N-phenylpyrazole derivative as well as preparation method and application thereof

Abstract

The invention relates to the technical field of compound synthesis and pesticides, in particular to an N-phenylpyrazole derivative and a preparation method and application thereof.The N-phenylpyrazole derivative has the 100% control effect on broadleaf weeds under the dosage of 37.5-150 g a.i. / ha, and part of compounds have the good control effect on grassy weeds; the compound can obtain a better weeding effect at a low dosage, can be used as a potential PPO inhibitor and broadleaf weed post-emergence herbicide for development and use, and has the advantages of novel structure, simple preparation process, low production cost and wide application prospect.

Description

Technical Field

[0001] This invention belongs to the field of compound pesticides, specifically relating to a... N -Phenylenol derivatives, their preparation methods and applications. Background Technology

[0002] Herbicides play a vital role in modern agriculture, effectively controlling weeds and increasing crop yields. Over the decades, the development and application of herbicides have undergone significant changes due to the need to address emerging challenges such as weed resistance, environmental concerns, and the demand for sustainable agriculture. Therefore, developing efficient and environmentally friendly herbicides is a major requirement in current agricultural production.

[0003] Protoporphyrinogen oxidase (PPO) catalyzes the oxidation of protoporphyrinogen IX to protoporphyrin IX, and is one of the most important targets discovered in herbicide research. Protoporphyrinogen oxidase is the penultimate enzyme in the biosynthesis of chlorophyll and heme, belonging to a large family of enzymes containing flavonoid adenine dinucleotides (FAD). It catalyzes the conversion of protoporphyrinogen IX to protoporphyrin IX. Inhibition of PPO by plants can lead to the toxic accumulation of protoporphyrin IX in the cytoplasm. Under light, protoporphyrin IX reacts with oxygen to produce reactive oxygen species, damaging cell membranes and causing rapid burn symptoms in plants. On the other hand, PPO inhibitors have many advantages, including broad-spectrum herbicidal activity, strong resistance to herbicides, environmental friendliness, low toxicity, and low usage rates.

[0004] Small molecules containing pyrazole rings are widely used in pharmaceuticals, pesticides, and materials. In the pesticide field, herbicides based on pyrazole that are already on the market include isopropalfen, pyrazosulfuron, and cyprodinil. Furthermore, research on pyrazole-containing herbicides has made some progress in recent years. For example, patent applications WO9602515A1, CN1151159A, WO0116112A1, CN1402979A, CN107518008A, and US20190069512A1 disclose the preparation and herbicidal activity of pyrazole herbicides. These compounds are characterized by high efficiency, broad spectrum, and low residue, especially effective against broadleaf weeds. However, these compounds also cause significant damage to broadleaf crops, and their safety profile still needs improvement. They also suffer from high production costs and low overall yields. N -Phenylonpyrazole is a PPO inhibitor with a relatively new skeletal structure and a novel mechanism of action, based on N The design and synthesis of small molecules of herbicides using phenylpyrazole units is in line with the current trend in the creation of new pesticides.

[0005] Most existing herbicides are not only highly effective against weeds but also cause significant damage to crops, making them unsuitable for use during crop growth. However, with the emergence of environmental pollution and weed resistance, and the high demand for weed control in actual production, the development of novel, highly efficient, low-toxicity, and environmentally friendly green herbicides is urgently needed. Summary of the Invention

[0006] This invention addresses the shortcomings of existing technologies by proposing a... N -Phenylenol derivatives, their preparation methods and applications.

[0007] To achieve the above objectives, the technical solution adopted by the present invention is as follows: One of the objectives of this invention is to provide: a N -Phenylenol derivatives, the N -The general structural formula of phenylpyrazole derivatives is shown in formula (I): In formula (I): X is selected from H, CH2, and CH3 respectively; Y is selected from O, S, and NR respectively. 7 ONCR 8 ; R 1 R 2 They were selected from CH3, CF3, Ph, and 4-CH3-Ph, respectively. R 3 R 4 The components are selected from hydrogen, halogen, -CN, C1-C6 alkyl, (C1-C6 haloalkyl)-O- or (C1-C6 alkyl)-SO2-, respectively. R 5 They are selected from hydrogen, halogen, C1-C6 alkyl, C1-C6 haloalkyl, and C1-C6 alkoxy, respectively; R 6 Selected from hydrogen, halogen, C1-C6 alkyl, C3-C6 alkenyl, C3-C6 haloalkenyl, C3-C6 alkynyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 cyano, C3-C6 cycloalkyl, C5-C6 aryl, C2-C6 heterocyclic, R 9 -OR 10 (CH2) n COX 2 R 11 ; n is selected from 0, 1, 2, 3, 4, 5, and 6 respectively; X 2 Other selections include O, S, and NR. 12NCR 13 ; R 7 R 8 Each of the following is independently selected from hydrogen, halogen, C1-C6 alkyl, C3-C6 alkenyl, C3-C6 haloalkenyl, C3-C6 alkynyl, C1-C6 haloalkyl, and C1-C6 alkoxy. R 9 R 10 R 11 Each of the following is independently selected from hydrogen, halogen, C1-C6 alkyl, C3-C6 alkenyl, C3-C6 haloalkenyl, C3-C6 alkynyl, C1-C6 haloalkyl, and C1-C6 alkoxy. R 12 R 13 Each of the following is independently selected from H, C1-C6 alkyl, C1-C6 haloalkyl, C3-C6 alkenyl, C3-C6 haloalkenyl, C3-C6 alkynyl, C1-C4 alkoxyC1-C6-alkyl, and C1-C4 haloalkoxyC1-C6 alkyl.

[0008] The N -Phenylenol derivatives, including compounds A1 to A50.

[0009] The second objective of this invention is to provide: the above-mentioned N The preparation method of phenylpyrazole derivatives includes the following steps: (1) Preparation of intermediate 2: Intermediate 1 was dissolved in 98% concentrated sulfuric acid to form a solution, which was then cooled in an ice bath. Subsequently, 65% concentrated nitric acid was added dropwise, and the reaction mixture was stirred for 30 minutes under ice bath conditions. The reaction mixture was then poured into ice and stirred vigorously for 30 minutes. The precipitate was collected by filtration, washed with water, and then dried under vacuum to obtain intermediate 2. (2) Preparation of intermediate 3: After mixing and stirring intermediate 2, ammonium chloride and 90% ethanol solution, the temperature was raised to 80 ℃, and then iron powder was slowly added. After the reaction system was reacted at 80 ℃ for 4 hours, the hot reaction mixture was filtered through a diatomaceous earth pad, and then successively subjected to extraction drying and column chromatography to obtain intermediate 3. (3) Preparation of intermediate 4: Intermediate 3 was dissolved in 80% ethanol, hydroxylamine hydrochloride was added, and the mixture was heated to 80 °C and reacted for 4 hours. After the reaction was completed, intermediate 4 was obtained by extraction, combining organic phases, drying, concentration and column chromatography purification. (4) Preparation of intermediate 5: Intermediate 4 was dissolved in DMF, and then 1,1,1-trifluoro-2,4-pentanedione and... O-(diphenylphosphono)hydroxylamine, heated to 85 °C; after the reaction was complete, the reaction mixture was poured into water and extracted with ethyl acetate. The combined organic phases were dried over anhydrous sodium sulfate and then concentrated under reduced pressure; the residue was purified by column chromatography to give intermediate 5; (5) Preparation of target compounds A1–A9: Intermediate 5 was dissolved in DMF, potassium carbonate and a substituted 2-chlorocarboxylic acid derivative were added, and the mixture was stirred at room temperature. After the reaction was completed, the product was subjected to extraction, separation of the organic layer, drying, concentration under reduced pressure, and column chromatography to obtain the final product. N -Phenylenol derivatives A1–A9; (6) Preparation of target compounds A10–A50: Intermediate 5 was dissolved in DMF and heated to 35 °C. Then, while stirring, the following was added to the solution: N -Chlorosuccinimide; after stirring continuously for 1 hour, the reaction solution was cooled to room temperature; then dichloromethane was added for extraction, and the organic phase was washed twice each with 1 mol / L hydrochloric acid and saturated brine; after drying with anhydrous sodium sulfate and filtering, the filtrate was cooled to 0–5 °C, and the substituted enoic acid derivative and triethylamine were slowly added dropwise. After the reaction was completed, the product was subjected to extraction, separation of the organic layer, drying, and column chromatography to obtain the final product. N -Phenylpyrazole derivatives A10–A50;.

[0010] In step (1), the amount of intermediate 1 and concentrated nitric acid is calculated as follows: intermediate 1: concentrated nitric acid = 1:1.25; the amount of concentrated sulfuric acid is controlled by adding 1 mL of concentrated sulfuric acid per millimol of intermediate 1.

[0011] In step (2), the amounts of intermediate 2, ammonium chloride, and iron powder are calculated in the following molar ratio: intermediate 1: ammonium chloride: iron powder = 1:3:3; the amount of 90% ethanol is controlled by adding 1 mL of 90% ethanol per millimol of intermediate 2.

[0012] In step (3), the amount of intermediate 3 and hydroxylamine hydrochloride is calculated in molar ratio as follows: intermediate 4: hydroxylamine hydrochloride = 1:2; the amount of 80% ethanol is controlled by adding 1 mL of 80% ethanol per millimol of intermediate 3.

[0013] In step (4), the intermediate 4, 1,1,1-trifluoro-2,4-pentanedione, O The amount of -(diphenylphosphono)hydroxylamine, calculated by molar ratio, is: Intermediate 4: 1,1,1-trifluoro-2,4-pentanedione: O -(diphenylphosphono)hydroxylamine = 1:1.1:1.5; the amount of 80% ethanol used is controlled by adding 1 mL of 80% ethanol per millimol of intermediate 4.

[0014] In step (5), the amounts of intermediate 5, substituted 2-chlorocarboxylic acid derivative, and potassium carbonate are calculated in the following molar ratio: intermediate 5: substituted 2-chlorocarboxylic acid derivative: potassium carbonate = 1:1.25:1.5; the amount of DMF is controlled by adding 1 mL of DMF per millimol of intermediate 5.

[0015] In step (6), the intermediate 5, N The amounts of -chlorosuccinimide, substituted olefinic acid derivative, and triethylamine, calculated in molar ratio, are as follows: Intermediate 5: N -Chlorosuccinimide:substituted enoic acid derivative:triethylamine = 1:1.2:1.5:1.5; the DMF is controlled by adding 1 mL of DMF per millimole of intermediate 5.

[0016] The N The preparation routes for -phenylpyrazole derivatives are any of the following: Route 1: Further optimization, The substituted intermediate 1 is 2-chloro-4-fluorobenzaldehyde, 2,4-difluorobenzaldehyde, 2,4-dichlorobenzaldehyde, or 4-chloro-2-fluorobenzaldehyde.

[0017] The substituted 2-chlorocarboxylic acid derivatives are methyl 2-chloroacetate, ethyl chloroacetate, propyl chloroacetate, butyl chloroacetate, amyl chloroacetate, benzyl chloroacetate, methyl 2-chloropropionate, ethyl 2-chloropropionate, propyl 2-chloropropionate, butyl 2-chloropropionate, amyl 2-chloropropionate, tert-butyl 2-chloropropionate, 2-methoxy-2-oxoethyl 2-chloropropionate, 1-methoxy-1-oxopropyl-2-yl 2-chloropropionate, and 3-methoxy-2-yl 2-chloropropionate. Any one of 3-oxypropyl ester, ethyl 2-((2-chloropropionyl)thio)acetate, ethyl 2-((2-chloropropionyl)thio)propionate, methyl 3-((2-chloropropionyl)thio)propionate, methyl 3-(2-chloropropamido)propionate, methyl 2-chloro-2-methylpropionate, ethyl 2-chloro-2-methylpropionate, methyl 2-chlorobutyrate, ethyl 2-chlorobutyrate, methyl 2-chloro-3-methylbutyrate, and ethyl 2-chloro-3-methylbutyrate.

[0018] The substituted olefin derivatives are methyl methacrylate, ethyl methacrylate, isopropyl methacrylate, tert-butyl methacrylate, propyl methacrylate, allyl methacrylate, sec-butyl methacrylate, butyl methacrylate, methoxyethyl methacrylate, 2,2,3,3-tetrafluoropropyl methacrylate, cyclohexyl methacrylate, phenyl methacrylate, methyl thiomethacrylate, ethyl thiomethacrylate, and propyl thiomethacrylate. N -Methylmethacrylamide,N,N -Dimethylmethylacrylamide, N -Ethylmethylacrylamide, N -Isopropylmethylacrylamide, N -Propylmethacrylamide, N -Butylmethacrylamide, 2-methoxy-2-oxoethyl methacrylate, 2-ethoxy-2-oxoethyl methacrylate, 2-propoxy-2-oxoethyl methacrylate, 1-methoxy-1-oxopropyl-2-yl methacrylate, 1-ethoxy-1-oxopropyl-2-ester methacrylate, 1-ethoxy-1-oxopropyl-2-ester methacrylate, glycidyl methacrylate, 2-epoxypentyl methacrylate.

[0019] Another object of the present invention is as described N Application of phenylpyrazole derivatives in the preparation of herbicides and weed growth enzyme inhibitors.

[0020] Specifically, the weeds include barnyard grass, foxtail grass, goosegrass, purslane, amaranth retroflexus, velvetleaf, gourd, seed amaranth, milkvetch, black millet, ryegrass, catnip, oats, hairy vetch, marigold, morning glory, zinnia, alfalfa, arrowroot, cassia seed, chicory, milk thistle, licorice, field clover, buffalo grass, sugar grass, kochia, duckweed, lamb's quarters, and dandelion.

[0021] Beneficial effects: This invention is based on N The phenylpyrazole structure was optimized and derived to create a drug with stable physicochemical properties and excellent drug-likeness. N - Phenylepiazole herbicides are small molecules; these derivatives are particularly effective in post-emergence inhibition of barnyard grass, goosegrass, foxtail grass, velvetleaf, amaranth, and purslane.

[0022] Post-emergence herbicidal activity tests revealed that some... N The phenylpyrazole compounds A10, A11, A12, A14, A15, A16, A18, A20, A22, A23, A24, A34, A35, A43, A44, A45, A46, A47, and A48 exhibited excellent herbicidal activity against barnyard grass, goosegrass, foxtail, amaranth, purslane, and velvetleaf at a dose of 150 g ai / ha. The weeds completely withered, and their growth was severely inhibited, with inhibition rates reaching 100%, comparable to the positive control isopyrazole. At a dose of 75 g ai / ha, compounds A10, A11, A12, A14, A15, A16, A18, A20, A22, A23, A24, A34, A35, A43, A44, A45, A46, A47, and A48 also showed excellent herbicidal activity against barnyard grass, goosegrass, foxtail, amaranth, purslane, and velvetleaf. At the ai / ha dosage, compounds A10, A11, A43, A44, A45, A46, A47, and A48 exhibited excellent herbicidal activity against barnyard grass, crabgrass, foxtail grass, velvetleaf, amaranth, and purslane, with inhibition rates reaching 100%.

[0023] This invention is designed and synthesizedN -Phenylepirazole derivatives have a simple structure and simple preparation process. They have good herbicidal activity against broadleaf weeds and relatively high safety for broadleaf crops. The raw materials are readily available, the production cost is low, the overall yield is high, and the preparation process is non-toxic and harmless, showing great application prospects. Attached Figure Description

[0024] Figure 1 Examples 1–50 N Preparation route diagram of phenylpyrazole derivatives; Detailed Implementation

[0025] The specific embodiments of the present invention will be described in further detail below, but the present invention is not limited to these embodiments. Any improvements or substitutions based on the basic spirit of these embodiments shall still fall within the scope of protection claimed by the claims of the present invention.

[0026] Example 1: ( E )-2-(((2-chloro-4-fluoro-5-(5-methyl-3-(trifluoromethyl)-1 H The preparation method of methyl pyrazol-1-yl)benzylidene)amino)oxy)propionate (i.e., compound A1) includes the following steps: (1) Preparation of 2-chloro-4-fluoro-5-nitrobenzaldehyde: 2-Chloro-4-fluorobenzaldehyde (50.00 g, 316.48 mmol) was dissolved in concentrated sulfuric acid (300 mL) to form a solution, which was then cooled in an ice bath. Subsequently, concentrated nitric acid (24.92 g, 395.60 mmol) was added dropwise, and the reaction mixture was stirred for 30 minutes in an ice bath. The reaction mixture was then poured into ice (300 g) and stirred vigorously for 30 minutes. The precipitate was collected by filtration, washed with water, and then dried under vacuum to give 41.32 g of 2-chloro-4-fluoro-5-nitrobenzaldehyde intermediate, yield 82.60%. (2) Preparation of 5-amino-2-chloro-4-fluorobenzaldehyde: 41.32 g (203.57 mmol), 32.67 g (610.71 mmol), and 90% EtOH (300 mL) were added to a flask, and the mixture was heated to 80 °C. Iron powder (34.20 g, 610.71 mmol) was then added in portions to the solution, and the reaction mixture was refluxed for 4 hours. After the reaction was complete, the hot reaction mixture was filtered through a diatomaceous earth mat. The residue was washed with 100 mL of ethyl acetate, and 200 mL of H2O was added to the filtrate. The residue was extracted with 200 mL of ethyl acetate, and the organic layers were combined. The mixture was dried over anhydrous Na2SO4 and concentrated by rotary evaporation to obtain 30.90 g of 5-amino-2-chloro-4-fluorobenzaldehyde intermediate, with a yield of 74.80%. (3) E Preparation of 5-amino-2-chloro-4-fluorobenzaldehyde oxime: 5-Amino-2-chloro-4-fluorobenzaldehyde (30.90 g, 164.34 mmol), hydroxylamine hydrochloride (22.84 g, 328.68 mmol), and EtOH (80%, 200 mL) were added to a flask, and the mixture was heated to 80 °C. The reaction mixture was then refluxed for 4 hours. After the reaction was complete, the mixture was extracted with 200 mL of ethyl acetate and 200 mL of water. The organic layers were combined, concentrated by rotary evaporation with anhydrous Na₂SO₄, and then subjected to column chromatography to obtain (…). E 27.35 g of 5-amino-2-chloro-4-fluorobenzaldehyde oxime intermediate, yield 88.50%; (4) E )-2-chloro-4-fluoro-5-(5-methyl-3-(trifluoromethyl)-1 H Preparation of 1-pyrazole-1-yl)benzaldehyde oxime: Will( E 5-Amino-2-chloro-4-fluorobenzaldehyde oxime (27.35 g, 145.46 mmol) was dissolved in DMF (150 mL), followed by the addition of 1,1,1-trifluoro-2,4-pentanedione (24.66 g, 160.01 mmol) and... O -(diphenylphosphono)hydroxylamine (50.88 g, 218.19 mmol), heated to 85 °C. The reaction was continued for 4 hours. After completion, the reaction mixture was poured into 200 mL of H₂O and extracted with 200 mL of ethyl acetate. The combined organic phases were dried over anhydrous Na₂SO₄ and then concentrated under reduced pressure. Column chromatography yielded (… E )-2-chloro-4-fluoro-5-(5-methyl-3-(trifluoromethyl)-1 H14.73 g of pyrazole-1-yl)benzaldehyde oxime intermediate, yield 53.80%; (5) E )-2-(((2-chloro-4-fluoro-5-(5-methyl-3-(trifluoromethyl)-1 H Preparation of methyl pyrazol-1-yl)benzylidene)amino)oxy)propionate: Pick( E )-2-chloro-4-fluoro-5-(5-methyl-3-(trifluoromethyl)-1 H 1-Pyrazole-1-yl)benzaldehyde oxime (200 mg, 622.99) µ Dissolve in 10 mL of DMF, add potassium carbonate (127.58 mg, 924.49 mol), and add potassium carbonate (924.49 mol). µ mol), stirred at room temperature for 30 minutes, then methyl 2-chloropropionate (85.86 mg, 700.86 mg) was added. µ The mixture was then reacted at room temperature for 6 hours. After the reaction was complete, it was poured into 40 mL of water, and the mixture was extracted with 40 mL of ethyl acetate. The organic layer was collected, dried over anhydrous Na2SO4, concentrated under reduced pressure, and the residue was obtained by column chromatography. E )-2-(((2-chloro-4-fluoro-5-(5-methyl-3-(trifluoromethyl)-1 H 1-pyrazol-1-yl)benzylidene)amino)oxy)methyl propionate, yield 67.50%.

