Synthesis method of 1, 3, 5-pyrazole compound

Abstract

The invention discloses a synthesis method of a 1, 3, 5-pyrazole compound, which comprises the following steps: in an air atmosphere, dissolving 0.20 mmol of alkyne imine, 0.30 mmol of TMSN3, 0.02 mmol of Sc (OTf) 3 and 0.02 mmol of CuI in 2ml of 1, 2-dichloroethane, heating to 70 DEG C in a sealed tube, reacting for 18 hours, after the reaction is finished, cooling a reaction system to room temperature, concentrating under reduced pressure, and performing rapid silica gel column chromatography purification to obtain the 1, 3, 5-pyrazole compound. The method has the advantages of simple operation, few reaction steps, high yield, good application value, and potential application prospect in the field of medicine.

Description

Technical Field

[0001] The invention relates to the technical field of organic chemistry, and in particular to a method for synthesizing 1,3,5-pyrazole compounds. Background Art

[0002] 1,3,5-Pyrazole compounds are the core skeletons of many drug candidates and natural products with antimalarial [1] , analgesia [2-3] , antibacterial [4-5] , anti-inflammatory [6-7] , Anti-cancer [8] , hypoglycemic [9] It has a wide range of application potentials in the field of agricultural chemicals.

[10] For example, celecoxib (I) is a cyclooxygenase-2 inhibitor used to treat rheumatoid arthritis and osteoarthritis [11-12] Razaxaban(II) is a highly potent, selective and orally bioavailable factor Xa inhibitor for the prevention of arterial thrombosis [13-14] Therefore, the construction methods of pyrazole compounds have attracted extensive attention from scientific researchers and have made remarkable progress.

[0003]

[0004] Pyrazoles have a wide range of biological activities and pharmacological properties and are important structural motifs in natural products and synthetic bioactive compounds. In addition, pyrazoles can also be used as ligands in metal complexes for carbon-carbon coupling reactions. However, current methods for synthesizing 1,3,5-pyrazoles are generally subject to certain limitations, such as complex raw materials, narrow substrate range, multi-step strategies, or lack of regioselectivity. Therefore, it is very necessary to develop new strategies to efficiently synthesize 1,3,5-pyrazoles.

[0005] Common methods for synthesizing 1,3,5-pyrazoles include: (1) Knorr reaction of hydrazine derivatives with 1,3-dicarbonyl compounds or their derivatives

[15] ; (2) 1,3-dipolar cycloaddition of diazo compounds with alkenes or alkynes

[16] However, these methods often lack regioselectivity or require the preparation of highly active reaction substrates to accelerate the cyclization and ensure regioselectivity. Therefore, there is still a need to explore efficient synthetic methods to synthesize 1,3,5-pyrazoles from easily available starting materials.

[0006] References

[0007] [1]Bekhit,A.A.;Hassan,A.M.M.;Abd El Razik,H.A.;El-Miligy,M.M.M.;El-Agroudy,E.J.;Bekhit,A.E.-D.A.New Heterocyclic Hybrids of Pyrazole and ItsBioisosteres:Design,Synthesis and Biological Evaluation as Dual ActingAntimalarial-Antileishmanial Agents.Eur.J.Med.Chem.2015,94,30-44.

[0008] [2]Schmidt,A.;Dreger,A.Recent Advances in the Chemistry ofPyrazoles.Properties,BiologicalActivities,and Syntheses.Curr.Org.Chem.2011,15,1423-1463.

[0009] [3]Moraes,P.A.;Brum,E.S.;Brusco,I.;Marangoni,M.A.;Lobo,M.M.;Camargo,A.F.;Nogara,P.A.;Bonacorso,H.G.;Martins,M.A.P.;Da Rocha,J.B.T.;Oliveira,S.M.;Zanatta,N.Pyrazole-Enaminones as Promising Prototypes for the DevelopmentofAnalgesic Drugs.ChemistrySelect.2020,5,14620-14625.

[0010] [4]Ningaiah,S.;Bhadraiah,U.K.;Doddaramappa,S.D.;Keshavamurthy,S.;Javarasetty,C.NovelPyrazole Integrated 1,3,4-Oxadiazoles:Synthesis,Characterization andAntimicrobial Evaluation.Bioorg.Med.Chem.Lett.2014,24,245-248.

[0011] [5]El Shehry,M.F.;Ghorab,M.M.;Abbas,S.Y.;Fayed,E.A.;Shedid,S.A.;Ammar,Y.A.Quinoline Derivatives Bearing Pyrazole Moiety:Synthesis andBiological Evaluation as PossibleAntibacterial andAntifungalAgents.Eur.J.Med.Chem.2018,143,1463-1473.

[0012] [6]Abdel-Aziz,H.A.;Al-Rashood,K.A.;ElTahir,K.E.H.;Suddek,G.M.Synthesis ofN-Benzenesulfonamide-1H-pyrazoles Bearing ArylsulfonylMoiety:Novel Celecoxib Analogs as PotentAnti-InflammatoryAgents.Eur.J.Med.Chem.2014,80,416-422.

[0013] [7]Mohamed,L.W.;Shaaban,M.A.;Zaher,A.F.;Alhamaky,S.M.;Elsahar,A.M.Synthesis ofNew Pyrazoles and Pyrozolo[3,4-b]Pyridines as Anti-Inflammatory Agents by Inhibition of COX-2Enzyme.Bioorg.Chem.2019,83,47-54.

[0014] [8]Bennani,F.E.;Doudach,L.;Cherrah,Y.;Ramli,Y.;Karrouchi,K.;Ansar,M.;Faouzi,M.E.A.Overview ofRecent Developments ofPyrazole Derivatives as anAnticancerAgent in Different Cell Line.Bioorg.Chem.2020,97,103470-103532.

[0015] [9]Fushimi,N.;Fujikura,H.;Shiohara,H.;Teranishi,H.;Shimizu,K.;Yonekubo,S.;Ohno,K.;Miyagi,T.;Itoh,F.;Shibazaki,T.;Tomae,M.;Ishikawa-Takemura,Y.;Nakabayashi,T.;Kamada,N.;Ozawa,T.;Kobayashi,S.;Isaji,M.Structure-Activity Relationship Studies of4-Benzyl-1H-pyrazol-3-ylβ-D-glucopyranosideDerivatives as Potent and Selective Sodium Glucose Co-Transporter 1(SGLT1)Inhibitors with Therapeutic Activity on Postprandial Hyperglycemia.Bioorg.Med.Chem.2012,20,6598-6612.

