J = 17.1 Hz, 1H), 3.74 - 3.68 (m, 1H), 2.78 (d, J = 6.9 Hz, 2H), 2.48 (s, 3H), 1.16 - 1.07 (m, 1H), 0.64 - 0.59 (m, 2H), 0.25 - 0.20 (m, 2H).

[0229] Synthesis Example 76 - Synthesis of Compound 1076 [ka] Compound 1076 was obtained through the same process as in Synthesis Example 1, except that 4-cyanobenzoyl chloride was used instead of cyclopropanecarbonyl chloride and SM2 was used instead of SM1.

[0230] 1H NMR (500 Hz, CDCl3): δ 8.83 (s, 1H), 7.96 - 7.91 (m, 2H), 7.80 (q, J = 1.8 Hz, 2H), 7.78 (d, J = 2.0 Hz, 1H), 7.74 (s, 1H), 7.68 (s, 1H), 7.60 - 7.56 (m, 2H), 7.48 (d, J = 8.5 Hz, 1H), 4.13 (d, J = 17.2 Hz, 1H), 3.71 (d, J = 17.2 Hz, 1H), 2.47 (s, 3H).

[0231] Synthesis Example 77 - Synthesis of Compound 1077 [ka] Compound 1077 was obtained through the same process as in Synthesis Example 1, except that 3-chloro-2-thiophenecarbonyl chloride was used instead of cyclopropanecarbonyl chloride and SM2 was used instead of SM1.

[0232] 1 H NMR (500 Hz, CDCl3): δ 9.58 (s, 1H), 7.80 (s, 1H), 7.74 (s, 1H), 7.67 (s, 1H), 7.63 (d, J = 5.3 Hz, 1H), 7.59 - 7.56 (m, 2H), 7.51 - 7.47 (m, 1H), 7.05 (d, J = 5.3 Hz, 1H), 4.13 (d, J = 17.2 Hz, 1H), 3.71 (d, J = 17.2 Hz, 1H), 2.49 (s, 3H).

[0233] Synthesis Example 78 - Synthesis of Compound 1078 [ka] Compound 1078 was obtained through the same process as in Synthesis Example 1, except that 2-thiazolecarbonyl chloride was used instead of cyclopropanecarbonyl chloride and SM2 was used instead of SM1.

[0234] 1 H NMR (500 Hz, CDCl3): δ 10.03 (s, 1H), 7.94 (d, J = 2.9 Hz, 1H), 7.81 (t, J = 1.9 Hz, 1H), 7.75 (s, 1H), 7.74 (d, J = 2.9 Hz, 1H), 7.69 - 7.67 (m, 1H), 7.59 (dd, J = 7.4, 0.7 Hz, 2H), 7.57 - 7.51 (m, 1H), 4.14 (d, J = 17.1 Hz, 1H), 3.72 (d, J = 17.2 Hz, 1H), 2.52 (s, 3H).

[0235] Synthesis Example 79 - Synthesis of Compound 1079 [ka] Compound 1079 was obtained through the same process as in Synthesis Example 1, except that 2-thiazolecarbonyl chloride was used instead of cyclopropanecarbonyl chloride.

[0236] 1 H NMR (500 Hz, CDCl3): δ 10.04 (s, 1H), 7.94 (d, J = 2.9 Hz, 1H), 7.73 (d, J = 2.9 Hz, 1H), 7.58 (dd, J = 7.3, 0.8 Hz, 2H), 7.56 - 7.52 (m, 1H), 7.50 (d, J = 2.0 Hz, 2H), 7.42 (t, J = 1.8 Hz, 1H), 4.08 (d, J = 17.2 Hz, 1H), 3.69 (d, J = 17.2 Hz, 1H), 2.51 (s, 3H).

[0237] Synthesis Example 80 - Synthesis of Compound 1080 [ka] Compound 1080 was obtained via the same process as in Synthesis Example 1, except that 5-methyl-3-isoxazolecarbonyl chloride was used instead of cyclopropanecarbonyl chloride.

[0238] 1 H NMR (500 MHz, DMSO-d6): δ 11.43 (s, 1H), 9.07 (d, J = 0.9 Hz, 1H), 7.82 (t, J = 1.9 Hz, 1H), 7.66 (s, 1H), 7.62 (dd, J = 8.2, 2.0 Hz, 3kiikiH), 7.55 (d, J = 8.1 Hz, 1H), 4.40 (d, J = 18.5 Hz, 1H), 4.32 (d, J = 18.5 Hz, 1H), 2.61 (s, 3H), 2.37 (s, 3H).

[0239] Synthesis Example 81 - Synthesis of Compound 1081 [ka] Compound 1081 was obtained through the same process as in Synthesis Example 1, except that 5-isoxazolecarbonyl chloride was used instead of cyclopropanecarbonyl chloride.

