Aryl formyl pyrazole compound and synthesis method thereof

Abstract

The invention belongs to the technical field of organic synthesis, and particularly relates to an aryl formyl pyrazole compound and a synthesis method thereof. The synthesis method comprises the following steps: uniformly dispersing an aryl formic acid compound as shown in a formula 1 and a pyrazole alcohol compound as shown in a formula 2 in an organic solvent, stirring at room temperature, and sequentially adding an organic alkali and an onium salt condensing agent, so that the aryl formyl pyrazole compound can be efficiently prepared, the yield of the target compound is as high as 93%, and the aryl formyl pyrazole compound can be prepared by modifying hydroxyl on a pyrazole ring. A prodrug of the drug molecule or a compound with potential biological activity is obtained; according to the method disclosed by the invention, esterification and rearrangement two-step reaction are completed by a one-pot method under a one-step condensation condition for the first time, reaction steps are effectively shortened, and the preparation cost is remarkably reduced while the atom economy is greatly improved. Meanwhile, the method effectively overcomes the harsh reaction conditions of using highly toxic pipe products such as acetone cyanohydrin and trimethylsilyl cyanide in the existing rearrangement technology, and overcomes the technical defects of complex substrate synthesis, limited range and the like.

Description

Technical Field

[0001] This invention relates to the field of organic synthesis technology, and in particular to an arylformylpyrazole compound and its synthesis method. Background Technology

[0002] Arylformylpyrazole compounds have a wide range of pharmaceutical applications. For example, in 1979, JP54009279A disclosed that pyrazolylpyridinones exhibited good herbicidal activity; in 2004, WO2004033431A2 disclosed that heterocyclic compounds with an arylformylpyrazole structure, such as pyridine, pyrazine, pyrimidine, and pyridazine, can be used as nicotinic acid receptor agonists for the prevention and treatment of metabolic-related diseases; in 2005, Syngenta disclosed in WO2005058037A1 that pyridine heterocyclic compounds with an arylformylpyrazole structure were effective herbicides; and in 2018, Qingdao Qingyuan Compounds Co., Ltd. disclosed in CN107674025A a 4-benzoylpyrazole compound with excellent post-emergence herbicidal activity and crop compatibility. Simultaneously, arylformylpyrazole compounds are also important intermediates in pharmaceutical and organic synthesis, widely used in the synthesis of pharmaceuticals and fine chemical products.

[0003] For the synthesis of arylformylpyrazole compounds, existing techniques generally employ a two-step "esterification-rearrangement" reaction: esterification is carried out using acyl chlorides or condensing agents (DCC, CMPI, etc.), and rearrangement is catalyzed by acetone cyanohydrin, AlCl3, or trimethylcyanosilane. However, these methods all suffer from low yields (10–50%) and high catalyst / solvent risks, as shown in the literature ( J. Agric. Food Chem (2015, 63, 5587-5596) Using acetone cyanohydrin (a highly toxic controlled substance), only 20–50% of the target compound was obtained; (Reference ( J. Agric. Food Chem (2023, 71, 3950-3959) Using trimethylcyanosilane (highly toxic, flammable, explosive, releases hydrogen cyanide upon contact with water), only 10–30% of the target compound was obtained; (References) Molecular Diversity (2020, 24, 1025-1042) Using AlCl3 (a toxic and corrosive chemical) as a catalyst and CS2 (highly toxic, flammable, and explosive) as a solvent results in a process that is both highly toxic and dangerous, with low yields, making it difficult to scale up. Therefore, developing a safe, efficient, simple, and universally applicable method for preparing arylformylpyrazole compounds is of great significance. Summary of the Invention

[0004] The purpose of this invention is to provide a novel synthetic method for arylformylpyrazole compounds. Using arylformic acid and pyrazole alcohol compounds as raw materials, these compounds are dispersed in a reaction solvent and stirred at room temperature. An organic base and an onium salt condensing agent are added sequentially to efficiently prepare arylformylpyrazole compounds, achieving a target compound yield of up to 93%. Furthermore, the hydroxyl groups on the pyrazole ring can be further functionalized to obtain drug prodrugs or compounds with potential biological activity. The synthetic method is simple and easy to operate, with mild synthetic conditions, broad substrate applicability, and good substituent tolerance. The separation and purification process is simple, enabling the generation of the target compound in good to excellent yields. This invention is the first to achieve a two-step reaction of esterification and rearrangement under one-step condensation conditions, effectively shortening the reaction steps, significantly improving atom economy, and significantly reducing preparation costs. Simultaneously, this invention effectively overcomes the technical shortcomings of existing rearrangement techniques, such as the use of highly toxic controlled substances like acetone cyanohydrin and trimethylcyanosilane under harsh reaction conditions, and the limitation of complex substrate synthesis. Therefore, it is a safe, economical, and efficient general synthetic strategy.