[0016]

[10] Karrouchi,K.;Radi,S.;Ramli,Y.;Taoufik,J.;Mabkhot,Y.N.;Al-Aizari,F.A.;Ansar,M.Synthesis and Pharmacological Activities of PyrazoleDerivatives:A Review.Molecules 2018,23,134-220.

[0017]

[11] Penning,T.D.;Talley,J.J.;Bertenshaw,S.R.;Carter,J.S.;Collins,P.W.;Docter,S.;Graneto,M.J.;Lee,L.F.;Malecha,J.W.;Miyashiro,J.M.;Rogers,R.S.;Rogier,D.J.;Yu,S.S.;Anderson,G.D.;Burton,E.G.;Cogburn,J.N.;Gregory,S.A.;Koboldt,C.M.;Perkins,W.E.;Seibert,K.;Veenhuizen,A.W.;Zhang,Y.Y.;Isakson,P.C.Synthesis and Biological Evaluation of the 1,5-Diarylpyrazole Class ofCyclooxygenase-2Inhibitors:Identification of4-[5-(4-Methylphenyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]benzenesulfonamide(SC-58635,Celecoxib).J.Med.Chem.1997,40,1347-1365.

[0018]

[12] Zhou,S.;Yang,S.;Huang,G.Design,Synthesis and Bioactivities ofCelecoxib Analogues or Derivatives.Bioorg.Med.Chem.2017,25,4887-4893.

[0019]

[13] Quan,M.L.;Lam,P.Y.S.;Han,Q.;Pinto,D.J.P.;He,M.Y.;Li,R.;Ellis,C.D.;Clark,C.G.;Teleha,C.A.;Sun,J.-H.;Alexander,R.S.;Bai,S.;Luettgen,J.M.;Knabb,R.M.;Wong,P.C.;Wexler,R.R.Discovery of1-(3'-Aminobenzisoxazol-5'-yl)-3-trifluoromethyl-N-[2-fluoro-4-[(2'-dimethylaminomethyl)imidazol-1-yl]phenyl]-1H-pyra-zole-5-carboxyamide Hydrochloride(Razaxaban),a Highly Potent,Selective,and Orally Bioavailable Factor Xa Inhibitor.J.Med.Chem.2005,48,1729-1744.

[0020]

[14] Wong,P.C.;Crain,E.J.;Watson,C.A.;Wexler,R.R.;Lam,P.Y.S.;Quan,M.L.;Knabb,R.M.Razaxaban,A Direct Factor Xa Inhibitor,in Combination withAspirin and / or Clopidogrel Improves Low-Dose Antithrombotic Activity WithoutEnhancing Bleeding Liability in Rabbits.J.Thromb.Thrombolys.2007,24,43-51.

[0021]

[15] Knorr,L.Synthetische Versuche mit dem Acetessigester.JustusLiebig’s Annalen der Chemie.Schmidt,1886,236,69-115.

[0022]

[16] Huisgen, R.1,3-Dipolar Cycloadditions.Past and Future.Angew.Chem.,Int.Ed.Engl.1963,2,565-632. Summary of the invention

[0023] Technical issues solved:

[0024] The purpose of the present invention is to overcome the problems existing in the prior art in the synthesis of 1,3,5-pyrazole compounds, such as complex raw materials, narrow substrate range, multi-step strategy, lack of regioselectivity or the need to prepare highly active reaction substrates to accelerate cyclization and ensure regioselectivity. The present application provides a method for synthesizing 1,3,5-pyrazole compounds with good controllability, good stability and good repeatability. The method requires simple operation, has few reaction steps, high yield, good application value, and has potential application prospects in the field of medicine.

[0025] Technical solution:

[0026] To achieve the above objectives, this application is implemented through the following technical solutions:

[0027] A method for synthesizing a 1,3,5-pyrazole compound comprises the following steps:

[0028] Step A: In an air atmosphere, 0.20 mmol of acetylenimine, 0.30 mmol of TMSN3, 0.02 mmol of catalyst, 0.02 mmol of additive and 2 ml of solvent were added into a sealed tube in a molar volume ratio, and reacted at 70° C. for 18 hours. The general synthesis formula is as follows:

[0029]

[0030] Step B: After the reaction is completed, the reaction system is cooled to room temperature, concentrated under reduced pressure, and then purified by rapid silica gel column chromatography to obtain 1,3,5-pyrazole compounds.

[0031] Preferably, the cooling in step B is air cooling.

[0032] Preferably, the instrument used for reduced pressure concentration in step B is a rotary evaporator.

[0033] Preferably, the eluent in the rapid silica gel column chromatography purification in step B is ethyl acetate:petroleum ether in a volume ratio of 1:5-20.

[0034] Preferably, the catalyst is Sc(OTf)3.

[0035] Preferably, the additive is CuI.

[0036] Preferably, the solvent is 1,2-dichloroethane.

[0037] Preferably, the step A is specifically to dissolve 0.20 mmol alkynyl imine, 0.30 mmol TMSN3, 0.02 mmol Sc(OTf)3 and 0.02 mmol CuI in 2 ml 1,2-dichloroethane under air atmosphere, heat to 70 degrees Celsius in a sealed tube, and react for 18 hours.

[0038] The structural formula of the synthesized 1,3,5-pyrazole compounds is as follows:

[0039]

[0040] Beneficial effects:

[0041] The present application provides a method for synthesizing 1,3,5-pyrazole compounds, which has the following beneficial effects:

[0042] 1. The present invention reports the cyclization reaction of acetylenic imine and trimethylsilyl azide, which can provide 1,3,5-pyrazole compounds with high yield and excellent regioselectivity;

[0043] 2. The present invention relates to 1,3,5-pyrazole compounds and a preparation method thereof. A series of 1,3,5-pyrazole compounds are synthesized using acetylenimine and trimethylsilyl azide as raw materials, Sc(OTf)3 as a catalyst, CuI as an additive, and 1,2-dichloroethane as a solvent;

[0044] 3. This method requires simple operation, few reaction steps, high yield, good application value, and potential application prospects in the medical field;

[0045] 4. This application has good controllability, stability and repeatability. DETAILED DESCRIPTION

[0046] The present invention is described in detail below in conjunction with specific embodiments. The following embodiments will help those skilled in the art to further understand the present invention, but are not intended to limit the present invention in any form. It should be noted that, for those of ordinary skill in the art, several variations and improvements may be made without departing from the concept of the present invention. These all belong to the protection scope of the present invention.