[0240] 1 H NMR (500 Hz, CDCl3): δ 9.09 (s, 1H), 8.41 (d, J = 1.8 Hz, 1H), 7.58 (dt, J = 7.6, 1.3 Hz, 2H), 7.53 - 7.50 (m, 1H), 7.50 (d, J = 2.0 Hz, 2H), 7.42 (q, J = 2.0 Hz, 1H), 7.09 (d, J = 1.8 Hz, 1H), 4.08 (d, J = 17.1 Hz, 1H), 3.69 (d, J = 17.2 Hz, 1H), 2.51 (s, 3H).

[0241] Synthesis Example 82 - Synthesis of Compound 1082 [ka] Compound 1082 was obtained through the same process as in Synthesis Example 1, except that 5-methyl-3-isoxazolecarbonyl chloride was used instead of cyclopropanecarbonyl chloride and SM2 was used instead of SM1.

[0242] 1 H NMR (500 MHz, DMSO-d6): δ 8.67 (s, 1H), 8.55 (d, J = 0.8 Hz, 1H), 7.80 (s, 1H), 7.74 (s, 1H), 7.68 (s, 1H), 7.58 (ddd, J = 3.8, 2.4, 0.6 Hz, 2H), 7.49 - 7.46 (m, 1H), 4.13 (d, J = 17.1 Hz, 1H), 3.71 (d, J = 17.2 Hz, 1H), 2.68 (d, J = 0.8 Hz, 3H), 2.47 (s, 3H).

[0243] Synthesis Example 83 - Synthesis of Compound 1083 [ka] Compound 1083 was obtained through the same process as in Synthesis Example 1, except that 5-isoxazolecarbonyl chloride was used instead of cyclopropanecarbonyl chloride and SM2 was used instead of SM1.

[0244] 1 H NMR (500 Hz, CDCl3): δ 9.08 (s, 1H), 8.41 (d, J = 1.8 Hz, 1H), 7.81 (s, 1H), 7.74 (s, 1H), 7.68 (s, 1H), 7.59 (ddd, J = 7.2, 1.7, 0.8 Hz, 2H), 7.53 - 7.49 (m, 1H), 7.09 (d, J = 1.8 Hz, 1H), 4.14 (d, J = 17.1 Hz, 1H), 3.72 (d, J = 17.2 Hz, 1H), 2.51 (s, 3H).

[0245] Synthesis Example 84 - Synthesis of Compound 1084 [ka] Compound 1084 was obtained through the same process as in Synthesis Example 1, except that 5-cyclopropyl-3-isoxazolecarbonyl chloride was used instead of cyclopropanecarbonyl chloride and SM2 was used instead of SM1.

[0246] 1 H NMR (500 Hz, CDCl3): δ 9.39 (s, 1H), 7.80 (s, 1H), 7.74 (s, 1H), 7.68 (s, 1H), 7.57 (ddd, J = 6.7, 1.7, 0.7 Hz, 2H), 7.50 (d, J = 8.7 Hz, 1H), 6.37 (s, 1H), 4.13 (d, J = 17.1 Hz, 1H), 3.71 (d, J = 17.2 Hz, 1H), 2.50 (s, 3H), 2.08 (tt, J = 8.5, 5.0 Hz, 1H), 1.17 - 1.12 (m, 2H), 1.03 - 0.97 (m, 2H).

[0247] Synthesis Example 85 - Synthesis of Compound 1085 [ka] Compound 1085 was obtained through the same process as in Synthesis Example 1, except that tetrahydro-2-furancarbonyl chloride was used instead of cyclopropanecarbonyl chloride and SM2 was used instead of SM1.

[0248] 1H NMR (500 Hz, CDCl3): δ 9.35 (s, 1H), 7.80 (s, 1H), 7.73 (s, 1H), 7.67 (s, 1H), 7.57 - 7.53 (m, 2H), 7.41 (d, J = 8.5 Hz, 1H), 4.44 (dd, J = 8.5, 6.0 Hz, 1H), 4.12 (d, J = 17.5 Hz, 1H), 4.00 (ddd, J = 8.5, 7.1, 6.0 Hz, 1H), 3.92 (dt, J = 8.5, 6.9 Hz, 1H), 3.70 (d, J = 17.2 Hz, 1H), 2.46 (s, 3H), 2.38 - 2.29 (m, 1H), 2.17 - 2.06 (m, 1H), 2.02 - 1.85 (m, 2H).

[0249] Examples 1-85 - Preparation of insecticide compositions Insecticide compositions were prepared by adjusting the concentration of each compound synthesized in Synthesis Examples 1 to 85 (for example, 100 ppm, 10 ppm, 3 ppm, 1 ppm, 0.3 ppm, and 0.1 ppm). In this case, distilled water and / or acetone was used as the solvent, and Triton X-100 was used as the surfactant.

[0250] Comparative Example 1 - Preparation of Insecticide Composition The concentration of the compound (fluxametamide) represented by the following formula was adjusted to prepare an insecticide composition. Specifically, distilled water and / or acetone was used as the solvent, and Triton X-100 was used as the surfactant.

[0251] [ka]

[0252] Comparative Example 2 - Preparation of Insecticide Composition Insecticide compositions were prepared by adjusting the concentration of the compound represented by the following formula (chlorantraniliprole), using distilled water and / or acetone as the solvent and Triton X-100 as the surfactant.