[0005] A method for synthesizing arylformylpyrazole compounds according to the present invention includes the following steps: Compounds of Formula 1 and Formula 2 are added sequentially to a reaction vessel and uniformly dispersed in an organic solvent. The mixture is stirred at room temperature, and then an organic base and an onium salt condensing agent are added sequentially to generate arylformylpyrazole compounds of the general formula. The synthetic route is shown in the following reaction equation: In the above reaction formula, C represents 6-20 Aromatic rings, C 3-20 A heterocyclic aromatic ring; wherein the heteroatom is selected from N, O, or S; m is selected from integers 0, 1, 2, and 3; R represents substituents on the ring, and each R is independently selected from hydrogen, halogen, C, and so on. 1-6 Alkyl, C 1-6 Alkoxy, C 6-20 Aryl, C 3-20 Heteroaryl, phenoxy, thio, nitro, wherein the heteroatom in the heteroaryl group is selected from N, O or S; R' is selected from C 1-6 Alkyl, C 1-6 cycloalkyl; R″ is selected from hydrogen, C 1-6 Alkyl, trifluoromethyl; The condensing agent is an onium salt condensing agent.

[0006] Preferably, it represents a pyridine ring, pyrimidine ring, pyridazine ring, pyrazine ring, quinoxaline ring, quinoline ring, isoquinoline ring, naphthidine ring, o-phenanthroline ring, benzene ring, cyclophosphine ring, benzopyran ring, or pyran ring; R represents The substituents on the ring, each R, are independently selected from at least one of one or two hydrogen, chlorine, bromine, fluorine, methyl, methoxy, phenyl, phenoxy, substituted phenyl, nitro, and methylthio; the substitution is a total substitution by at least one of hydrogen, fluorine, chlorine, bromine, iodine, nitro, and isopropylsulfonyl. R′ is selected from methyl, ethyl, propyl, cyclopropyl, butyl, and cyclobutyl; R″ is selected from hydrogen, methyl, ethyl, propyl, cyclopropyl, and trifluoromethyl.

[0007] The organic solvent is selected from one or more of the following: methanol, ethanol, tert-butanol, isopropanol, acetonitrile, ethyl acetate, toluene, tetrahydrofuran, toluene, propanol, chlorobenzene, trifluoromethylbenzene, dichloromethane, dichloroethane, and DMF; preferably, the organic solvent is acetonitrile. The amount of solvent used is sufficient to ensure uniform dispersion of the reactants and facilitate stirring.

[0008] The onium salt condensing agent is selected from at least one of tetramethylchlorourea hexafluorophosphate (TCFH), tetramethylfluorourea hexafluorophosphate (TFFH), benzotriazole-1-yloxytris(dimethylamino)phosphonium hexafluorophosphate (BOP), benzotriazole-1-yloxytripyrrolylphosphonium hexafluorophosphate (PyBOP), 2-(7-azabenzotriazole)-N,N,N',N'-tetramethylurea hexafluorophosphate (HATU), and O-benzotriazole-tetramethylurea hexafluorophosphate (HBTU); preferably, the onium salt condensing agent is tetramethylchlorourea hexafluorophosphate (TCFH). The organic base is at least one of N-methylimidazolium (NMI) and N-methylmorpholine (NMM); preferably, the organic base is N-methylimidazolium (NMI).

[0009] The reaction temperature is rt-70℃, preferably rt.

[0010] The molar ratio of compounds 1 and 2 in the formula is 1:1-1.25; the molar ratio of onium salt condensing agent and organic base is 1-1.25:1-3.0; preferably, the molar ratio of compounds 1 and 2 in the formula is 1:1.25; the molar ratio of onium salt condensing agent and organic base is 1.25:3.0.

