Preparation method of pyrazolone amino-acid ester derivative

Abstract

The invention discloses a preparation method of a pyrazolone amino-acid ester derivative. The pyrazolone amino-acid ester derivative is obtained through three-component cascade reaction by taking pyrazolone imine, a pentafluorophenylacetate derivative and alcohol as reactants and chiral isothiourea as a catalyst. According to the invention, challenges of competitive side reactions between a plurality of reaction substrates and intermediates and stereoselectivity control are overcome, the application range of the substrate combination of the existing system is broken through, and synthesis of a series of pyrazolone amino-acid ester derivatives is realized in a green and efficient manner. According to the method disclosed by the invention, substrate preassembly is not needed, transition metal catalysis is not needed, raw materials and the catalyst are cheap and easy to obtain, reaction conditions are mild, and the substrate application range is wide. In addition, the invention also provides a new way for introducing the medicine bioactive molecules into the synthesis of the pyrazolone amino-acid ester compound.

Description

Technical Field

[0001] The invention belongs to the field of organic synthesis, and particularly relates to a method for preparing a pyrazolone amino acid ester derivative. Background Art

[0002] Nitrogen heterocyclic compounds occupy a dominant position in the pharmaceutical field, among which pyrazolone, as an important class of five-membered nitrogen heterocyclic compounds, has a wide range of applications in combinatorial chemistry and medicinal chemistry. Such compounds can serve as important synthetic skeletons and play an important role in antibacterial drugs, anti-inflammatory drugs, anticancer drugs and pesticide molecules.

[0003] In view of this, people have conducted in-depth research on the synthesis of pyrazolone and its derivatives. The synthetic methods currently developed rely on the use of two-component tandem reactions containing pyrazolone molecules. For example, two-component tandem reactions using functionalized pyrazolone, unsaturated pyrazolone, 4-isothiocyanatopyrazolone and pyrazolone-derived MBH carbonate as substrates. Although these methods can synthesize a variety of pyrazolone nitrogen heterocyclic derivatives, there are still some disadvantages, such as: the use of multi-step synthetic modified raw materials, the reaction route requires the pre-synthesis of precursors or active intermediates, the use of expensive, toxic and difficult to obtain catalysts, harsh reaction conditions and difficult subsequent transformation of products, especially the lack of effective ways to introduce drug bioactive molecules in subsequent product derivatization.

[0004] Multi-component one-pot synthesis is an efficient and economical synthesis strategy that can directly synthesize various structurally differentiated compounds from basic raw materials. This strategy has the advantages of simple operation, high selectivity, mild conditions, and can fully utilize the main structural fragments in the reactant components, so it is more in line with the principle of atom economy. Although this strategy has many advantages, there are no reports in the literature on the efficient synthesis of chiral pyrazolone and its derivatives by multi-component one-pot method. Therefore, the design and development of more efficient and practical multi-component one-pot method for the synthesis of chiral pyrazolone derivatives, especially the synthesis of pyrazolone derivatives with introduced pharmaceutical bioactive molecules, has broad application prospects. Summary of the invention

[0005] The purpose of the present invention is to provide a method for preparing pyrazolone amino acid ester derivatives. The present invention provides a new synthesis and application transformation route for the synthesis of pyrazolone amino acid ester derivatives and the introduction of drug bioactive molecule transformation.

[0006] To achieve the above object, the present invention provides the following solutions:

[0007] The present invention provides a pyrazolone amino acid ester derivative, the structural formula of which is shown in Formula I:

[0008]

[0009] Among them, R 1 is aryl, substituted aryl or alkyl, wherein the substituted aryl is substituted by one or more substituents selected from halogen, alkyl, alkoxy, nitro, heteroaryl; R 2 is aryl, substituted aryl or alkyl, wherein the substituted aryl is substituted by one or more substituents selected from alkyl, alkoxy, or halogen; R 3 is aryl or substituted aryl, wherein the substituted aryl is substituted by one or more substituents selected from alkyl, halogen, ester or heteroaryl; R 4 is an alkyl group, an aryl group or a substituted aryl group, wherein the substituted aryl group is substituted by one or more substituents selected from the group consisting of an alkyl group, an alkoxy group and a halogen group.