[0027] Example 2: ( E )-2-(((2-chloro-4-fluoro-5-(5-methyl-3-(trifluoromethyl)-1 H The preparation method of ethyl pyrazol-1-yl)benzylidene)amino)oxy)propionate (i.e., compound A2) includes the following steps: Steps (1)-(4): Same as steps (1)-(4) in Example 1; (5) E )-2-(((2-chloro-4-fluoro-5-(5-methyl-3-(trifluoromethyl)-1 H Preparation of ethyl pyrazol-1-yl)benzylidene)amino)oxy)propionate: Pick( E )-2-chloro-4-fluoro-5-(5-methyl-3-(trifluoromethyl)-1 H 1-Pyrazole-1-yl)benzaldehyde oxime (200 mg, 622.99) µ Dissolve in 10 mL of DMF, add potassium carbonate (127.58 mg, 924.49 mol), and add potassium carbonate (924.49 mol). µmol), stirred at room temperature for 30 minutes, then ethyl 2-chloropropionate (95.67 mg, 700.86 mol) was added. µ The mixture was then reacted at room temperature for 6 hours. After the reaction was complete, it was poured into 40 mL of water, and the mixture was extracted with 40 mL of ethyl acetate. The organic layer was collected, dried over anhydrous Na2SO4, concentrated under reduced pressure, and the residue was obtained by column chromatography. E )-2-(((2-chloro-4-fluoro-5-(5-methyl-3-(trifluoromethyl)-1 H ethyl pyrazol-1-yl)benzylidene)amino)oxy)propionate, yield 58.03%.

[0028] Example 3: ( E )-2-(((2-chloro-4-fluoro-5-(5-methyl-3-(trifluoromethyl)-1 H The preparation method of propyl pyrazol-1-yl)benzylidene)amino)oxy)propionate (i.e., compound A3) includes the following steps: Steps (1)-(4): Same as steps (1)-(4) in Example 1; (5) E )-2-(((2-chloro-4-fluoro-5-(5-methyl-3-(trifluoromethyl)-1 H Preparation of propyl pyrazol-1-yl)benzylidene)amino)oxy)propionate: Pick( E )-2-chloro-4-fluoro-5-(5-methyl-3-(trifluoromethyl)-1 H 1-Pyrazole-1-yl)benzaldehyde oxime (200 mg, 622.99) µ Dissolve in 10 mL of DMF, add potassium carbonate (127.58 mg, 924.49 mol), and add potassium carbonate (924.49 mol). µ mol), stirred at room temperature for 30 minutes, then propyl 2-chloropropionate (105.48 mg, 700.86 mol) was added. µ The mixture was then reacted at room temperature for 6 hours. After the reaction was complete, it was poured into 40 mL of water, and the mixture was extracted with 40 mL of ethyl acetate. The organic layer was collected, dried over anhydrous Na2SO4, concentrated under reduced pressure, and the residue was obtained by column chromatography. E )-2-(((2-chloro-4-fluoro-5-(5-methyl-3-(trifluoromethyl)-1 H 1-Pyrazol-1-yl)benzylidene)amino)oxy)propyl propionate, yield 53.90%.

[0029] Example 4: ( E )-2-(((2-chloro-4-fluoro-5-(5-methyl-3-(trifluoromethyl)-1 HThe preparation method of 1-pyrazol-1-yl)benzyl)amino)oxy)butyl)propionate (i.e., compound A4) includes the following steps: Steps (1)-(4): Same as steps (1)-(4) in Example 1; (5) E )-2-(((2-chloro-4-fluoro-5-(5-methyl-3-(trifluoromethyl)-1 H Preparation of 1-pyrazole-1-yl)benzylidene)amino)oxy)butyl propionate: Pick( E )-2-chloro-4-fluoro-5-(5-methyl-3-(trifluoromethyl)-1 H 1-Pyrazole-1-yl)benzaldehyde oxime (200 mg, 622.99) µ Dissolve in 10 mL of DMF, add potassium carbonate (127.58 mg, 924.49 mol), and add potassium carbonate (924.49 mol). µ mol), stirred at room temperature for 30 minutes, then butyl 2-chloropropionate (115.29 mg, 700.86 mol) was added. µ The mixture was then reacted at room temperature for 6 hours. After the reaction was complete, it was poured into 40 mL of water, and the mixture was extracted with 40 mL of ethyl acetate. The organic layer was collected, dried over anhydrous Na2SO4, concentrated under reduced pressure, and the residue was obtained by column chromatography. E )-2-(((2-chloro-4-fluoro-5-(5-methyl-3-(trifluoromethyl)-1 H 1-Pyrazol-1-yl)benzylidene)amino)oxy)butyl propionate, yield 72.50%.

[0030] Example 5: ( E )-2-(((2-chloro-4-fluoro-5-(5-methyl-3-(trifluoromethyl)-1 H The preparation method of 1-pyrazol-1-yl)benzylidene)amino)oxy)pentyl propionate (i.e., compound A5) includes the following steps: Steps (1)-(4): Same as steps (1)-(4) in Example 1; (5) E )-2-(((2-chloro-4-fluoro-5-(5-methyl-3-(trifluoromethyl)-1 H Preparation of 1-pyrazol-1-yl)benzylidene)amino)oxy)pentyl propionate: Pick( E )-2-chloro-4-fluoro-5-(5-methyl-3-(trifluoromethyl)-1 H 1-Pyrazole-1-yl)benzaldehyde oxime (200 mg, 622.99) µ Dissolve in 10 mL of DMF, add potassium carbonate (127.58 mg, 924.49 mol), and add potassium carbonate (924.49 mol).µ mol), stirred at room temperature for 30 minutes, then added 125.10 mg of 2-chloropropionate (700.86 mol). µ The mixture was then reacted at room temperature for 6 hours. After the reaction was complete, it was poured into 40 mL of water, and the mixture was extracted with 40 mL of ethyl acetate. The organic layer was collected, dried over anhydrous Na2SO4, concentrated under reduced pressure, and the residue was obtained by column chromatography. E )-2-(((2-chloro-4-fluoro-5-(5-methyl-3-(trifluoromethyl)-1 H -pyrazol-1-yl)benzylidene)amino)oxy)amyl propionate, yield 61.20%. Example 6: ( E )-2-(((2-chloro-4-fluoro-5-(5-methyl-3-(trifluoromethyl)-1 H The preparation method of methyl pyrazol-1-yl)benzyl)amino)oxy)acetate (i.e., compound A6) includes the following steps: Steps (1)-(4): Same as steps (1)-(4) in Example 1; (5) E )-2-(((2-chloro-4-fluoro-5-(5-methyl-3-(trifluoromethyl)-1 H Preparation of methyl pyrazol-1-yl)benzylidene)amino)oxy)acetate: Pick( E )-2-chloro-4-fluoro-5-(5-methyl-3-(trifluoromethyl)-1 H 1-Pyrazole-1-yl)benzaldehyde oxime (200 mg, 622.99) µ Dissolve in 10 mL of DMF, add potassium carbonate (127.58 mg, 924.49 mol), and add potassium carbonate (924.49 mol). µ mol), stirred at room temperature for 30 minutes, then methyl 2-chloroacetate (76.04 mg, 700.86 mol) was added. µ The mixture was then reacted at room temperature for 6 hours. After the reaction was complete, it was poured into 40 mL of water, and the mixture was extracted with 40 mL of ethyl acetate. The organic layer was collected, dried over anhydrous Na2SO4, concentrated under reduced pressure, and the residue was obtained by column chromatography. E )-2-(((2-chloro-4-fluoro-5-(5-methyl-3-(trifluoromethyl)-1 H 1-Pyrazol-1-yl)benzyl)amino)oxy)methyl acetate, yield 74.60%. Example 7: ( E )-2-(((2-chloro-4-fluoro-5-(5-methyl-3-(trifluoromethyl)-1 H The preparation method of 1-pyrazol-1-yl)benzylidene)amino)oxy)ethyl acetate (i.e., compound A7) includes the following steps: Steps (1)-(4): Same as steps (1)-(4) in Example 1; (5) E )-2-(((2-chloro-4-fluoro-5-(5-methyl-3-(trifluoromethyl)-1 H Preparation of 1-pyrazol-1-yl)benzylidene)amino)oxy)ethyl acetate: Pick( E )-2-chloro-4-fluoro-5-(5-methyl-3-(trifluoromethyl)-1 H 1-Pyrazole-1-yl)benzaldehyde oxime (200 mg, 622.99) µ Dissolve in 10 mL of DMF, add potassium carbonate (127.58 mg, 924.49 mol), and add potassium carbonate (924.49 mol). µ mol), stirred at room temperature for 30 min, then added ethyl 2-chloroacetate (85.86 mg, 700.86 mol). µ The mixture was then reacted at room temperature for 6 hours. After the reaction was complete, it was poured into 40 mL of water, and the mixture was extracted with 40 mL of ethyl acetate. The organic layer was collected, dried over anhydrous Na2SO4, concentrated under reduced pressure, and the residue was obtained by column chromatography. E )-2-(((2-chloro-4-fluoro-5-(5-methyl-3-(trifluoromethyl)-1 H -pyrazol-1-yl)benzyl)amino)oxy)ethyl acetate, yield 74.60%. Example 8: ( E )-2-(((2-chloro-4-fluoro-5-(5-methyl-3-(trifluoromethyl)-1 H The preparation method of 1-pyrazol-1-yl)benzyl)amino)oxy)propyl acetate (i.e., compound A8) includes the following steps: Steps (1)-(4): Same as steps (1)-(4) in Example 1; (5) E )-2-(((2-chloro-4-fluoro-5-(5-methyl-3-(trifluoromethyl)-1 H Preparation of 1-pyrazol-1-yl)benzylidene)amino)oxy)propyl acetate: Pick( E )-2-chloro-4-fluoro-5-(5-methyl-3-(trifluoromethyl)-1 H 1-Pyrazole-1-yl)benzaldehyde oxime (200 mg, 622.99) µ Dissolve in 10 mL of DMF, add potassium carbonate (127.58 mg, 924.49 mol), and add potassium carbonate (924.49 mol). µ mol), stirred at room temperature for 30 minutes, then propyl 2-chloroacetate (95.67 mg, 700.86 mol) was added. µThe mixture was then reacted at room temperature for 6 hours. After the reaction was complete, it was poured into 40 mL of water, and the mixture was extracted with 40 mL of ethyl acetate. The organic layer was collected, dried over anhydrous Na2SO4, concentrated under reduced pressure, and the residue was obtained by column chromatography. E )-2-(((2-chloro-4-fluoro-5-(5-methyl-3-(trifluoromethyl)-1 H -pyrazol-1-yl)benzyl)amino)oxy)propyl acetate, yield 80.20%. Example 9: ( E )-2-(((2-chloro-4-fluoro-5-(5-methyl-3-(trifluoromethyl)-1 H The preparation method of 1-pyrazol-1-yl)benzyl)amino)oxy)butyl acetate (i.e., compound A9) includes the following steps: Steps (1)-(4): Same as steps (1)-(4) in Example 1; (5) E )-2-(((2-chloro-4-fluoro-5-(5-methyl-3-(trifluoromethyl)-1 H Preparation of 1-pyrazole-1-yl)benzylidene)amino)oxy)butyl acetate: Pick( E )-2-chloro-4-fluoro-5-(5-methyl-3-(trifluoromethyl)-1 H 1-Pyrazole-1-yl)benzaldehyde oxime (200 mg, 622.99) µ Dissolve in 10 mL of DMF, add potassium carbonate (127.58 mg, 924.49 mol), and add potassium carbonate (924.49 mol). µ mol), stirred at room temperature for 30 min, then butyl 2-chloroacetate (105.48 mg, 700.86 mol) was added. µ The mixture was then reacted at room temperature for 6 hours. After the reaction was complete, it was poured into 40 mL of water, and the mixture was extracted with 40 mL of ethyl acetate. The organic layer was collected, dried over anhydrous Na2SO4, concentrated under reduced pressure, and the residue was obtained by column chromatography. E )-2-(((2-chloro-4-fluoro-5-(5-methyl-3-(trifluoromethyl)-1 H 1-Pyrazol-1-yl)benzylidene)amino)oxy)butyl acetate, yield 60.80%.

[0031] Example 10: 3-(2-chloro-4-fluoro-5-(5-methyl-3-(trifluoromethyl)-1 H The preparation method of methyl pyrazol-1-yl)phenyl)-5-methyl-4,5-dihydroisoxazole-5-carboxylic acid (i.e., compound A10) includes the following steps: Steps (1)-(4): Same as steps (1)-(4) in Example 1; (5) 3-(2-chloro-4-fluoro-5-(5-methyl-3-(trifluoromethyl)-1 H Preparation of methyl pyrazol-1-yl)phenyl)-5-methyl-4,5-dihydroisoxazole-5-carboxylic acid: Take ( E )-2-chloro-4-fluoro-5-(5-methyl-3-(trifluoromethyl)-1 H 1-Pyrazole-1-yl)benzaldehyde oxime (200 mg, 622.99 mg) µ Dissolve 1 mol of the solution in 10 mL of DMF, heat to 35 °C, and add the following to the solution while stirring: N -Chlorosuccinimide (99.80 mg, 747.59 mg) µ After stirring continuously for 1 hour, the reaction solution was cooled to room temperature. Then, 10 mL of dichloromethane was added for extraction, and the organic phase was washed twice each with 1 mol / L hydrochloric acid and saturated brine. After drying with anhydrous Na₂SO₄ and filtering, the filtrate was cooled to 0–5 °C, and methyl methacrylate (93.45 mg, 934.49 mg) was slowly added dropwise. µ mol) and triethylamine (94.38 mg, 934.49 mg) µ (mol). After the reaction was complete, the mixture was extracted with 10 mL of water, the organic layers were combined, dried over anhydrous Na₂SO₄, concentrated by rotary evaporation, and column chromatography was performed to obtain 3-(2-chloro-4-fluoro-5-(5-methyl-3-(trifluoromethyl)-1 H 3-(pyrazol-1-yl)phenyl)-5-methyl-4,5-dihydroisoxazole-5-carboxylic acid methyl ester, yield 45.80%. Example 11: 3-(2-chloro-4-fluoro-5-(5-methyl-3-(trifluoromethyl)-1 H The preparation method of ethyl pyrazol-1-yl)phenyl)-5-methyl-4,5-dihydroisoxazole-5-carboxylate (i.e., compound A11) includes the following steps: Steps (1)-(4): Same as steps (1)-(4) in Example 1; (5) 3-(2-chloro-4-fluoro-5-(5-methyl-3-(trifluoromethyl)-1 H Preparation of ethyl pyrazol-1-yl)phenyl)-5-methyl-4,5-dihydroisoxazole-5-carboxylic acid: Take ( E )-2-chloro-4-fluoro-5-(5-methyl-3-(trifluoromethyl)-1 H 1-Pyrazole-1-yl)benzaldehyde oxime (200 mg, 622.99 mg) µ Dissolve 1 mol of the solution in 10 mL of DMF, heat to 35 °C, and add the following to the solution while stirring: N-Chlorosuccinimide (99.80 mg, 747.59 mg) µ After stirring continuously for 1 hour, the reaction solution was cooled to room temperature. Then, 10 mL of dichloromethane was added for extraction, and the organic phase was washed twice each with 1 mol / L hydrochloric acid and saturated brine. After drying with anhydrous Na₂SO₄ and filtering, the filtrate was cooled to 0–5 °C, and ethyl methacrylate (106.53 mg, 934.49 mg) was slowly added dropwise. µ mol) and triethylamine (94.38 mg, 934.49 mg) µ (mol). After the reaction was complete, the mixture was extracted with 10 mL of water, the organic layers were combined, dried over anhydrous Na₂SO₄, concentrated by rotary evaporation, and column chromatography was performed to obtain 3-(2-chloro-4-fluoro-5-(5-methyl-3-(trifluoromethyl)-1 H 3-(pyrazol-1-yl)phenyl)-5-methyl-4,5-dihydroisoxazole-5-carboxylic acid ethyl ester, yield 72.40%. Example 12: 3-(2-chloro-4-fluoro-5-(5-methyl-3-(trifluoromethyl)-1 H The preparation method of isopropyl pyrazol-1-yl)phenyl)-5-methyl-4,5-dihydroisoxazole-5-carboxylic acid (i.e., compound A12) includes the following steps: Steps (1)-(4): Same as steps (1)-(4) in Example 1; (5) 3-(2-chloro-4-fluoro-5-(5-methyl-3-(trifluoromethyl)-1 H Preparation of isopropyl pyrazol-1-yl)phenyl)-5-methyl-4,5-dihydroisoxazole-5-carboxylic acid: Take ( E )-2-chloro-4-fluoro-5-(5-methyl-3-(trifluoromethyl)-1 H 1-Pyrazole-1-yl)benzaldehyde oxime (200 mg, 622.99 mg) µ Dissolve 1 mol of the solution in 10 mL of DMF, heat to 35 °C, and add the following to the solution while stirring: N -Chlorosuccinimide (99.80 mg, 747.59 mg) µ After stirring continuously for 1 hour, the reaction solution was cooled to room temperature. Then, 10 mL of dichloromethane was added for extraction, and the organic phase was washed twice each with 1 mol / L hydrochloric acid and saturated brine. After drying with anhydrous Na₂SO₄ and filtering, the filtrate was cooled to 0–5 °C, and isopropyl methacrylate (119.61 mg, 934.49 mol) was slowly added dropwise. µ mol) and triethylamine (94.38 mg, 934.49 mg) µ(mol). After the reaction was complete, the mixture was extracted with 10 mL of water, the organic layers were combined, dried over anhydrous Na₂SO₄, concentrated by rotary evaporation, and column chromatography was performed to obtain 3-(2-chloro-4-fluoro-5-(5-methyl-3-(trifluoromethyl)-1 H -Pyrazol-1-yl)phenyl)-5-methyl-4,5-dihydroisoxazole-5-carboxylic acid isopropyl ester, yield 67.40%.