[0047] Embodiment 1:

[0048] A method for synthesizing a 1,3,5-pyrazole compound comprises the following steps:

[0049] Step A: In an air atmosphere, 0.20 mmol of acetylenic imine 1a, 0.30 mmol of TMSN3, 0.02 mmol of catalyst Sc(OTf)3, 0.02 mmol of additive CuI and 2 ml of solvent 1,2-dichloroethane were added into a sealed tube in a molar volume ratio, and reacted at 70°C for 18 hours;

[0050] Step B: After the reaction is completed, the reaction system is cooled to room temperature, concentrated under reduced pressure, and then purified by rapid silica gel column chromatography to obtain 1,3,5-pyrazole compound 3a as a yellow oil with a yield of 85%. The eluent in the rapid silica gel column chromatography purification is ethyl acetate / petroleum ether in a volume ratio of 1:5-20.

[0051]

[0052] The chemical formula of 5-methylthio-3-phenyl-1-p-tolyl-1H-pyrazole 3a is:

[0053]

[0054] The characterization data are:

[0055] 1 H NMR (400MHz, CDCl3, ppm) δ7.89 (s, 2H), 7.56-7.53 (m, 2H), 7.44 (d, J = 7.2Hz, 2H), 7.36-7.30 (m, 3H), 6.67 (s, 1H), 2.44 (s, 3H), 2.43 (s, 3H).

[0056] 13 C NMR (100MHz, CDCl3, ppm) δ152.0,139.0,138.1,137.2,133.0,129.7,128.7,128.1,125.8,124.9,105.4,21.3,18.2.

[0057] HRMS(EI-TOF)m / z:[M] + Calcd for C 17 H 17 N2S + 281.1107; Found 281.1109.

[0058] Embodiment 2:

[0059] A method for synthesizing a 1,3,5-pyrazole compound comprises the following steps:

[0060] Step A: In an air atmosphere, 0.20 mmol of acetylenic imine 1b, 0.30 mmol of TMSN3, 0.02 mmol of catalyst Sc(OTf)3, 0.02 mmol of additive CuI and 2 ml of solvent 1,2-dichloroethane were added into a sealed tube in a molar volume ratio, and reacted at 70°C for 18 hours;

[0061] Step B: After the reaction is completed, the reaction system is cooled to room temperature, concentrated under reduced pressure, and then purified by rapid silica gel column chromatography to obtain 1,3,5-pyrazole compound 3b as a yellow oil with a yield of 86%. The eluent in the rapid silica gel column chromatography purification is ethyl acetate / petroleum ether in a volume ratio of 1:5-20.

[0062]

[0063] The chemical formula of 1-(4-tert-butyl-phenyl)-5-methylthio-3-phenyl-1H-pyrazole 3b is:

[0064]

[0065] The characterization data are:

[0066] 1 H NMR (400MHz, CDCl3, ppm) δ7.89(d,J=7.0Hz,2H),7.59(d,J=6.5Hz,2H),7.53-7.50( m,2H),7.45-7.41(m,2H),7.36-7.32(m,1H),6.67(s,1H),2.44(s,3H),1.38(s,9H).

[0067] 13 C NMR (100MHz, CDCl3, ppm) δ152.0,151.2,139.0,137.1,133.0,128.7,128.1,126.0,125.7,124.5,105.3,34.8,31.4,18.2.

[0068] HRMS(EI-TOF)m / z:[M] + Calcd for C 20 H 23 N2S + 323.1576; Found 323.1566.

[0069] Embodiment 3:

[0070] A method for synthesizing a 1,3,5-pyrazole compound comprises the following steps:

[0071] Step A: In an air atmosphere, 0.20 mmol of acetylenic imine 1c, 0.30 mmol of TMSN3, 0.02 mmol of catalyst Sc(OTf)3, 0.02 mmol of additive CuI and 2 ml of solvent 1,2-dichloroethane were added into a sealed tube in a molar volume ratio, and reacted at 70°C for 18 hours;

[0072] Step B: After the reaction is completed, the reaction system is cooled to room temperature, concentrated under reduced pressure, and then purified by rapid silica gel column chromatography to obtain 1,3,5-pyrazole compound 3c as a yellow oil with a yield of 88%. The eluent in the rapid silica gel column chromatography purification is ethyl acetate / petroleum ether in a volume ratio of 1:5-20.

[0073]

[0074] The chemical formula of 1-(4-methoxyphenyl)-5-methylthio-3-phenyl-1H-pyrazole 3c is:

[0075]

[0076] The characterization data are:

[0077] 1 H NMR (400MHz, CDCl3, ppm) δ7.90-7.85(m,2H),7.55(d,J=8.9Hz,2H),7.44-7.40(m,2 H),7.36-7.32(m,1H),7.01(d,J=9.0Hz,2H),6.65(s,1H),3.86(s,3H),2.41(s,3H).

[0078] 13 C NMR (100MHz, CDCl3, ppm) δ159.3,151.9,139.1,133.0,132.8,128.7,128.1,126.5,125.7,114.2,105.1,55.6,18.1.

[0079] HRMS(EI-TOF)m / z:[M] + Calcd for C 17 H 17 N2OS + 297.1056; Found 297.1052.

[0080] Example 4

[0081] A method for synthesizing a 1,3,5-pyrazole compound comprises the following steps:

[0082] Step A: In an air atmosphere, 0.20 mmol of acetylenimine 1d, 0.30 mmol of TMSN3, 0.02 mmol of catalyst Sc(OTf)3, 0.02 mmol of additive CuI and 2 ml of solvent 1,2-dichloroethane were added into a sealed tube in a molar volume ratio, and reacted at 70°C for 18 hours;

[0083] Step B: After the reaction is completed, the reaction system is cooled to room temperature, concentrated under reduced pressure, and then purified by rapid silica gel column chromatography to obtain 1,3,5-pyrazole compound 3d as a yellow oil with a yield of 83%. The eluent in the rapid silica gel column chromatography purification is ethyl acetate / petroleum ether in a volume ratio of 1:5-20.

[0084]

[0085] The chemical formula of 1-(4-fluorophenyl)-5-methylthio-3-phenyl-1H-pyrazole 3d is:

[0086]

[0087] The characterization data are:

[0088] 1 H NMR (400MHz, CDCl3, ppm) δ7.86 (s, 2H), 7.63 (d, J = 4.1Hz, 2H), 7.42 (s, 2H), 7.34 (s, 1H), 7.19 (d, J = 8.3Hz, 2H), 6.67 (s, 1H), 2.43 (s, 3H).