[0010] The preparation method of the above-mentioned pyrazolone amino acid ester derivative comprises the following steps:

[0011] The pyrazolone imine of the structure shown in formula II and the chiral isothiourea catalyst are dissolved in an organic solvent, and then the pentafluorophenylacetic acid ester of the structure shown in formula IV, an organic base and the alcohol of the structure shown in formula III are added to the reaction system, and the obtained mixed solution is stirred for reaction under certain temperature conditions. After the reaction is completed, the reaction solution is post-treated to obtain the pyrazolone amino acid ester derivative of the structure shown in formula I.

[0012] The specific synthetic route of the reaction involved in the present invention is as follows:

[0013]

[0014] The preparation method is that pentafluorophenylacetic acid ester IV generates a nucleophilic intermediate under the action of chiral isothiourea as a catalyst and a base, and further attacks pyrazolone imine II to generate a zwitterionic intermediate. Then, the zwitterionic intermediate and alcohol III undergo a nucleophilic substitution reaction to finally obtain a pyrazolone amino acid ester derivative I.

[0015] As a preference, R 1 is one of phenyl, methyl substituted phenyl, methoxy substituted phenyl, halogen substituted phenyl or tert-butyl; R 2 is one of phenyl, methyl substituted phenyl, methoxy substituted phenyl, halogen substituted phenyl, methyl, ethyl or butyl; R 3 is one of phenyl, methyl substituted phenyl, methoxy substituted phenyl, halogen substituted phenyl, thienyl or indomethacin; R 4 It is one of methyl, ethyl, butyl, cyclopentyl, cyclohexyl, phenethyl, phenylpropyl or acetyl substituted phenyl.

[0016] Preferably, the reaction temperature is 0°C and the reaction time is 10 min-180 min.

[0017] Preferably, the reaction environment is air atmosphere, and stirring is performed under ice bath conditions.

[0018] Preferably, the molar ratio of the pyrazolone imine of the structure represented by formula II, the alcohol of the structure represented by formula III and the pentafluorophenylacetic acid ester of the structure represented by formula IV is 1:10-20:1-2; more preferably, the molar ratio of the three is 1:10-15:(1-1.5); and even more preferably, the molar ratio of the three is 1:10:1.

[0019] Preferably, the base is selected from one of isopropylethylamine (DIPEA), triethylamine, diisopropylethylamine, 1,8-diazabicyclo[5.4.0]undec-7-ene, sodium carbonate, and cesium carbonate. Further preferably, the base is selected from one of DIPEA or triethylamine.

[0020] Preferably, the solvent is selected from one or more of acetonitrile, tetrahydrofuran, chloroform, dichloromethane or an alcohol of the structure shown in formula III. Further preferably, the solvent is selected from one of the alcohols of the structure shown in formula III or dichloromethane.

[0021] The structural formula of the chiral isothiourea catalyst is:

[0022]

[0023] The post-treatment method is column chromatography separation.

[0024] The column chromatography separation adopts silica gel column chromatography separation.

[0025] The present invention is based on a three-component tandem reaction of pyrazolone imine, pentafluorophenylacetic acid ester derivatives and alcohol, overcomes the challenges of competitive side reactions between multiple reaction substrates and intermediates and stereoselective control, breaks through the application scope of the existing system substrate combination, and realizes the chiral synthesis of a series of pyrazolone amino acid ester derivatives in a green and efficient manner.

[0026] Compared with the prior art, the present invention has the following advantages:

[0027] 1. Different from the traditional two-component method of constructing pyrazolone derivatives, the present invention utilizes a one-pot three-component tandem reaction strategy, without the need for pre-assembly of functional groups, to highly selectively synthesize pyrazolone amino acid ester derivatives containing multiple substitution sites.

[0028] 2. The method of the present invention does not require pre-assembly or transition metal catalysis, and the reaction uses commercially available organic catalysts and cheap and readily available raw materials, which is green and environmentally friendly.