[0032] Example 13: 3-(2-chloro-4-fluoro-5-(5-methyl-3-(trifluoromethyl)-1 H The preparation method of 1-pyrazol-1-yl)phenyl)-5-methyl-4,5-dihydroisoxazole-5-carboxylic acid tert-butyl ester (i.e., compound A13) includes the following steps: Steps (1)-(4): Same as steps (1)-(4) in Example 1; (5) 3-(2-chloro-4-fluoro-5-(5-methyl-3-(trifluoromethyl)-1 H Preparation of tert-butyl pyrazol-1-yl)phenyl)-5-methyl-4,5-dihydroisoxazole-5-carboxylic acid: Take ( E )-2-chloro-4-fluoro-5-(5-methyl-3-(trifluoromethyl)-1 H 1-Pyrazole-1-yl)benzaldehyde oxime (200 mg, 622.99 mg) µ Dissolve 1 mol of the solution in 10 mL of DMF, heat to 35 °C, and add the following to the solution while stirring: N -Chlorosuccinimide (99.80 mg, 747.59 mg) µ After stirring continuously for 1 hour, the reaction solution was cooled to room temperature. Then, 10 mL of dichloromethane was added for extraction, and the organic phase was washed twice each with 1 mol / L hydrochloric acid and saturated brine. After drying with anhydrous Na₂SO₄ and filtering, the filtrate was cooled to 0–5 °C, and tert-butyl methacrylate (132.70 mg, 934.49 mg) was slowly added dropwise. µ mol) and triethylamine (94.38 mg, 934.49 mg) µ (mol). After the reaction was complete, the mixture was extracted with 10 mL of water, the organic layers were combined, dried over anhydrous Na₂SO₄, concentrated by rotary evaporation, and column chromatography was performed to obtain 3-(2-chloro-4-fluoro-5-(5-methyl-3-(trifluoromethyl)-1 H 5-Pyrazol-1-yl)phenyl)-5-methyl-4,5-dihydroisoxazole-5-carboxylic acid tert-butyl ester, yield 57.80%.

[0033] Example 14: 3-(2-chloro-4-fluoro-5-(5-methyl-3-(trifluoromethyl)-1 HThe preparation method of propyl pyrazol-1-yl)phenyl)-5-methyl-4,5-dihydroisoxazole-5-carboxylate (i.e., compound A14) includes the following steps: Steps (1)-(4): Same as steps (1)-(4) in Example 1; (5) 3-(2-chloro-4-fluoro-5-(5-methyl-3-(trifluoromethyl)-1 H Preparation of propyl 5-pyrazol-1-yl)phenyl)-5-methyl-4,5-dihydroisoxazole-5-carboxylate: Take ( E )-2-chloro-4-fluoro-5-(5-methyl-3-(trifluoromethyl)-1 H 1-Pyrazole-1-yl)benzaldehyde oxime (200 mg, 622.99 mg) µ Dissolve 1 mol of the solution in 10 mL of DMF, heat to 35 °C, and add the following to the solution while stirring: N -Chlorosuccinimide (99.80 mg, 747.59 mg) µ After stirring continuously for 1 hour, the reaction solution was cooled to room temperature. Then, 10 mL of dichloromethane was added for extraction, and the organic phase was washed twice each with 1 mol / L hydrochloric acid and saturated brine. After drying with anhydrous Na₂SO₄ and filtering, the filtrate was cooled to 0–5 °C, and propyl methacrylate (119.61 mg, 934.49 mol) was slowly added dropwise. µ mol) and triethylamine (94.38 mg, 934.49 mg) µ (mol). After the reaction was complete, the mixture was extracted with 10 mL of water, the organic layers were combined, dried over anhydrous Na₂SO₄, concentrated by rotary evaporation, and column chromatography was performed to obtain 3-(2-chloro-4-fluoro-5-(5-methyl-3-(trifluoromethyl)-1 H 4,5-Pyrazol-1-yl)phenyl)-5-methyl-4,5-dihydroisoxazole-5-carboxylic acid propyl ester, yield 46.50%.

[0034] Example 15: 3-(2-chloro-4-fluoro-5-(5-methyl-3-(trifluoromethyl)-1 H The preparation method of pyrazol-1-yl)phenyl)-5-methyl-4,5-dihydroisoxazole-5-carboxylic acid allyl ester (i.e., compound A15) includes the following steps: Steps (1)-(4): Same as steps (1)-(4) in Example 1; (5) 3-(2-chloro-4-fluoro-5-(5-methyl-3-(trifluoromethyl)-1 H Preparation of pyrazol-1-yl)phenyl)-5-methyl-4,5-dihydroisoxazole-5-carboxylic acid allyl ester: Take ( E)-2-chloro-4-fluoro-5-(5-methyl-3-(trifluoromethyl)-1 H 1-Pyrazole-1-yl)benzaldehyde oxime (200 mg, 622.99 mg) µ Dissolve 1 mol of the solution in 10 mL of DMF, heat to 35 °C, and add the following to the solution while stirring: N -Chlorosuccinimide (99.80 mg, 747.59 mg) µ After stirring continuously for 1 hour, the reaction solution was cooled to room temperature. Then, 10 mL of dichloromethane was added for extraction, and the organic phase was washed twice each with 1 mol / L hydrochloric acid and saturated brine. After drying with anhydrous Na₂SO₄ and filtering, the filtrate was cooled to 0–5 °C, and allyl methacrylate (117.75 mg, 934.49 mol) was slowly added dropwise. µ mol) and triethylamine (94.38 mg, 934.49 mg) µ (mol). After the reaction was complete, the mixture was extracted with 10 mL of water, the organic layers were combined, dried over anhydrous Na₂SO₄, concentrated by rotary evaporation, and column chromatography was performed to obtain 3-(2-chloro-4-fluoro-5-(5-methyl-3-(trifluoromethyl)-1 H -Pyrazol-1-yl)phenyl)-5-methyl-4,5-dihydroisoxazole-5-carboxylic acid allyl ester, yield 46.50%.

[0035] Example 16: 3-(2-chloro-4-fluoro-5-(5-methyl-3-(trifluoromethyl)-1 H The preparation method of 2-pyrazol-1-yl)phenyl)-5-methyl-4,5-dihydroisoxazole-5-carboxylic acid sec-butyl ester (i.e., compound A16) includes the following steps: Steps (1)-(4): Same as steps (1)-(4) in Example 1; (5) 3-(2-chloro-4-fluoro-5-(5-methyl-3-(trifluoromethyl)-1 H Preparation of sec-butyl pyrazol-1-yl)phenyl)-5-methyl-4,5-dihydroisoxazole-5-carboxylic acid: Take ( E )-2-chloro-4-fluoro-5-(5-methyl-3-(trifluoromethyl)-1 H 1-Pyrazole-1-yl)benzaldehyde oxime (200 mg, 622.99 mg) µ Dissolve 1 mol of the solution in 10 mL of DMF, heat to 35 °C, and add the following to the solution while stirring: N -Chlorosuccinimide (99.80 mg, 747.59 mg) µAfter stirring continuously for 1 hour, the reaction solution was cooled to room temperature. Then, 10 mL of dichloromethane was added for extraction, and the organic phase was washed twice each with 1 mol / L hydrochloric acid and saturated brine. After drying with anhydrous Na₂SO₄ and filtering, the filtrate was cooled to 0–5 °C, and sec-butyl methacrylate (132.70 mg, 934.49 mg) was slowly added dropwise. µ mol) and triethylamine (94.38 mg, 934.49 mg) µ (mol). After the reaction was complete, the mixture was extracted with 10 mL of water, the organic layers were combined, dried over anhydrous Na₂SO₄, concentrated by rotary evaporation, and column chromatography was performed to obtain 3-(2-chloro-4-fluoro-5-(5-methyl-3-(trifluoromethyl)-1 H 5-Pyrazol-1-yl)phenyl)-5-methyl-4,5-dihydroisoxazole-5-carboxylic acid sec-butyl ester, yield 55.70%.

[0036] Example 17: 3-(2-chloro-4-fluoro-5-(5-methyl-3-(trifluoromethyl)-1 H The preparation method of butyl pyrazol-1-yl)phenyl)-5-methyl-4,5-dihydroisoxazole-5-carboxylate (i.e., compound A17) includes the following steps: Steps (1)-(4): Same as steps (1)-(4) in Example 1; (5) 3-(2-chloro-4-fluoro-5-(5-methyl-3-(trifluoromethyl)-1 H Preparation of butyl 5-pyrazol-1-yl)phenyl)-5-methyl-4,5-dihydroisoxazole-5-carboxylate: Take ( E )-2-chloro-4-fluoro-5-(5-methyl-3-(trifluoromethyl)-1 H 1-Pyrazole-1-yl)benzaldehyde oxime (200 mg, 622.99 mg) µ Dissolve 1 mol of the solution in 10 mL of DMF, heat to 35 °C, and add the following to the solution while stirring: N -Chlorosuccinimide (99.80 mg, 747.59 mg) µ After stirring continuously for 1 hour, the reaction solution was cooled to room temperature. Then, 10 mL of dichloromethane was added for extraction, and the organic phase was washed twice each with 1 mol / L hydrochloric acid and saturated brine. After drying with anhydrous Na₂SO₄ and filtering, the filtrate was cooled to 0–5 °C, and butyl methacrylate (132.70 mg, 934.49 mg) was slowly added dropwise. µ mol) and triethylamine (94.38 mg, 934.49 mg) µ(mol). After the reaction was complete, the mixture was extracted with 10 mL of water, the organic layers were combined, dried over anhydrous Na₂SO₄, concentrated by rotary evaporation, and column chromatography was performed to obtain 3-(2-chloro-4-fluoro-5-(5-methyl-3-(trifluoromethyl)-1 H 1-Pyrazol-1-yl)phenyl)-5-methyl-4,5-dihydroisoxazole-5-carboxylate, yield 68.20%.

[0037] Example 18: 3-(2-chloro-4-fluoro-5-(5-methyl-3-(trifluoromethyl)-1 H The preparation method of 2-methoxyethyl pyrazol-1-yl)phenyl)-5-methyl-4,5-dihydroisoxazole-5-carboxylic acid (i.e., compound A18) includes the following steps: Steps (1)-(4): Same as steps (1)-(4) in Example 1; (5) 3-(2-chloro-4-fluoro-5-(5-methyl-3-(trifluoromethyl)-1 H Preparation of 2-methoxyethyl pyrazol-1-yl)phenyl)-5-methyl-4,5-dihydroisoxazole-5-carboxylic acid: Take ( E )-2-chloro-4-fluoro-5-(5-methyl-3-(trifluoromethyl)-1 H 1-Pyrazole-1-yl)benzaldehyde oxime (200 mg, 622.99 mg) µ Dissolve 1 mol of the solution in 10 mL of DMF, heat to 35 °C, and add the following to the solution while stirring: N -Chlorosuccinimide (99.80 mg, 747.59 mg) µ After stirring continuously for 1 hour, the reaction solution was cooled to room temperature. Then, 10 mL of dichloromethane was added for extraction, and the organic phase was washed twice each with 1 mol / L hydrochloric acid and saturated brine. After drying with anhydrous Na₂SO₄ and filtering, the filtrate was cooled to 0–5 °C, and methoxyethyl methacrylate (134.73 mg, 934.49 mol) was slowly added dropwise. µ mol) and triethylamine (94.38 mg, 934.49 mg) µ (mol). After the reaction was complete, the mixture was extracted with 10 mL of water, the organic layers were combined, dried over anhydrous Na₂SO₄, concentrated by rotary evaporation, and column chromatography was performed to obtain 3-(2-chloro-4-fluoro-5-(5-methyl-3-(trifluoromethyl)-1 H 2-Pyrazol-1-yl)phenyl)-5-methyl-4,5-dihydroisoxazole-5-carboxylic acid 2-methoxyethyl ester, yield 54.70%.

[0038] Example 19: 2,2,3,3-Tetrafluoropropyl 3-(2-chloro-4-fluoro-5-(5-methyl-3-(trifluoromethyl)-1H The preparation method of pyrazol-1-yl)phenyl)-5-methyl-4,5-dihydroisoxazole-5-carboxylic acid ester (i.e., compound A19) includes the following steps: Steps (1)-(4): Same as steps (1)-(4) in Example 1; (5) 2,2,3,3-Tetrafluoropropyl 3-(2-chloro-4-fluoro-5-(5-methyl-3-(trifluoromethyl)-1 H Preparation of pyrazol-1-yl)phenyl)-5-methyl-4,5-dihydroisoxazole-5-carboxylic acid ester: Take ( E )-2-chloro-4-fluoro-5-(5-methyl-3-(trifluoromethyl)-1 H 1-Pyrazole-1-yl)benzaldehyde oxime (200 mg, 622.99 mg) µ Dissolve 1 mol of the solution in 10 mL of DMF, heat to 35 °C, and add the following to the solution while stirring: N -Chlorosuccinimide (99.80 mg, 747.59 mg) µ After stirring continuously for 1 hour, the reaction solution was cooled to room temperature. Then, 10 mL of dichloromethane was added for extraction, and the organic phase was washed twice each with 1 mol / L hydrochloric acid and saturated brine. After drying with anhydrous Na₂SO₄ and filtering, the filtrate was cooled to 0–5 °C, and 2,2,3,3-tetrafluoropropyl methacrylate (187.02 mg, 934.49 mg) was slowly added dropwise. µ mol) and triethylamine (94.38 mg, 934.49 mg) µ (mol). After the reaction was complete, the mixture was extracted with 10 mL of water, the organic layers were combined, and the solution was concentrated by rotary evaporation using anhydrous Na₂SO₄. Column chromatography yielded 2,2,3,3-tetrafluoropropyl3-(2-chloro-4-fluoro-5-(5-methyl-3-(trifluoromethyl)-1 H -pyrazol-1-yl)phenyl)-5-methyl-4,5-dihydroisoxazole-5-carboxylic acid ester, yield 58.30%.

[0039] Example 20: 3-(2-chloro-4-fluoro-5-(5-methyl-3-(trifluoromethyl)-1 H The preparation method of cyclohexyl pyrazol-1-yl)phenyl)-5-methyl-4,5-dihydroisoxazole-5-carboxylic acid ester (i.e., compound A20) includes the following steps: Steps (1)-(4): Same as steps (1)-(4) in Example 1; (5) 3-(2-chloro-4-fluoro-5-(5-methyl-3-(trifluoromethyl)-1 HPreparation of cyclohexyl pyrazol-1-yl)phenyl)-5-methyl-4,5-dihydroisoxazole-5-carboxylic acid ester: Take ( E )-2-chloro-4-fluoro-5-(5-methyl-3-(trifluoromethyl)-1 H 1-Pyrazole-1-yl)benzaldehyde oxime (200 mg, 622.99 mg) µ Dissolve 1 mol of the solution in 10 mL of DMF, heat to 35 °C, and add the following to the solution while stirring: N -Chlorosuccinimide (99.80 mg, 747.59 mg) µ After stirring continuously for 1 hour, the reaction solution was cooled to room temperature. Then, 10 mL of dichloromethane was added for extraction, and the organic phase was washed twice each with 1 mol / L hydrochloric acid and saturated brine. After drying with anhydrous Na₂SO₄ and filtering, the filtrate was cooled to 0–5 °C, and cyclohexyl methacrylate (157.21 mg, 934.49 mol) was slowly added dropwise. µ mol) and triethylamine (94.38 mg, 934.49 mg) µ (mol). After the reaction was complete, the mixture was extracted with 10 mL of water, the organic layers were combined, dried over anhydrous Na₂SO₄, concentrated by rotary evaporation, and column chromatography was performed to obtain 3-(2-chloro-4-fluoro-5-(5-methyl-3-(trifluoromethyl)-1 H 5-Pyrazol-1-yl)phenyl)-5-methyl-4,5-dihydroisoxazole-5-carboxylic acid cyclohexyl ester, yield 53.80%.

