A pyrazole compound and its preparation method and application

Abstract

The present invention belongs to the technical field of organic synthesis, and specifically relates to a pyrazole compound, a preparation method thereof, and an application thereof. The pyrazole compound provided by the present invention has a structure shown in Formula I; wherein R1 and R2 are independently aryl, substituted aryl, or alkyl. The pyrazole compound provided by the present invention contains both amide and ester functional groups in its parent structure and can be used as a new drug skeleton. The preparation method provided by the present invention has the advantages of simple process, mild conditions, easy control, high reaction efficiency, cheap and readily available raw materials, no use of metal catalysts, and good functional group tolerance. The prepared pyrazole compound has a high purity of 98.5% to 99.9%, and has great market promotion value. Compared with multi-step synthesis reactions, the target product can be obtained in a one-step reaction, and the reaction yield reaches 77%, which has the advantages of high reaction efficiency and step economy.

Description

Technical Field

[0001] The present invention belongs to the technical field of organic synthesis, and in particular relates to a pyrazole compound and a preparation method and application thereof. Background Art

[0002] Pyrazole derivatives are an important class of compounds with a wide range of applications due to their anti-inflammatory and antibacterial activities. Pyrazole is one of the most important scaffolds in pharmaceuticals, and many pyrazole scaffold drugs contain pyrazole derivatives, which exhibit a wide range of biological activities. For example, celecoxib, a nonsteroidal anti-inflammatory drug used to relieve arthritis symptoms, contains a pyrazole derivative. Due to their excellent biological activity and synthetic applications, the construction of pyrazole scaffolds has attracted considerable attention in recent years.

[0003] Jie-Ping Wan et al. (Demao Chen, Liyun Zhou, Yunyun Liu, Jie-Ping Wan. Three-component synthesis of N-naphthyl pyrazoles via Rh(iii)-catalyzed cascadepyrazole annulation and Satoh-Miura benzannulation [J]. Chemical Communications, 2023, 59(27): 4036-4039.) reported the formation of pyrazoles from enaminones, arylhydrazines, and alkynes under rhodium catalysis. The chemical reaction is as follows:

[0004]

[0005] However, the above-mentioned pyrazole compounds have the disadvantage that the raw materials and catalysts are difficult to obtain. Summary of the Invention

[0006] The purpose of the present invention is to provide a pyrazole compound and its preparation method and application. The pyrazole compound provided by the present invention has both amide and ester structural units in its structure and can be used as a new drug skeleton. It also has the advantage of readily available raw materials.

[0007] In order to achieve the above object, the present invention provides the following technical solutions:

[0008] The present invention provides a pyrazole compound having the structure shown in Formula I:

[0009]

[0010] wherein R1 and R2 are independently aryl, substituted aryl or alkyl.

[0011] Preferably, the number of carbon atoms in the alkyl group is 2 to 6;

[0012] The substituent group of the substituted aryl group includes one or more of an alkyl group, an alkoxy group, a nitro group, an ester group and a halogen group.

[0013] Preferably, it has the following structure:

[0014]

[0015]

[0016] The present invention also provides a method for preparing the pyrazole compound described in the above technical solution, comprising the following steps:

[0017] mixing an acrylamide compound, a diazoacetate, an oxidant, an alkaline reagent and an organic solvent to carry out a coupling addition reaction to obtain the pyrazole compound;

[0018] The acrylamide compound has a structure shown in Formula II:

[0019]

[0020] The diazoacetate has a structure shown in Formula III:

[0021]

[0022] Preferably, the acrylamide compounds include N-phenylacrylamide, N-(4-methylphenyl)acrylamide, N-(4-methoxyphenyl)acrylamide, N-(4-fluorophenyl)acrylamide, N-(4-chlorophenyl)acrylamide, N-(4-bromophenyl)acrylamide, N-(4-trifluoromethylphenyl)acrylamide, 4-acrylamide ethyl benzoate, N-(3-fluorophenyl)acrylamide, N-(3-chlorophenyl)acrylamide, N-(2-methylphenyl)acrylamide, N-(2-fluorophenyl)acrylamide, N-(2-chlorophenyl)acrylamide, N-(2 N-(2,4-dimethylphenyl)acrylamide, N-(2,4-dimethoxyphenyl)acrylamide, N-(2,4-dichlorophenyl)acrylamide, N-(2-methoxy-4-nitrophenyl)acrylamide, N-(2,4-dichlorophenyl)acrylamide, N-(3-bromo-4-methylphenyl)acrylamide, N-(2,5-dichlorophenyl)acrylamide, N-(2,3-dimethylphenyl)acrylamide, N-(2,4,6-trimethylphenyl)acrylamide, N-cyclohexylacrylamide or N-(naphthalen-2-yl)prop-2-enamide.

[0023] Preferably, the diazoacetate includes ethyl diazoacetate, benzyl diazoacetate, phenoxyethylene glycol diazoacetate or tert-butyl diazoacetate.

[0024] Preferably, the molar ratio of the acrylamide compound to the diazoacetic acid ester is 1:1 to 1.25.

[0025] Preferably, the oxidant is 2,2,6,6-tetramethylpiperidinyl oxide;

[0026] The molar ratio of the acrylamide compound to the oxidant is 1:2-2.5.

[0027] Preferably, the coupling addition reaction is carried out at a temperature of 80 to 100° C. and for a time of 12 to 24 hours.

[0028] The present invention also provides the use of the pyrazole compound described in the above technical solution or the pyrazole compound obtained by the preparation method described in the above technical solution in the preparation of medicines or pesticides.

[0029] The present invention provides a pyrazole compound having the structure shown in Formula I; wherein R1 and R2 are independently aryl, substituted aryl, or alkyl. The pyrazole compound provided by the present invention has a novel structure, with both amide and ester structural units in its parent structure, and can be used as a new drug backbone.

[0030]

[0031] The preparation method provided by the present invention has the advantages of simple process, mild conditions, easy control, high reaction efficiency, readily available and inexpensive raw materials, no metal catalysts, and good functional group tolerance. The prepared pyrazole compound has a high purity of 98.5-99.9%, which has great market value. Compared with multi-step synthesis reactions, the present invention can obtain the target product in a single step with a reaction yield of 77%, which has the advantages of high reaction efficiency and process economy. DETAILED DESCRIPTION

[0032] The present invention provides a pyrazole compound having the structure shown in Formula I:

[0033]

[0034] wherein R1 and R2 are independently aryl, substituted aryl or alkyl.

[0035] In the present invention, unless otherwise specified, all raw materials are commercially available products well known to those skilled in the art or products prepared by those skilled in the art using conventional methods.

[0036] In the present invention, the number of carbon atoms of the alkyl group is preferably 2 to 6, more preferably 4 to 6; the alkyl group is preferably ethyl, tert-butyl or cycloalkyl; the cycloalkyl group is preferably cyclohexyl.

[0037] In the present invention, the aryl group preferably includes a phenyl group or a naphthyl group.