[0089] 13 C NMR (100MHz, CDCl3, ppm) δ162.1 (d, J = 246), 152.4, 139.2, 135.8, 132.8, 128.8, 128.3, 126.9 (d, J = 8), 125.8, 116.0 (d, J = 23), 105.8, 18.3.

[0090] 19 F NMR (376MHz, CDCl3): δ-114.26.

[0091] HRMS(EI-TOF)m / z:[M] + Calcd for C 16 H 14 FN2S + 285.0856; Found 285.0848.

[0092] Example 5

[0093] A method for synthesizing a 1,3,5-pyrazole compound comprises the following steps:

[0094] Step A: In an air atmosphere, 0.20 mmol of acetylenic imine 1e, 0.30 mmol of TMSN3, 0.02 mmol of catalyst Sc(OTf)3, 0.02 mmol of additive CuI and 2 ml of solvent 1,2-dichloroethane were added into a sealed tube in a molar volume ratio, and reacted at 70°C for 18 hours;

[0095] Step B: After the reaction is completed, the reaction system is cooled to room temperature, concentrated under reduced pressure, and then purified by rapid silica gel column chromatography to obtain 1,3,5-pyrazole compound 3e as a light yellow oil with a yield of 82%. The eluent in the rapid silica gel column chromatography purification is ethyl acetate / petroleum ether in a volume ratio of 1:5-20.

[0096]

[0097] The chemical structure of ethyl 4-(5-(methylthio)-3-phenyl-1H-pyrazol-1-yl)benzoate 3e is:

[0098]

[0099] The characterization data are:

[0100] 1 H NMR (400MHz, CDCl3, ppm) δ8.17(d,J=8.1Hz,2H),7.86(d,J=7.3Hz,2H),7.83-7.80(m,2H),7.43(dd,J=8. 2,7.3Hz,2H),7.37-7.32(m,1H),6.69(s,1H),4.42(q,J=8.0Hz,2H),2.46(s,3H),1.42(t,J=7.1Hz,3H).

[0101] 13 C NMR (100MHz, CDCl3, ppm) δ166.1,152.9,143.3,139.5,132.6,130.6,129.4,128.9,128.5,125.9,124.0,106.5,61.4,18.4,14.5.

[0102] HRMS(EI-TOF)m / z:[M] + Calcd for C 19 H 19 N2O2S + 339.1162; Found 339.1155.

[0103] Example 6

[0104] A method for synthesizing a 1,3,5-pyrazole compound comprises the following steps:

[0105] Step A: In an air atmosphere, 0.20 mmol of acetylenic imine 1f, 0.30 mmol of TMSN3, 0.02 mmol of catalyst Sc(OTf)3, 0.02 mmol of additive CuI and 2 ml of solvent 1,2-dichloroethane were added into a sealed tube in a molar volume ratio, and reacted at 70°C for 18 hours;

[0106] Step B: After the reaction is completed, the reaction system is cooled to room temperature, concentrated under reduced pressure, and then purified by rapid silica gel column chromatography to obtain 1,3,5-pyrazole compound 3f as a yellow oil with a yield of 86%. The eluent in the rapid silica gel column chromatography purification is ethyl acetate / petroleum ether in a volume ratio of 1:5-20.

[0107]

[0108] The chemical formula of 5-(methylthio)-1-naphthyl-3-phenyl-1H-pyrazole 3f is:

[0109]

[0110] The characterization data are:

[0111] 1 H NMR (400MHz, CDCl3, ppm) δ8.14-8.12(m,1H),7.99-7.95(m,1H),7.94-7.89(m,4H),7.84(dd,J=8. 7,2.1Hz,1H),7.58-7.52(m,2H),7.47-7.42(m,2H),7.38-7.33(m,1H),6.72(s,1H),2.45(s,3H).

[0114] 13 C NMR (100MHz, CDCl3, ppm) δ152.5,139.5,137.2,133.2,132.9,132.6,129.1, 128.8,128.4,128.3,127.9,126.9,126.7,125.9,123.3,123.0,105.7,18.3.

[0116] HRMS(EI-TOF)m / z:[M] + Calcd for C 20 H 17 N2S +317.1107; Found 317.1101.

[0117] Example 7

[0118] A method for synthesizing a 1,3,5-pyrazole compound comprises the following steps:

[0119] Step A: In an air atmosphere, 0.20 mmol of acetylenic imine 1 g, 0.30 mmol of TMSN3, 0.02 mmol of catalyst Sc(OTf)3, 0.02 mmol of additive CuI and 2 ml of solvent 1,2-dichloroethane were added into a sealed tube in a molar volume ratio, and reacted at 70°C for 18 hours;

[0120] Step B: After the reaction is completed, the reaction system is cooled to room temperature, concentrated under reduced pressure, and then purified by rapid silica gel column chromatography to obtain 3 g of 1,3,5-pyrazole compound in the form of yellow oil with a yield of 86%. The eluent in the rapid silica gel column chromatography purification is ethyl acetate / petroleum ether in a volume ratio of 1:5-20.

[0121]

[0122] The chemical structure of 1-(1,1'-biphenyl)-5-(methylthio)-3-phenyl-1H-pyrazole 3g is:

[0123]

[0124] The characterization data are:

[0125] 1 H NMR (400MHz, CDCl3, ppm) δ7.91-7.87(m,2H),7.77-7.71(m,4H),7.67-7.63(m,2H),7.50-7.34(m,6H),6.70(d,J=0.8Hz,1H),2.48(s,3H).

[0127] 13 C NMR (100MHz, CDCl3, ppm) δ152.3,140.9,140.3,139.2,138.9,132.9,129.0,128.8,128.3,127.8,127.8,127.3,125.8,125.1,105.7,18.3.

[0129] HRMS(EI-TOF)m / z:[M] + Calcd for C 22 H 19 N2S +343.1263; Found 343.1256.