[0253] [ka]

[0254] Comparative Example 3 - Preparation of Insecticide Composition The insecticide compositions were prepared by adjusting the concentration of the compound (isocycloseram) represented by the following formula: Specifically, distilled water and / or acetone were used as the solvent, and Triton X-100 was used as the surfactant.

[0255] [ka]

[0256] Test Example 1 - Insecticidal activity test against diamondback moth (Plutella xylostella) by leaf immersion method Cabbage (Daiya) leaves were cut into pieces 5.8 cm in diameter and immersed in each of the insecticide compositions prepared in the Examples (a 5% acetone solution containing each compound (concentration: 100 ppm) from the Synthesis Examples) for 30 seconds, then thoroughly dried in the shade. The shade-dried cabbage leaves were then placed in a Petri dish (8.8 cm in diameter) covered with filter paper and inoculated with third-instar larvae of the diamondback moth (Plutella xylostella), 10 larvae per inoculation, three times. Specifically, diamondback moth (Plutella xylostella) larvae collected near Gyeongju, South Korea, in 2000 and reared in a rearing room for multiple generations were used. The leaves were then stored under conditions of a 16-hour light / 8-hour dark cycle, 25±1°C, and 50-60% relative humidity. The number of surviving diamondback moth (Plutella xylostella) larvae was counted 48 hours after inoculation. The density after treatment was then corrected using the density before treatment as a reference, and this was converted into the corrected mortality rate for the untreated control to calculate the larval mortality rate, as shown in the following formulas 1 and 2 (Reference: A method of computing the effectiveness of an insecticide. J. Econ. Entomol. 18:265-267. Abbott, 1925).

[0257] [Formula 1] Larval mortality rate (control value, %) = {(survival rate of larvae in the untreated group - survival rate of larvae in the treated group) / (survival rate of larvae in the untreated group)} x 100 [Formula 2] Larval survival rate = (larval density after treatment / larval density before treatment) x 100

[0258] As a result of tests carried out using the compounds of Synthesis Examples 1 to 85, it was found that the insecticide compositions prepared using the compounds of Synthesis Examples 1, 1a, 1b, 2, 2a, 2b, 3, 3a, 3b, 4, 5, 6, 8, 9, 10, 11, 12, 13, 14, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 37, 39, 40, 45, 46, 47, 49, 50, 52, 53, 55, 56, 57, 58, 59, 65, 66, 67, 68, 69, 70, 71, 72, 75, 76, 78, 79, 80, 81, 82, 83, 84 and 85 had no effect on the diamondback moth (Plutella xylostella), the mortality rate of larvae was over 80%.

[0259] On the other hand, the insecticidal activity of the insecticide composition of Example 2 prepared using the compound of Synthesis Example 2 and the insecticide compositions of Comparative Examples 1 and 2 against diamondback moth (Plutella xylostella) was similarly tested, and the results are shown in Table 1 below.

[0260] Test Example 2 - Insecticidal activity against common cutworm (Spodoptera litura) by leaf dipping method Cabbage (Daiya) leaves were cut into pieces 5.8 cm in diameter and immersed in each of the insecticide compositions prepared in the Examples (a 5% acetone solution containing each compound (concentration: 100 ppm) from the Synthesis Examples) for 30 seconds and thoroughly dried in the shade. The shade-dried cabbage leaves were then placed in a Petri dish (8.8 cm in diameter) covered with filter paper and inoculated with second-instar larvae of the common cutworm (Spodoptera litura) three times, each containing 10 larvae. The Spodoptera litura larvae were purchased from the Bio-Utilization Research Institute (Andong, Korea). The Spodoptera litura larvae were then stored under conditions of a 16-hour light / 8-hour dark cycle at 25±1°C and 50-60% relative humidity. The number of surviving Spodoptera litura larvae was counted 48 hours after inoculation. Thereafter, the mortality rate of the larvae was calculated in the same manner as in Test Example 1 above.

[0261] As a result of tests carried out using the compounds of Synthesis Examples 1 to 85, it was found that the insecticide compositions prepared using the compounds of Synthesis Examples 1, 1a, 1b, 2, 2a, 2b, 3, 3a, 3b, 4, 5, 6, 8, 9, 10, 11, 12, 13, 14, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 37, 39, 40, 45, 46, 47, 49, 50, 52, 53, 55, 56, 57, 58, 59, 65, 66, 67, 68, 69, 70, 71, 72, 75, 76, 78, 79, 80, 81, 82, 83, 84 and 85 had excellent insecticidal activity against Spodoptera litura ( litura), the mortality rate was over 80%.

[0262] On the other hand, the insecticidal activity of the insecticide composition of Example 2 prepared using the compound of Synthesis Example 2 and the insecticidal compositions of Comparative Examples 1 and 2 against common cutworm (Spodoptera litura) was similarly tested, and the results are shown in Table 1 below.