[0038] In the present invention, the number of substituent groups of the substituted aryl is preferably 1 to 3, more preferably 1 to 2; the substituent groups of the substituted aryl are preferably one or more of alkyl, alkoxy, nitro, ester and halogen groups; the number of carbon atoms of the alkyl group is preferably 1; the alkoxy group is preferably methoxy or ethoxy; the ester group is preferably ethyl formate, methyl formate, benzyl formate, tert-butyl formate, phenoxy formate; the halogen group is preferably F-, Cl-, -CF3, Br- or I-.

[0039] In the present invention, the pyrazole compound preferably has the following structure:

[0040]

[0041]

[0042] The present invention also provides a method for preparing the pyrazole compound described in the above technical solution, comprising the following steps:

[0043] mixing an acrylamide compound, a diazoacetate, an oxidant, an alkaline reagent and an organic solvent to carry out a coupling addition reaction to obtain the pyrazole compound;

[0044] The acrylamide compound has a structure shown in Formula II:

[0045]

[0046] The diazoacetate has a structure shown in Formula III:

[0047]

[0048] In the present invention, the acrylamide compounds preferably include N-phenylacrylamide, N-(4-methylphenyl)acrylamide, N-(4-methoxyphenyl)acrylamide, N-(4-fluorophenyl)acrylamide, N-(4-chlorophenyl)acrylamide, N-(4-bromophenyl)acrylamide, N-(4-trifluoromethylphenyl)acrylamide, 4-acrylamide ethyl benzoate, N-(3-fluorophenyl)acrylamide, N-(3-chlorophenyl)acrylamide, N-(2-methylphenyl)acrylamide, N-(2-fluorophenyl)acrylamide, N-(2-chlorophenyl)acrylamide, N- (2-bromophenyl)acrylamide, N-(2,4-dimethylphenyl)acrylamide, N-(2,4-dimethoxyphenyl)acrylamide, N-(2,4-dichlorophenyl)acrylamide, N-(2-methoxy-4-nitrophenyl)acrylamide, N-(2,4-dichlorophenyl)acrylamide, N-(3-bromo-4-methylphenyl)acrylamide, N-(2,5-dichlorophenyl)acrylamide, N-(2,3-dimethylphenyl)acrylamide, N-(2,4,6-trimethylphenyl)acrylamide, N-cyclohexylacrylamide or N-(naphthalen-2-yl)prop-2-enamide.

[0049] In the present invention, the diazoacetate preferably includes ethyl diazoacetate, benzyl diazoacetate, phenoxyethylene diazoacetate or tert-butyl diazoacetate; the diazoacetate preferably has the structure shown below:

[0050]

[0051] In the present invention, the molar ratio of the acrylamide compound to the diazoacetic acid ester is preferably 1:1-1.25, more preferably 1:1.1-1.25.

[0052] In the present invention, the oxidizing agent is preferably 2,2,6,6-tetramethylpiperidinyloxide.

[0053] In the present invention, the molar ratio of the acrylamide compound to the oxidant is preferably 1:2-2.5, more preferably 1:2.2-2.5.

[0054] In the present invention, the alkaline agent preferably includes an inorganic alkaline agent and / or an organic alkaline agent; the inorganic alkaline agent preferably includes one or more of potassium phosphate, sodium carbonate and potassium carbonate, more preferably potassium phosphate and / or sodium carbonate; the organic alkaline agent preferably includes one or more of sodium ethoxide, sodium acetate and potassium tert-butoxide, more preferably sodium ethoxide.

[0055] In the present invention, the molar ratio of the acrylamide compound to the alkaline agent is preferably 1:1-2, more preferably 1:1.5-2.

[0056] In the present invention, the organic solvent preferably includes acetonitrile, tetrahydrofuran, dichloromethane, N,N-dimethylformamide, dimethyl sulfoxide or toluene, more preferably tetrahydrofuran, N,N-dimethylformamide, dimethyl sulfoxide or toluene, and most preferably N,N-dimethylformamide or toluene.

[0057] In the present invention, the usage ratio of the polar organic solvent to the acrylamide compound is preferably 1 L: 0.1-0.4 mol, more preferably 1 L: 0.1-0.2 mol.

[0058] The present invention has no particular limitation on the mixing process, and the materials can be mixed uniformly according to a process well known in the art.

[0059] In the present invention, the coupling addition reaction is preferably carried out at a temperature of 80 to 100° C., more preferably 90 to 100° C., and for a time of 12 to 24 hours, more preferably 12 hours. The coupling addition reaction is preferably carried out under stirring. The present invention does not particularly limit the stirring rate; the stirring rate may be carried out according to procedures well known in the art to ensure smooth reaction.

[0060] After the coupling addition reaction, the present invention preferably includes purifying the resulting product system; the purification method is preferably column chromatography; the eluent used for the column chromatography is preferably a mixed solvent of petroleum ether and ethyl acetate; the volume ratio of petroleum ether to ethyl acetate in the mixed solvent is preferably 1 to 20:1, more preferably 2 to 4:1. The present invention does not have any particular limitations on the specific process of the column chromatography, and methods familiar to those skilled in the art can be used. The present invention uses petroleum ether and ethyl acetate as eluents for purification, which can obtain the target compound with high purity.

[0061] The present invention also provides the use of the pyrazole compound described in the above technical solution or the pyrazole compound obtained by the preparation method described in the above technical solution in the preparation of medicines or pesticides.

[0062] The present invention does not have any special restrictions on the application process of the pyrazole compounds in the preparation of medicines or pesticides, and methods well known to those skilled in the art can be used.

[0063] To further illustrate the present invention, the pyrazole compounds provided by the present invention, their preparation methods and applications are described in detail below with reference to the following examples, but they should not be construed as limiting the scope of protection of the present invention.

[0064] Example 1

[0065] The pyrazole compound obtained in this embodiment has the following structure:

[0066]

[0067] 0.2 mmol N-phenylacrylamide, 0.25 mmol ethyl diazoacetate, 0.5 mmol 2,2,6,6-tetramethylpiperidinyl oxide as an oxidant, 0.4 mmol sodium ethoxide, and 2 mL toluene were added to a reaction tube, and the mixture was stirred at 100°C for 12 h. After the reaction, the mixture was separated and purified by column chromatography. The volume ratio of petroleum ether to ethyl acetate in the column chromatography eluent was 4:1, and the purified target product was obtained with a yield of 77% and a purity of 99.9%.

[0068] The structure of the obtained product was characterized, and the structural characterization data are as follows:

[0069] 1 H NMR (400MHz, DMSO-d6, ppm) δ14.50 (s, 1H), 10.24 (s, 1H), 7.82 (d, J = 8.0hz, 2H), 7.32 (t, J = 7 .8hz,2H),7.06(t,J=7.4hz,1H),4.29(q,J=7.1hz,2H),3.63(s,1H),1.28(t,J=7.1hz,3H);

[0070] 13 C{ 1 H}NMR (100MHz, DMSO-d6, ppm) δ160.9,156.8,142.3,138.8,129.1,124.3,120.8,120.7,109.2,61.2,14.6;

[0071] MS(EI,70eV)m / z 259,214,167,121,93,77.