[0040] Example 21: 3-(2-chloro-4-fluoro-5-(5-methyl-3-(trifluoromethyl)-1 H The preparation method of phenyl pyrazol-1-yl)phenyl)-5-methyl-4,5-dihydroisoxazole-5-carboxylic acid ester (i.e., compound A21) includes the following steps: Steps (1)-(4): Same as steps (1)-(4) in Example 1; (5) 3-(2-chloro-4-fluoro-5-(5-methyl-3-(trifluoromethyl)-1 H Preparation of phenyl pyrazol-1-yl)phenyl)-5-methyl-4,5-dihydroisoxazole-5-carboxylic acid ester: Take ( E )-2-chloro-4-fluoro-5-(5-methyl-3-(trifluoromethyl)-1 H 1-Pyrazole-1-yl)benzaldehyde oxime (200 mg, 622.99 mg) µ Dissolve 1 mol of the solution in 10 mL of DMF, heat to 35 °C, and add the following to the solution while stirring: N -Chlorosuccinimide (99.80 mg, 747.59 mg) µAfter stirring continuously for 1 hour, the reaction solution was cooled to room temperature. Then, 10 mL of dichloromethane was added for extraction, and the organic phase was washed twice each with 1 mol / L hydrochloric acid and saturated brine. After drying with anhydrous Na₂SO₄ and filtering, the filtrate was cooled to 0–5 °C, and phenyl methacrylate (151.56 mg, 934.49 mol) was slowly added dropwise. µ mol) and triethylamine (94.38 mg, 934.49 mg) µ (mol). After the reaction was complete, the mixture was extracted with 10 mL of water, the organic layers were combined, dried over anhydrous Na₂SO₄, concentrated by rotary evaporation, and column chromatography was performed to obtain 3-(2-chloro-4-fluoro-5-(5-methyl-3-(trifluoromethyl)-1 H -Pyrazol-1-yl)phenyl)-5-methyl-4,5-dihydroisoxazole-5-carboxylic acid phenyl ester, yield 55.50%.

[0041] Example 22: 3-(2,4-difluoro-5-(5-methyl-3-(trifluoromethyl)-1 H The preparation method of methyl pyrazol-1-yl)phenyl)-5-methyl-4,5-dihydroisoxazole-5-carboxylic acid (i.e., compound A22) includes the following steps: (1) Preparation of 2,4-difluoro-5-nitrobenzaldehyde: 2,4-Difluorobenzaldehyde (30.00 g, 211.24 mmol) was dissolved in concentrated sulfuric acid (200 mL) to form a solution, which was then cooled in an ice bath. Subsequently, concentrated nitric acid (16.64 g, 264.05 mmol) was added dropwise, and the reaction mixture was stirred for 30 minutes in an ice bath. The reaction mixture was then poured into ice (250 g) and stirred vigorously for 30 minutes. The precipitate was collected by filtration, washed with water, and then dried under vacuum to give 23.55 g of 2,4-difluoro-5-nitrobenzaldehyde intermediate, yield 78.50%. (2) Preparation of 5-amino-2,4-difluorobenzaldehyde: 2,4-Difluoro-5-nitrobenzaldehyde (23.55 g, 125.93 mmol), NH4Cl (20.21 g, 377.79 mmol), and EtOH (90%, 200 mL) were added to a flask, and the mixture was heated to 80 °C. Iron powder (21.16 g, 377.79 mmol) was then added in portions to the solution, and the reaction mixture was refluxed for 4 hours. After the reaction was complete, the hot reaction mixture was filtered through a diatomaceous earth mat. The residue was washed with ethyl acetate (100 mL), and H2O (200 mL) was added to the filtrate. The mixture was extracted with 200 mL of ethyl acetate, and the organic layers were combined. The residue was dried over anhydrous Na2SO4 and concentrated by rotary evaporation to obtain 18.32 g of 5-amino-2,4-difluorobenzaldehyde intermediate, with a yield of 77.80%. (3) E Preparation of 5-amino-2,4-difluorobenzaldehyde oxime: 5-Amino-2,4-difluorobenzaldehyde (18.32 g, 116.67 mmol), hydroxylamine hydrochloride (15.52 g, 223.34 mmol), and EtOH (80%, 200 mL) were added to a flask, and the mixture was heated to 80 °C. The reaction mixture was then refluxed for 4 hours. After the reaction was complete, the mixture was extracted with 200 mL of ethyl acetate and 200 mL of water. The organic layers were combined, dried over anhydrous Na₂SO₄, concentrated by rotary evaporation, and then subjected to column chromatography to obtain (…). E 15.68 g of 5-amino-2,4-difluorobenzaldehyde oxime intermediate, yield 85.60%; (4) E )-2,4-difluoro-5-(5-methyl-3-(trifluoromethyl)-1 H Preparation of 1-pyrazole-1-yl)benzaldehyde oxime: Will( E 5-Amino-2,4-difluorobenzaldehyde oxime (15.68 g, 91.14 mmol) was dissolved in DMF (150 mL), followed by the addition of 1,1,1-trifluoro-2,4-pentanedione (15.05 g, 100.25 mmol) and... O -(diphenylphosphono)hydroxylamine (31.88 g, 136.71 mmol), heated to 85 °C. The reaction was continued for 4 hours. After completion, the reaction mixture was poured into 200 mL of H₂O and extracted with 200 mL of ethyl acetate. The combined organic phases were dried over anhydrous Na₂SO₄ and then concentrated under reduced pressure. Column chromatography yielded (… E )-2,4-difluoro-5-(5-methyl-3-(trifluoromethyl)-1 H 9.24 g of pyrazole-1-yl)benzaldehyde oxime intermediate, yield 58.90%; (5) 3-(2,4-difluoro-5-(5-methyl-3-(trifluoromethyl)-1 H Preparation of methyl pyrazol-1-yl)phenyl)-5-methyl-4,5-dihydroisoxazole-5-carboxylic acid: Take ( E )-2,4-difluoro-5-(5-methyl-3-(trifluoromethyl)-1 H 1-Pyrazole-1-yl)benzaldehyde oxime (200 mg, 655.61 mg) µ Dissolve 1 mol of the solution in 10 mL of DMF, heat to 35 °C, and add the following to the solution while stirring: N -Chlorosuccinimide (105.03 mg, 786.73 mg) µ After stirring continuously for 1 hour, the reaction solution was cooled to room temperature. Then, 10 mL of dichloromethane was added for extraction, and the organic phase was washed twice each with 1 mol / L hydrochloric acid and saturated brine. After drying with anhydrous Na₂SO₄ and filtering, the filtrate was cooled to 0–5 °C, and methyl methacrylate (98.34 mg, 983.42 mg) was slowly added dropwise. µ mol) and triethylamine (79.46 mg, 983.42 mg) µ (mol). After the reaction was complete, the mixture was extracted with 10 mL of water, the organic layers were combined, dried over anhydrous Na₂SO₄, concentrated by rotary evaporation, and column chromatography was performed to obtain 3-(2,4-difluoro-5-(5-methyl-3-(trifluoromethyl)-1 H 5-Pyrazol-1-yl)phenyl)-5-methyl-4,5-dihydroisoxazole-5-carboxylic acid methyl ester, yield 54.70%.

[0042] Example 23: 3-(2,4-difluoro-5-(5-methyl-3-(trifluoromethyl)-1 H The preparation method of ethyl pyrazol-1-yl)phenyl)-5-methyl-4,5-dihydroisoxazole-5-carboxylate (i.e., compound A23) includes the following steps: Steps (1)-(4): Same as steps (1)-(4) in Example 22; (5) 3-(2,4-difluoro-5-(5-methyl-3-(trifluoromethyl)-1 H Preparation of ethyl pyrazol-1-yl)phenyl)-5-methyl-4,5-dihydroisoxazole-5-carboxylic acid: Take ( E )-2,4-difluoro-5-(5-methyl-3-(trifluoromethyl)-1 H 1-Pyrazole-1-yl)benzaldehyde oxime (200 mg, 655.61 mg) µDissolve 1 mol of the solution in 10 mL of DMF, heat to 35 °C, and add the following to the solution while stirring: N -Chlorosuccinimide (105.03 mg, 786.73 mg) µ After stirring continuously for 1 hour, the reaction solution was cooled to room temperature. Then, 10 mL of dichloromethane was added for extraction, and the organic phase was washed twice each with 1 mol / L hydrochloric acid and saturated brine. After drying with anhydrous Na₂SO₄ and filtering, the filtrate was cooled to 0–5 °C, and ethyl methacrylate (112.12 mg, 983.42 mg) was slowly added dropwise. µ mol) and triethylamine (79.46 mg, 983.42 mg) µ (mol). After the reaction was complete, the mixture was extracted with 10 mL of water, the organic layers were combined, dried over anhydrous Na₂SO₄, concentrated by rotary evaporation, and column chromatography was performed to obtain 3-(2,4-difluoro-5-(5-methyl-3-(trifluoromethyl)-1 H 5-Pyrazol-1-yl)phenyl)-5-methyl-4,5-dihydroisoxazole-5-carboxylic acid ethyl ester, yield 58.60%.

[0043] Example 24: 3-(2,4-difluoro-5-(5-methyl-3-(trifluoromethyl)-1 H The preparation method of propyl pyrazol-1-yl)phenyl)-5-methyl-4,5-dihydroisoxazole-5-carboxylate (i.e., compound A24) includes the following steps: Steps (1)-(4): Same as steps (1)-(4) in Example 22; (5) 3-(2,4-difluoro-5-(5-methyl-3-(trifluoromethyl)-1 H Preparation of propyl 5-pyrazol-1-yl)phenyl)-5-methyl-4,5-dihydroisoxazole-5-carboxylate: Take ( E )-2,4-difluoro-5-(5-methyl-3-(trifluoromethyl)-1 H 1-Pyrazole-1-yl)benzaldehyde oxime (200 mg, 655.61 mg) µ Dissolve 1 mol of the solution in 10 mL of DMF, heat to 35 °C, and add the following to the solution while stirring: N -Chlorosuccinimide (105.03 mg, 786.73 mg) µ After stirring continuously for 1 hour, the reaction solution was cooled to room temperature. Then, 10 mL of dichloromethane was added for extraction, and the organic phase was washed twice each with 1 mol / L hydrochloric acid and saturated brine. After drying with anhydrous Na₂SO₄ and filtering, the filtrate was cooled to 0–5 °C, and propyl methacrylate (125.88 mg, 983.42 mol) was slowly added dropwise. µmol) and triethylamine (79.46 mg, 983.42 mg) µ (mol). After the reaction was complete, the mixture was extracted with 10 mL of water, the organic layers were combined, dried over anhydrous Na₂SO₄, concentrated by rotary evaporation, and column chromatography was performed to obtain 3-(2,4-difluoro-5-(5-methyl-3-(trifluoromethyl)-1 H 5-Pyrazol-1-yl)phenyl)-5-methyl-4,5-dihydroisoxazole-5-carboxylic acid propyl ester, yield 64.50%.

[0044] Example 25: 3-(2,4-difluoro-5-(5-methyl-3-(trifluoromethyl)-1 H The preparation method of pyrazol-1-yl)phenyl)-5-methyl-4,5-dihydroisoxazole-5-carboxylic acid allyl ester (i.e., compound A25) includes the following steps: Steps (1)-(4): Same as steps (1)-(4) in Example 22; (5) 3-(2,4-difluoro-5-(5-methyl-3-(trifluoromethyl)-1 H Preparation of pyrazol-1-yl)phenyl)-5-methyl-4,5-dihydroisoxazole-5-carboxylic acid allyl ester: Take ( E )-2,4-difluoro-5-(5-methyl-3-(trifluoromethyl)-1 H 1-Pyrazole-1-yl)benzaldehyde oxime (200 mg, 655.61 mg) µ Dissolve 1 mol of the solution in 10 mL of DMF, heat to 35 °C, and add the following to the solution while stirring: N -Chlorosuccinimide (105.03 mg, 786.73 mg) µ After stirring continuously for 1 hour, the reaction solution was cooled to room temperature. Then, 10 mL of dichloromethane was added for extraction, and the organic phase was washed twice each with 1 mol / L hydrochloric acid and saturated brine. After drying with anhydrous Na₂SO₄ and filtering, the filtrate was cooled to 0–5 °C, and allyl methacrylate (123.91 mg, 983.42 mg) was slowly added dropwise. µ mol) and triethylamine (79.46 mg, 983.42 mg) µ (mol). After the reaction was complete, the mixture was extracted with 10 mL of water, the organic layers were combined, dried over anhydrous Na₂SO₄, concentrated by rotary evaporation, and column chromatography was performed to obtain 3-(2,4-difluoro-5-(5-methyl-3-(trifluoromethyl)-1 H -Pyrazol-1-yl)phenyl)-5-methyl-4,5-dihydroisoxazole-5-carboxylic acid allyl ester, yield 54.40%.

[0045] Example 26: 3-(4-chloro-2-fluoro-5-(5-methyl-3-(trifluoromethyl)-1 H The preparation method of methyl pyrazol-1-yl)phenyl)-5-methyl-4,5-dihydroisoxazole-5-carboxylic acid (i.e., compound A26) includes the following steps: (1) Preparation of 4-chloro-2-fluoro-5-nitrobenzaldehyde: 4-Chloro-2-fluorobenzaldehyde (30.00 g, 189.88 mmol) was dissolved in concentrated sulfuric acid (200 mL) to form a solution, which was then cooled in an ice bath. Subsequently, concentrated nitric acid (14.95 g, 237.35 mmol) was added dropwise, and the reaction mixture was stirred for 30 minutes in an ice bath. The reaction mixture was then poured into ice (250 g) and stirred vigorously for 30 minutes. The precipitate was collected by filtration, washed with water, and then dried under vacuum to give 24.06 g of 4-chloro-2-fluoro-5-nitrobenzaldehyde intermediate, yield 80.20%. (2) Preparation of 5-amino-4-chloro-2-fluorobenzaldehyde: 24.06 g (139.08 mmol) of 4-chloro-2-fluoro-5-nitrobenzaldehyde, 22.32 g (417.24 mmol) of NH4Cl, and 90% (200 mL) of EtOH were added to a flask, and the mixture was heated to 80 °C. Iron powder (26.29 g, 417.24 mmol) was then added in portions to the solution, and the reaction mixture was refluxed for 4 hours. After the reaction was complete, the hot reaction mixture was filtered through a diatomaceous earth mat, and the residue was washed with 100 mL of ethyl acetate. 200 mL of H2O was added to the filtrate, and the mixture was extracted with 200 mL of ethyl acetate. The organic layers were combined, dried over anhydrous Na2SO4, and concentrated by rotary evaporation to obtain 18.14 g of 5-amino-4-chloro-2-fluorobenzaldehyde intermediate, with a yield of 75.40%. (3) E Preparation of 5-amino-4-chloro-2-fluorobenzaldehyde oxime: 5-Amino-4-chloro-2-fluorobenzaldehyde (18.14 g, 104.86 mmol), hydroxylamine hydrochloride (14.58 g, 209.72 mmol), and EtOH (80%, 200 mL) were added to a flask, and the mixture was heated to 80 °C. The reaction mixture was then refluxed for 4 hours. After the reaction was complete, the mixture was extracted with 200 mL of ethyl acetate and 200 mL of water. The combined organic layers were concentrated by rotary evaporation over anhydrous Na₂SO₄ and then subjected to column chromatography to obtain (…). E 14.53 g of 5-amino-4-chloro-2-fluorobenzaldehyde oxime intermediate, yield 80.10%; (4) E)-4-chloro-2-fluoro-5-(5-methyl-3-(trifluoromethyl)-1 H Preparation of 1-pyrazole-1-yl)benzaldehyde oxime: Will( E 5-Amino-4-chloro-2-fluorobenzaldehyde oxime (14.53 g, 77.28 mmol) was dissolved in DMF (150 mL), followed by the addition of 1,1,1-trifluoro-2,4-pentanedione (13.01 g, 85.01 mmol) and... O -(diphenylphosphono)hydroxylamine (25.87 g, 115.92 mmol), heated to 85 °C. The reaction was continued for 4 hours. After the reaction was complete, the reaction mixture was poured into 200 mL of H₂O and extracted with 200 mL of ethyl acetate. The combined organic phases were dried over anhydrous Na₂SO₄ and then concentrated under reduced pressure. Column chromatography yielded (… E )-4-chloro-2-fluoro-5-(5-methyl-3-(trifluoromethyl)-1 H 9.24 g of pyrazole-1-yl)benzaldehyde oxime intermediate, yield 58.90%; (5) 3-(4-chloro-2-fluoro-5-(5-methyl-3-(trifluoromethyl)-1 H Preparation of methyl pyrazol-1-yl)phenyl)-5-methyl-4,5-dihydroisoxazole-5-carboxylic acid: Take ( E )-4-chloro-2-fluoro-5-(5-methyl-3-(trifluoromethyl)-1 H 1-Pyrazole-1-yl)benzaldehyde oxime (200 mg, 622.99 mg) µ Dissolve 1 mol of the solution in 10 mL of DMF, heat to 35 °C, and add the following to the solution while stirring: N -Chlorosuccinimide (105.03 mg, 747.59 mg) µ After stirring continuously for 1 hour, the reaction solution was cooled to room temperature. Then, 10 mL of dichloromethane was added for extraction, and the organic phase was washed twice each with 1 mol / L hydrochloric acid and saturated brine. After drying with anhydrous Na₂SO₄ and filtering, the filtrate was cooled to 0–5 °C, and methyl methacrylate (93.45 mg, 934.49 mg) was slowly added dropwise. µ mol) and triethylamine (94.38 mg, 934.49 mg) µ (mol). After the reaction was complete, the mixture was extracted with 10 mL of water, the organic layers were combined, dried over anhydrous Na₂SO₄, concentrated by rotary evaporation, and column chromatography was performed to obtain 3-(4-chloro-2-fluoro-5-(5-methyl-3-(trifluoromethyl)-1 H 4,5-Dihydroisoxazole-5-carboxylic acid methyl ester, yield 43.60%.

[0046] Example 27: 3-(4-chloro-2-fluoro-5-(5-methyl-3-(trifluoromethyl)-1 H The preparation method of ethyl pyrazol-1-yl)phenyl)-5-methyl-4,5-dihydroisoxazole-5-carboxylate (i.e., compound A27) includes the following steps: Steps (1)-(4): Same as steps (1)-(4) in Example 26; (5) 3-(4-chloro-2-fluoro-5-(5-methyl-3-(trifluoromethyl)-1 H Preparation of ethyl pyrazol-1-yl)phenyl)-5-methyl-4,5-dihydroisoxazole-5-carboxylic acid: Take ( E )-4-chloro-2-fluoro-5-(5-methyl-3-(trifluoromethyl)-1 H 1-Pyrazole-1-yl)benzaldehyde oxime (200 mg, 622.99 mg) µ Dissolve 1 mol of the solution in 10 mL of DMF, heat to 35 °C, and add the following to the solution while stirring: N -Chlorosuccinimide (105.03 mg, 747.59 mg) µ After stirring continuously for 1 hour, the reaction solution was cooled to room temperature. Then, 10 mL of dichloromethane was added for extraction, and the organic phase was washed twice each with 1 mol / L hydrochloric acid and saturated brine. After drying with anhydrous Na₂SO₄ and filtering, the filtrate was cooled to 0–5 °C, and ethyl methacrylate (106.53 mg, 934.49 mg) was slowly added dropwise. µ mol) and triethylamine (94.38 mg, 934.49 mg) µ (mol). After the reaction was complete, the mixture was extracted with 10 mL of water, the organic layers were combined, dried over anhydrous Na₂SO₄, concentrated by rotary evaporation, and column chromatography was performed to obtain 3-(4-chloro-2-fluoro-5-(5-methyl-3-(trifluoromethyl)-1 H 4,5-Dihydroisoxazole-5-carboxylic acid ethyl ester, yield 45.70%.