[0130] Example 8

[0131] A method for synthesizing a 1,3,5-pyrazole compound comprises the following steps:

[0132] Step A: In an air atmosphere, 0.20 mmol of acetylenimine 1h, 0.30 mmol of TMSN3, 0.02 mmol of catalyst Sc(OTf)3, 0.02 mmol of additive CuI and 2 ml of solvent 1,2-dichloroethane were added into a sealed tube in a molar volume ratio, and reacted at 70°C for 18 hours;

[0133] Step B: After the reaction is completed, the reaction system is cooled to room temperature, concentrated under reduced pressure, and then purified by rapid silica gel column chromatography to obtain 1,3,5-pyrazole compound 3h as a yellow oil with a yield of 87%. The eluent in the rapid silica gel column chromatography purification is ethyl acetate / petroleum ether in a volume ratio of 1:5-20.

[0134]

[0135] The chemical structure of 1-(1,1'-biphenyl)-5-(methylthio)-3-(p-tolyl)-1H-pyrazole 3h is:

[0136]

[0137] The characterization data are:

[0138] 1 H NMR (400MHz, CDCl3, ppm) δ7.74 (dd, J=21.3, 7.9Hz, 6H), 7.63 (d, J=6.7Hz, 2H), 7.46 (t, J=7 .6Hz,2H),7.40-7.34(m,1H),7.23(d,J=7.7Hz,2H),6.65(s,1H),2.44(s,3H),2.38(s,3H).

[0139] 13 C NMR (100MHz, CDCl3, ppm) δ152.4,140.8,140.3,139.0,138.9,138.1,130.1,129.5,129.0,127.8,127.7,127.3,125.7,125.1,105.6,21.5,18.3.

[0140] HRMS(EI-TOF)m / z:[M] + Calcd for C 23 H21 N2S + 357.1420; Found 357.1415.

[0141] Example 9

[0142] A method for synthesizing a 1,3,5-pyrazole compound comprises the following steps:

[0143] Step A: In an air atmosphere, 0.20 mmol of acetylenic imine 1i, 0.30 mmol of TMSN3, 0.02 mmol of catalyst Sc(OTf)3, 0.02 mmol of additive CuI and 2 ml of solvent 1,2-dichloroethane were added into a sealed tube in a molar volume ratio, and reacted at 70°C for 18 hours;

[0144] Step B: After the reaction is completed, the reaction system is cooled to room temperature, concentrated under reduced pressure, and then purified by rapid silica gel column chromatography to obtain 1,3,5-pyrazole compound 3i as a yellow oil with a yield of 89%. The eluent in the rapid silica gel column chromatography purification is ethyl acetate / petroleum ether in a volume ratio of 1:5-20.

[0145]

[0146] The chemical formula of 1-(1,1'-biphenyl)-3-(4-methoxyphenyl)-5-(methylthio)-1H-pyrazole 3i is:

[0147]

[0148] The characterization data are:

[0149] 1 H NMR (400MHz, CDCl3, ppm) δ7.84-7.81(m,2H),7.76-7.70(m,4H),7.66-7.63(m,2H),7.50- 7.46(m,2H),7.42-7.37(m,1H),6.99-6.95(m,2H),6.63(s,1H),3.85(s,3H),2.46(s,3H).

[0150] 13 C NMR (100MHz, CDCl3, ppm) δ159.8,152.2,140.7,140.3,139.0,138.9,129.0,127.8,127.7,127.3,127.1,125.7,125.0,114.2,105.4,55.4,18.3.

[0151] HRMS(EI-TOF)m / z:[M] +Calcd for C 23 H 21 N2OS + 373.1369; Found 373.1361.

[0152] Example 10

[0153] A method for synthesizing a 1,3,5-pyrazole compound comprises the following steps:

[0154] Step A: In an air atmosphere, 0.20 mmol of acetylenimine 1j, 0.30 mmol of TMSN3, 0.02 mmol of catalyst Sc(OTf)3, 0.02 mmol of additive CuI and 2 ml of solvent 1,2-dichloroethane were added into a sealed tube in a molar volume ratio, and reacted at 70°C for 18 hours;

[0155] Step B: After the reaction is completed, the reaction system is cooled to room temperature, concentrated under reduced pressure, and then purified by rapid silica gel column chromatography to obtain 1,3,5-pyrazole compound 3j as a yellow oil with a yield of 81%. The eluent in the rapid silica gel column chromatography purification is ethyl acetate / petroleum ether in a volume ratio of 1:5-20.

[0156]

[0157] The chemical structure of 1-(1,1'-biphenyl)-3-(4-chlorophenyl)-5-(methylthio)-1H-pyrazole 3j is:

[0158]

[0159] The characterization data are:

[0160] 1 H NMR (400MHz, CDCl3, ppm) δ7.84-7.79(m,2H),7.72(s,4H),7.66-7.60(m,2H),7.48(t,J=7.5Hz,2H),7.41-7.36(m,3H),6.65(s,1H),2.47(s,3H).

[0161] 13 C NMR (100MHz, CDCl3, ppm) δ151.3,141.1,140.3,139.5,138.8,134.0,131.5,129.0,129.0,127.8,127.3,127.1,125.1,105.6,18.3.

[0162] HRMS(EI-TOF)m / z:[M] + Calcd for C22 H 18 ClN2S + 377.0874; Found 377.0862.

[0163] Embodiment 11

[0164] A method for synthesizing a 1,3,5-pyrazole compound comprises the following steps:

[0165] Step A: In an air atmosphere, 0.20 mmol of acetylenic imine 1k, 0.30 mmol of TMSN3, 0.02 mmol of catalyst Sc(OTf)3, 0.02 mmol of additive CuI and 2 ml of solvent 1,2-dichloroethane were added into a sealed tube in a molar volume ratio, and reacted at 70°C for 18 hours;

[0166] Step B: After the reaction is completed, the reaction system is cooled to room temperature, concentrated under reduced pressure, and then purified by rapid silica gel column chromatography to obtain 1,3,5-pyrazole compound 3k as a yellow solid with a yield of 79%. The eluent in the rapid silica gel column chromatography purification is ethyl acetate / petroleum ether in a volume ratio of 1:5-20.

[0167]

[0168] The chemical formula of 1-(1,1'-biphenyl)-5-(methylthio)-3-(4-(trifluoromethyl)phenyl)-1H-pyrazole 3k is:

[0169]

[0170] The characterization data are:

[0171] 1 H NMR (400MHz, Chloroform-d) δ7.99(d,J=8.1Hz,2H),7.73(s,4H),7.69-7.63(m,4H),7.48(t,J=7.4Hz,2H),7.42-7.38(m,1H),6.73(s,1H),2.49(s,3H).

[0172] 13 C NMR (100MHz, CDCl3, ppm): δ174.7,145.3,144.9,141.9,139.2,135.4,134.8,1 28.2,128.0,127.9,127.7,126.4,123.0,122.9,108.3,72.5,26.7,14.5,12.5.