[0011] The purification process includes the following steps: After the reaction is complete, the reaction solution is allowed to stand overnight to allow the target compound to precipitate. The solution is then filtered, washed with petroleum ether, and dried. If no solid precipitates, the organic phase is concentrated under reduced pressure to obtain the residue. The residue is then separated by silica gel column chromatography using a 200-300 mesh silica gel column to obtain the target product shown in Formula 3. The elution solvent for the column chromatography separation is a mixture of dichloromethane and ethyl acetate or a mixture of dichloromethane, ethyl acetate, and methanol. The volume ratio of the dichloromethane and ethyl acetate mixture is 2:1 to 1:1. The volume ratio of the dichloromethane, ethyl acetate, and methanol mixture is 30:30:1 to 5:5:1.

[0012] Compared with the prior art, the method of the present invention has the following beneficial effects: (1) This invention uses arylformic acid and pyrazol compounds as raw materials, disperses them in an organic solvent, stirs at room temperature, and sequentially adds an organic base and an onium salt condensing agent. Using the organic base as a catalyst, arylformylpyrazole compounds can be efficiently prepared with a target compound yield as high as 93%. Furthermore, the hydroxyl groups on the pyrazole ring can be further functionalized to obtain drug prodrugs or compounds with potential biological activity. The synthetic method is simple and easy to operate, with mild synthetic conditions, broad substrate applicability, and good substituent tolerance. The separation and purification process is simple to operate and can generate the target compound in good to excellent yields.

[0013] (2) This invention is the first to achieve a two-step reaction of esterification and rearrangement under one-step condensation conditions, which effectively shortens the reaction steps, greatly improves atom economy, and significantly reduces preparation costs. At the same time, this invention effectively overcomes the technical defects of existing rearrangement technologies, such as the use of highly toxic controlled substances like acetone cyanohydrin and trimethylcyanosilane, and solves the limitations of complex substrate synthesis. It has the advantages of safe, efficient, economical and green production process. Attached Figure Description Figure 1 This is the 1H NMR spectrum of the arylformylpyrazole compound 4 prepared in Example 1 of this invention; Figure 2 This is the carbon NMR spectrum of arylformylpyrazole compound 4 obtained in Example 1 of this invention; Figure 3 This is the 1H NMR spectrum of the arylformylpyrazole compound 8 prepared in Example 7 of this invention; Figure 4 This is the carbon NMR spectrum of the arylformylpyrazole compound 8 prepared in Example 7 of this invention; Detailed Implementation The present invention will be further described in detail below with reference to specific embodiments. However, the present invention is not limited to these embodiments, and 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. In the following text, unless otherwise specified, the methods used are conventional methods in the art, the raw material compounds used are synthesized and prepared according to known methods in the prior art, and all reagents used are obtained through commercial channels without further purification.

[0014] Example 1 Quinoline-2-carboxylic acid (1.0 mmol) as shown in Formula 1a and 1,3-dimethyl-5-hydroxypyrazole (1.25 mmol) as shown in Formula 2a were added to a round-bottom flask. The starting materials were dispersed in 8 ml of ultra-dry acetonitrile and stirred. Then, NMI (3.0 mmol) and TCFH (1.25 mmol) were added sequentially. The reactor was stirred at room temperature for 4 h. After the starting materials were completely consumed as monitored by TLC, the reaction solution was filtered and washed with petroleum ether to obtain the arylformylpyrazole compound shown in Formula 4, with a yield of 93%, as an orange solid. Its characterization by 1H NMR was as follows: Figure 1 As shown, the carbon NMR characterization is as follows: Figure 2 As shown, the NMR data are as follows: 1 HNMR (400 MHz, CDCl3) δ 8.53 – 8.48 (m, 2H), 8.21 (d, J = 9.2 Hz, 1H), 7.98 (d, J =7.6 Hz, 1H), 7.90 (t, J = 8.4 Hz, 1H), 7.75 (t, J = 8.4 Hz, 1H), 3.66 (s, 3H), 2.53 (s, 3H). 13 C NMR (101 MHz, CDCl3) δ 180.08, 157.17, 153.98, 152.41, 142.83, 139.99, 131.86, 129.59, 129.42, 128.21, 126.55, 121.05, 103.47, 33.32, 16.85. Example 2 The onium salt condensing agents were replaced with TFFH, HATU, HBTU, BOP, and PyBOP, respectively, and the other conditions and operations were the same as in Example 1. The yields of the target compounds were 89%, 71%, 84%, 54%, and 47%, respectively.