[0047] Example 28: 3-(4-chloro-2-fluoro-5-(5-methyl-3-(trifluoromethyl)-1 H The preparation method of propyl pyrazol-1-yl)phenyl)-5-methyl-4,5-dihydroisoxazole-5-carboxylate (i.e., compound A28) includes the following steps: Steps (1)-(4): Same as steps (1)-(4) in Example 26; (5) 3-(4-chloro-2-fluoro-5-(5-methyl-3-(trifluoromethyl)-1 HPreparation of propyl 5-pyrazol-1-yl)phenyl)-5-methyl-4,5-dihydroisoxazole-5-carboxylate: Take ( E )-4-chloro-2-fluoro-5-(5-methyl-3-(trifluoromethyl)-1 H 1-Pyrazole-1-yl)benzaldehyde oxime (200 mg, 622.99 mg) µ Dissolve 1 mol of the solution in 10 mL of DMF, heat to 35 °C, and add the following to the solution while stirring: N -Chlorosuccinimide (105.03 mg, 747.59 mg) µ After stirring continuously for 1 hour, the reaction solution was cooled to room temperature. Then, 10 mL of dichloromethane was added for extraction, and the organic phase was washed twice each with 1 mol / L hydrochloric acid and saturated brine. After drying with anhydrous Na₂SO₄ and filtering, the filtrate was cooled to 0–5 °C, and propyl methacrylate (119.61 mg, 934.49 mol) was slowly added dropwise. µ mol) and triethylamine (94.38 mg, 934.49 mg) µ (mol). After the reaction was complete, the mixture was extracted with 10 mL of water, the organic layers were combined, dried over anhydrous Na₂SO₄, concentrated by rotary evaporation, and column chromatography was performed to obtain 3-(4-chloro-2-fluoro-5-(5-methyl-3-(trifluoromethyl)-1 H 4,5-Pyrazol-1-yl)phenyl)-5-methyl-4,5-dihydroisoxazole-5-carboxylic acid propyl ester, yield 48.50%.

[0048] Example 29: 3-(4-chloro-2-fluoro-5-(5-methyl-3-(trifluoromethyl)-1 H The preparation method of pyrazol-1-yl)phenyl)-5-methyl-4,5-dihydroisoxazole-5-carboxylic acid allyl ester (i.e., compound A29) includes the following steps: Steps (1)-(4): Same as steps (1)-(4) in Example 26; (5) 3-(4-chloro-2-fluoro-5-(5-methyl-3-(trifluoromethyl)-1 H Preparation of pyrazol-1-yl)phenyl)-5-methyl-4,5-dihydroisoxazole-5-carboxylic acid allyl ester: Take ( E )-4-chloro-2-fluoro-5-(5-methyl-3-(trifluoromethyl)-1 H 1-Pyrazole-1-yl)benzaldehyde oxime (200 mg, 622.99 mg) µ Dissolve 1 mol of the solution in 10 mL of DMF, heat to 35 °C, and add the following to the solution while stirring: N -Chlorosuccinimide (105.03 mg, 747.59 mg)µ After stirring continuously for 1 hour, the reaction solution was cooled to room temperature. Then, 10 mL of dichloromethane was added for extraction, and the organic phase was washed twice each with 1 mol / L hydrochloric acid and saturated brine. After drying with anhydrous Na₂SO₄ and filtering, the filtrate was cooled to 0–5 °C, and allyl methacrylate (117.75 mg, 934.49 mol) was slowly added dropwise. µ mol) and triethylamine (94.38 mg, 934.49 mg) µ (mol). After the reaction was complete, the mixture was extracted with 10 mL of water, the organic layers were combined, dried over anhydrous Na₂SO₄, concentrated by rotary evaporation, and column chromatography was performed to obtain 3-(4-chloro-2-fluoro-5-(5-methyl-3-(trifluoromethyl)-1 H -Pyrazol-1-yl)phenyl)-5-methyl-4,5-dihydroisoxazole-5-carboxylic acid allyl ester, yield 50.60%.

[0049] Example 30: 3-(2,4-dichloro-5-(5-methyl-3-(trifluoromethyl)-1 H The preparation method of methyl pyrazol-1-yl)phenyl)-5-methyl-4,5-dihydroisoxazole-5-carboxylic acid (i.e., compound A30) includes the following steps: (1) Preparation of 2,4-dichloro-5-nitrobenzaldehyde: 2,4-Dichlorobenzaldehyde (30.00 g, 172.45 mmol) was dissolved in concentrated sulfuric acid (200 mL) to form a solution, which was then cooled in an ice bath. Subsequently, concentrated nitric acid (14.95 g, 215.56 mmol) was added dropwise, and the reaction mixture was stirred for 30 minutes in an ice bath. The reaction mixture was then poured into ice (250 g) and stirred vigorously for 30 minutes. The precipitate was collected by filtration, washed with water, and then dried under vacuum to give 22.71 g of 2,4-dichloro-5-nitrobenzaldehyde intermediate, yield 75.70%. (2) Preparation of 5-amino-2,4-dichlorobenzaldehyde: 2,4-Dichloro-5-nitrobenzaldehyde (22.71 g, 103.72 mmol), NH4Cl (16.65 g, 311.16 mmol), and EtOH (90%, 200 mL) were added to a flask, and the mixture was heated to 80 °C. Iron powder (17.42 g, 311.16 mmol) was then added in portions to the solution, and the reaction mixture was refluxed for 4 hours. After the reaction was complete, the hot reaction mixture was filtered through a diatomaceous earth mat. The residue was washed with ethyl acetate (100 mL), and H2O (200 mL) was added to the filtrate. The mixture was extracted with 200 mL of ethyl acetate, and the organic layers were combined. The extract was concentrated by rotary evaporation after drying with anhydrous Na2SO4 to obtain 17.53 g of 5-amino-2,4-dichlorobenzaldehyde intermediate, with a yield of 77.20%. (3) E Preparation of 5-amino-2,4-dichlorobenzaldehyde oxime: 5-Amino-2,4-dichlorobenzaldehyde (17.53 g, 92.77 mmol), hydroxylamine hydrochloride (12.90 g, 185.54 mmol), and EtOH (80%, 200 mL) were added to a flask, and the mixture was heated to 80 °C. The reaction mixture was then refluxed for 4 hours. After the reaction was complete, the mixture was extracted with 200 mL of ethyl acetate and 200 mL of water. The organic layers were combined, dried over anhydrous Na₂SO₄, concentrated by rotary evaporation, and then subjected to column chromatography to obtain (…). E 13.78 g of 5-amino-2,4-dichlorobenzaldehyde oxime intermediate, yield 78.60%; (4) E )-2,4-dichloro-5-(5-methyl-3-(trifluoromethyl)-1 H Preparation of 1-pyrazole-1-yl)benzaldehyde oxime: Will( E 5-Amino-2,4-dichlorobenzaldehyde oxime (13.78 g, 67.55 mmol) was dissolved in DMF (150 mL), followed by the addition of 1,1,1-trifluoro-2,4-pentanedione (11.45 g, 74.31 mmol) and... O -(diphenylphosphono)hydroxylamine (23.64 g, 101.33 mmol), heated to 85 °C. The reaction was continued for 4 hours. After the reaction was complete, the reaction mixture was poured into 200 mL of H₂O and extracted with 200 mL of ethyl acetate. The combined organic phases were dried over anhydrous Na₂SO₄ and then concentrated under reduced pressure. Column chromatography yielded (… E )-2,4-dichloro-5-(5-methyl-3-(trifluoromethyl)-1 H 8.61 g of pyrazole-1-yl)benzaldehyde oxime intermediate, yield 62.50%; (5) 3-(2,4-dichloro-5-(5-methyl-3-(trifluoromethyl)-1 H Preparation of methyl pyrazol-1-yl)phenyl)-5-methyl-4,5-dihydroisoxazole-5-carboxylic acid: Take ( E )-2,4-dichloro-5-(5-methyl-3-(trifluoromethyl)-1 H 1-Pyrazole-1-yl)benzaldehyde oxime (200 mg, 593.47) µ Dissolve 1 mol of the solution in 10 mL of DMF, heat to 35 °C, and add the following to the solution while stirring: N -Chlorosuccinimide (95.07 mg, 712.16 mg) µ After stirring continuously for 1 hour, the reaction solution was cooled to room temperature. Then, 10 mL of dichloromethane was added for extraction, and the organic phase was washed twice each with 1 mol / L hydrochloric acid and saturated brine. After drying with anhydrous Na₂SO₄ and filtering, the filtrate was cooled to 0–5 °C, and methyl methacrylate (89.02 mg, 890.21 mg) was slowly added dropwise. µ mol) and triethylamine (89.91 mg, 890.21 mg) µ (mol). After the reaction was complete, the mixture was extracted with 10 mL of water, the organic layers were combined, dried over anhydrous Na₂SO₄, concentrated by rotary evaporation, and column chromatography was performed to obtain 3-(2,4-dichloro-5-(5-methyl-3-(trifluoromethyl)-1 H 5-Pyrazol-1-yl)phenyl)-5-methyl-4,5-dihydroisoxazole-5-carboxylic acid methyl ester, yield 56.50%.

[0050] Example 31: 3-(2,4-dichloro-5-(5-methyl-3-(trifluoromethyl)-1 H The preparation method of ethyl pyrazol-1-yl)phenyl)-5-methyl-4,5-dihydroisoxazole-5-carboxylate (i.e., compound A31) includes the following steps: Steps (1)-(4): Same as steps (1)-(4) of Example 30; (5) 3-(2,4-dichloro-5-(5-methyl-3-(trifluoromethyl)-1 H Preparation of ethyl pyrazol-1-yl)phenyl)-5-methyl-4,5-dihydroisoxazole-5-carboxylic acid: Take ( E )-2,4-dichloro-5-(5-methyl-3-(trifluoromethyl)-1 H 1-Pyrazole-1-yl)benzaldehyde oxime (200 mg, 593.47) µ Dissolve 1 mol of the solution in 10 mL of DMF, heat to 35 °C, and add the following to the solution while stirring:N -Chlorosuccinimide (95.07 mg, 712.16 mg) µ After stirring continuously for 1 hour, the reaction solution was cooled to room temperature. Then, 10 mL of dichloromethane was added for extraction, and the organic phase was washed twice each with 1 mol / L hydrochloric acid and saturated brine. After drying with anhydrous Na₂SO₄ and filtering, the filtrate was cooled to 0–5 °C, and ethyl methacrylate (101.48 mg, 890.21 mg) was slowly added dropwise. µ mol) and triethylamine (89.91 mg, 890.21 mg) µ (mol). After the reaction was complete, the mixture was extracted with 10 mL of water, the organic layers were combined, dried over anhydrous Na₂SO₄, concentrated by rotary evaporation, and column chromatography was performed to obtain 3-(2,4-dichloro-5-(5-methyl-3-(trifluoromethyl)-1 H 4,5-Dihydroisoxazole-5-carboxylic acid ethyl ester, yield 44.80%.

[0051] Example 32: 3-(2,4-dichloro-5-(5-methyl-3-(trifluoromethyl)-1 H The preparation method of propyl pyrazol-1-yl)phenyl)-5-methyl-4,5-dihydroisoxazole-5-carboxylate (i.e., compound A32) includes the following steps: Steps (1)-(4): Same as steps (1)-(4) of Example 30; (5) 3-(2,4-dichloro-5-(5-methyl-3-(trifluoromethyl)-1 H Preparation of propyl 5-pyrazol-1-yl)phenyl)-5-methyl-4,5-dihydroisoxazole-5-carboxylate: Take ( E )-2,4-dichloro-5-(5-methyl-3-(trifluoromethyl)-1 H 1-Pyrazole-1-yl)benzaldehyde oxime (200 mg, 593.47) µ Dissolve 1 mol of the solution in 10 mL of DMF, heat to 35 °C, and add the following to the solution while stirring: N -Chlorosuccinimide (95.07 mg, 712.16 mg) µ After stirring continuously for 1 hour, the reaction solution was cooled to room temperature. Then, 10 mL of dichloromethane was added for extraction, and the organic phase was washed twice each with 1 mol / L hydrochloric acid and saturated brine. After drying with anhydrous Na₂SO₄ and filtering, the filtrate was cooled to 0–5 °C, and propyl methacrylate (113.95 mg, 890.21 mol) was slowly added dropwise. µ mol) and triethylamine (89.91 mg, 890.21 mg) µ(mol). After the reaction was complete, the mixture was extracted with 10 mL of water, the organic layers were combined, dried over anhydrous Na₂SO₄, concentrated by rotary evaporation, and column chromatography was performed to obtain 3-(2,4-dichloro-5-(5-methyl-3-(trifluoromethyl)-1 H 5-Pyrazol-1-yl)phenyl)-5-methyl-4,5-dihydroisoxazole-5-carboxylic acid propyl ester, yield 52.50%.

[0052] Example 33: 3-(2,4-dichloro-5-(5-methyl-3-(trifluoromethyl)-1 H The preparation method of pyrazol-1-yl)phenyl)-5-methyl-4,5-dihydroisoxazole-5-carboxylic acid allyl ester (i.e., compound A33) includes the following steps: Steps (1)-(4): Same as steps (1)-(4) of Example 30; (5) 3-(2,4-dichloro-5-(5-methyl-3-(trifluoromethyl)-1 H Preparation of pyrazol-1-yl)phenyl)-5-methyl-4,5-dihydroisoxazole-5-carboxylic acid allyl ester: Take ( E )-2,4-dichloro-5-(5-methyl-3-(trifluoromethyl)-1 H 1-Pyrazole-1-yl)benzaldehyde oxime (200 mg, 593.47) µ Dissolve 1 mol of the solution in 10 mL of DMF, heat to 35 °C, and add the following to the solution while stirring: N -Chlorosuccinimide (95.07 mg, 712.16 mg) µ After stirring continuously for 1 hour, the reaction solution was cooled to room temperature. Then, 10 mL of dichloromethane was added for extraction, and the organic phase was washed twice each with 1 mol / L hydrochloric acid and saturated brine. After drying with anhydrous Na₂SO₄ and filtering, the filtrate was cooled to 0–5 °C, and allyl methacrylate (112.17 mg, 890.21 mg) was slowly added dropwise. µ mol) and triethylamine (89.91 mg, 890.21 mg) µ (mol). After the reaction was complete, the mixture was extracted with 10 mL of water, the organic layers were combined, dried over anhydrous Na₂SO₄, concentrated by rotary evaporation, and column chromatography was performed to obtain 3-(2,4-dichloro-5-(5-methyl-3-(trifluoromethyl)-1 H -Pyrazol-1-yl)phenyl)-5-methyl-4,5-dihydroisoxazole-5-carboxylic acid allyl ester, yield 54.60%.

[0053] Example 34: 3-(2-chloro-4-fluoro-5-(5-methyl-3-(trifluoromethyl)-1 HThe preparation method of methyl pyrazol-1-yl)phenyl)-5-methyl-4,5-dihydroisoxazole-5-thiocarboxylate (i.e., compound A34) includes the following steps: Steps (1)-(4): Same as steps (1)-(4) in Example 1; (5) 3-(2-chloro-4-fluoro-5-(5-methyl-3-(trifluoromethyl)-1 H Preparation of methyl pyrazol-1-yl)phenyl)-5-methyl-4,5-dihydroisoxazole-5-thiocarboxylic acid: Take ( E )-2-chloro-4-fluoro-5-(5-methyl-3-(trifluoromethyl)-1 H 1-Pyrazole-1-yl)benzaldehyde oxime (200 mg, 622.99 mg) µ Dissolve 1 mol of the solution in 10 mL of DMF, heat to 35 °C, and add the following to the solution while stirring: N -Chlorosuccinimide (99.80 mg, 747.59 mg) µ After stirring continuously for 1 hour, the reaction solution was cooled to room temperature. Then, 10 mL of dichloromethane was added for extraction, and the organic phase was washed twice each with 1 mol / L hydrochloric acid and saturated brine. After drying with anhydrous Na₂SO₄ and filtering, the filtrate was cooled to 0–5 °C, and methyl thioacrylate (108.40 mg, 934.49 mg) was slowly added dropwise. µ mol) and triethylamine (94.38 mg, 934.49 mg) µ (mol). After the reaction was complete, the mixture was extracted with 10 mL of water, the organic layers were combined, dried over anhydrous Na₂SO₄, concentrated by rotary evaporation, and column chromatography was performed to obtain 3-(2-chloro-4-fluoro-5-(5-methyl-3-(trifluoromethyl)-1 H 4-pyrazol-1-yl)phenyl)-5-methyl-4,5-dihydroisoxazole-5-thiocarboxylic acid methyl ester, yield 61.60%.

[0054] Example 35: 3-(2-chloro-4-fluoro-5-(5-methyl-3-(trifluoromethyl)-1 H The preparation method of ethyl pyrazol-1-yl)phenyl)-5-methyl-4,5-dihydroisoxazole-5-thiocarboxylate (i.e., compound A35) includes the following steps: Steps (1)-(4): Same as steps (1)-(4) in Example 1; (5) 3-(2-chloro-4-fluoro-5-(5-methyl-3-(trifluoromethyl)-1 H Preparation of ethyl pyrazol-1-yl)phenyl)-5-methyl-4,5-dihydroisoxazole-5-thiocarboxylate: Take ( E)-2-chloro-4-fluoro-5-(5-methyl-3-(trifluoromethyl)-1 H 1-Pyrazole-1-yl)benzaldehyde oxime (200 mg, 622.99 mg) µ Dissolve 1 mol of the solution in 10 mL of DMF, heat to 35 °C, and add the following to the solution while stirring: N -Chlorosuccinimide (99.80 mg, 747.59 mg) µ After stirring continuously for 1 hour, the reaction solution was cooled to room temperature. Then, 10 mL of dichloromethane was added for extraction, and the organic phase was washed twice each with 1 mol / L hydrochloric acid and saturated brine. After drying with anhydrous Na₂SO₄ and filtering, the filtrate was cooled to 0–5 °C, and ethyl thioacrylate (121.48 mg, 934.49 mol) was slowly added dropwise. µ mol) and triethylamine (94.38 mg, 934.49 mg) µ (mol). After the reaction was complete, the mixture was extracted with 10 mL of water, the organic layers were combined, dried over anhydrous Na₂SO₄, concentrated by rotary evaporation, and column chromatography was performed to obtain 3-(2-chloro-4-fluoro-5-(5-methyl-3-(trifluoromethyl)-1 H 5-Pyrazol-1-yl)phenyl)-5-methyl-4,5-dihydroisoxazole-5-thiocarboxylic acid ethyl ester, yield 51.20%.