[0173] 19F NMR (376MHz, CDCl3): δ-62.86.Mp: 185-186℃.

[0174] HRMS(EI-TOF)m / z:[M] + Calcd for C 23 H 18 F3N2S + 411.1137; Found 411.1128.

[0175] Example 12

[0176] A method for synthesizing a 1,3,5-pyrazole compound comprises the following steps:

[0177] Step A: In an air atmosphere, 0.20 mmol of acetylenic imine 1l, 0.30 mmol of TMSN3, 0.02 mmol of catalyst Sc(OTf)3, 0.02 mmol of additive CuI and 2 ml of solvent 1,2-dichloroethane were added into a sealed tube in a molar volume ratio, and reacted at 70°C for 18 hours;

[0178] Step B: After the reaction is completed, the reaction system is cooled to room temperature, concentrated under reduced pressure, and then purified by rapid silica gel column chromatography to obtain 1,3,5-pyrazole compound 31 as a yellow oil with a yield of 84%. The eluent in the rapid silica gel column chromatography purification is ethyl acetate / petroleum ether in a volume ratio of 1:5-20.

[0179]

[0180] The chemical formula of 1-(1,1'-biphenyl)-5-(methylthio)-3-thiophene-1H-pyrazole 3l is:

[0181]

[0182] The characterization data are:

[0183] 1 H NMR (400MHz, CDCl3, ppm) δ7.71 (s, 4H), 7.66-7.64 (m, 2H), 7.63 (t, J = 1.4Hz, 1H), 7.55- 7.54(m,1H),7.49-7.45(m,2H),7.37(dd,J=5.0,2.7Hz,2H),6.58(s,1H),2.46(s,3H).

[0184] 13C NMR (100MHz, CDCl3, ppm) δ150.1,141.7,140.3,139.0,138.8,134.8,129.0,127.8,127.3,126.1,125.2,121.2,106.1,18.3.

[0185] HRMS(EI-TOF)m / z:[M] + Calcd for C 20 H 17 N2S2 + 349.0828; Found 349.0817.

[0186] Example 13

[0187] A method for synthesizing a 1,3,5-pyrazole compound comprises the following steps:

[0188] Step A: In an air atmosphere, 0.20 mmol of acetylenic imine 1m, 0.30 mmol of TMSN3, 0.02 mmol of catalyst Sc(OTf)3, 0.02 mmol of additive CuI and 2 ml of solvent 1,2-dichloroethane were added into a sealed tube in a molar volume ratio, and reacted at 70°C for 18 hours;

[0189] Step B: After the reaction is completed, the reaction system is cooled to room temperature, concentrated under reduced pressure, and then purified by rapid silica gel column chromatography to obtain 1,3,5-pyrazole compound 3m as a yellow oil with a yield of 80%. The eluent in the rapid silica gel column chromatography purification is ethyl acetate / petroleum ether in a volume ratio of 1:5-20.

[0190]

[0191] The chemical structure of methyl (E)-3-(2-(5-(methylthio)-3-phenyl-1H-pyrazolyl)phenyl)acrylate 3m is:

[0192]

[0193] The characterization data are:

[0194] 1 H NMR (400MHz, CDCl3, ppm) δ7.84 (d, J = 7.6Hz, 2H), 7.81-7.75 (m, 1H), 7.55-7.49 (m, 2H), 7.48-7. 37(m,4H),7.34(t,J=6.9Hz,1H),6.72(s,1H),6.33(d,J=16.8Hz,1H),3.72(s,3H),2.37(s,3H).

[0195] 13 C NMR (100MHz, CDCl3, ppm) δ167.1,152.9,140.9,139.7,138.6,132.8,132.6,13 0.7,129.9,129.0,128.8,128.3,127.6,126.0,120.6,105.7,51.9,29.9,18.4.

[0196] HRMS(EI-TOF)m / z:[M] + Calcd for C 20 H 19 N2O2S + Found 351.1162.

[0197] Embodiment 14

[0198] A method for synthesizing a 1,3,5-pyrazole compound comprises the following steps:

[0199] Step A: In an air atmosphere, 0.20 mmol of acetylenic imine 1n, 0.30 mmol of TMSN3, 0.02 mmol of catalyst Sc(OTf)3, 0.02 mmol of additive CuI and 2 ml of solvent 1,2-dichloroethane were added into a sealed tube in a molar volume ratio, and reacted at 70°C for 18 hours;

[0200] Step B: After the reaction is completed, the reaction system is cooled to room temperature, concentrated under reduced pressure, and then purified by rapid silica gel column chromatography to obtain 1,3,5-pyrazole compound 3n as a yellow oil with a yield of 81%. The eluent in the rapid silica gel column chromatography purification is ethyl acetate / petroleum ether in a volume ratio of 1:5-20.

[0201]

[0202] The chemical structure of methyl (E)-3-(2-(5-(methylthio)-3-(p-tolyl)-1H-pyrazolyl)phenyl)acrylate 3n is:

[0203]

[0204] The characterization data are:

[0205] 1H NMR (400MHz, CDCl3, ppm) δ7.79-7.75(m,1H),7.73(d,J=8.2Hz,2H),7.54-7.49(m,2H),7.47-7.44(m,1H),7.42(d, J=16.1Hz,1H),7.22(d,J=7.9Hz,2H),6.69(s,1H),6.33(d,J=16.0Hz,1H),3.72(s,3H),2.38(s,3H),2.37(s,3H).

[0206] 13 C NMR (100MHz, CDCl3, ppm) δ167.0,152.9,140.7,139.7,138.6,138.1,132.5,13 0.7,130.0,129.8,129.5,129.0,127.5,125.8,120.5,105.5,51.9,21.4,18.3.

[0207] HRMS(EI-TOF)m / z:[M] + Calcd for C 21 H 21 N2O2S + 365.1318; Found 365.1314.

[0208] Embodiment 15

[0209] A method for synthesizing a 1,3,5-pyrazole compound comprises the following steps:

[0210] Step A: In an air atmosphere, 0.20 mmol of acetylenimine 1o, 0.30 mmol of TMSN3, 0.02 mmol of catalyst Sc(OTf)3, 0.02 mmol of additive CuI and 2 ml of solvent 1,2-dichloroethane were added into a sealed tube in a molar volume ratio, and reacted at 70°C for 18 hours;

[0211] Step B: After the reaction is completed, the reaction system is cooled to room temperature, concentrated under reduced pressure, and then purified by rapid silica gel column chromatography to obtain 1,3,5-pyrazole compound 3o as a yellow oil with a yield of 75%. The eluent in the rapid silica gel column chromatography purification is ethyl acetate / petroleum ether in a volume ratio of 1:5-20.