[0015] Example 3 The organic bases were replaced with NMM, 4-dimethylaminopyridine (DMAP), 1-hydroxybenzotriazole (HOBT), and triethylenediamine (DABCO), respectively, and the other conditions and operations were the same as in Example 1. The yields of the target compounds were 0, 88%, 0, and 0, respectively.

[0016] Example 4 The reaction solvents were replaced with methanol, DCM, and tetrahydrofuran, respectively, and the other conditions and operations were the same as in Example 1. The yields of the target compounds were 0%, 52%, and 46%, respectively.

[0017] Example 5 The equivalents of NMI were replaced with 1.2 mmol and 2.2 mmol, respectively, and the other conditions and operations were the same as in Example 1. The yields of the target compounds were 5% and 51%, respectively.

[0018] Example 6 The equivalent of 1,3-dimethyl-5-hydroxypyrazole was replaced with 1.0 mmol, and the other conditions and operations were the same as in Example 1. The yield of the target compound was 74%.

[0019] Example 7 1.0 mmol of 6-chloroquinoline-2-carboxylic acid (Formula 1b) and 1.25 mmol of 1,3-dimethyl-5-hydroxypyrazole (Formula 2a) were added to a round-bottom flask. The reactants were dispersed in 8 ml of ultra-dry acetonitrile and stirred. Then, 3.0 mmol of NMI and 1.25 mmol of TCFH were added sequentially. The reactor was refluxed at 70 °C for 4 h. After complete consumption of the reactants was monitored by TLC, the reaction solution was allowed to stand overnight, and a solid precipitated. The solid was filtered and washed with petroleum ether to obtain the arylformylpyrazole compound shown in Formula 8, with a yield of 91%, as an orange-red solid. Its characterization by 1H NMR was as follows: Figure 3 As shown, the carbon NMR characterization is as follows: Figure 4 As shown, the NMR data are as follows: 1 H NMR (500 MHz, CDCl3) δ 8.10 (d, J = 9.0 Hz, 1H), 7.97 (d, J = 9.0 Hz, 1H), 8.08 (d, J = 9.0 Hz, 1H), 7.93 (s, 1H), 7.79 (d, J = 9.0 Hz, 1H), 3.63 (s, 3H), 2.49 (s, 3H). 13C NMR (126 MHz, CDCl3) δ 179.82, 156.61, 154.26, 152.45, 141.38, 138.79, 135.52, 132.78, 130.08, 128.19, 126.91, 122.06, 103.25, 33.35, 16.79. Example 8 Substrate Expansion Experiments: Based on the optimal experimental conditions (Examples 1 or 7), the universality, substituent tolerance, and yield of the target compounds under these optimal catalytic reaction conditions were further investigated. The results are shown below: The general formulas of compounds 4, 5, and 6 are: ,in: Compound 4: R′=CH3, R′′=CH3, yield 93%; Compound 5: R′=CH2CH3, R′′=H, yield 56%; following the method of Example 1, 1,3-dimethyl-5-hydroxypyrazole was replaced with 1-ethyl-1H-pyrazole-5-ol; Compound 6: R′=CH3, R′′=H, yield 61%; following the method of Example 1, 1,3-dimethyl-5-hydroxypyrazole was replaced with 1-methyl-5-hydroxypyrazole; Compound 7: The yield was 63%; following the method of Example 1, quinoline-2-carboxylic acid was replaced with 4-methoxyquinoline-2-carboxylic acid; Compound 8: The yield was 91%. The general formulas of compounds 9 and 10 are: ,in: Compound 9: R′=CH3, R′′=CH3, yield 39%; following the method of Example 1, quinoline-2-carboxylic acid was replaced with 2-quinoxaloline carboxylic acid; Compound 10: R′=CH3, R′′=H, yield 68%; following the method of Example 1, quinoline-2-carboxylic acid was replaced with 2-quinoxalolinecarboxylic acid; 1,3-dimethyl-5-hydroxypyrazole was replaced with 1-methyl-5-hydroxypyrazole; The general formulas of compounds 11 and 12 are: ,in: Compound 11: R′=CH3, R′′=CH3, yield 74%; following the method of Example 1, quinoline-2-carboxylic