[0055] Example 36: 3-(2-chloro-4-fluoro-5-(5-methyl-3-(trifluoromethyl)-1 H The preparation method of propyl pyrazol-1-yl)phenyl)-5-methyl-4,5-dihydroisoxazole-5-thiocarboxylate (i.e., compound A36) includes the following steps: Steps (1)-(4): Same as steps (1)-(4) in Example 1; (5) 3-(2-chloro-4-fluoro-5-(5-methyl-3-(trifluoromethyl)-1 H Preparation of propyl 5-pyrazol-1-yl)phenyl)-5-methyl-4,5-dihydroisoxazole-5-thiocarboxylate: Take ( E )-2-chloro-4-fluoro-5-(5-methyl-3-(trifluoromethyl)-1 H 1-Pyrazole-1-yl)benzaldehyde oxime (200 mg, 622.99 mg) µ Dissolve 1 mol of the solution in 10 mL of DMF, heat to 35 °C, and add the following to the solution while stirring: N -Chlorosuccinimide (99.80 mg, 747.59 mg) µAfter stirring continuously for 1 hour, the reaction solution was cooled to room temperature. Then, 10 mL of dichloromethane was added for extraction, and the organic phase was washed twice each with 1 mol / L hydrochloric acid and saturated brine. After drying with anhydrous Na₂SO₄ and filtering, the filtrate was cooled to 0–5 °C, and thiopropyl methacrylate (134.57 mg, 934.49 mol) was slowly added dropwise. µ mol) and triethylamine (94.38 mg, 934.49 mg) µ (mol). After the reaction was complete, the mixture was extracted with 10 mL of water, the organic layers were combined, dried over anhydrous Na₂SO₄, concentrated by rotary evaporation, and column chromatography was performed to obtain 3-(2-chloro-4-fluoro-5-(5-methyl-3-(trifluoromethyl)-1 H 5-Pyrazol-1-yl)phenyl)-5-methyl-4,5-dihydroisoxazole-5-thiocarboxylic acid propyl ester, yield 54.50%.

[0056] Example 37: 3-(2-chloro-4-fluoro-5-(5-methyl-3-(trifluoromethyl)-1 H -pyrazole-1-yl)phenyl)- N The preparation method of 5-dimethyl-4,5-dihydroisoxazole-5-carboxamide (i.e., compound A37) includes the following steps: Steps (1)-(4): Same as steps (1)-(4) in Example 1; (5) 3-(2-chloro-4-fluoro-5-(5-methyl-3-(trifluoromethyl)-1 H -pyrazole-1-yl)phenyl)- N Preparation of 5-dimethyl-4,5-dihydroisoxazole-5-carboxamide: Take ( E )-2-chloro-4-fluoro-5-(5-methyl-3-(trifluoromethyl)-1 H 1-Pyrazole-1-yl)benzaldehyde oxime (200 mg, 622.99 mg) µ Dissolve 1 mol of the solution in 10 mL of DMF, heat to 35 °C, and add the following to the solution while stirring: N -Chlorosuccinimide (99.80 mg, 747.59 mg) µ After stirring continuously for 1 hour, the reaction solution was cooled to room temperature. Then, 10 mL of dichloromethane was added for extraction, and the organic phase was washed twice each with 1 mol / L hydrochloric acid and saturated brine. After drying with anhydrous Na₂SO₄ and filtering, the filtrate was cooled to 0–5 °C, and the solution was slowly added dropwise. N -Methylmethacrylamide (92.64 mg, 934.49 mg) µ mol) and triethylamine (94.38 mg, 934.49 mg) µ(mol). After the reaction was complete, the mixture was extracted with 10 mL of water, the organic layers were combined, dried over anhydrous Na₂SO₄, concentrated by rotary evaporation, and column chromatography was performed to obtain 3-(2-chloro-4-fluoro-5-(5-methyl-3-(trifluoromethyl)-1 H -pyrazole-1-yl)phenyl)- N 5-Dimethyl-4,5-dihydroisoxazole-5-carboxamide, yield 60.10%.

[0057] Example 38: 3-(2-chloro-4-fluoro-5-(5-methyl-3-(trifluoromethyl)-1 H -pyrazole-1-yl)phenyl)- N , N The preparation method of 5-trimethyl-4,5-dihydroisoxazole-5-carboxamide (i.e., compound A38) includes the following steps: Steps (1)-(4): Same as steps (1)-(4) in Example 1; (5) 3-(2-chloro-4-fluoro-5-(5-methyl-3-(trifluoromethyl)-1 H -pyrazole-1-yl)phenyl)- N , N Preparation of 5-trimethyl-4,5-dihydroisoxazole-5-carboxamide: Take ( E )-2-chloro-4-fluoro-5-(5-methyl-3-(trifluoromethyl)-1 H 1-Pyrazole-1-yl)benzaldehyde oxime (200 mg, 622.99 mg) µ Dissolve 1 mol of the solution in 10 mL of DMF, heat to 35 °C, and add the following to the solution while stirring: N -Chlorosuccinimide (99.80 mg, 747.59 mg) µ After stirring continuously for 1 hour, the reaction solution was cooled to room temperature. Then, 10 mL of dichloromethane was added for extraction, and the organic phase was washed twice each with 1 mol / L hydrochloric acid and saturated brine. After drying with anhydrous Na₂SO₄ and filtering, the filtrate was cooled to 0–5 °C, and the solution was slowly added dropwise. N,N -Dimethylmethacrylamide (105.75 mg, 934.49 mg) µ mol) and triethylamine (94.38 mg, 934.49 mg) µ (mol). After the reaction was complete, the mixture was extracted with 10 mL of water, the organic layers were combined, dried over anhydrous Na₂SO₄, concentrated by rotary evaporation, and column chromatography was performed to obtain 3-(2-chloro-4-fluoro-5-(5-methyl-3-(trifluoromethyl)-1 H -pyrazole-1-yl)phenyl)- N , N5-Trimethyl-4,5-dihydroisoxazole-5-carboxamide, yield 72.40%.

[0058] Example 39: 3-(2-chloro-4-fluoro-5-(5-methyl-3-(trifluoromethyl)-1 H -pyrazole-1-yl)phenyl)- N The preparation method of ethyl-5-methyl-4,5-dihydroisoxazole-5-carboxamide (i.e., compound A39) includes the following steps: Steps (1)-(4): Same as steps (1)-(4) in Example 1; (5) 3-(2-chloro-4-fluoro-5-(5-methyl-3-(trifluoromethyl)-1 H -pyrazole-1-yl)phenyl)- N Preparation of 5-ethyl-5-methyl-4,5-dihydroisoxazole-5-carboxamide: Take ( E )-2-chloro-4-fluoro-5-(5-methyl-3-(trifluoromethyl)-1 H 1-Pyrazole-1-yl)benzaldehyde oxime (200 mg, 622.99 mg) µ Dissolve 1 mol of the solution in 10 mL of DMF, heat to 35 °C, and add the following to the solution while stirring: N -Chlorosuccinimide (99.80 mg, 747.59 mg) µ After stirring continuously for 1 hour, the reaction solution was cooled to room temperature. Then, 10 mL of dichloromethane was added for extraction, and the organic phase was washed twice each with 1 mol / L hydrochloric acid and saturated brine. After drying with anhydrous Na₂SO₄ and filtering, the filtrate was cooled to 0–5 °C, and the solution was slowly added dropwise. N -Ethylmethylacrylamide (105.75 mg, 934.49 mg) µ mol) and triethylamine (94.38 mg, 934.49 mg) µ (mol). After the reaction was complete, the mixture was extracted with 10 mL of water, the organic layers were combined, dried over anhydrous Na₂SO₄, concentrated by rotary evaporation, and column chromatography was performed to obtain 3-(2-chloro-4-fluoro-5-(5-methyl-3-(trifluoromethyl)-1 H -pyrazole-1-yl)phenyl)- N -Ethyl-5-methyl-4,5-dihydroisoxazole-5-carboxamide, yield 70.50%.

[0059] Example 40: 3-(2-chloro-4-fluoro-5-(5-methyl-3-(trifluoromethyl)-1 H -pyrazole-1-yl)phenyl)- NThe preparation method of -isopropyl-5-methyl-4,5-dihydroisoxazole-5-carboxamide (i.e., compound A40) includes the following steps: Steps (1)-(4): Same as steps (1)-(4) in Example 1; (5) 3-(2-chloro-4-fluoro-5-(5-methyl-3-(trifluoromethyl)-1 H -pyrazole-1-yl)phenyl)- N Preparation of -isopropyl-5-methyl-4,5-dihydroisoxazole-5-carboxamide: Take ( E )-2-chloro-4-fluoro-5-(5-methyl-3-(trifluoromethyl)-1 H 1-Pyrazole-1-yl)benzaldehyde oxime (200 mg, 622.99 mg) µ Dissolve 1 mol of the solution in 10 mL of DMF, heat to 35 °C, and add the following to the solution while stirring: N -Chlorosuccinimide (99.80 mg, 747.59 mg) µ After stirring continuously for 1 hour, the reaction solution was cooled to room temperature. Then, 10 mL of dichloromethane was added for extraction, and the organic phase was washed twice each with 1 mol / L hydrochloric acid and saturated brine. After drying with anhydrous Na₂SO₄ and filtering, the filtrate was cooled to 0–5 °C, and the solution was slowly added dropwise. N -Isopropyl methacrylamide (118.68 mg, 934.49 mg) µ mol) and triethylamine (94.38 mg, 934.49 mg) µ (mol). After the reaction was complete, the mixture was extracted with 10 mL of water, the organic layers were combined, dried over anhydrous Na₂SO₄, concentrated by rotary evaporation, and column chromatography was performed to obtain 3-(2-chloro-4-fluoro-5-(5-methyl-3-(trifluoromethyl)-1 H -pyrazole-1-yl)phenyl)- N - Isopropyl-5-methyl-4,5-dihydroisoxazole-5-carboxamide, yield 70.50%.

[0060] Example 41: 3-(2-chloro-4-fluoro-5-(5-methyl-3-(trifluoromethyl)-1 H -pyrazole-1-yl)phenyl)-5-methyl- N The preparation method of propyl-4,5-dihydroisoxazole-5-carboxamide (i.e., compound A41) includes the following steps: Steps (1)-(4): Same as steps (1)-(4) in Example 1; (5) 3-(2-chloro-4-fluoro-5-(5-methyl-3-(trifluoromethyl)-1 H -pyrazole-1-yl)phenyl)-5-methyl-N Preparation of propyl-4,5-dihydroisoxazole-5-formamide: Take ( E )-2-chloro-4-fluoro-5-(5-methyl-3-(trifluoromethyl)-1 H 1-Pyrazole-1-yl)benzaldehyde oxime (200 mg, 622.99 mg) µ Dissolve 1 mol of the solution in 10 mL of DMF, heat to 35 °C, and add the following to the solution while stirring: N -Chlorosuccinimide (99.80 mg, 747.59 mg) µ After stirring continuously for 1 hour, the reaction solution was cooled to room temperature. Then, 10 mL of dichloromethane was added for extraction, and the organic phase was washed twice each with 1 mol / L hydrochloric acid and saturated brine. After drying with anhydrous Na₂SO₄ and filtering, the filtrate was cooled to 0–5 °C, and the solution was slowly added dropwise. N -Propylmethacrylamide (118.68 mg, 934.49 mg) µ mol) and triethylamine (94.38 mg, 934.49 mg) µ (mol). After the reaction was complete, the mixture was extracted with 10 mL of water, the organic layers were combined, dried over anhydrous Na₂SO₄, concentrated by rotary evaporation, and column chromatography was performed to obtain 3-(2-chloro-4-fluoro-5-(5-methyl-3-(trifluoromethyl)-1 H -pyrazole-1-yl)phenyl)-5-methyl- N -propyl-4,5-dihydroisoxazole-5-carboxamide, yield 66.90%.

[0061] Example 42: N -Butyl-3-(2-chloro-4-fluoro-5-(5-methyl-3-(trifluoromethyl)-1 H The preparation method of (-pyrazol-1-yl)phenyl)-5-methyl-4,5-dihydroisoxazole-5-carboxamide (i.e., compound A42) includes the following steps: Steps (1)-(4): Same as steps (1)-(4) in Example 1; (5) N -Butyl-3-(2-chloro-4-fluoro-5-(5-methyl-3-(trifluoromethyl)-1 H Preparation of pyrazol-1-yl)phenyl)-5-methyl-4,5-dihydroisoxazole-5-carboxamide: Take ( E )-2-chloro-4-fluoro-5-(5-methyl-3-(trifluoromethyl)-1 H 1-Pyrazole-1-yl)benzaldehyde oxime (200 mg, 622.99 mg) µDissolve 1 mol of the solution in 10 mL of DMF, heat to 35 °C, and add the following to the solution while stirring: N -Chlorosuccinimide (99.80 mg, 747.59 mg) µ After stirring continuously for 1 hour, the reaction solution was cooled to room temperature. Then, 10 mL of dichloromethane was added for extraction, and the organic phase was washed twice each with 1 mol / L hydrochloric acid and saturated brine. After drying with anhydrous Na₂SO₄ and filtering, the filtrate was cooled to 0–5 °C, and the solution was slowly added dropwise. N -Butylmethacrylamide (131.96 mg, 934.49 mg) µ mol) and triethylamine (94.38 mg, 934.49 mg) µ (mol). After the reaction was complete, the mixture was extracted with 10 mL of water, the organic layers were combined, dried over anhydrous Na₂SO₄, concentrated by rotary evaporation, and then subjected to column chromatography to obtain... N -Butyl-3-(2-chloro-4-fluoro-5-(5-methyl-3-(trifluoromethyl)-1 H -pyrazol-1-yl)phenyl)-5-methyl-4,5-dihydroisoxazole-5-carboxamide, yield 70.20%.

[0062] Example 43: 2-Methoxy-2-oxoethyl 3-(2-chloro-4-fluoro-5-(5-methyl-3-(trifluoromethyl)-1 H The preparation method of pyrazol-1-yl)phenyl)-5-methyl-4,5-dihydroisoxazole-5-carboxylic acid ester (i.e., compound A43) includes the following steps: Steps (1)-(4): Same as steps (1)-(4) in Example 1; (5) 2-Methoxy-2-oxoethyl 3-(2-chloro-4-fluoro-5-(5-methyl-3-(trifluoromethyl)-1 H Preparation of pyrazol-1-yl)phenyl)-5-methyl-4,5-dihydroisoxazole-5-carboxylic acid ester: Take ( E )-2-chloro-4-fluoro-5-(5-methyl-3-(trifluoromethyl)-1 H 1-Pyrazole-1-yl)benzaldehyde oxime (200 mg, 622.99 mg) µ Dissolve 1 mol of the solution in 10 mL of DMF, heat to 35 °C, and add the following to the solution while stirring: N -Chlorosuccinimide (99.80 mg, 747.59 mg) µAfter stirring continuously for 1 hour, the reaction solution was cooled to room temperature. Then, 10 mL of dichloromethane was added for extraction, and the organic phase was washed twice each with 1 mol / L hydrochloric acid and saturated brine. After drying with anhydrous Na₂SO₄ and filtering, the filtrate was cooled to 0–5 °C, and 2-methoxy-2-oxoethyl methacrylate (147.65 mg, 934.49 mol) was slowly added dropwise. µ mol) and triethylamine (94.38 mg, 934.49 mg) µ mol). After the reaction was complete, the mixture was extracted with 10 mL of water, the organic layers were combined, dried over anhydrous Na₂SO₄, concentrated by rotary evaporation, and column chromatography was performed to give 2-methoxy-2-oxoethyl 3-(2-chloro-4-fluoro-5-(5-methyl-3-(trifluoromethyl)-1 H -pyrazol-1-yl)phenyl)-5-methyl-4,5-dihydroisoxazole-5-carboxylic acid ester, yield 65.40%.

[0063] Example 44: 2-ethoxy-2-oxoethyl 3-(2-chloro-4-fluoro-5-(5-methyl-3-(trifluoromethyl)-1 H The preparation method of pyrazol-1-yl)phenyl)-5-methyl-4,5-dihydroisoxazole-5-carboxylic acid ester (i.e., compound A44) includes the following steps: Steps (1)-(4): Same as steps (1)-(4) in Example 1; (5) 2-ethoxy-2-oxoethyl 3-(2-chloro-4-fluoro-5-(5-methyl-3-(trifluoromethyl)-1 H Preparation of pyrazol-1-yl)phenyl)-5-methyl-4,5-dihydroisoxazole-5-carboxylic acid ester: Take ( E )-2-chloro-4-fluoro-5-(5-methyl-3-(trifluoromethyl)-1 H 1-Pyrazole-1-yl)benzaldehyde oxime (200 mg, 622.99 mg) µ Dissolve 1 mol of the solution in 10 mL of DMF, heat to 35 °C, and add the following to the solution while stirring: N -Chlorosuccinimide (99.80 mg, 747.59 mg) µ After stirring continuously for 1 hour, the reaction solution was cooled to room temperature. Then, 10 mL of dichloromethane was added for extraction, and the organic phase was washed twice each with 1 mol / L hydrochloric acid and saturated brine. After drying with anhydrous Na₂SO₄ and filtering, the filtrate was cooled to 0–5 °C, and 2-ethoxy-2-oxoethyl methacrylate (160.73 mg, 934.49 mol) was slowly added dropwise. µ mol) and triethylamine (94.38 mg, 934.49 mg) µmol). After the reaction was complete, the mixture was extracted with 10 mL of water, the organic layers were combined, dried over anhydrous Na₂SO₄, concentrated by rotary evaporation, and column chromatography was performed to give 2-ethoxy-2-oxoethyl 3-(2-chloro-4-fluoro-5-(5-methyl-3-(trifluoromethyl)-1 H -pyrazol-1-yl)phenyl)-5-methyl-4,5-dihydroisoxazole-5-carboxylic acid ester, yield 62.60%.