[0029] 3. The reaction conditions of the present invention are mild, the operation is simple, and the substrate has a wide range of applicability. In particular, it can directly introduce active molecules of biological drugs into the product, which effectively solves the comprehensive problems existing in the methods described in the background technology and has good application prospects. BRIEF DESCRIPTION OF THE DRAWINGS

[0030] Figure 1 The product obtained in Example 1 of the present invention 1 HNMR spectrum;

[0031] Figure 2 The product obtained in Example 1 of the present invention 13 CNMR spectrum;

[0032] Figure 3 The product obtained in Example 2 of the present invention 1 HNMR spectrum;

[0033] Figure 4 The product obtained in Example 2 of the present invention 13 CNMR spectrum;

[0034] Figure 5 The product obtained in Example 3 of the present invention 1 HNMR spectrum;

[0035] Figure 6 The product obtained in Example 3 of the present invention 13 CNMR spectrum;

[0036] Figure 7 The product obtained in Example 4 of the present invention 1 HNMR spectrum;

[0037] Figure 8 The product obtained in Example 4 of the present invention 13 CNMR spectrum;

[0038] Fig. 9 The product obtained in Example 5 of the present invention 1 HNMR spectrum;

[0039] Fig.10 The product obtained in Example 5 of the present invention 13 CNMR spectrum;

[0040] Fig.11 The product obtained in Example 6 of the present invention 1 HNMR spectrum;

[0041] Fig.12 The product obtained in Example 6 of the present invention 13 CNMR spectrum;

[0042] Fig.13 The product obtained in Example 7 of the present invention 1 HNMR spectrum;

[0043] Fig.14 The product of Example 7 of the present invention 13 CNMR spectrum;

[0044] Fig.15 The product obtained in Example 8 of the present invention 1 HNMR spectrum;

[0045] Fig.16 The product obtained in Example 8 of the present invention 13 CNMR spectrum;

[0046] Fig.17 The product obtained in Example 9 of the present invention 1 HNMR spectrum;

[0047] Fig.18 The product obtained in Example 9 of the present invention 13 CNMR spectrum;

[0048] Fig.19 The product obtained in Example 10 of the present invention 1 HNMR spectrum;

[0049] Fig. 20 The product obtained in Example 10 of the present invention 13 CNMR spectrum. DETAILED DESCRIPTION

[0050] The present invention will be further described below in conjunction with examples, but the present invention is not limited to the following examples.

[0051] Example 1

[0052] Method: In a reaction flask, pyrazolone imine 1a (28.7 mg, 0.1 mmol) and chiral isothiourea catalyst (2.5 mg, 10 mol%) were dissolved in 1.0 mL of ethanol 2a, and then pentafluorobenzene-phenylacetate 3a (45.3 mg, 0.15 mmol) and diisopropylethylamine (34.8 μL, 0.2 mmol) were added. The reaction mixture was stirred at 0°C for 30 minutes until the raw materials disappeared completely. The reaction solution was then cooled to room temperature, separated and purified by column chromatography (petroleum ether: ethyl acetate = 3:1 as the developing solvent) and concentrated under reduced pressure to obtain compound 4a with a yield of 93%, >20:1dr, 99%ee. 1H NMR (600MHz, CDCl3): δ = 1.27 (t, J = 7.2Hz, 3H), 1.37 (s, 9H), 2.03 (s, 3H), 3.87 (s, 1H), 4.26 (q, J = 6.0Hz, 2H), 6.68 (s,1H),7.16(t,J=7.2Hz,1H),7.22-7.24(m,3H),7.27-7.31(m,2H),7.35(t,J=7.8Hz,2H),7.71(d,J=7.2Hz,2H). 13 C NMR (150MHz, CDCl3): δ = 13.7, 13.9, 28.2 (3C), 53.7, 62.4, 67.1, 81.5, 119.0 (2C), 125.0, 128.3 (2C),128.7(2C),129.0,129.8(2C),130,1,137.7,153.6,158.2,169.0,170.1.HRMS(ESI):m / z calcd for C 25 H 29 N3NaO5[M+Na] + :474.1999,found:474.2002.