acid was replaced with 1,8-naphthyl-2-carboxylic acid; Compound 12: R′=CH3, R′′=H, yield 34%; following the method of Example 1, quinoline-2-carboxylic acid was replaced with 1,8-naphthyl-2-carboxylic acid; 1,3-dimethyl-5-hydroxypyrazole was replaced with 1-methyl-5-hydroxypyrazole; Compound 13: The yield was 37%, and the reaction temperature was 70°C. Following the method of Example 7, quinoline-2-carboxylic acid was replaced with 1,7-naphthyl-2-carboxylic acid. Compound 14: The yield was 67%; following the method of Example 1, quinoline-2-carboxylic acid was replaced with 1,6-naphthyl-2-carboxylic acid; Compound 15: The yield was 62%; following the method of Example 1, quinoline-2-carboxylic acid was replaced with 1,10-phenanthroline-2-carboxylic acid; Compound 16: The yield was 15%; following the method of Example 1, quinoline-2-carboxylic acid was replaced with isoquinoline carboxylic acid; Compound 17: The yield was 71%; following the method of Example 1, quinoline-2-carboxylic acid was replaced with isoquinoline-3-carboxylic acid; The general formulas of compounds 18, 19, and 20 are: ,in: Compound 18: R=H, yield 65%; following the method of Example 1, quinoline-2-carboxylic acid was replaced with pyridazine-3-carboxylic acid; Compound 19: R=OCH3, yield 83%, reaction temperature 70°C; following the method of Example 7, quinoline-2-carboxylic acid was replaced with 6-methoxypyridazine-3-carboxylic acid; Compound 20: R=Cl, yield 84%; following the method of Example 1, quinoline-2-carboxylic acid was replaced with 6-chloropyridazine-3-carboxylic acid; The general formulas of compounds 21, 22, and 23 are: ,in: Compound 21: R′=CH3, R′′=CH3, yield 65%; following the method of Example 1, quinoline-2-carboxylic acid was replaced with 6-phenylpyridine-2-carboxylic acid; Compound 22: R′=CH2CH3, R′′=H, yield 83%, reaction temperature 70℃; referring to the method of Example 7, quinoline-2-carboxylic acid was replaced with 6-phenylpyridine-2-carboxylic acid, and 1,3-dimethyl-5-hydroxypyrazole was replaced with 1-ethyl-1H-pyrazole-5-ol; Compound 23: R′=CH3, R′′=H, yield 84%; following the method of Example 1, quinoline-2-carboxylic acid was replaced with 6-phenylpyridine-2-carboxylic acid, and 1,3-dimethyl-5-hydroxypyrazole was replaced with 1-methyl-5-hydroxypyrazole; Compound 24: The yield was 50%; following the method of Example 1, quinoline-2-carboxylic acid was replaced with 6-(4-(1-methylethyl)sulfonyl)phenyl)-2-carboxylic acid; Compound 25: The yield was 50%; following the method of Example 1, quinoline-2-carboxylic acid was replaced with 6-(2-chlorophenyl)-2-pyridinecarboxylic acid; Compound 26: The yield was 82%; following the method of Example 1, quinoline-2-carboxylic acid was replaced with 6-(3-nitrophenyl)-2-pyridinecarboxylic acid; The general formulas of compounds 27, 28, and 29 are: ,in: Compound 27: R=H, yield 62%, reaction temperature 70°C; following the method of Example 7, quinoline-2-carboxylic acid was replaced with 2-pyridinecarboxylic acid; Compound 28: R=CH3, yield 64%, reaction temperature 70°C; following the method of Example 7, quinoline-2-carboxylic acid was replaced with 6-methylpyridine-2-carboxylic acid; Compound 29: R=OPh, yield 48%, reaction temperature 70°C; following the method of Example 7, quinoline-2-carboxylic acid was replaced with 6-phenoxypyridine-2-carboxylic acid; The general formulas of compounds 30, 31, and 32 are: ,in: Compound 30: R′=CH3, R′′=CH3, yield 84%; following the method of Example 1, quinoline-2-carboxylic acid was replaced with 4-bromopyridine-2-carboxylic acid; Compound 31: R′=CH2CH3, R′′=H, yield 26%; following the method of Example 1, quinoline-2-carboxylic acid was replaced with 4-bromopyridine-2-carboxylic acid, and 1,3-dimethyl-5-hydroxypyrazole was replaced with 1-ethyl-1H-pyrazole-5-ol; Compound 32: R′=CH3, R′′=H, yield 68%; following the method of Example 1, quinoline-2-carboxylic acid was replaced with 4-bromopyridine-2-carboxylic acid, and 1,3-dimethyl-5-hydroxypyrazole was replaced with 1-methyl-5-hydroxypyrazole; Compound 33: The yield was 82%; following the method of Example 1, quinoline-2-carboxylic acid was replaced with 5-nitropyridine-2-carboxylic acid; Compound 34: The yield was 78%; following the method of Example 1, quinoline-2-carboxylic acid was replaced with 2-pyrazinic acid; Compound 35: The yield was 22%, and the reaction temperature was 70°C. Following the method of Example 7, quinoline-2-carboxylic acid was replaced with 5-chloropyrazine-2-carboxylic acid. Compound 36: The yield was 67%, and the reaction temperature was 70°C. Following the method of Example 7, quinoline-2-carboxylic acid was replaced with 6-methoxypyrazine-2-carboxylic acid. Compound 37: The yield was 78%, and the reaction temperature was 70°C. Following the method of Example 7, quinoline-2-carboxylic acid was replaced with 5,6-dimethylpyrazine-2-carboxylic acid. Compound 38: The yield was 83%; following the method of Example 1, quinoline-2-carboxylic acid was replaced with pyrimidine-2-carboxylic acid; Compound 39: The yield was 90%; following the method of Example 1, quinoline-2-carboxylic acid was replaced with 4-phenylpyrimidine-2-carboxylic acid; Compound 40: The yield was 50%, and the reaction temperature was 70°C; following the method of Example 7, quinoline-2-carboxylic acid was replaced with 2-phenylpyrimidine-4-carboxylic acid; The general formulas of compounds 41, 42, and 43 are: ,in: Compound 41: R′=CH3, R′′=CH3, yield 36%; following the method of Example 1, quinoline-2-carboxylic acid was replaced with pyrimidine-4-carboxylic acid; Compound 42: R′=CH2CH3, R′′=H, yield 83%; following the method of Example 1, quinoline-2-carboxylic acid was replaced with pyrimidin-4-carboxylic acid, and 1,3-dimethyl-5-hydroxypyrazole was replaced with 1-ethyl-1H-pyrazole-5-ol; Compound 43: R′=CH3, R′′=H, yield 42%; following the method of Example 1, quinoline-2-carboxylic acid was replaced with pyrimidine-4-carboxylic acid, and 1,3-dimethyl-5-hydroxypyrazole was replaced with 1-methyl-5-hydroxypyrazole; The general formulas of compounds 44 and 45 are: ,in: Compound 44: R=CH3CHCH3, yield 47%; following the method of Example 1, quinoline-2-carboxylic acid was replaced with 2-isopropylpyrimidine-4-carboxylic acid; Compound 45: R=SCH3, yield 62%, reaction temperature 70°C; following the method of Example 7, quinoline-2-carboxylic acid was replaced with 2-methylthio-pyrimidine-4-carboxylic acid; Compound 46: The yield was 73%, and the reaction temperature was 70°C. Following the method of Example 7, quinoline-2-carboxylic acid was replaced with 2,6-dimethylpyrimidin-4-carboxylic acid. Compound 47: The yield was 63%, and the reaction temperature was 70°C. Following the method of Example 7, quinoline-2-carboxylic acid was replaced with 2,6-dimethoxypyrimidine-4-carboxylic acid. Compound 48: The yield was 53%; following the method of Example 1, quinoline-2-carboxylic acid was replaced with 4-benzopyranone-2-carboxylic acid; Compound 49: The yield was 64%; following the method of Example 1, quinoline-2-carboxylic acid was replaced with kaomolybdic acid; Table 1. Spectral data of the target compounds obtained in Examples 1-8