[0064] Example 45: 2-Oxo-2-propoxyethyl 3-(2-chloro-4-fluoro-5-(5-methyl-3-(trifluoromethyl)-1 H The preparation method of pyrazol-1-yl)phenyl)-5-methyl-4,5-dihydroisoxazole-5-carboxylic acid ester (i.e., compound A45) includes the following steps: Steps (1)-(4): Same as steps (1)-(4) in Example 1; (5) 2-Oxo-2-propoxyethyl 3-(2-chloro-4-fluoro-5-(5-methyl-3-(trifluoromethyl)-1 H Preparation of pyrazol-1-yl)phenyl)-5-methyl-4,5-dihydroisoxazole-5-carboxylic acid ester: Take ( E )-2-chloro-4-fluoro-5-(5-methyl-3-(trifluoromethyl)-1 H 1-Pyrazole-1-yl)benzaldehyde oxime (200 mg, 622.99 mg) µ Dissolve 1 mol of the solution in 10 mL of DMF, heat to 35 °C, and add the following to the solution while stirring: N -Chlorosuccinimide (99.80 mg, 747.59 mg) µ After stirring continuously for 1 hour, the reaction solution was cooled to room temperature. Then, 10 mL of dichloromethane was added for extraction, and the organic phase was washed twice each with 1 mol / L hydrochloric acid and saturated brine. After drying with anhydrous Na₂SO₄ and filtering, the filtrate was cooled to 0–5 °C, and 2-propoxy-2-oxoethyl methacrylate (173.82 mg, 934.49 mol) was slowly added dropwise. µ mol) and triethylamine (94.38 mg, 934.49 mg) µ mol). After the reaction was complete, the mixture was extracted with 10 mL of water, the organic layers were combined, dried over anhydrous Na₂SO₄, concentrated by rotary evaporation, and column chromatography was performed to give 2-oxo-2-propoxyethyl 3-(2-chloro-4-fluoro-5-(5-methyl-3-(trifluoromethyl)-1 H -pyrazol-1-yl)phenyl)-5-methyl-4,5-dihydroisoxazole-5-carboxylic acid ester, yield 65.80%.

[0065] Example 46: 1-Methoxy-1-oxopropyl-2-yl 3-(2-chloro-4-fluoro-5-(5-methyl-3-(trifluoromethyl)-1 H The preparation method of pyrazol-1-yl)phenyl)-5-methyl-4,5-dihydroisoxazole-5-carboxylic acid ester (i.e., compound A46) includes the following steps: Steps (1)-(4): Same as steps (1)-(4) in Example 1; (5) 1-Methoxy-1-oxopropyl-2-yl 3-(2-chloro-4-fluoro-5-(5-methyl-3-(trifluoromethyl)-1 H Preparation of pyrazol-1-yl)phenyl)-5-methyl-4,5-dihydroisoxazole-5-carboxylic acid ester: Take ( E )-2-chloro-4-fluoro-5-(5-methyl-3-(trifluoromethyl)-1 H 1-Pyrazole-1-yl)benzaldehyde oxime (200 mg, 622.99 mg) µ Dissolve 1 mol of the solution in 10 mL of DMF, heat to 35 °C, and add the following to the solution while stirring: N -Chlorosuccinimide (99.80 mg, 747.59 mg) µ After stirring continuously for 1 hour, the reaction solution was cooled to room temperature. Then, 10 mL of dichloromethane was added for extraction, and the organic phase was washed twice each with 1 mol / L hydrochloric acid and saturated brine. After drying with anhydrous Na₂SO₄ and filtering, the filtrate was cooled to 0–5 °C, and 1-methoxy-1-oxopropyl-2-yl methacrylate (160.73 mg, 934.49 mol) was slowly added dropwise. µ mol) and triethylamine (94.38 mg, 934.49 mg) µ (mol). After the reaction was complete, the mixture was extracted with 10 mL of water, the organic layers were combined, and the solution was concentrated by rotary evaporation after drying with anhydrous Na₂SO₄. Column chromatography yielded 1-methoxy-1-oxopropyl-2-yl-3-(2-chloro-4-fluoro-5-(5-methyl-3-(trifluoromethyl)-1 H -pyrazol-1-yl)phenyl)-5-methyl-4,5-dihydroisoxazole-5-carboxylic acid ester, yield 61.70%.

[0066] Example 47: 1-Ethoxy-1-oxopropyl-2-yl 3-(2-chloro-4-fluoro-5-(5-methyl-3-(trifluoromethyl)-1 H The preparation method of pyrazol-1-yl)phenyl)-5-methyl-4,5-dihydroisoxazole-5-carboxylic acid ester (i.e., compound A47) includes the following steps: Steps (1)-(4): Same as steps (1)-(4) in Example 1; (5) 1-Ethoxy-1-oxopropyl-2-yl 3-(2-chloro-4-fluoro-5-(5-methyl-3-(trifluoromethyl)-1 H Preparation of pyrazol-1-yl)phenyl)-5-methyl-4,5-dihydroisoxazole-5-carboxylic acid ester: Take ( E )-2-chloro-4-fluoro-5-(5-methyl-3-(trifluoromethyl)-1 H 1-Pyrazole-1-yl)benzaldehyde oxime (200 mg, 622.99 mg) µ Dissolve 1 mol of the solution in 10 mL of DMF, heat to 35 °C, and add the following to the solution while stirring: N -Chlorosuccinimide (99.80 mg, 747.59 mg) µ After stirring continuously for 1 hour, the reaction solution was cooled to room temperature. Then, 10 mL of dichloromethane was added for extraction, and the organic phase was washed twice each with 1 mol / L hydrochloric acid and saturated brine. After drying with anhydrous Na₂SO₄ and filtering, the filtrate was cooled to 0–5 °C, and 1-ethoxy-1-oxopropyl-2-methacrylate (173.81 mg, 934.49 mg) was slowly added dropwise. µ mol) and triethylamine (94.38 mg, 934.49 mg) µ (mol). After the reaction was complete, the mixture was extracted with 10 mL of water, the organic layers were combined, concentrated by rotary evaporation with anhydrous Na₂SO₄, and column chromatography was performed to give 1-ethoxy-1-oxopropyl-2-yl3-(2-chloro-4-fluoro-5-(5-methyl-3-(trifluoromethyl)-1 H -pyrazol-1-yl)phenyl)-5-methyl-4,5-dihydroisoxazole-5-carboxylic acid ester, yield 72.30%.

[0067] Example 48: 1-oxo-1-propoxypropyl-2-yl 3-(2-chloro-4-fluoro-5-(5-methyl-3-(trifluoromethyl)-1 H The preparation method of pyrazol-1-yl)phenyl)-5-methyl-4,5-dihydroisoxazole-5-carboxylic acid ester (i.e., compound A48) includes the following steps: Steps (1)-(4): Same as steps (1)-(4) in Example 1; (5) 1-oxo-1-propoxypropyl-2-yl 3-(2-chloro-4-fluoro-5-(5-methyl-3-(trifluoromethyl)-1 H Preparation of pyrazol-1-yl)phenyl)-5-methyl-4,5-dihydroisoxazole-5-carboxylic acid ester: Take ( E )-2-chloro-4-fluoro-5-(5-methyl-3-(trifluoromethyl)-1 H1-Pyrazole-1-yl)benzaldehyde oxime (200 mg, 622.99 mg) µ Dissolve 1 mol of the solution in 10 mL of DMF, heat to 35 °C, and add the following to the solution while stirring: N -Chlorosuccinimide (99.80 mg, 747.59 mg) µ After stirring continuously for 1 hour, the reaction solution was cooled to room temperature. Then, 10 mL of dichloromethane was added for extraction, and the organic phase was washed twice each with 1 mol / L hydrochloric acid and saturated brine. After drying with anhydrous Na₂SO₄ and filtering, the filtrate was cooled to 0–5 °C, and 1-ethoxy-1-oxopropyl-2-methacrylate (173.81 mg, 934.49 mg) was slowly added dropwise. µ mol) and triethylamine (94.38 mg, 934.49 mg) µ (mol). After the reaction was complete, the mixture was extracted with 10 mL of water, the organic layers were combined, concentrated by rotary evaporation with anhydrous Na₂SO₄, and column chromatography was performed to obtain 1-oxo-1-propoxypropyl-2-yl3-(2-chloro-4-fluoro-5-(5-methyl-3-(trifluoromethyl)-1 H -pyrazol-1-yl)phenyl)-5-methyl-4,5-dihydroisoxazole-5-carboxylic acid ester, yield 63.50%.

[0068] Example 49: 3-(2-chloro-4-fluoro-5-(5-methyl-3-(trifluoromethyl)-1 H The preparation method of pyrazol-1-yl)phenyl)-5-methyl-4,5-dihydroisoxazole-5-carboxylic acid epoxide-2-yl methyl ester (i.e., compound A49) includes the following steps: Steps (1)-(4): Same as steps (1)-(4) in Example 1; (5) 3-(2-chloro-4-fluoro-5-(5-methyl-3-(trifluoromethyl)-1 H Preparation of pyrazol-1-yl)phenyl)-5-methyl-4,5-dihydroisoxazole-5-carboxylic acid epoxide-2-ylmethyl ester: Take ( E )-2-chloro-4-fluoro-5-(5-methyl-3-(trifluoromethyl)-1 H 1-Pyrazole-1-yl)benzaldehyde oxime (200 mg, 622.99 mg) µ Dissolve 1 mol of the solution in 10 mL of DMF, heat to 35 °C, and add the following to the solution while stirring: N -Chlorosuccinimide (99.80 mg, 747.59 mg) µAfter stirring continuously for 1 hour, the reaction solution was cooled to room temperature. Then, 10 mL of dichloromethane was added for extraction, and the organic phase was washed twice each with 1 mol / L hydrochloric acid and saturated brine. After drying with anhydrous Na₂SO₄ and filtering, the filtrate was cooled to 0–5 °C, and glycidyl methacrylate (132.84 mg, 934.49 mg) was slowly added dropwise. µ mol) and triethylamine (94.38 mg, 934.49 mg) µ (mol). After the reaction was complete, the mixture was extracted with 10 mL of water, the organic layers were combined, dried over anhydrous Na₂SO₄, concentrated by rotary evaporation, and column chromatography was performed to obtain 3-(2-chloro-4-fluoro-5-(5-methyl-3-(trifluoromethyl)-1 H 5-Pyrazol-1-yl)phenyl)-5-methyl-4,5-dihydroisoxazole-5-carboxylic acid epoxide-2-ylmethyl ester, yield 54.50%.

[0069] Example 50: 3-(2-chloro-4-fluoro-5-(5-methyl-3-(trifluoromethyl)-1 H The preparation method of methyl pyrazol-1-yl)phenyl)-5-methyl-4,5-dihydroisoxazole-5-carboxylic acid (tetrahydrofuran-2-yl) ester (i.e., compound A50) includes the following steps: Steps (1)-(4): Same as steps (1)-(4) in Example 1; (5) 3-(2-chloro-4-fluoro-5-(5-methyl-3-(trifluoromethyl)-1 H Preparation of methyl 4,5-dihydroisoxazole-5-carboxylic acid (tetrahydrofuran-2-yl) ester: Take ( E )-2-chloro-4-fluoro-5-(5-methyl-3-(trifluoromethyl)-1 H 1-Pyrazole-1-yl)benzaldehyde oxime (200 mg, 622.99 mg) µ Dissolve 1 mol of the solution in 10 mL of DMF, heat to 35 °C, and add the following to the solution while stirring: N -Chlorosuccinimide (99.80 mg, 747.59 mg) µ After stirring continuously for 1 hour, the reaction solution was cooled to room temperature. Then, 10 mL of dichloromethane was added for extraction, and the organic phase was washed twice each with 1 mol / L hydrochloric acid and saturated brine. After drying with anhydrous Na₂SO₄ and filtering, the filtrate was cooled to 0–5 °C, and 2-epoxypentyl methacrylate (159.06 mg, 934.49 mol) was slowly added dropwise. µ mol) and triethylamine (94.38 mg, 934.49 mg) µ(mol). After the reaction was complete, the mixture was extracted with 10 mL of water, the organic layers were combined, dried over anhydrous Na₂SO₄, concentrated by rotary evaporation, and column chromatography was performed to obtain 3-(2-chloro-4-fluoro-5-(5-methyl-3-(trifluoromethyl)-1 H 5-Pyrazol-1-yl)phenyl)-5-methyl-4,5-dihydroisoxazole-5-carboxylic acid (tetrahydrofuran-2-yl) methyl ester, yield 61.40%.

[0070] The structural and molecular formulas of the target compounds obtained in the above examples are shown in Table 1, and their spectroscopic data are shown in Table 2. Table 1. Molecular formulas and structural formulas of the target compounds obtained in Examples 1–50

[0071] Table 2. Spectral data of the target compounds obtained in Examples 1–50

[0072] Post-emergence activity test of target compounds: This experiment used a spray method with various weeds as test targets. Weed seeds were directly sown and evenly scattered in 8×8 cm plastic pots filled with two-thirds organic substrate soil, and then grown in a greenhouse. The compounds were tested when both grass and broadleaf weeds reached the two- to three-leaf stage. The compounds were then used in 100... μ Dissolve L DMF and dilute with 0.1% Tween-80 to a dose of 37.5–150 g ai / ha. Isopropylene was used as a positive control and target compound to spray all weeds. After treatment, the weeds were placed in a greenhouse for 15 days, and their herbicidal activity was evaluated visually in the control group (CK), repeated three times.

[0073] Table 3. Post-emergence herbicidal activity of target compounds in Examples 1–50

[0074] Table 3 shows that at a dose of 150 g ai / ha, compounds A10, A11, A12, A14, A15, A16, A18, A20, A22, A23, A24, A34, A35, A43, A44, A45, A46, A47, and A48 exhibited excellent herbicidal activity against barnyard grass, goosegrass, foxtail, amaranth, purslane, and velvetleaf. The weeds completely withered, and their growth was severely inhibited, with inhibition rates reaching 100%, comparable to the positive control isopyridine. At 75 g ai / ha... At the ai / ha dosage, compounds A10, A11, A43, A44, A45, A46, A47 and A48 exhibited excellent herbicidal activity against barnyard grass, goosegrass, foxtail grass, amaranth, purslane and velvetleaf, with inhibition rates reaching 100%.

[0075] Crop safety testing of target compounds: This experiment used a spray method, with seven typical compounds as test subjects. Crop seeds were directly sown and evenly scattered in 8×8 cm plastic flowerpots filled with two-thirds organic substrate soil, and then grown in a greenhouse. The compounds were tested using 100... μ L DMF was dissolved and diluted with 0.1% Tween-80 to a dose of 150 g ai / ha. Isopropylene was used as a positive control and the target compound to spray all weeds. After treatment, the crops were placed in a greenhouse for 30 days, and crop safety was evaluated by visual inspection of the control group (CK group), repeated three times.

[0076] Table 4. Crop safety of target compounds in Examples 43 and 46 at a dose of 150 g ai / ha.

[0077] As shown in Table 4, isopyridine caused serious damage to several typical crops, while compound A46 showed good crop safety (20–40%) in rice, corn, wheat, sorghum, peanut, soybean, and cotton at a dose of 150 g ai / ha. In contrast, isopyridine caused a mortality rate of up to 70% in sorghum, peanut, soybean, and cotton plants, indicating severe phytotoxicity.

[0078] In summary, this series N Phenylepirazole derivatives possess novel structures, readily available raw materials, and simple preparation processes. Some compounds also exhibit excellent post-emergence herbicidal activity and good crop safety. Therefore, this series of compounds has great potential to become PPO inhibitors, post-emergence herbicides, and selective herbicides, which can be further developed for application in more farmlands.

[0079] The above description is merely a preferred embodiment of the present invention and is not intended to limit the present invention in any way. Any simple modifications, equivalent changes, and alterations made to the above embodiments based on the technical essence of the present invention without departing from the scope of the present invention shall still fall within the scope of the present invention.

Claims

1. A kind N -Phenylated pyrazole derivative, characterized in that The N -The general structural formula of phenylpyrazole derivatives is shown in formula (I): In formula (I): X is selected from H, CH2, and CH3 respectively; Y is selected from O, S, and NR respectively. 7 ONCR 8 ; R 1 R 2 They were selected from CH3, CF3, Ph, and 4-CH3-Ph, respectively. R 3 R 4 The components are selected from hydrogen, halogen, -CN, C1-C6 alkyl, (C1-C6 haloalkyl)-O- or (C1-C6 alkyl)-SO2-, respectively. R 5 They are selected from hydrogen, halogen, C1-C6 alkyl, C1-C6 haloalkyl, and C1-C6 alkoxy, respectively; R 6 Selected from hydrogen, halogen, C1-C6 alkyl, C3-C6 alkenyl, C3-C6 haloalkenyl, C3-C6 alkynyl, C1-C6 haloalkyl, C1-C6 alkoxy, C1-C6 cyano, C3-C6 cycloalkyl, C5-C6 aryl, C2-C6 heterocyclic, R 9 -OR 10 (CH2) n COX 2 R 11 ; n is selected from 0, 1, 2, 3, 4, 5, and 6 respectively; X 2 Other selections include O, S, and NR. 12 NCR 13 ; R 7 R 8 Each of the following is independently selected from hydrogen, halogen, C1-C6 alkyl, C3-C6 alkenyl, C3-C6 haloalkenyl, C3-C6 alkynyl, C1-C6 haloalkyl, and C1-C6 alkoxy. R 9 R 10 R 11 Each of the following is independently selected from hydrogen, halogen, C1-C6 alkyl, C3-C6 alkenyl, C3-C6 haloalkenyl, C3-C6 alkynyl, C1-C6 haloalkyl, and C1-C6 alkoxy. R 12 R 13 Each of the following is independently selected from H, C1-C6 alkyl, C1-C6 haloalkyl, C3-C6 alkenyl, C3-C6 haloalkenyl, C3-C6 alkynyl, C1-C4 alkoxyC1-C6-alkyl, and C1-C4 haloalkoxyC1-C6 alkyl.