[0072] Example 2

[0073] The pyrazole compound obtained in this embodiment has the following structure:

[0074]

[0075] 0.2 mmol N-(4-methylphenyl)acrylamide, 0.25 mmol ethyl diazoacetate, 0.5 mmol 2,2,6,6-tetramethylpiperidinyl oxide as an oxidant, 0.4 mmol sodium ethoxide, and 2 mL toluene were added to a reaction tube, and the mixture was stirred at 100°C for 12 hours. After the reaction, the mixture was separated and purified by column chromatography. The volume ratio of petroleum ether to ethyl acetate in the column chromatography eluent was 4:1, and the purified target product was obtained with a yield of 80% and a purity of 99.9%.

[0076] 1H NMR (400MHz, DMSO-d6, ppm) δ10.25 (s, 1H), 7.66 (d, J = 8.4hz, 2H), 7.44 (s, 1H), 7 .14(d,J=8.3hz,2H),4.30(q,J=7.1hz,2H),2.26(s,3H),1.31(t,J-7.1hz,3H);

[0077] 13 C{ 1 H}NMR(100MHz,DMSO-d6,ppm)δ161.1,158.5,143.0,140.6,136.5,133.3,129.5,120.7,109.1,61.0,20.9,14.6;

[0078] MS(EI,70eV)m / z 273,227,199,167,121,107,93.

[0079] Example 3

[0080] The pyrazole compound obtained in this embodiment has the following structure:

[0081]

[0082] 0.2 mmol N-(4-methoxyphenyl)acrylamide, 0.25 mmol ethyl diazoacetate, 0.5 mmol 2,2,6,6-tetramethylpiperidinyl oxide as an oxidant, 0.4 mmol sodium ethoxide, and 2 mL toluene were added to a reaction tube and stirred at 100°C for 12 hours. After the reaction, the product was separated and purified by column chromatography. The volume ratio of petroleum ether to ethyl acetate in the column chromatography eluent was 3:1, and the purified target product was obtained with a yield of 84% and a purity of 99.9%.

[0083] The structure of the obtained product was characterized, and the structural characterization data are as follows:

[0084] 1 H NMR(400MHz,DMSO-d6,ppm)δ10.17(s,1H),7.70-7.68(m,2H),7.47(s,1H),6 .93-6.91(m,2H),4.32(q,J=7.1hz,2H),3.73(s,3H),1.31(t,J=7.1hz,3H);

[0085] 13 C{ 1H}NMR (100MHz, DMSO-d6, ppm) δ160.9,158.0,156.2,131.9,122.4,114.3,108.9,61.2,55.6,14.6;

[0086] MS(EI,70eV)m / z 289,243,200,167,123,108,95.

[0087] Example 4

[0088] The pyrazole compound obtained in this embodiment has the following structure:

[0089]

[0090] 0.2 mmol N-(4-fluorophenyl)acrylamide, 0.25 mmol ethyl diazoacetate, 0.5 mmol 2,2,6,6-tetramethylpiperidinyl oxide as an oxidant, 0.4 mmol sodium ethoxide, and 2 mL toluene were added to a reaction tube, and the mixture was stirred at 100°C for 12 hours. After the reaction, the mixture was separated and purified by column chromatography. The volume ratio of petroleum ether to ethyl acetate in the column chromatography eluent was 4:1, and the purified target product was obtained with a yield of 84% and a purity of 99.9%.

[0091] The structure of the obtained product was characterized, and the structural characterization data are as follows:

[0092] 1 H NMR (400MHz, DMSO-d6, ppm) δ10.40(s,1H),7.84-7.79(m,2H),7.44(s,1H),7.18(t,J=8.9hz,2H),4.31(q,J=7.1hz,2H),1.30(t,J=7.1hz,3H);

[0093] 13 C{ 1 H}NMR(100MHz,DMSO-d6,ppm)δ160.0,159.7(d,J=223.0hz),157.6,143.2,140 .1,135.4(d,J=3.0hz),122.6(d,J=8hz),115.7(d,J=22hz),109.2,61.1,14.6;

[0094] MS(EI,70eV)m / z 277,231,203,167,139,121,111,93.

[0095] Example 5

[0096] The pyrazole compound obtained in this embodiment has the following structure:

[0097]

[0098] 0.2 mmol N-(4-chlorophenyl)acrylamide, 0.25 mmol ethyl diazoacetate, 0.5 mmol 2,2,6,6-tetramethylpiperidinyl oxide as an oxidant, 0.4 mmol sodium ethoxide, and 2 mL toluene were added to a reaction tube, and the mixture was stirred at 100°C for 12 hours. After the reaction, the mixture was separated and purified by column chromatography. The volume ratio of petroleum ether to ethyl acetate in the column chromatography eluent was 4:1, and the purified target product was obtained with a yield of 77% and a purity of 99.9%.

[0099] The structure of the obtained product was characterized, and the structural characterization data are as follows:

[0100] 1 H NMR (400MHz, DMSO-d6, ppm) δ14.54(s,1H),10.40(s,1H),7.85-7.81(m,2H),7.46-7.38(m,3H),4.32(q,J=7.1hz,2H),1.31(t,J=7.1hz,3H);

[0101] 13 C{ 1 H}NMR (100MHz, DMSO-d6, ppm) δ160.7,158.7,139.4,136.9,131.9,129.8,126.8,122.3,109.9,62.0,16.1;

[0102] MS(EI,70eV)m / z 293,247,212,167,127,121,111,93.

[0103] Example 6

[0104] The pyrazole compound obtained in this embodiment has the following structure:

[0105]

[0106] 0.2 mmol N-(4-bromophenyl)acrylamide, 0.25 mmol ethyl diazoacetate, 0.5 mmol 2,2,6,6-tetramethylpiperidinyl oxide as an oxidant, 0.4 mmol sodium ethoxide, and 2 mL toluene were added to a reaction tube, and the mixture was stirred at 100°C for 12 hours. After the reaction, the mixture was separated and purified by column chromatography. The volume ratio of petroleum ether to ethyl acetate in the column chromatography eluent was 4:1, and the purified target product was obtained with a yield of 73% and a purity of 99.9%.

[0107] The structure of the obtained product was characterized, and the structural characterization data are as follows:

[0108] 1 H NMR (400MHz, DMSO-d6, ppm) δ10.45(s,1H),7.79-7.76(m,2H),7.53-7.49(m,2H),7.44(s,1H),4.30(q,J=7.1hz,2H),1.30(t,J=7.1hz,3H);

[0109] 13 C{ 1 H}NMR (100MHz, DMSO-d6, ppm) δ165.5,163.5,148.0,144.8,143.2,136.7,127.4,120.8,114.1,65.9,19.4;

[0110] MS(EI,70eV)m / z 337,292,171,167,127,121,102,91.