Claims

1. A method for synthesizing arylformylpyrazole compounds, characterized in that, Includes the following steps: Arylformic acid compounds represented by Formula 1 and pyrazol compounds represented by Formula 2 are added sequentially to a reaction vessel and uniformly dispersed in an organic solvent. The mixture is stirred at room temperature, and then an organic base and an onium salt condensing agent are added sequentially to generate arylformylpyrazole compounds represented by Formula 3. The synthetic route is as follows: In the above reaction formula, Indicate C 6-20 Aromatic rings, C 3-20 A heterocyclic aromatic ring; wherein the heteroatom is selected from N, O, or S; m is selected from integers 0, 1, 2, and 3; R represents substituents on the ring, and each R is independently selected from hydrogen, halogen, C, and so on. 1-6 Alkyl, C 1-6 Alkoxy, C 6-20 Aryl, C 3-20 Heteroaryl, phenoxy, thio, nitro, wherein the heteroatom in the heteroaryl group is selected from N, O or S; R' is selected from C 1-6 Alkyl, C 1-6 cycloalkyl; R″ is selected from hydrogen, C 1-6 Alkyl, trifluoromethyl; The condensing agent is an onium salt condensing agent.

2. The method for synthesizing arylformylpyrazole compounds according to claim 1, characterized in that, It represents pyridine ring, pyrimidine ring, pyridazine ring, pyrazine ring, quinoxaline ring, quinoline ring, isoquinoline ring, naphthidine ring, o-phenanthroline ring, benzene ring, cyclophosphine ring, benzopyran ring, or pyran ring; R represents The substituents on the ring, each R, are independently selected from at least one of one or two hydrogen, chlorine, bromine, fluorine, methyl, methoxy, phenyl, phenoxy, substituted phenyl, nitro, and methylthio; the substitution is a total substitution by at least one of hydrogen, fluorine, chlorine, bromine, iodine, nitro, and isopropylsulfonyl. R′ is selected from methyl, ethyl, propyl, cyclopropyl, butyl, and cyclobutyl; R″ is selected from hydrogen, methyl, ethyl, propyl, cyclopropyl, and trifluoromethyl.

3. The method for synthesizing arylformylpyrazole compounds according to claim 1 or 2, characterized in that, The organic solvent is selected from one or a mixture of several of the following: methanol, ethanol, tert-butanol, isopropanol, acetonitrile, ethyl acetate, toluene, tetrahydrofuran, toluene, propanol, chlorobenzene, trifluoromethylbenzene, dichloromethane, dichloroethane, and DMF.

4. The method for synthesizing arylformylpyrazole compounds according to claim 1 or 2, characterized in that, The onium salt condensing agent is selected from at least one of tetramethylchlorourea hexafluorophosphate (TCFH), tetramethylfluorourea hexafluorophosphate (TFFH), benzotriazole-1-yloxytris(dimethylamino)phosphonium hexafluorophosphate (BOP), benzotriazole-1-yl-oxytripyrrolylphosphonium hexafluorophosphate (PyBOP), 2-(7-azabenzotriazole)-N,N,N',N'-tetramethylurea hexafluorophosphate (HATU), and O-benzotriazole-tetramethylurea hexafluorophosphate (HBTU); the organic base is N-methylimidazolium (NMI) or N-methylmorpholine (NMM).

5. The method for synthesizing arylformylpyrazole compounds according to claim 1 or 2, characterized in that, The reaction temperature is rt-70℃.

6. The method for synthesizing arylformylpyrazole compounds according to claim 1 or 2, characterized in that, The molar ratio of the compound of Formula 1 to the compound of Formula 2 is 1:1-1.25; the molar ratio of the onium salt condensing agent and the organic base is 1.25:1.2-3.

2.

7. The method for synthesizing arylformylpyrazole compounds according to claim 1 or 2, characterized in that, The purification process includes the following steps: after the reaction is complete, the reaction solution is allowed to stand overnight to precipitate the target compound, filtered, washed with petroleum ether, and dried; if no solid precipitates, the organic phase is concentrated under reduced pressure to obtain the residue, and the residue is separated by silica gel column chromatography to obtain the target product shown in Formula 3.

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