2. As described in claim 1 N -Phenylated pyrazole derivative, characterized in that Including the following compounds: Compound A1: ( E )-2-(((2-chloro-4-fluoro-5-(5-methyl-3-(trifluoromethyl)-1 H methyl pyrazol-1-yl)benzyl)amino)oxy)propionate; Compound A2: ( E )-2-(((2-chloro-4-fluoro-5-(5-methyl-3-(trifluoromethyl)-1 H ethyl pyrazol-1-yl)benzyl)amino)oxy)propionate; Compound A3: ( E )-2-(((2-chloro-4-fluoro-5-(5-methyl-3-(trifluoromethyl)-1 H 1-pyrazole-1-yl)benzyl)amino)oxy)propyl propionate; Compound A4: ( E )-2-(((2-chloro-4-fluoro-5-(5-methyl-3-(trifluoromethyl)-1 H -Pyrazol-1-yl)benzyl)amino)oxy)butyl propionate; Compound A5: ( E )-2-(((2-chloro-4-fluoro-5-(5-methyl-3-(trifluoromethyl)-1 H -pyrazol-1-yl)benzyl)amino)oxy)amyl propionate; Compound A6: ( E )-2-(((2-chloro-4-fluoro-5-(5-methyl-3-(trifluoromethyl)-1 H -pyrazol-1-yl)benzyl)amino)oxy)methyl acetate; Compound A7: ( E )-2-(((2-chloro-4-fluoro-5-(5-methyl-3-(trifluoromethyl)-1 H -pyrazol-1-yl)benzyl)amino)oxy)ethyl acetate; Compound A8: ( E )-2-(((2-chloro-4-fluoro-5-(5-methyl-3-(trifluoromethyl)-1 H -pyrazol-1-yl)benzyl)amino)oxy)propyl acetate; Compound A9: ( E )-2-(((2-chloro-4-fluoro-5-(5-methyl-3-(trifluoromethyl)-1 H -pyrazol-1-yl)benzyl)amino)oxy)butyl acetate; Compound A10: 3-(2-chloro-4-fluoro-5-(5-methyl-3-(trifluoromethyl)-1 H methyl pyrazol-1-yl)phenyl)-5-methyl-4,5-dihydroisoxazole-5-carboxylic acid ester; Compound A11: 3-(2-chloro-4-fluoro-5-(5-methyl-3-(trifluoromethyl)-1 H ethyl pyrazol-1-yl)phenyl)-5-methyl-4,5-dihydroisoxazole-5-carboxylate; Compound A12: 3-(2-chloro-4-fluoro-5-(5-methyl-3-(trifluoromethyl)-1 H -Pyrazol-1-yl)phenyl)-5-methyl-4,5-dihydroisooxazol-5-carboxylic acid isopropyl ester; Compound A13: 3-(2-chloro-4-fluoro-5-(5-methyl-3-(trifluoromethyl)-1 H -Pyrazol-1-yl)phenyl)-5-methyl-4,5-dihydroisoxazole-5-carboxylic acid tert-butyl ester; Compound A14: 3-(2-chloro-4-fluoro-5-(5-methyl-3-(trifluoromethyl)-1 H 5-Pyrazol-1-yl)phenyl)-5-methyl-4,5-dihydroisoxazole-5-carboxylic acid propyl ester; Compound A15: 3-(2-chloro-4-fluoro-5-(5-methyl-3-(trifluoromethyl)-1 H -Pyrazol-1-yl)phenyl)-5-methyl-4,5-dihydroisoxazole-5-carboxylic acid allyl ester; Compound A16: 3-(2-chloro-4-fluoro-5-(5-methyl-3-(trifluoromethyl)-1 H -Pyrazol-1-yl)phenyl)-5-methyl-4,5-dihydroisoxazole-5-carboxylic acid sec-butyl ester; Compound A17: 3-(2-chloro-4-fluoro-5-(5-methyl-3-(trifluoromethyl)-1 H 1-Pyrazol-1-yl)phenyl)-5-methyl-4,5-dihydroisoxazole-5-carboxylate butyl ester; Compound A18: 3-(2-chloro-4-fluoro-5-(5-methyl-3-(trifluoromethyl)-1 H 2-pyrazol-1-yl)phenyl)-5-methyl-4,5-dihydroisoxazole-5-carboxylic acid 2-methoxyethyl ester; Compound A19: 2,2,3,3-Tetrafluoropropyl 3-(2-chloro-4-fluoro-5-(5-methyl-3-(trifluoromethyl)-1 H -Pyrazol-1-yl)phenyl)-5-methyl-4,5-dihydroisoxazole-5-carboxylic acid ester; Compound A20: 3-(2-chloro-4-fluoro-5-(5-methyl-3-(trifluoromethyl)-1 H -Pyrazol-1-yl)phenyl)-5-methyl-4,5-dihydroisoxazole-5-carboxylic acid cyclohexyl ester; Compound A21: 3-(2-chloro-4-fluoro-5-(5-methyl-3-(trifluoromethyl)-1 H -Pyrazol-1-yl)phenyl)-5-methyl-4,5-dihydroisoxazole-5-carboxylic acid phenyl ester; Compound A22: 3-(2,4-difluoro-5-(5-methyl-3-(trifluoromethyl)-1 H methyl pyrazol-1-yl)phenyl)-5-methyl-4,5-dihydroisoxazole-5-carboxylic acid ester; Compound A23: 3-(2,4-difluoro-5-(5-methyl-3-(trifluoromethyl)-1 H ethyl pyrazol-1-yl)phenyl)-5-methyl-4,5-dihydroisoxazole-5-carboxylate; Compound A24: 3-(2,4-difluoro-5-(5-methyl-3-(trifluoromethyl)-1 H 5-Pyrazol-1-yl)phenyl)-5-methyl-4,5-dihydroisoxazole-5-carboxylic acid propyl ester; Compound A25: 3-(2,4-difluoro-5-(5-methyl-3-(trifluoromethyl)-1 H -Pyrazol-1-yl)phenyl)-5-methyl-4,5-dihydroisoxazole-5-carboxylic acid allyl ester; Compound A26: 3-(4-chloro-2-fluoro-5-(5-methyl-3-(trifluoromethyl)-1 H methyl pyrazol-1-yl)phenyl)-5-methyl-4,5-dihydroisoxazole-5-carboxylic acid ester; Compound A27: 3-(4-chloro-2-fluoro-5-(5-methyl-3-(trifluoromethyl)-1 H ethyl pyrazol-1-yl)phenyl)-5-methyl-4,5-dihydroisoxazole-5-carboxylate; Compound A28: 3-(4-chloro-2-fluoro-5-(5-methyl-3-(trifluoromethyl)-1 H 5-Pyrazol-1-yl)phenyl)-5-methyl-4,5-dihydroisoxazole-5-carboxylic acid propyl ester; Compound A29: 3-(4-chloro-2-fluoro-5-(5-methyl-3-(trifluoromethyl)-1 H -Pyrazol-1-yl)phenyl)-5-methyl-4,5-dihydroisoxazole-5-carboxylic acid allyl ester; Compound A30: 3-(2,4-dichloro-5-(5-methyl-3-(trifluoromethyl)-1 H methyl pyrazol-1-yl)phenyl)-5-methyl-4,5-dihydroisoxazole-5-carboxylic acid ester; Compound A31: 3-(2,4-dichloro-5-(5-methyl-3-(trifluoromethyl)-1 H ethyl pyrazol-1-yl)phenyl)-5-methyl-4,5-dihydroisoxazole-5-carboxylate; Compound A32: 3-(2,4-dichloro-5-(5-methyl-3-(trifluoromethyl)-1 H 5-Pyrazol-1-yl)phenyl)-5-methyl-4,5-dihydroisoxazole-5-carboxylic acid propyl ester; Compound A33: 3-(2,4-dichloro-5-(5-methyl-3-(trifluoromethyl)-1 H -Pyrazol-1-yl)phenyl)-5-methyl-4,5-dihydroisoxazole-5-carboxylic acid allyl ester; Compound A34: 3-(2-chloro-4-fluoro-5-(5-methyl-3-(trifluoromethyl)-1 H methyl pyrazol-1-yl)phenyl)-5-methyl-4,5-dihydroisoxazole-5-thiocarboxylic acid ester; Compound A35: 3-(2-chloro-4-fluoro-5-(5-methyl-3-(trifluoromethyl)-1 H ethyl pyrazol-1-yl)phenyl)-5-methyl-4,5-dihydroisoxazole-5-thiocarboxylate; Compound A36: 3-(2-chloro-4-fluoro-5-(5-methyl-3-(trifluoromethyl)-1 H 5-Pyrazol-1-yl)phenyl)-5-methyl-4,5-dihydroisoxazole-5-thiocarboxylic acid propyl ester; Compound A37: 3-(2-chloro-4-fluoro-5-(5-methyl-3-(trifluoromethyl)-1 H -pyrazole-1-yl)phenyl)- N 5-Dimethyl-4,5-dihydroisoxazole-5-carboxamide; Compound A38: 3-(2-chloro-4-fluoro-5-(5-methyl-3-(trifluoromethyl)-1 H -pyrazole-1-yl)phenyl)- N , N 5-Trimethyl-4,5-dihydroisoxazole-5-carboxamide; Compound A39: 3-(2-chloro-4-fluoro-5-(5-methyl-3-(trifluoromethyl)-1 H -pyrazole-1-yl)phenyl)- N 5-Ethyl-5-methyl-4,5-dihydroisoxazole-5-carboxamide; Compound A40: 3-(2-chloro-4-fluoro-5-(5-methyl-3-(trifluoromethyl)-1 H -pyrazole-1-yl)phenyl)- N -Isopropyl-5-methyl-4,5-dihydroisoxazole-5-carboxamide; Compound A41: 3-(2-chloro-4-fluoro-5-(5-methyl-3-(trifluoromethyl)-1 H -pyrazole-1-yl)phenyl)-5-methyl- N -propyl-4,5-dihydroisoxazole-5-formamide; Compound A42: N -Butyl-3-(2-chloro-4-fluoro-5-(5-methyl-3-(trifluoromethyl)-1 H -pyrazol-1-yl)phenyl)-5-methyl-4,5-dihydroisoxazole-5-carboxamide; Compound A43: 2-Methoxy-2-oxoethyl 3-(2-chloro-4-fluoro-5-(5-methyl-3-(trifluoromethyl)-1 H -Pyrazol-1-yl)phenyl)-5-methyl-4,5-dihydroisoxazole-5-carboxylic acid ester; Compound A44: 2-ethoxy-2-oxoethyl 3-(2-chloro-4-fluoro-5-(5-methyl-3-(trifluoromethyl)-1 H -Pyrazol-1-yl)phenyl)-5-methyl-4,5-dihydroisoxazole-5-carboxylic acid ester; Compound A45: 2-oxo-2-propoxyethyl 3-(2-chloro-4-fluoro-5-(5-methyl-3-(trifluoromethyl)-1 H -Pyrazol-1-yl)phenyl)-5-methyl-4,5-dihydroisoxazole-5-carboxylic acid ester; Compound A46: 1-Methoxy-1-oxopropyl-2-yl 3-(2-chloro-4-fluoro-5-(5-methyl-3-(trifluoromethyl)-1 H -Pyrazol-1-yl)phenyl)-5-methyl-4,5-dihydroisoxazole-5-carboxylic acid ester; Compound A47: 1-ethoxy-1-oxopropyl-2-yl 3-(2-chloro-4-fluoro-5-(5-methyl-3-(trifluoromethyl)-1 H -Pyrazol-1-yl)phenyl)-5-methyl-4,5-dihydroisoxazole-5-carboxylic acid ester; Compound A48: 1-oxo-1-propoxypropyl-2-yl-3-(2-chloro-4-fluoro-5-(5-methyl-3-(trifluoromethyl)-1 H -Pyrazol-1-yl)phenyl)-5-methyl-4,5-dihydroisoxazole-5-carboxylic acid ester; Compound A49: 3-(2-chloro-4-fluoro-5-(5-methyl-3-(trifluoromethyl)-1 H -Pyrazol-1-yl)phenyl)-5-methyl-4,5-dihydroisoxazole-5-carboxylic acid epoxide-2-ylmethyl ester; Compound A50: 3-(2-chloro-4-fluoro-5-(5-methyl-3-(trifluoromethyl)-1 H 5-Pyrazol-1-yl)phenyl)-5-methyl-4,5-dihydroisoxazole-5-carboxylic acid (tetrahydrofuran-2-yl) methyl ester.

3. As described in any one of claims 1-2 N The method for preparing phenylpyrazole derivatives is characterized by, Includes the following steps: (1) Preparation of intermediate 2: Intermediate 1 was dissolved in 98% concentrated sulfuric acid to form a solution, which was then cooled in an ice bath. Subsequently, 65% concentrated nitric acid was added dropwise, and the reaction mixture was stirred for 30 minutes under ice bath conditions. The reaction mixture was then poured into ice and stirred vigorously for 30 minutes. The precipitate was collected by filtration, washed with water, and then dried under vacuum to obtain intermediate 2. (2) Preparation of intermediate 3: After mixing and stirring intermediate 2, ammonium chloride and 90% ethanol solution, the temperature was raised to 80 ℃, and then iron powder was slowly added. After the reaction system was reacted at 80 ℃ for 4 hours, the hot reaction mixture was filtered through a diatomaceous earth pad, and then successively subjected to extraction drying and column chromatography to obtain intermediate 3. (3) Preparation of intermediate 4: Intermediate 3 was dissolved in 80% ethanol, hydroxylamine hydrochloride was added, and the mixture was heated to 80 °C and reacted for 4 hours. After the reaction was completed, intermediate 4 was obtained by extraction, combining organic phases, drying, concentration and column chromatography purification. (4) Preparation of intermediate 5: Intermediate 4 was dissolved in DMF, and then 1,1,1-trifluoro-2,4-pentanedione and... O -(diphenylphosphono)hydroxylamine, heated to 85 °C; after the reaction was complete, the reaction mixture was poured into water and extracted with ethyl acetate. The combined organic phases were dried over anhydrous sodium sulfate and then concentrated under reduced pressure; the residue was purified by column chromatography to give intermediate 5; (5) Preparation of target compounds A1–A9: Intermediate 5 was dissolved in DMF, potassium carbonate and a substituted 2-chlorocarboxylic acid derivative were added, and the mixture was stirred at room temperature. After the reaction was completed, the product was subjected to extraction, separation of the organic layer, drying, concentration under reduced pressure, and column chromatography to obtain the final product. N -Phenylenol derivatives A1–A9; (6) Preparation of target compounds A10–A50: Intermediate 5 was dissolved in DMF and heated to 35 °C. Then, while stirring, the following was added to the solution: N -Chlorosuccinimide; After stirring continuously for 1 hour, the reaction solution was cooled to room temperature. Dichloromethane was then added for extraction, and the organic phase was washed twice each with 1 mol / L hydrochloric acid and saturated brine. The solution was dried over anhydrous sodium sulfate and filtered. The filtrate was cooled to 0–5 °C, and the substituted enoic acid derivative and triethylamine were slowly added dropwise. After the reaction was complete, the solution was subjected to extraction, separation of the organic layer, drying, and column chromatography to obtain the final product. N -Phenylpyrazole derivatives A10–A50.

4. As described in claim 3 N The method for preparing phenylpyrazole derivatives is characterized by, The substituted intermediate 1 is 2-chloro-4-fluorobenzaldehyde, 2,4-difluorobenzaldehyde, 2,4-dichlorobenzaldehyde, or 4-chloro-2-fluorobenzaldehyde.

5. As described in claim 3 N The method for preparing phenylpyrazole derivatives is characterized by, The substituted 2-chlorocarboxylic acid derivatives are methyl 2-chloroacetate, ethyl 2-chloroacetate, propyl 2-chloroacetate, butyl 2-chloroacetate, pentyl 2-chloroacetate, benzyl 2-chloroacetate, methyl 2-chloropropionate, ethyl 2-chloropropionate, propyl 2-chloropropionate, butyl 2-chloropropionate, pentyl 2-chloropropionate, tert-butyl 2-chloropropionate, 2-methoxy-2-oxoethyl 2-chloropropionate, 1-methoxy-1-oxopropyl-2-yl 2-chloropropionate, 3-methoxy-3-oxopropyl 2-chloropropionate, ethyl 2-((2-chloropropionyl)thio)acetate, ethyl 2-((2-chloropropionyl)thio)propionate, methyl 3-((2-chloropropionyl)thio)propionate, and 3-(2-chloropropionamide). The substituted olefinic acid derivative is any one of methyl methacrylate, methyl 2-chloro-2-methylpropionate, ethyl 2-chloro-2-methylpropionate, methyl 2-chlorobutyrate, ethyl 2-chlorobutyrate, methyl 2-chloro-3-methylbutyrate, and ethyl 2-chloro-3-methylbutyrate; the substituted olefinic acid derivative is methyl methacrylate, ethyl methacrylate, isopropyl methacrylate, tert-butyl methacrylate, propyl methacrylate, allyl methacrylate, sec-butyl methacrylate, butyl methacrylate, methoxyethyl methacrylate, 2,2,3,3-tetrafluoropropyl methacrylate, cyclohexyl methacrylate, phenyl methacrylate, methyl thiomethacrylate, ethyl thiomethacrylate, and propyl thiomethacrylate. N -Methylmethacrylamide, N,N -Dimethylmethylacrylamide, N -Ethylmethylacrylamide, N -Isopropylmethylacrylamide, N -Propylmethacrylamide, N -Butylmethacrylamide, 2-methoxy-2-oxoethyl methacrylate, 2-ethoxy-2-oxoethyl methacrylate, 2-propoxy-2-oxoethyl methacrylate, 1-methoxy-1-oxopropyl-2-yl methacrylate, 1-ethoxy-1-oxopropyl-2-ester methacrylate, 1-ethoxy-1-oxopropyl-2-ester methacrylate, glycidyl methacrylate, 2-epoxypentyl methacrylate.

6. As described in claim 1 or 2 N Application of phenylpyrazole derivatives in the preparation of herbicides and weed growth enzyme inhibitors.

7. As described in claim 6 N The application of phenylpyrazole in the preparation of herbicides and weed growth enzyme inhibitors is characterized by... The weeds mentioned are barnyard grass, foxtail grass, goosegrass, purslane, amaranth retroflexus, velvetleaf, gourd, seed amaranth, milkvetch, black millet, ryegrass, catnip, oats, hairy vetch, marigold, morning glory, zinnia, alfalfa, arrowroot, cassia seed, chicory, milk thistle, licorice, field clover, buffalo grass, sugar grass, kochia, duckweed, lamb's quarters, and dandelion.

Images