[0263] Test Example 3 - Insecticidal activity test against western flower thrips (Frankliniella occidentalis) by spray method A filter paper (9.0 cm diameter) soaked in water was placed in an insect rearing dish (Lab Guide®) with a diameter of 9.0 cm and a height of 4.0 cm, and parafilm (4.0 cm width x 4.0 cm height) was placed on top of it. Before treatment with the insecticide composition, adult Frankliniella occidentalis was inoculated into the Petri dish at 10 insects per dish using a No. 4 brush. The adult Frankliniella occidentalis was purchased from the Bio-Utilization Research Institute (Andong, Korea). Next, each insecticide composition prepared in the Examples (diluted solution of each compound in the Synthesis Examples (concentration: 100 ppm); solvent: distilled water + acetone 50,000 mg / L + Triton X 100 mg / L) was placed in a 100 mL small sprayer and sprayed 10 to 12 times from a distance of 30 cm and a height of 50 cm. Each spray was applied to one cotyledon of a host plant, soybean. Adult Frankliniella occidentalis was then stored under conditions of 16 hours of light and 8 hours of darkness, 25±1°C, and 50-60% relative humidity. 48 hours after inoculation, the number of surviving Frankliniella occidentalis adults was counted. Larval mortality was then calculated as in Test Example 1 above.

[0264] Tests were carried out using the compounds of Synthesis Examples 1 to 85. As a result, it was found that the insecticide compositions prepared using the compounds of Synthesis Examples 1, 1a, 1b, 2, 2a, 2b, 3, 3a, 3b, 4, 5, 6, 8, 9, 10, 11, 12, 13, 14, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 37, 39, 40, 45, 46, 47, 49, 50, 52, 53, 55, 56, 57, 58, 59, 65, 66, 67, 68, 69, 70, 71, 72, 75, 76, 78, 79, 80, 81, 82, 83, 84, and 85 were effective against western flower thrips (Frankliniella occidentalis), the mortality rate was over 80%.

[0265] Meanwhile, the insecticidal activity of the insecticide composition of Example 2 prepared using the compound of Synthesis Example 2, and the insecticide compositions of Comparative Examples 1 and 2 against western flower thrips (Frankliniella occidentalis) was similarly tested, and the results are shown in Table 1 below.

[0266] Test Example 4 - Insecticidal activity test against beet armyworm (Spodoptera exigua) by leaf immersion method Cabbage (Daiya) leaves were cut into pieces 5.8 cm in diameter and immersed for 30 seconds in an insecticide composition (solvent: distilled water + acetone 50,000 mg / L + Triton X-100 100 mg / L) prepared by diluting the compound from Synthesis Example 2, and then thoroughly dried in the shade. Next, the shade-dried cabbage leaves were placed in a Petri dish (8.8 cm in diameter) covered with filter paper and inoculated with second- to third-instar larvae of the beet armyworm (Spodoptera exigua) three to five times, with 10 larvae per inoculation. Specifically, the beet armyworm (Spodoptera exigua) larvae were purchased from the Bio-Utilization Research Institute (Andong, Korea). Next, the beet armyworm (Spodoptera exigua) larvae were stored under conditions of a 16-hour light / 8-hour dark period, 25±1°C, and a relative humidity of 50-60%, and the number of surviving beet armyworm (Spodoptera exigua) larvae was counted 24, 48, and 72 hours after inoculation. The larval mortality rate was then calculated in the same manner as in Test Example 1 above.

[0267] Meanwhile, tests were carried out under the same conditions using the insecticide compositions of Comparative Examples 1 and 2, and the results are shown in Table 1 below.

[0268] Test Example 5 - Insecticidal activity test against Spodoptera frugiperda by leaf dipping method Cabbage (Daiya) leaves were cut into pieces 5.8 cm in diameter and immersed for 30 seconds in an insecticide composition (solvent: distilled water + acetone 50,000 mg / L + Triton X 100 mg / L) prepared by diluting the compound from Synthesis Example 2, and then thoroughly dried in the shade. Next, the shade-dried cabbage leaves were placed in a Petri dish (8.8 cm in diameter) covered with filter paper and inoculated with second- to third-instar larvae of the fall armyworm (Spodoptera frugiperda) three to five times, with 10 larvae per inoculation. Specifically, the fall armyworm (Spodoptera frugiperda) larvae were provided by Chungbuk National University (Korea) and reared indoors for successive generations. Next, the fall armyworm (Spodoptera frugiperda) larvae were stored under conditions of a 16-hour light / 8-hour dark period, 25±1°C, and a relative humidity of 50-60%, and the number of surviving fall armyworm (Spodoptera frugiperda) larvae was counted 24 hours, 48 hours, and 72 hours after inoculation. The larval mortality rate was then calculated in the same manner as in Test Example 1 above.

[0269] Meanwhile, a test was carried out under the same conditions using the insecticide composition of Comparative Example 1, and the results are shown in Table 1 below.