[0212]

[0213] The chemical structure of methyl (E)-3-(2-(5-(methylthio)-3-(4-(trifluoromethyl)phenyl)-1H-pyrazolyl)phenyl)acrylate 3o is:

[0214]

[0215] The characterization data are:

[0216] 1 H NMR(400MHz, CDCl3, ppm) δ7.94(d,J=8.0Hz,2H),7.82-7.77(m,1H),7.66(d,J=8.1Hz,2H),7.57-7.50(m,2H ),7.48-7.44(m,1H),7.39(d,J=16.1Hz,1H),6.75(s,1H),6.35(d,J=16.0Hz,1H),3.72(s,3H),2.39(s,3H).

[0217] 13 C NMR (100MHz, CDCl3, ppm) δ167.0,151.5,141.6,139.5,138.4,136.2,132.5,13 0.8,130.1,129.9,128.8,127.6,126.1,125.8,120.7,105.8,51.9,29.9,18.3.

[0218] 19 F NMR (376 MHz, CDCl3): δ-62.75.

[0219] HRMS(EI-TOF)m / z:[M] + Calcd for C 21 H 18 F3N2O2S + 419.1036; Found 419.1025.

[0220] Example 16

[0221] A method for synthesizing a 1,3,5-pyrazole compound comprises the following steps:

[0222] Step A: In an air atmosphere, 0.20 mmol of acetylenic imine 1p, 0.30 mmol of TMSN3, 0.02 mmol of catalyst Sc(OTf)3, 0.02 mmol of additive CuI and 2 ml of solvent 1,2-dichloroethane were added into a sealed tube in a molar volume ratio, and reacted at 70°C for 18 hours;

[0223] Step B: After the reaction is completed, the reaction system is cooled to room temperature, concentrated under reduced pressure, and then purified by rapid silica gel column chromatography to obtain 1,3,5-pyrazole compound 3p as a yellow oil with a yield of 78%. The eluent in the rapid silica gel column chromatography purification is ethyl acetate / petroleum ether in a volume ratio of 1:5-20.

[0224]

[0225] The chemical structure of methyl (E)-3-(2-(5-(methylthio)-3-naphthyl-1H-pyrazolyl)phenyl)acrylate 3p is:

[0226]

[0227] The characterization data are:

[0228] 1 H NMR (400MHz, CDCl3, ppm) δ8.31 (s, 1H), 8.00 (dd, J = 8.6, 1.7Hz, 1H), 7.89 (d, J = 8.9Hz, 2H), 7.86 -7.77(m,2H),7.55-7.44(m,6H),6.86(s,1H),6.36(d,J=16.0Hz,1H),3.71(s,3H),2.41(s,3H).

[0229] 13 C NMR (100MHz, CDCl3, ppm) δ167.0,152.9,141.2,139.7,138.6,133.7,133.4,132.6,130.7,130.2, 129.9,129.0,128.5,128.4,127.9,127.6,126.4,126.1,124.6,124.1,120.6,105.8,51.9,18.3.

[0230] HRMS(EI-TOF)m / z:[M] + Calcd for C 24 H 21 N2O2S + 401.1318; Found 401.1316.

[0231] Embodiment 17

[0232] A method for synthesizing a 1,3,5-pyrazole compound comprises the following steps:

[0233] Step A: In an air atmosphere, 0.20 mmol of acetylenimine 1q, 0.30 mmol of TMSN3, 0.02 mmol of catalyst Sc(OTf)3, 0.02 mmol of additive CuI and 2 ml of solvent 1,2-dichloroethane were added into a sealed tube in a molar volume ratio, and reacted at 70°C for 18 hours;

[0234] Step B: After the reaction is completed, the reaction system is cooled to room temperature, concentrated under reduced pressure, and then purified by rapid silica gel column chromatography to obtain 1,3,5-pyrazole compound 3q as a yellow oil with a yield of 85%. The eluent in the rapid silica gel column chromatography purification is ethyl acetate / petroleum ether in a volume ratio of 1:5-20.

[0235]

[0236] The chemical formula of 1-(4-(tert-butyl)phenyl)-5-(methylseleno)-3-phenyl-1H-pyrazole 3q is:

[0237]

[0238] The characterization data are:

[0239] 1 H NMR (400MHz, CDCl3, ppm) δ7.87 (d, J = 7.1Hz, 2H), 7.56-7.49 (m, 4H), 7.44-7.39 (m, 2H), 7.35-7.31 (m, 1H), 6.72 (s, 1H), 2.30 (s, 3H), 1.37 (s, 9H).

[0240] 13 C NMR (100MHz, CDCl3, ppm) δ152.6,151.3,137.8,133.0,130.4,128.7,128.1,126.1,125.8,124.6,108.0,34.9,31.5,9.4.

[0241] HRMS(EI-TOF)m / z:[M] + Calcd for C 20 H 23 N2S + 371.1021; Found 371.1022.

[0242] Embodiment 18

[0243] A method for synthesizing a 1,3,5-pyrazole compound comprises the following steps:

[0244] Step A: In an air atmosphere, 0.20 mmol of acetylenic imine 1r, 0.30 mmol of TMSN3, 0.02 mmol of catalyst Sc(OTf)3, 0.02 mmol of additive CuI and 2 ml of solvent 1,2-dichloroethane were added into a sealed tube in a molar volume ratio, and reacted at 70°C for 18 hours;

[0245] Step B: After the reaction is completed, the reaction system is cooled to room temperature, concentrated under reduced pressure, and then purified by rapid silica gel column chromatography to obtain 1,3,5-pyrazole compound 3r as a yellow oil with a yield of 88%. The eluent in the rapid silica gel column chromatography purification is ethyl acetate / petroleum ether in a volume ratio of 1:5-20.

[0246]

[0247] The chemical formula of 1-(4-methoxyphenyl)-5-(methylseleno)-3-phenyl-1H-pyrazole 3r is:

[0248]

[0249] The characterization data are:

[0250] 1 H NMR (400MHz, CDCl3, ppm) δ7.85 (d, J = 7.0Hz, 2H), 7.53-7.49 (m, 2H), 7.43-7.39 (m, 2 H),7.34-7.30(m,1H),7.00(d,J=9.0Hz,2H),6.70(s,1H),3.87(s,3H),2.27(s,3H).