[0111] Example 7

[0112] The pyrazole compound obtained in this embodiment has the following structure:

[0113]

[0114] 0.2 mmol N-(4-trifluoromethylphenyl)acrylamide, 0.25 mmol ethyl diazoacetate, 0.5 mmol 2,2,6,6-tetramethylpiperidinyl oxide as an oxidant, 0.4 mmol sodium ethoxide, and 2 mL toluene were added to a reaction tube, and the mixture was stirred at 100°C for 12 hours. After the reaction, the mixture was separated and purified by column chromatography. The volume ratio of petroleum ether to ethyl acetate in the column chromatography eluent was 4:1, and the purified target product was obtained with a yield of 85% and a purity of 99.9%.

[0115] The structure of the obtained product was characterized, and the structural characterization data are as follows:

[0116] 1 H NMR (400MHz, DMSO-d6, ppm) δ10.73 (s, 1H), 8.03 (d, J = 8.5hz, 2H), 7.68 (d, J = 8.5hz, 2H), 7.39 (s, 1H), 4.28 (q, J = 7.1hz, 3H), 1.29 (t,

[0117] J = 7.1 Hz, 3H);

[0118] 13 C{ 1 H}NMR (100MHz, DMSO-d6, ppm) δ161.4,159.8,143.6,142.9,140.8,126.3(q,J=10.0hz),124.4,123.7(d,J=30.0hz),120.4,109.7,60.8,14.6;

[0119] MS(EI,70eV)m / z 327,308,282,167,139,121,113,93.

[0120] Example 8

[0121] The pyrazole compound obtained in this embodiment has the following structure:

[0122]

[0123] 0.2 mmol of ethyl 4-acrylamidobenzoate, 0.25 mmol of ethyl diazoacetate, 0.5 mmol of 2,2,6,6-tetramethylpiperidinyl oxide as an oxidant, 0.4 mmol of sodium ethoxide, and 2 mL of toluene were added to a reaction tube, and the mixture was stirred at 100°C for 12 hours. After the reaction, the mixture was separated and purified by column chromatography. The volume ratio of petroleum ether to ethyl acetate in the column chromatography eluent was 3:1, and the purified target product was obtained with a yield of 88% and a purity of 99.9%.

[0124] The structure of the obtained product was characterized, and the structural characterization data are as follows:

[0125] 1 H NMR (400MHz, DMSO-d6, ppm) δ10.61 (s, 1H), 7.94 (q, J = 9.0hz, 4H), 7.43 (s, 1H), 4.32-4.24 (m, 4H), 1.29 (t, J = 7.1hz, 6H);

[0126] 13 C{ 1 H}NMR(100MHz,DMSO-d6,ppm)δ165.8,161.1,159.4,143.6,143.4,140.6,130.5,125.0,119.9,109.6,61.0,60.9,14.61,14.59;

[0127] MS(EI,70eV)m / z 331,296,240,167,121,93.

[0128] Example 9

[0129] The pyrazole compound obtained in this embodiment has the following structure:

[0130]

[0131] 0.2 mmol N-(3-fluorophenyl)acrylamide, 0.25 mmol ethyl diazoacetate, 0.5 mmol 2,2,6,6-tetramethylpiperidinyl oxide as an oxidant, 0.4 mmol sodium ethoxide, and 2 mL toluene were added to a reaction tube, and the mixture was stirred at 100°C for 12 hours. After the reaction, the mixture was separated and purified by column chromatography. The volume ratio of petroleum ether to ethyl acetate in the column chromatography eluent was 4:1, and the purified target product was obtained with a yield of 88% and a purity of 99.9%.

[0132] The structure of the obtained product was characterized, and the structural characterization data are as follows:

[0133] 1 H NMR (400MHz, DMSO-d6, ppm) δ10.60 (s, 1H), 7.77 (dt, J=11.8, 2.3hz, 1H), 7.60 (ddd, J=8.2, 2.0, 0.9hz, 1H), 7.41-7.33 (m, 2H), 6.91 (tdd,

[0134] J=8.5,2.6,0.9hz,1H),4.30(q,J=7.1hz,2H),1.30(t,J=7.1hz,3H);

[0135] 13 C{ 1 H}NMR (100MHz, DMSO-d6, ppm) δ160.9,158.0,156.2,131.9,122.4,114.3,108.9,61.2,55.6,14.6;

[0136] MS(EI,70eV)m / z 277,232,203,167,139,121,111,93.

[0137] Example 10

[0138] The pyrazole compound obtained in this embodiment has the following structure:

[0139]

[0140] 0.2 mmol N-(3-chlorophenyl)acrylamide, 0.25 mmol ethyl diazoacetate, 0.5 mmol 2,2,6,6-tetramethylpiperidinyl oxide as an oxidant, 0.4 mmol sodium ethoxide, and 2 mL toluene were added to a reaction tube and stirred at 100°C for 12 hours. After the reaction, the product was separated and purified by column chromatography. The volume ratio of petroleum ether to ethyl acetate in the column chromatography eluent was 4:1, and the purified target product was obtained with a yield of 83% and a purity of 99.9%.

[0141] The structure of the obtained product was characterized, and the structural characterization data are as follows:

[0142] 1 H NMR (400MHz, DMSO-d6, ppm) δ10.45 (s, 1H), 7.98 (t, J = 2.0hz, 1H), 7.74-7.72 (m, 1H) ,7.45-73.4(m,2H),7.16-7.09(m,1H),4.32(q,J=7.1hz,2H),1.31(t,J=7.1hz,3H);

[0143] 13 C{ 1 H}NMR (100MHz, DMSO-d6, ppm) δ160.5,158.9,145.9,140.5,139.9,133.5,130.8,124.0,120.1,119.1,109.4,61.3,14.6;

[0144] MS(EI,70eV)m / z 293,248,185,167,127,121,111,93.

[0145] Example 11

[0146] The pyrazole compound obtained in this embodiment has the following structure:

[0147]

[0148] 0.2 mmol N-(2-methylphenyl)acrylamide, 0.25 mmol ethyl diazoacetate, 0.5 mmol 2,2,6,6-tetramethylpiperidinyl oxide as an oxidant, 0.4 mmol sodium ethoxide, and 2 mL toluene were added to a reaction tube and stirred at 100°C for 12 hours. After the reaction, the product was separated and purified by column chromatography. The volume ratio of petroleum ether to ethyl acetate in the column chromatography eluent was 4:1 to obtain the purified target product with a yield of 86% and a purity of 99.9%.

[0149] The structure of the obtained product was characterized, and the structural characterization data are as follows:

[0150] 1 H NMR (400MHz, DMSO-d6, ppm) δ9.90 (s, 1H), 7.45 (d, J = 7.4hz, 2H), 7.27-7.15 (m, 3H), 4.32 (q, J = 7.1hz, 2H), 2.25 (s, 3H), 1.31 (t, J = 7.1hz, 3H);

[0151] 13 C{ 1 H}NMR(100MHz,DMSO-d6,ppm)δ160.8,158.6,140.1,136.0,133.4,130.8,126.6,126.4,126.3,109.1,61.1,18.2,14.6;

[0152] MS(EI,70eV)m / z 273,255,199,167,139,121,107,91.