[0270] Test Example 6 - Insecticidal activity test against bean moth (Maruca vitrta) using artificial diet immersion method Cabbage leaves (Daiei) were cut into pieces measuring 1 cm x 1 cm x 1 cm and immersed for 30 seconds in an insecticide composition prepared by diluting the compound of Synthesis Example 2 (solvent = distilled water + acetone 50,000 mg / L + Triton X-100 100 mg / L), and then placed on aluminum foil and thoroughly dried in the shade. In this case, the artificial diet used was prepared as follows: (1) 13 g of agar powder and 625 mL of doubly distilled water were placed in a 1-L beaker and boiled in a microwave for 10 minutes; (2) the microwave-boiled agar was placed in a blender, and 75 g of soybean powder, 20 g of adzuki bean powder, 10 g of malt powder, and 175 mL of doubly distilled water were added and mixed; and (3) the resulting mixture was cooled to 50°C, and then 5 g of a vitamin mixture, 4 g of ascorbic acid, 1 g of sorbic acid, 1 g of β-sitosterol, 10 g of glucose, 10 g of cellulose, 3 g of cholesterol, 1.5 g of methyl-p-hydroxybenzoate, 0.5 g of aureomycin, and 0.4 g of Fumidil B were added, mixed, and thoroughly cooled. Before placing the artificial diet pieces in a Petri dish (φ90 mm × 15 m), they were treated with distilled water to maintain humidity, and a piece of parafilm (5.1 cm × 5.1 cm) was placed on top of the filter paper (φ90 mm), and the artificial diet pieces were placed on top of the parafilm.

[0271] Next, 2nd- to 3rd-instar larvae of the bean borer (Maruca vitrta) were inoculated into the container 3 to 5 times, with 10 larvae per inoculation. The bean borer (Maruca vitrta) larvae were purchased from the Bio-Utilization Research Institute (Andong, Korea). The container was then stored under conditions of 16 hours of light and 8 hours of darkness, 25±1°C, and 50-60% relative humidity. The number of surviving bean borer (Maruca vitrta) larvae was counted 24, 48, and 72 hours after inoculation. Larval mortality was then calculated in the same manner as in Test Example 1 above.

[0272] Meanwhile, tests were carried out under the same conditions using the insecticide compositions of Comparative Examples 1 and 2, and the results are shown in Table 1 below.

[0273] Test Example 7 - Insecticidal activity test against radish leaf beetle (Phaedon brassicae) by leaf immersion method Cabbage (Daiya) leaves were cut into pieces 5.8 cm in diameter and immersed for 30 seconds in an insecticide composition (solvent = distilled water + acetone 50,000 mg / L + Triton X-100 100 mg / L) prepared by diluting the compound of Synthesis Example 2, and then thoroughly dried in the shade. Next, the shade-dried cabbage leaves were placed in a Petri dish (8.8 cm in diameter) covered with filter paper and inoculated with radish leaf beetle (Phaedon brassicae) larvae, 10 larvae per inoculation, 3 to 5 times. Specifically, the radish leaf beetle (Phaedon brassicae) larvae used were those reared for successive generations at Andong National University (Korea).

[0274] After inoculation, the radish leaf beetle (Phaedon brassicae) larvae were stored under conditions of 16 hours of light and 8 hours of darkness, 25±1°C, and 50-60% relative humidity. The number of surviving radish leaf beetle (Phaedon brassicae) larvae was counted 24 hours, 48 hours, and 72 hours after inoculation. The larval mortality rate was then calculated in the same manner as in Test Example 1 above.

[0275] Meanwhile, tests were carried out under the same conditions using the insecticide compositions of Comparative Examples 1 and 2, and the results are shown in Table 1 below.

[0276] Test Example 8 - Insecticidal activity test against onion thrips (Thrips tabaci Lindeman) by spray method A water-soaked filter paper (9.0 cm diameter) was placed in a 9.0 cm diameter, 4.0 cm high insect rearing dish (Lab Guide®), and Parafilm (4.0 cm wide x 4.0 cm high) was placed on top. Prior to treatment with the insecticide composition, adult onion thrips (Thrips tabaci Lindeman) were inoculated into each Petri dish at 10 individuals using a No. 4 brush. The adult onion thrips (Thrips tabaci Lindeman) were collected near Andong National University (South Korea) and reared for multiple generations. Next, a 100 mL small sprayer was charged with a diluted insecticide composition (solvent: distilled water + acetone 50,000 mg / L + Triton X-100 100 mg / L) containing the compound from Synthesis Example 2. The composition was sprayed 10 to 12 times from a distance of 30 cm and a height of 50 cm, and each spray was performed with one cotyledon of the host plant, soybean, added. Next, adult onion thrips (Thrips tabaci Lindeman) were stored under conditions of a 16-hour light / 8-hour dark cycle, 25±1°C, and 50-60% relative humidity. 24 and 48 hours after inoculation, the number of surviving adult onion thrips (Thrips tabaci Lindeman) was counted. Larval mortality was then calculated in the same manner as in Test Example 1 above.

[0277] Meanwhile, tests were carried out under the same conditions using the insecticide compositions of Comparative Examples 1 and 3, and the results are shown in Table 1 below.