[0251] 13 C NMR (100MHz, CDCl3, ppm) δ159.5,152.5,133.6,130.7,128.8,128.1,126.7,125.8,114.3,108.0,55.7,9.3.

[0252] HRMS(EI-TOF)m / z:[M] + Calcd for C 17 H 17 nnJC + 345.0501; Found 345.0501.

[0253] Embodiment 19

[0254] A method for synthesizing a 1,3,5-pyrazole compound comprises the following steps:

[0255] Step A: In an air atmosphere, 0.20 mmol of acetylenimine 1s, 0.30 mmol of TMSN3, 0.02 mmol of catalyst Sc(OTf)3, 0.02 mmol of additive CuI and 2 ml of solvent 1,2-dichloroethane were added into a sealed tube in a molar volume ratio, and reacted at 70°C for 18 hours;

[0256] Step B: After the reaction is completed, the reaction system is cooled to room temperature, concentrated under reduced pressure, and then purified by rapid silica gel column chromatography to obtain 1,3,5-pyrazole compound 3s as a yellow oil with a yield of 86%. The eluent in the rapid silica gel column chromatography purification is ethyl acetate / petroleum ether in a volume ratio of 1:5-20.

[0257]

[0258] The chemical formula of 5-methylseleno-1-naphthyl-3-phenyl-1H-pyrazole 3s is:

[0259]

[0260] The characterization data are:

[0261] 1 H NMR (400MHz, CDCl3, ppm) δ8.00 (dd, J=7.4, 1.8Hz, 1H), 7.96-7.88 (m, 3H), 7.61-7.60 (m, 1H),7.59-7.50(m,2H),7.49-7.40(m,4H),7.37-7.32(m,1H),6.85(s,1H),2.17(s,3H).

[0262] 13 C NMR (100MHz, CDCl3, ppm) δ152.9,136.6,134.4,133.0,132.6,130.8,130.0,128.8,128.2,127.5,126.9,125.9,125.7,125.1,123.4,107.8,9.4.

[0263] HRMS(EI-TOF)m / z:[M] + Calcd for C 20 H 17 N2S + 365.0551; Found 365.0547.

[0264] Embodiment 20

[0265] A method for synthesizing a 1,3,5-pyrazole compound comprises the following steps:

[0266] Step A: In an air atmosphere, 0.20 mmol of acetylenic imine 1t, 0.30 mmol of TMSN3, 0.02 mmol of catalyst Sc(OTf)3, 0.02 mmol of additive CuI and 2 ml of solvent 1,2-dichloroethane were added into a sealed tube in a molar volume ratio, and reacted at 70°C for 18 hours;

[0267] Step B: After the reaction is completed, the reaction system is cooled to room temperature, concentrated under reduced pressure, and then purified by rapid silica gel column chromatography to obtain 1,3,5-pyrazole compound 3t as a yellow oil with a yield of 86%. The eluent in the rapid silica gel column chromatography purification is ethyl acetate / petroleum ether in a volume ratio of 1:5-20.

[0268]

[0269] The chemical structure of 1-(1,1'-biphenyl)-5-(methylseleno)-3-phenyl-1H-pyrazole 3t is:

[0270]

[0271] The characterization data are:

[0272] 1 H NMR (400MHz, CDCl3, ppm) δ7.89(d,J=7.1Hz,2H),7.72(d,J=1.0Hz,3H),7.65(d,J=8.2Hz,2H),7.51-7.33(m,7H),6.76(s,1H),2.34(s,3H).

[0273] 13 C NMR (100MHz, CDCl3, ppm) δ152.9,141.0,140.3,139.5,132.9,130.5,129.0,128.8,128.2,127.8,127.3,125.9,125.3,108.5,9.5,1.2.

[0274] HRMS(EI-TOF)m / z:[M] + Calcd for C 22 H 19 N2S + 391.0708; Found 391.0694.

[0275] The above description of the examples is to facilitate the understanding and use of the invention by those skilled in the art. It is obvious that those skilled in the art can easily make various modifications to these embodiments and apply the general principles described herein to other embodiments without creative work. Therefore, the present invention is not limited to the above embodiments, and improvements and modifications made by those skilled in the art based on the disclosure of the present invention without departing from the scope of the present invention should be within the scope of protection of the present invention.

Claims

1. A method for synthesizing 1,3,5-pyrazole compounds, characterized in that: The following steps are involved: Step A: In an air atmosphere, 0.20 mmol of acetylenimine, 0.30 mmol of TMSN3, 0.02 mmol of catalyst, 0.02 mmol of additive and 2 ml of solvent were added into a sealed tube in a molar volume ratio, and reacted at 70° C. for 18 hours. The general synthesis formula is as follows: Step B: After the reaction is completed, the reaction system is cooled to room temperature, concentrated under reduced pressure, and then purified by rapid silica gel column chromatography to obtain 1,3,5-pyrazole compounds.

2. The method for synthesizing 1,3,5-pyrazole compounds according to claim 1, characterized in that: The cooling in step B is air cooling.

3. The method for synthesizing 1,3,5-pyrazole compounds according to claim 1, characterized in that: The instrument used for the reduced pressure concentration in step B is a rotary evaporator.

4. The method for synthesizing 1,3,5-pyrazole compounds according to claim 1, characterized in that: The eluent in the rapid silica gel column chromatography purification in step B is ethyl acetate:petroleum ether in a volume ratio of 1:5-20.

5. The method for synthesizing 1,3,5-pyrazole compounds according to claim 1, characterized in that: The catalyst is Sc(OTf)3.

6. The method for synthesizing 1,3,5-pyrazole compounds according to claim 1, characterized in that: The additive is CuI.

7. The method for synthesizing 1,3,5-pyrazole compounds according to claim 1, characterized in that: The solvent is 1,2-dichloroethane.

8. The method for synthesizing 1,3,5-pyrazole compounds according to any one of claims 1 to 7, characterized in that: The step A specifically comprises dissolving 0.20 mmol of acetylenic imine, 0.30 mmol of TMSN3, 0.02 mmol of Sc(OTf)3 and 0.02 mmol of CuI in 2 ml of 1,2-dichloroethane under air atmosphere, heating to 70 degrees Celsius in a sealed tube, and reacting for 18 hours.

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