[0053] The reaction formula is as follows:

[0054]

[0055] Example 2

[0056] Method: Except that pentafluorobenzene-4-chlorophenylacetate represented by structural formula 3b is used instead of pentafluorobenzene-phenylacetate represented by structural formula 3a in Example 1, the remaining steps are the same as those in Example 1, and compound 4b is isolated with a yield of 90%, >20:1dr, and 99%ee. 1 H NMR (600MHz, CDCl3): δ = 1.29 (t, J = 7.2Hz, 3H), 1.37 (s, 9H), 2.03 (s, 3H), 3.83 (s, 1H), 4.25 -4.31(m,2H),6.69(s,1H),7.16-7.21(m,5H),7.36(t,J=7.8Hz,2H),7.71(d,J=7.8Hz,2H). 13C NMR (150MHz, CDCl3): δ = 13.6, 13.9, 28.0 (3C), 52.8, 62.7, 67.0, 81.7, 119.0 (2C), 125.2, 128.5 (2C),128.6,128.8(2C),131.0(2C),135.1,137.6,153.9,158.0,168.6,169.9.HRMS(ESI):m / z calcd for C 25 H 28 ClN3NaO5[M+Na] + :508.1610,found:508.1615.

[0057] The reaction formula is as follows:

[0058]

[0059] Example 3

[0060] Method: Except that pentafluorobenzene-4-methylphenylacetate represented by structural formula 3c was used instead of pentafluorobenzene-phenylacetate represented by structural formula 3a in Example 1, the remaining steps were the same as those in Example 1 to separate compound 4c with a yield of 86%, >20:1 dr, and 99% ee. 1 H NMR (600MHz, CDCl3): δ = 1.26 (t, J = 7.2Hz, 3H), 1.37 (s, 9H), 2.03 (s, 3H), 2.28 (s, 3H), 3.83 (s, 1H), 4.23-4.26 ( m,2H),6.62(s,1H),7.04(d,J=7.8Hz,2H),7.16(t,J=7.2Hz,3H),7.35(t,J=7.2Hz,2H),7.74(d,J=7.8Hz,2H). 13 C NMR (150MHz, CDCl3): δ=13.8,13.9,21.1,28.0(3C),53.6,62.3,67.1,82.0,119.0(2C),125.0,12 7.0,128.7(2C),129.1(2C),129.6(2C),137.8,138.9,154.1,158.2,169.1,170.2.HRMS(ESI):m / z calcdfor C 26 H 32 N3O5[M+H] + :466.2337,found:466.2322.

[0061] The reaction formula is as follows:

[0062]

[0063] Example 4

[0064] Method: Except that pentafluorobenzene-3,4-dimethoxyphenylacetate represented by structural formula 3d is used instead of pentafluorobenzene-phenylacetate represented by structural formula 3a in Example 1, the remaining operation steps are the same as those in Example 1, and compound 4d is isolated with a yield of 77%, >20:1dr, and 99%ee. 1 H NMR (600MHz, CDCl3): δ=1.29(t,J=7.2Hz,3H),1.37(s,9H),2.04(s,3H),3.44(s,3H),3.83(s,4H),4.26-4.29(m,2H ),6.61(s,1H),6.72-6.76(m,2H),6.79(s,1H),7.15(t,J=7.2Hz,1H),7.34(t,J=7.8Hz,2H),7.76(d,J=7.2Hz,2H). 13 C NMR (150MHz, CDCl3): δ=13.8,14.0,28.0(3C),53.5,55.3,55.7,62.4,67.3,82.7,110.4,112.2,118.6( 2C),122.3,122.5,125.0,128.8(2C),137.8,148.6,149.5,155.3,158.3,168.8,170.3.HRMS(ESI):m / z calcd for C 27 H 33 N3NaO7[M+Na] + :534.2211,found:534.2214.