[0278] Test Example 9 - Insecticidal activity test against gypsy moth (Lymantria dispar) by leaf immersion method Maple leaves were immersed for 30 seconds in an insecticide composition (solvent: distilled water + acetone 50,000 mg / L + Triton X-100 100 mg / L) prepared by diluting the compound of Synthesis Example 2, and then placed on aluminum foil to thoroughly dry in the shade. The leaves were then placed on a Petri dish (9.0 cm diameter) covered with filter paper (9.0 cm diameter) treated with distilled water to maintain humidity, and five third-instar nymphs of Lymantria dispar were inoculated into the leaves four times. Specifically, Lymantria dispar nymphs were collected from Jukjeong-myeon, Buk-gu, Pohang City, Gyeongsangbuk-do, South Korea. Next, gypsy moth (Lymantria dispar) larvae were stored under conditions of 16 hours light: 8 hours dark, 25±1°C, and 50-60% relative humidity, and the number of gypsy moth (Lymantria dispar) larvae was counted 24 hours, 48 hours, and 72 hours after inoculation. Thereafter, the larval mortality rate was calculated in the same manner as in Test Example 1 above.

[0279] Meanwhile, tests were carried out under the same conditions using the insecticide compositions of Comparative Examples 1 and 3, and the results are shown in Table 1 below.

[0280] Test Example 10 - Insecticidal activity test against the oriental fruit moth (Grapholita molesta) by spraying method An insecticide composition (solvent: distilled water + acetone 50,000 mg / L + Triton X-100 100 mg / L) prepared by diluting the compound of Synthesis Example 2 was directly sprayed onto apples using a CO2Sprayer (registered trademark) [nozzle type: Teejet 8002VS (flat fan type), pressure: 800 psi]. After one hour, the apples were collected and inoculated with Grapholita molesta larvae, three per apple, five to six times. Specifically, the Grapholita molesta larvae were collected at the R&D center of Kyung Nong Co., Ltd. (Gyeongju, Korea) and allowed to acclimate indoors for 24 hours before use. Next, the oriental fruit moth (Grapholita molesta) larvae were stored under conditions of a 16-hour light / 8-hour dark period, 25±1°C, and a relative humidity of 50-60%, and the number of surviving oriental fruit moth (Grapholita molesta) larvae was counted 24 hours, 72 hours, and 192 hours after inoculation. The larval mortality rate was then calculated in the same manner as in Test Example 1 above.

[0281] Meanwhile, a test was carried out under the same conditions using the insecticide composition of Comparative Example 1, and the results are shown in Table 1 below.

[0282] Test Example 11 - Insecticidal activity test against the black-and-white moth (Rhopobota naevana) by spraying method Apple leaves were harvested along with the stems, and three to four basal leaves were cut into 5cm x 5cm x 5cm pieces and placed in a tray oasis submerged in water. Next, an insecticide composition (solvent: distilled water + acetone 50,000mg / L + Triton X-100 100mg / L) containing the compound from Synthesis Example 2 was loaded into a 150mL small sprayer and sprayed onto the apple leaves. After one hour, the apple leaves were repeatedly inoculated 5 to 6 times per apple leaf. Specifically, larvae of the black-headed moth (Rhopobota naevana) were collected at the R&D center of Kyung Nong Co., Ltd. (Gyeongju City) and used after 24 hours of indoor acclimation. Next, the black-and-white moth (Rhopobota naevana) larvae were stored under conditions of a 16-hour light / 8-hour dark cycle, 25±1°C, and a relative humidity of 50-60%, and the number of surviving black-and-white moth (Rhopobota naevana) larvae was counted 24, 48, and 72 hours after inoculation. The larval mortality rate was then calculated in the same manner as in Test Example 1 above.

[0283] On the other hand, a test was carried out under the same conditions using the insecticide composition of Comparative Example 1, and the results are shown in Table 1.

[0284] Test Example 12 - Insecticidal activity test against white corngrass (Manulea degenerella) by spray method A water-soaked filter paper (9.0 cm diameter) was placed in an insect rearing dish (Lab Guide®) with a diameter of 9.0 cm and a height of 4.0 cm, and a Parafilm (4.0 cm wide x 4.0 cm high) was placed on top. Prior to treatment with the insecticide composition, 10 third-instar Manulea degenerella larvae were inoculated per rearing dish using a No. 4 brush. Specifically, Manulea degenerella larvae collected in Icheon, Gyeonggi Province, South Korea were used. Next, the insecticide composition (solvent = distilled water + acetone 50,000 mg / L + Triton X-100 100 mg / L) prepared by diluting the compound of Synthesis Example 2 was loaded into a 100 mL small sprayer and sprayed 10 to 12 times from a distance of 30 cm and a height of 50 cm, adding one cotyledon of the host plant, persimmon, to each spray. Next, the white-spotted moth (Manulea degenerella) larvae were stored under conditions of a 16-hour light / 8-hour dark period, 25±1°C, and a relative humidity of 50-60%, and the number of surviving white-spotted moth (Manulea degenerella) larvae was counted 24, 48, and 72 hours after inoculation. The larval mortality rate was then calculated in the same manner as in Test Example 1 above.