[0153] Example 12

[0154] The pyrazole compound obtained in this embodiment has the following structure:

[0155]

[0156] 0.2 mmol N-(2-fluorophenyl)acrylamide, 0.25 mmol ethyl diazoacetate, 0.5 mmol 2,2,6,6-tetramethylpiperidinyl oxide as an oxidant, 0.4 mmol sodium ethoxide, and 2 mL toluene were added to a reaction tube and stirred at 100°C for 12 hours. After the reaction, the product was separated and purified by column chromatography. The volume ratio of petroleum ether to ethyl acetate in the column chromatography eluent was 4:1, and the purified target product was obtained with a yield of 67% and a purity of 99.9%.

[0157] The structure of the obtained product was characterized, and the structural characterization data are as follows:

[0158] 1 H NMR (400MHz, DMSO-d6, ppm) δ10.09 (s, 1H), 7.74 (td, J = 7.7, 2.3hz, 1H), 7.40-7.19 (m, 4H), 4.31 (q, J = 7.1hz, 2H), 1.31 (t, J = 7.1hz, 3H);

[0159] 13 C{ 1H}NMR (100MHz, DMSO-d6, ppm) δ160.7, 158.9, 155.5 (d, J = 150.0hz), 143.4, 139.8, 127.0 (d, J = 8. 0hz), 126.4, 125.6 (d, J = 12.0hz), 124.9 (d, J = 4.0hz), 116.2 (d, J = 9.0hz), 109.35, 61.15, 14.60;

[0160] MS(EI,70eV)m / z 277,232,212,167,139,121,111,93.

[0161] Example 13

[0162] The pyrazole compound obtained in this embodiment has the following structure:

[0163]

[0164] 0.2 mmol N-(2-chlorophenyl)acrylamide, 0.25 mmol ethyl diazoacetate, 0.5 mmol 2,2,6,6-tetramethylpiperidinyl oxide as an oxidant, 0.4 mmol sodium ethoxide, and 2 mL toluene were added to a reaction tube and stirred at 100°C for 12 hours. After the reaction, the product was separated and purified by column chromatography. The volume ratio of petroleum ether to ethyl acetate in the column chromatography eluent was 4:1, and the purified target product was obtained with a yield of 57% and a purity of 99.9%.

[0165] The structure of the obtained product was characterized, and the structural characterization data are as follows:

[0166] 1 H NMR (400MHz, DMSO-d6, ppm) δ9.95 (s, 1H), 7.92 (dd, J = 8.2, 1.6hz, 1H), 7.55 (dd, J =8.1,1.4hz,1H),7.41-7.21(m,3H),4.31(q,J=7.1hz,2H),1.31(t,J=7.1hz,3H);

[0167] 13 C{ 1 H}NMR (100MHz, DMSO-d6, ppm) δ160.4,159.0,134.8,130.0,128.2,127.0,125.8,109.3,61.2,14.6;

[0168] MS(EI,70eV)m / z 293,258,212,167,127,121,106,93.

[0169] Example 14

[0170] The pyrazole compound obtained in this embodiment has the following structure:

[0171]

[0172] 0.2 mmol N-(2-bromophenyl)acrylamide, 0.25 mmol ethyl diazoacetate, 0.5 mmol 2,2,6,6-tetramethylpiperidinyl oxide as an oxidant, 0.4 mmol sodium ethoxide, and 2 mL toluene were added to a reaction tube, and the mixture was stirred at 100°C for 12 hours. After the reaction, the mixture was separated and purified by column chromatography. The volume ratio of petroleum ether to ethyl acetate in the column chromatography eluent was 4:1, and the purified target product was obtained with a yield of 67% and a purity of 99.9%.

[0173] The structure of the obtained product was characterized, and the structural characterization data are as follows:

[0174] 1 H NMR (400MHz, DMSO-d6, ppm) δ9.87 (s, 1H), 7.91 (d, J = 8.1hz, 1H), 7.70 (dd, J = 8.1, 1.4hz, 1H), 7.44-7.38(m,2H),7.16(td,J=7.7,1.7hz,1H),4.33(q,J=7.1hz,2H),1.31(t,J=7.1hz,3H);

[0175] 13 C{ 1 H}NMR (100MHz, DMSO-d6, ppm) δ160.0,158.8,144.7,138.8136.0,133.1,128.8,127.5,126.1,117.8,109.3,61.4,14.6;

[0176] MS(EI,70eV)m / z 337,292,258,171,139,121,106,91.

[0177] Example 15

[0178] The pyrazole compound obtained in this embodiment has the following structure:

[0179]

[0180] 0.2 mmol N-(2,4-dimethylphenyl)acrylamide, 0.25 mmol ethyl diazoacetate, 0.5 mmol 2,2,6,6-tetramethylpiperidinyl oxide as an oxidant, 0.4 mmol sodium ethoxide, and 2 mL toluene were added to a reaction tube, and the mixture was stirred at 100°C for 12 hours. After the reaction, the mixture was separated and purified by column chromatography. The volume ratio of petroleum ether to ethyl acetate in the column chromatography eluent was 4:1, and the purified target product was obtained with a yield of 79% and a purity of 99.9%.

[0181] The structure of the obtained product was characterized, and the structural characterization data are as follows:

[0182] 1 H NMR (400MHz, DMSO-d6, ppm) δ9.87 (s, 1H), 7.43 (s, 1H), 7.30 (d, J = 7.9hz, 1H), 7.05- 6.99(m,2H),4.31(q,J=7.1hz,2H),2.26(s,3H),2.20(s,3H),1.31(t,J=7.1hz,3H);

[0183] 13 C{ 1 H}NMR(100MHz,DMSO-d6,ppm)δ161.0,158.6,143.0,140.4,135.5,133.4,133.2,131.3,127.0,126.3,109.0,61.1,20.9,18.2,14.6;

[0184] MS(EI,70eV)m / z 287,259,213,167,127,121,106,91.

[0185] Example 16

[0186] The pyrazole compound obtained in this embodiment has the following structure:

[0187]

[0188] 0.2 mmol N-(2,4-dimethoxyphenyl)acrylamide, 0.25 mmol ethyl diazoacetate, 0.5 mmol 2,2,6,6-tetramethylpiperidinyl oxide as an oxidant, 0.4 mmol sodium ethoxide, and 2 mL toluene were added to a reaction tube, and the mixture was stirred at 100°C for 12 hours. After the reaction, the mixture was separated and purified by column chromatography. The volume ratio of petroleum ether to ethyl acetate in the column chromatography eluent was 2:1, and the purified target product was obtained with a yield of 66% and a purity of 99.9%.