[0065] The reaction formula is as follows:

[0066]

[0067] Example 5

[0068] Method: Except that pentafluorobenzene-indomethacrylic acid ester represented by structural formula 3e was used instead of pentafluorobenzene-phenylacetic acid ester represented by structural formula 3a in Example 1, the remaining steps were the same as those in Example 1 to separate compound 4e with a yield of 66%, 6:1 dr, and 99% ee. 1H NMR (600MHz, CDCl3): δ=1.26(s,3H),1.38(s,9H),2.09(s,3H),2.31(s,3H),3.57(s,3H),4.18- 4.28(m,3H),6.61(s,1H),6.88(s,2H),7.11(d,J=40.2Hz,2H),7.30(s,2H),7.44-7.60(m,6H). 13 C NMR (150MHz, CDCl3): δ=14.0,14.2,17.6,28.1(3C),55.3,62.5,67.3,71.3,82.6,103.3,110.6,112.7,114.3,119.4,125.1(2C),128 .6(2C),129.2(2C),130.9,131.4(2C),133.3,137.1,137.7,139.8,141.9,154.8,155.7,159.0,168.4,169.8,170.6.HRMS(ESI):m / z calcd for C 36 H 37 ClN4NaO[M+Na] + :695.2243,found:695.2246.

[0069] The reaction formula is as follows:

[0070]

[0071] Embodiment 6:

[0072] Method: Except for using nitrogen-2-chlorobenzene-pyrazolone imine of structural formula 1b instead of pyrazolone imine of structural formula 1a in Example 1, the remaining steps are the same as Example 1 to isolate compound 4f with a yield of 67%, 6:1dr, and 99%ee. 1 H NMR (600MHz, CDCl3): δ = 1.26 (t, J = 7.2Hz, 3H), 1.43 (s, 9H), 2.04 (s, 3H), 3.91 (s, 1H), 4.25 (q, J = 7.2Hz, 2H), 6.6 7(s,1H),7.24-7.29(m,2H),7.32-7.33(m,1H),7.35(t,J=8.4Hz,3H),7.39(d,J=7.2Hz,2H),7.44-7.45(m,1H). 13C NMR (150MHz, CDCl3): δ = 13.9 (2C), 28.1 (3C), 53.3, 62.4, 65.7, 81.2, 127.3, 128.6 (3C), 128. 8,128.9,129.2,130.0(2C),130.2,130.3,135.0,154.0,158.6,169.0,169.5.HRMS(ESI):m / z calcd forC 25 H 28 ClN3NaO5[M+Na] + :508.1610,found:508.1613.

[0073] The reaction formula is as follows:

[0074]

[0075] Example 7

[0076] Method: Except for using nitrogen-tert-butylpyrazolone imine shown in structure 1c instead of pyrazolone imine shown in structure 1a in Example 1, the remaining steps are the same as Example 1, and 4g of compound is isolated with a yield of 86%, 6:1dr, and 99%ee. 1 H NMR (600MHz, CDCl3): δ=1.29(t,J=6.6Hz,3H),1.41(s,18H),1.91(s,3H),3.77(s,1H),4.26(t,J=5.4Hz,2H),6.46(s,1H),7.30(s,5H). 13 C NMR (150MHz, CDCl3): δ = 13.9, 14.0, 27.8 (3C), 28.1 (3C), 57.6, 59.4, 62.1, 66.6, 80. 7,128.0(2C),128.7,130.0(2C),130.5,153.9,155.3,169.2,172.0.HRMS(ESI):m / z calcd for C 23 H 33 N3NaO5[M+Na] + :454.2312,found:454.2314. The reaction formula is as follows:

[0077]

[0078] Example 8

[0079] Method: Except for using 3-phenylpyrazolone imine of structural formula 1d instead of pyrazolone imine of structural formula 1a in Example 1, the remaining steps were the same as in Example 1 to isolate compound 4h with a yield of 92%, 6:1 dr, and 99% ee. 1 H NMR (600MHz, CDCl3): δ=1.27(t,J=7.2Hz,12H),4.09(s,1H),4.19-4.29(m,2H),6.92(d,J=7.8Hz,2H),7.04(t,J =7.2Hz,2H),7.19(t,J=7.2Hz,2H),7.25(s,1H),7.37-7.44(m,5H),7.78(t,J=7.8Hz,2H),7.85(d,J=7.2Hz,2H). 13 C NMR (150MHz, CDCl3): δ = 13.9, 28.0 (3C), 54.4, 62.4, 67.0, 82.4, 119.2 (2C), 125.3, 126.4 (2C), 127.7 (2C), 128.6(2C),128.7(3C),129.7,130.1(2C),130.4,130.6,137.7,154.9,158.5,168.9,170.6.HRMS(ESI):m / z calcd for C 30 H 31 N3NaO5[M+Na] + :536.2156,found:536.2161.