[0285] On the other hand, a test was carried out under the same conditions using the insecticide composition of Comparative Example 1, and the results are shown in Table 1.

[0286] Test Example 13 - Insecticidal activity test against cotton bollworm (Helicoverpa armigera) by leaf immersion method Cabbage (Daiya) leaves were cut into pieces 5.8 cm in diameter and immersed for 30 seconds in an insecticide composition (solvent = distilled water + acetone 50,000 mg / L + Triton X-100 100 mg / L) prepared by diluting the compound from Synthesis Example 2, and then thoroughly dried in the shade. Next, the shade-dried cabbage leaves were placed in a Petri dish (8.8 cm in diameter) covered with filter paper, and ten third-instar larvae of the cotton bollworm (Helicoverpa armigera) were inoculated into each dish three to five times. In this case, the cotton bollworm (Helicoverpa armigera) larvae were purchased from Andong National University (Korea). Next, the cotton bollworm (Helicoverpa armigera) larvae were stored under conditions of a 16-hour light / 8-hour dark period, 25±1°C, and a relative humidity of 50-60%, and the number of surviving cotton bollworm (Helicoverpa armigera) larvae was counted 24, 48, and 72 hours after inoculation. The larval mortality rate was then calculated in the same manner as in Test Example 1 above.

[0287] On the other hand, a test was carried out under the same conditions using the insecticide composition of Comparative Example 1, and the results are shown in Table 1.

[0288] [Table 1]

[0289] Referring to Table 1 above, it can be seen that the insecticide compositions according to the present disclosure exhibit excellent mortality against pests such as insects and moths, even when the insecticide compositions contain relatively low concentrations of compounds. In particular, the insecticide compositions according to the present disclosure exhibit significantly high mortality against diamondback moth (Plutella xylostella), bean leafroller (Maruca vitrta), common cutworm (Spodoptera litura), gypsy moth (Lymantria dispar), white-spotted grasshoppers (Manulea degenerella), and cotton bollworm (Helicoverpa armigera), even when the insecticide compositions contain a very low concentration of compounds, such as 0.1 ppm. Furthermore, it can be seen that the insecticide compositions according to the present disclosure exhibit high mortality even against onion thrips (Thrips tabaci Lindeman) and western flower thrips (Frankliniella occidentalis).

[0290] Test Example 14 - Resistance (tolerance) test against diamondback moth (Plutella xylostella) Resistance (tolerance) tests to insecticide compositions were conducted on diamondback moths (Plutella xylostella). Resistant diamondback moths (Plutella xylostella) were obtained as follows: in the rearing room of Chungbuk National University (South Korea), radish sprouts were germinated in acrylic cages (25 cm x 30 cm x 30 cm) to induce egg laying, and adults were collected using an InsectaVac Aspirator (BioQuip®). Selection pressure was applied once a month using 12.5 ppm diamide-based chlorantraniliprole to induce egg laying again, and the moths were reared for successive generations.

[0291] Cabbage leaves were immersed in a diluted insecticide composition (solvent: distilled water + acetone 50,000 mg / L + Triton X-100 100 mg / L) for 30 seconds and thoroughly dried in the shade. The shade-dried cabbage leaves were then placed in a Petri dish (8.8 cm diameter) covered with filter paper and inoculated with resistant diamondback moth (Plutella xylostella) third-instar larvae (10 larvae per inoculation) three to five times. The diamondback moth (Plutella xylostella) larvae were then stored under conditions of 16 hours of light and 8 hours of darkness, 25±1°C, and 50-60% relative humidity. The number of surviving cotton bollworm (Helicoverpa armigera) larvae was counted 24 and 48 hours after inoculation. Larval mortality was then calculated as in Test Example 1 above, and the results are shown in Table 2 below. [Table 2] Referring to Table 2 above, it can be seen that the insecticide compositions of the present disclosure showed little resistance (tolerance) and high mortality, whereas the insecticide compositions of Comparative Examples 1 and 2 showed resistance and significantly reduced mortality.