[0189] The structure of the obtained product was characterized, and the structural characterization data are as follows:

[0190] 1 H NMR (400MHz, DMSO-d6, ppm) δ9.39 (s, 1H), 7.89 (d, J = 8.8hz, 1H), 7.29 (s, 1H), 6.67 (d, J = 2.7hz, 1H), 6.54(dd,J=8.8,2.6hz,1H),4.31(q,J=7.1hz,2H),3.85(s,3H),3.76(s,3H),1.31(t,J=7.1hz,3H);

[0191] 13 C{ 1 H}NMR (100MHz, DMSO-d6, ppm) δ160.4,158.6,157.4,151.5,139.0,123.1,120.2,108.9,104.7,99.3,61.2,56.4,55.8,14.6;

[0192] MS(EI,70eV)m / z 319,273,242,167,121,109,93.

[0193] Example 17

[0194] The pyrazole compound obtained in this embodiment has the following structure:

[0195]

[0196] 0.2 mmol N-(2,4-dichlorophenyl)acrylamide, 0.25 mmol ethyl diazoacetate, 0.5 mmol 2,2,6,6-tetramethylpiperidinyl oxide as an oxidant, 0.4 mmol sodium ethoxide, and 2 mL toluene were added to a reaction tube, and the mixture was stirred at 100°C for 12 hours. After the reaction, the mixture was separated and purified by column chromatography. The volume ratio of petroleum ether to ethyl acetate in the column chromatography eluent was 4:1, and the purified target product was obtained with a yield of 68% and a purity of 99.9%.

[0197] The structure of the obtained product was characterized, and the structural characterization data are as follows:

[0198] 1 H NMR (400MHz, DMSO-d6, ppm) δ9.95 (s, 1H), 7.93 (d, J = 8.8hz, 1H), 7.69 (d, J =2.4hz,1H),7.46-35(m,2H),4.31(q,J=7.1hz,2H),1.31(t,J=7.0hz,3H);

[0199] 13 C{ 1 H}NMR(100MHz,DMSO-d6,ppm)δ160.1,159.0,144.2,138.8,133.9,130.1,129.4,128.3,128.0,126.8,109.4,61.4,14.6;

[0200] MS(EI,70eV)m / z 327,292,246,167,139,121,109,93.

[0201] Example 18

[0202] The pyrazole compound obtained in this embodiment has the following structure:

[0203]

[0204] 0.2 mmol N-(2-methoxy-4-nitrophenyl)acrylamide, 0.25 mmol ethyl diazoacetate, 0.5 mmol 2,2,6,6-tetramethylpiperidinyl oxide as an oxidant, 0.4 mmol sodium ethoxide, and 2 mL toluene were added to a reaction tube, and the mixture was stirred at 100°C for 12 hours. After the reaction, the mixture was separated and purified by column chromatography. The volume ratio of petroleum ether to ethyl acetate in the column chromatography eluent was 2:1, and the purified target product was obtained with a yield of 80% and a purity of 99.9%.

[0205] The structure of the obtained product was characterized, and the structural characterization data are as follows:

[0206] 11 H NMR (400MHz, DMSO-d6, ppm) δ9.66 (s, 1H), 8.49 (d, J = 9.0hz, 1H), 7.92-7.79 (m ,2H),7.19(s,1H),4.31(q,J=7.1hz,2H),4.04(s,3H),1.31(t,J=7.1hz,3H);

[0207] 13 C{ 1 H}NMR(100MHz,DMSO-d6,ppm)δ159.9,159.5,148.3,145.8,143.0,138.2,133.9,118.4,117.7,109.3,106.2,61.3,57.2,14.5;

[0208] MS(EI,70eV)m / z 334,289,167,139,73.

[0209] Example 19

[0210] The pyrazole compound obtained in this embodiment has the following structure:

[0211]

[0212] 0.2 mmol N-(2,4-dichlorophenyl)acrylamide, 0.25 mmol ethyl diazoacetate, 0.5 mmol 2,2,6,6-tetramethylpiperidinyl oxide as an oxidant, 0.4 mmol sodium ethoxide, and 2 mL toluene were added to a reaction tube, and the mixture was stirred at 100°C for 12 hours. After the reaction, the mixture was separated and purified by column chromatography. The volume ratio of petroleum ether to ethyl acetate in the column chromatography eluent was 4:1, and the purified target product was obtained with a yield of 86% and a purity of 99.9%.

[0213] The structure of the obtained product was characterized, and the structural characterization data are as follows:

[0214] 1 H NMR (400MHz, DMSO-d6, ppm) δ10.54 (s, 1H), 8.16 (d, J = 2.4hz, 1H), 7.79 (dd, J = 8.9, 2.5h z,1H),7.59(d,J=8.8hz,1H),7.44(s,1H),4.34(q,J=7.1hz,2H),1.33(t,J=7.1hz,3H);

[0215] 13 C{ 1 H}NMR (100MHz, DMSO-d6, ppm) δ171.9,161.0,143.5,139.4,139.1,131.4,131.0,125.8,121.9,120.7,109.5,61.3,14.6;

[0216] MS(EI,70eV)m / z 327,282,219,167,139,121,109,93.

[0217] Example 20

[0218] The pyrazole compound obtained in this embodiment has the following structure:

[0219]

[0220] 0.2 mmol N-(3-bromo-4-methylphenyl)acrylamide, 0.25 mmol ethyl diazoacetate, 0.5 mmol 2,2,6,6-tetramethylpiperidinyl oxide as an oxidant, 0.4 mmol sodium ethoxide, and 2 mL toluene were added to a reaction tube and stirred at 100°C for 12 hours. After the reaction, the product was separated and purified by column chromatography. The volume ratio of petroleum ether to ethyl acetate in the column chromatography eluent was 4:1, and the purified target product was obtained with a yield of 87% and a purity of 99.9%.

[0221] The structure of the obtained product was characterized, and the structural characterization data are as follows:

[0222] 1 H NMR (400MHz, DMSO-d6, ppm) δ10.37 (s, 1H), 7.80 (d, J = 2.5hz, 1H), 7.62-7.45 (m, 3H), 4.32 (q, J = 7.1hz, 2H), 2.33 (s, 3H), 1.32 (t, J = 7.1hz, 3H);

[0223] 13 C{ 1 H}NMR(100MHz,DMSO-d6,ppm)δ160.8,158.7,140.0,138.5,137.8,132.58,123.0,120.1,118.6,109.3,61.1,23.1,14.6;

[0224] MS(EI,70eV)m / z 351,306,185,167,139,121,104,93.

[0225] Example 21

[0226] The pyrazole compound obtained in this embodiment has the following structure:

[0227]

[0228] 0.2 mmol N-(2,5-dichlorophenyl)acrylamide, 0.25 mmol ethyl diazoacetate, 0.5 mmol 2,2,6,6-tetramethylpiperidinyl oxide as an oxidant, 0.4 mmol sodium ethoxide, and 2 mL toluene were added to a reaction tube, and the mixture was stirred at 100°C for 12 hours. After the reaction, the mixture was separated and purified by column chromatography. The volume ratio of petroleum ether to ethyl acetate in the column chromatography eluent was 4:1, and the purified target product was obtained with a yield of 20% and a purity of 99.9%.