Claims

1. Formula 1 below: 【Chemical 1】 [In formula 1, R 1 are each independently hydrogen, halogen, cyano (CN), C 1-5 Alkyl or C 1-5 is haloalkyl, R 2 is hydrogen, halogen, C 1-5 Alkyl or C 1-5 is haloalkyl, R 3 is hydrogen, C 1-5 Alkyl, C 3-10 Cycloalkyl, -C(=O)-C 3-10 Cycloalkyl; C 1-5 Alkyl, C 1-5 Haloalkyl and C 3-10 -C substituted with one or more cycloalkyl 1-5 Alkylene-OC(=O)H; or halogen, C 1-5 Alkyl, C 1-5 Haloalkyl and C 3-10 C substituted with one or more selected from the group consisting of cycloalkyl 1-10 is alkyl, R 4 is C 1-5 Alkyl, C 1-5 Haloalkyl, C 3-10 Cycloalkyl, C 5-12 Spiroalkyl, 3-10 membered heterocycloalkyl, 3-10 membered heterocycloalkylene-C(=O)-OC 1-5 Alkyl, C 2-10 Alkenyl, C 6-20 Aryl, 3-10 membered heteroaryl; C 3-10 C substituted by cycloalkyl 1-5 Alkyl; Cyano (CN), Halogen, C 1-5 Alkyl, C 1-5 Haloalkyl and C 3-10 C substituted with one or more selected from the group consisting of cycloalkyl 3-10 Cycloalkyl; halogen, C 1-5 Alkyl, C 1-5 Haloalkyl and C 3-10 3-10 membered heterocycloalkyl substituted with one or more cycloalkyls; C 1-5 Alkyl and C 6-20 C substituted with one or more selected from the group consisting of aryl 2-10 Alkenyl; Cyano (CN), Halogen, C 1-5 Alkyl and C 1-5 C substituted with one or more selected from the group consisting of haloalkyl 6-20 aryl; or halogen, C 1-5 Alkyl, C 1-5 Haloalkyl and C 3-10 cycloalkyl; Q is C 6-20 Arylene, 3- to 10-membered heteroarylene, or halogen and C 1-5 C substituted with one or more selected from the group consisting of alkyl 6-20 is an arylene, a is an integer from 1 to 5, wherein the heterocycloalkyl, heteroaryl, heterocycloalkylene, and heteroarylene each contain at least one heteroatom selected from the group consisting of N, O, and S. a compound represented by the formula:

2. Q is, 【Chemistry 2】 and R 5 is hydrogen, halogen or C 1-5 is alkyl, X is N, O or S; The compound according to claim 1, its stereoisomer, its hydrate or a salt thereof.

3. The above formula 1 is represented by the following formulas 1A to 1E: 【Chemistry 3】 【Chemistry 4】 【Chemistry 5】 【Chemistry 6】 【Chemistry 7】 [In formulas 1A to 1E, R 1' are each independently halogen, cyano (CN), C 1-5 Alkyl or C 1-5 is haloalkyl, R 2 ~R 4 The definition of is the same as that defined in claim 1, R 5 is hydrogen, halogen or C 1-5 alkyl] indicated by one of the following: The compound according to claim 1, its stereoisomer, its hydrate or a salt thereof.

4. R 1' are each independently cyano (CN), chlorine (Cl), fluorine (F) or C 1-3 is haloalkyl, R 2 But C 1-3 haloalkyl, The compound according to claim 3, its stereoisomer, its hydrate or a salt thereof.

5. R 3 But hydrogen, methyl, ethyl, 【Chemistry 8】 That is, The compound according to claim 1, its stereoisomer, its hydrate or a salt thereof.

6. R 4 But C 3-6 Cycloalkyl, C 5-8 Spiroalkyl, 3-6 membered heterocycloalkyl, 3-6 membered heterocycloalkylene-C(=O)-OC 1-3 Alkyl, C 2-5 Alkenyl, C 6-10 Aryl, 3-6 membered heteroaryl; C 3-6 C substituted by cycloalkyl 1-3 Alkyl; Cyano (CN), halogen and C 1-3 C substituted with one or more selected from the group consisting of alkyl 3-6 Cycloalkyl; C 6-10 C substituted by aryl 2-5 Alkenyl; C substituted by cyano (CN) 6-10 aryl; or halogen, C 1-3 Alkyl, C 1-3 Haloalkyl and C 3-6 cycloalkyl; The compound according to claim 1, its stereoisomer, its hydrate or a salt thereof.

7. R 4 but, 【Chemistry 9】 That is, The compound according to claim 1, its stereoisomer, its hydrate or a salt thereof.

8. The above formula 1 is the following compounds 1001 to 1085: 【Chemistry 10】 【Chemistry 11】 【Chemistry 12】 【Chemistry 13】 【Chemistry 14】 【Chemistry 15】 【Chemistry 16】 【Chemistry 17】 【Chemistry 18】 Indicated by one of the following: The compound according to claim 1, its stereoisomer, its hydrate or a salt thereof.

9. An insecticide composition comprising, as an active ingredient, one or more compounds selected from the group consisting of the compound according to any one of claims 1 to 8, its stereoisomers, its hydrates, and salts thereof.

10. 10. The insecticide composition of claim 9, wherein the composition is for controlling pests of the order Thysanoptera or Lepidoptera.

11. The composition is effective against Frankliniella occidentalis, Frankliniella tenuicornis, Frankliniella intonsa, Frankliniella lilivora, Thrips palmi Karny, Thrips tabaci Lindeman, Phaedon brassicae, Myzus persicae, Riptortus clavatus, Lymantria dispar, Helicoverpa armigera, Manulea degenerella, Rhopobota japonica ... naevana), pear fruit moth (Grapholita molesta), diamondback moth (Plutella xylostella), common cutworm (Spodoptera litura), beet armyworm (Spodoptera exigua), leaf fall armyworm (Spodoptera frugiperda) or bean diet moth (Maruca vitrta), 10. The insecticide composition of claim 9.

12. 10. A method of controlling pests comprising treating a crop or its habitat with the insecticide composition of claim 9.

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