[0229] The structure of the obtained product was characterized, and the structural characterization data are as follows:

[0230] 1 H NMR (400MHz, DMSO-d6, ppm) δ9.59 (s, 1H), 8.10 (s, 1H), 7.57 (d, J = 8.2hz, 1H), 7.23-7.27 (m, 2H), 4.32 (q, J = 6.8hz, 2H), 1.32 (t, J = 6.7hz, 3H);

[0231] 13 C{ 1 H}NMR(100MHz,DMSO-d6,ppm)δ160.1,159.2,144.6,138.7,135.9,132.3,131.3,126.4,124.8,124.3,109.5,61.5,14.6;

[0232] MS(EI,70eV)m / z 327,292,246,139,121,109,93,65.

[0233] Example 22

[0234] The pyrazole compound obtained in this embodiment has the following structure:

[0235]

[0236] 0.2 mmol N-(2,3-dimethylphenyl)acrylamide, 0.25 mmol ethyl diazoacetate, 0.5 mmol 2,2,6,6-tetramethylpiperidinyl oxide as an oxidant, 0.4 mmol sodium ethoxide, and 2 mL toluene were added to a reaction tube, and the mixture was stirred at 100°C for 12 hours. After the reaction, the mixture was separated and purified by column chromatography. The volume ratio of petroleum ether to ethyl acetate in the column chromatography eluent was 4:1, and the purified target product was obtained with a yield of 85% and a purity of 99.9%.

[0237] The structure of the obtained product was characterized, and the structural characterization data are as follows:

[0238] 1 H NMR (400MHz, DMSO-d6, ppm) δ10.01(s,1H),7.43(s,1H),7.24-7.07(m,3H),4.33(q,J=7.1hz,2H),2.28(s,3H),2.12(s,3H),1.33(t,J=7.1hz,3H);

[0239] 13 C{ 1H}NMR(100MHz,DMSO-d6,ppm)δ161.1,158.8,143.0,140.5,137.5,135.9,132.4,127.9,125.8,124.5,109.0,61.0,20.6,14.6,14.6;

[0240] MS(EI,70eV)m / z 287,269,199,167,139,121,106,91.

[0241] Example 23

[0242] The pyrazole compound obtained in this embodiment has the following structure:

[0243]

[0244] 0.2 mmol N-(2,3-dimethylphenyl)acrylamide, 0.25 mmol ethyl diazoacetate, 0.5 mmol 2,2,6,6-tetramethylpiperidinyl oxide as an oxidant, 0.4 mmol sodium ethoxide, and 2 mL toluene were added to a reaction tube, and the mixture was stirred at 100°C for 12 hours. After the reaction, the mixture was separated and purified by column chromatography. The volume ratio of petroleum ether to ethyl acetate in the column chromatography eluent was 4:1, and the purified target product was obtained with a yield of 89% and a purity of 99.9%.

[0245] The structure of the obtained product was characterized, and the structural characterization data are as follows:

[0246] 1 H NMR (400MHz, DMSO-d6, ppm) δ9.81 (s, 1H), 7.46 (s, 1H), 6.90 (s, 2H), 4.32 (d, J = 7.1hz, 2H), 2.23 (s, 3H), 2.13 (s, 6H), 1.31 (t, J = 7.1hz, 3H);

[0247] 13 C{ 1 H}NMR (100MHz, DMSO-d6, ppm) δ171.0,161.0,158.6,140.4,136.4,135.7,132.1,128.8,108.9,61.2,20.9,18.3,14.5;

[0248] MS(EI,70eV)m / z 301,283,181,167,134,121,105,91.

[0249] Example 24

[0250] The pyrazole compound obtained in this embodiment has the following structure:

[0251]

[0252] 0.2 mmol N-cyclohexylacrylamide, 0.25 mmol ethyl diazoacetate, 0.5 mmol 2,2,6,6-tetramethylpiperidinyl oxide as an oxidant, 0.4 mmol sodium ethoxide, and 2 mL toluene were added to a reaction tube, and the mixture was stirred at 100°C for 12 hours. After the reaction, the mixture was separated and purified by column chromatography. The volume ratio of petroleum ether to ethyl acetate in the column chromatography eluent was 4:1, and the purified target product was obtained with a yield of 69% and a purity of 99.9%.

[0253] The structure of the obtained product was characterized, and the structural characterization data are as follows:

[0254] 1 H NMR(400MHz,DMSO-d6,ppm)δ8.96(d,J=8.1hz,1H),7.99(s,1H),4.96(q,J=7 .1hz,2H),4.41(dt,J=7.7,3.7hz,1H),2.50-2.25(m,5H),2.02-1.89(m,8H);

[0255] 13 C{ 1 H}NMR (100MHz, DMSO-d6, ppm) δ161.3,158.6,142.2,140.9,108.4,60.9,48.3,32.8,25.6,25.3,14.6;

[0256] MS(EI,70eV)m / z 265,222,184,167,127,138,121,98.

[0257] Example 25

[0258] The pyrazole compound obtained in this embodiment has the following structure:

[0259]

[0260] 0.2 mmol N-(naphthalen-2-yl)prop-2-enamide, 0.25 mmol ethyl diazoacetate, 0.5 mmol 2,2,6,6-tetramethylpiperidinyl oxide as an oxidant, 0.4 mmol sodium ethoxide, and 2 mL toluene were added to a reaction tube and stirred at 100°C for 12 hours. After the reaction, the product was separated and purified by column chromatography. The volume ratio of petroleum ether to ethyl acetate in the column chromatography eluent was 4:1 to obtain the purified target product with a yield of 80% and a purity of 99.9%.

[0261] The structure of the obtained product was characterized, and the structural characterization data are as follows:

[0262] 1 H NMR (400MHz, DMSO-d6, ppm) δ10.49 (s, 1H), 8.46 (s, 1H), 7.91-7.84 (m, 4H), 7.55-7.40 (m, 3H), 4.34 (q, J = 7.1hz, 2H), 1.33 (t, J = 7.1hz, 3H);

[0263] 13 C{ 1 H}NMR(100MHz,DMSO-d6,ppm)δ160.7,158.7,136.6,133.7,130.5,128.8,127.9,127.9,126.9,125.4,121.2,117.1,109.3,61.2,14.6;

[0264] MS(EI,70eV)m / z 309,263,235,167,143,121,93,65.

[0265] Example 26

[0266] The pyrazole compound obtained in this embodiment has the following structure:

[0267]

[0268] 0.2 mmol N-(phenyl)acrylamide, 0.25 mmol tert-butyl diazoacetate, 0.5 mmol 2,2,6,6-tetramethylpiperidinyl oxide as an oxidant, 0.4 mmol sodium ethoxide, and 2 mL toluene were added to a reaction tube and stirred at 100°C for 12 hours. After the reaction, the product was separated and purified by column chromatography. The volume ratio of petroleum ether to ethyl acetate in the column chromatography eluent was 4:1, and the purified target product was obtained with a yield of 68% and a purity of 99.9%.

[0269] The structure of the obtained product was characterized, and the structural characterization data are as follows:

[0270] 1 H NMR (400MHz, DMSO-d6, ppm) δ10.27(s,1H),7.80(d,J=8.0Hz,2H),7.35(dd,J=14.5,6.8Hz,3H),7.09(t,J=7.4Hz,1H),1.54(s,9H);

[0271] 13 C{ 1 H}NMR (100MHz, DMSO-d6, ppm) δ159.9,158.8,153.8139.0,129.1,124.3,120.8,109.0,82.0,28.3;

[0272] HRMS (ESI) m / z [M+H] + calcd for C 15 H 17 N3O3288.1343,found 288.1340.

[0273] Example 27

[0274] The pyrazole compound obtained in this embodiment has the following structure:

[0275]

[0276] 0.2 mmol N-(phenyl)acrylamide, 0.25 mmol benzyl diazoacetate, 0.5 mmol 2,2,6,6-tetramethylpiperidinyl oxide as an oxidant, 0.4 mmol sodium ethoxide, and 2 mL toluene were added to a reaction tube, and the mixture was stirred at 100°C for 12 hours. After the reaction, the mixture was separated and purified by column chromatography. The volume ratio of petroleum ether to ethyl acetate in the column chromatography eluent was 4:1, and the purified target product was obtained with a yield of 78% and a purity of 99.9%.

[0277] The structure of the obtained product was characterized, and the structural characterization data are as follows:

[0278] 1 H NMR (400MHz, DMSO-d6, ppm) δ10.32 (s, 1H), 7.82-7.80 (m, 2H), 7.58 (s, 1H), 7.549-7.33 (m, 7H), 7.10 (t, J = 7.4Hz, 1H), 5.37 (s, 2H);

[0279] 13 C{ 1H}NMR(100MHz,DMSO-d6,ppm)δ160.9,158.4,142.9,141.3,140.0,136.3,129.2,129.0128.7,124.4,120.8,109.4,66.6;

[0280] MS(EI,70eV)m / z 321,215,187,121,77;

[0281] HRMS (ESI) m / z [M+H] + calcd for C 18 H 15 N3O3322.1186,found 322.1185.

[0282] Example 28

[0283] The pyrazole compound obtained in this embodiment has the following structure:

[0284]

[0285] 0.2 mmol N-(phenyl)acrylamide, 0.25 mmol phenoxyethanol diazoacetate, 0.5 mmol 2,2,6,6-tetramethylpiperidinyl oxide as an oxidant, 0.4 mmol sodium ethoxide, and 2 mL toluene were added to a reaction tube, and the mixture was stirred at 100°C for 12 hours. After the reaction, the mixture was separated and purified by column chromatography. The volume ratio of petroleum ether to ethyl acetate in the column chromatography eluent was 4:1, and the purified target product was obtained with a yield of 79% and a purity of 99.9%.

[0286] The structure of the obtained product was characterized, and the structural characterization data are as follows:

[0287] 1 H NMR (400MHz, DMSO-d6, ppm) δ13.51(s,1H),10.30(s,1H),7.79(d,J=8.1Hz,2H),7.55(s,1H),7.32(dt,J=23.5 ,8.0Hz,4H),7.11(t,J=7.4Hz,1H),6.96(dd,J=17.7,7.8Hz,3H),4.63(t,J=4.4Hz,2H),4.31(t,J=4.4Hz,2H);

[0288] 13 C{ 1H}NMR (100MHz, DMSO-d6, ppm) δ163.3,158.6,158.3,150.0,146.3,138.9,130.0,129.2,124.4,121.4,120.8,115.0,109.3,66.1,63.8;

[0289] MS(EI,70eV)m / z 351,258,214,165,121,77;

[0290] HRMS (ESI) m / z [M+H] + calcd for C 19 H 17 N3O4352.1230,found 352.1298.

[0291] The above examples demonstrate that the preparation method provided by the present invention has the advantages of simple process, mild conditions, easy control, high reaction efficiency, readily available and inexpensive raw materials, no metal catalysts, and good functional group tolerance. Furthermore, the prepared pyrazole compounds have a high purity of 98.5-99.9%, which is highly marketable. Compared with multi-step synthesis reactions, the present invention can obtain the target product in a single step, with a reaction yield of 77%, offering the advantages of high reaction efficiency and process economy.

[0292] Although the above embodiment provides a detailed description of the present invention, it is only a part of the embodiments of the present invention, not all of the embodiments. Other embodiments can be obtained based on this embodiment without creativity, and these embodiments all fall within the scope of protection of the present invention.

Claims

1. A method for preparing a pyrazole compound, characterized in that: The following steps are involved: An acrylamide compound, a diazoacetate, an oxidant, an alkaline reagent and an organic solvent are mixed to carry out a coupling addition reaction to obtain the pyrazole compound; the oxidant is 2,2,6,6-tetramethylpiperidinyl oxide; The acrylamide compound has a structure shown in Formula II: Formula II; The diazoacetate has a structure shown in Formula III: Formula III; The pyrazole compound has the following structure: 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 、 or .

2. The preparation method according to claim 1, characterized in that The acrylamide compounds are N-phenylacrylamide, N-(4-methylphenyl)acrylamide, N-(4-methoxyphenyl)acrylamide, N-(4-fluorophenyl)acrylamide, N-(4-chlorophenyl)acrylamide, N-(4-bromophenyl)acrylamide, N-(4-trifluoromethylphenyl)acrylamide, 4-acrylamide ethyl benzoate, N-(3-fluorophenyl)acrylamide, N-(3-chlorophenyl)acrylamide, N-(2-methylphenyl)acrylamide, N-(2-fluorophenyl)acrylamide, N-(2-chlorophenyl)acrylamide, N-(2-bromophenyl)acrylamide, N-(2,4-dimethylphenyl)acrylamide, N-(2,4-dimethoxyphenyl)acrylamide, N-(2,4-dichlorophenyl)acrylamide, N-(2-methoxy-4-nitrophenyl)acrylamide, N-(3,4-dichlorophenyl)acrylamide, N-(3-bromo-4-methylphenyl)acrylamide, N-(2,5-dichlorophenyl)acrylamide, N-(2,3-dimethylphenyl)acrylamide, N-(2,4,6-trimethylphenyl)acrylamide, N-cyclohexylacrylamide or N-(naphthalen-2-yl)prop-2-enamide.

3. The preparation method according to claim 1, characterized in that The diazoacetic acid ester is ethyl diazoacetate, benzyl diazoacetate, phenoxyethylene glycol diazoacetate or tert-butyl diazoacetate.

4. The preparation method according to any one of claims 1 to 3, characterized in that The molar ratio of the acrylamide compound to the diazoacetic acid ester is 1:1-1.

25.

5. The preparation method according to claim 1, characterized in that The molar ratio of the acrylamide compound to the oxidant is 1:2-2.

5.

6. The preparation method according to claim 1, characterized in that The coupling addition reaction is carried out at a temperature of 80-100° C. and for a time of 12-24 hours.

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