[0080] The reaction formula is as follows:

[0081]

[0082] Example 9

[0083] Method: Except for using geraniol represented by structural formula 2b instead of ethanol represented by structural formula 1a in Example 1, the remaining steps were the same as in Example 1 to separate compound 4i with a yield of 74%, 6:1 dr, and 99% ee. 1H NMR (600MHz, CDCl3): δ=1.35(s,9H),1.58(s,3H),1.67(s,6H),2.00-2.07(m,7H),3.86(s,1H),4.65-4.68(m,1H),4.74-4.77(m,1H),5.05(s,1H) ),5.31(t,J=7.2Hz,1H),6.62(s,1H),7.15(t,J=7.2Hz,1H),7.22-7.25 (m,2H),7.28-7.30(m,3H),7.34(t,J=7.8Hz,2H),7.72(d,J=7.2Hz,2H). 13 C NMR (150MHz, CDCl3): δ=13.8,16.5,17.6,25.6,26.2,28.0(3C),39.4,53.7,63.1,67.1,81.6,117.2,119.0,123.6(2C),1 25.0,128.3(2C),128.6(2C),129.0,129.8(2C),130.1,131.8,137.8,143.8,155.2,158.7,168.8,170.0.HRMS(ESI):m / z calcdfor C 33 H 41 N3NaO5[M+Na] + :582.2938,found:582.2942.

[0084] The reaction formula is as follows:

[0085]

[0086] Example 10

[0087] Method: Except that piperonyl alcohol represented by structure 2c was used instead of ethanol represented by structure 2a in Example 1, the remaining steps were the same as those in Example 1, and compound 4j was isolated with a yield of 71%, >20:1 dr, and 99% ee. 1H NMR (600MHz, CDCl3): δ=1.35(s,9H),1.99(s,3H),3.89(s,1H),5.06(d,J=12.0Hz,1H),5.18(d,J=11.4Hz,1H),5.95(s,2H),6.51(s,1H),6.74(d,J =7.8Hz,1H),6.80(d,J=11.4Hz,2H),7.16(t,J=7.2Hz,1H),7.21-7.24(m ,4H),7.29(t,J=7.2Hz,1H),7.35(t,J=7.8Hz,2H),7.71(d,J=7.8Hz,2H). 13 C NMR (150MHz, CDCl3): δ=13.8,28.0(3C),53.3,68.2,70.8,81.9,101.2,108.2,109.23,119.0(2C),122.7,125.0,126.8, 128.4(2C),128.7(2C),129.1,129.8(2C),129.9,137.7,147.8,147.9,154.9,160.4,168.7,170.1.HRMS(ESI):m / zcalcd for C 31 H 31 N3NaO7[M+Na] + :580.2054,found:580.2056.

[0088] The reaction formula is as follows:

[0089]

[0090] The above description is only a preferred specific implementation manner of the present invention, and the protection scope of the present invention is not limited thereto. Any simple change or equivalent replacement of the technical solution that can be obviously obtained by any person familiar with the technical field within the technical scope disclosed in the present invention falls within the protection scope of the present invention.

Claims

1. A method for preparing a pyrazolone amino acid ester derivative, characterized in that: The following steps are involved: The pyrazolone imine of the structure shown in formula II and the chiral isothiourea catalyst are dissolved in an organic solvent, and then the pentafluorophenylacetic acid ester of the structure shown in formula IV, an organic base and the alcohol of the structure shown in formula III are added to the reaction system, and the obtained reaction mixture is continuously stirred for reaction. After the reaction is completed, the reaction solution is post-treated to obtain the pyrazolone amino acid ester derivative of the structure shown in formula I; Among them, R 1 is selected from one of aryl, substituted aryl or alkyl; R 2 is selected from one of aryl, substituted aryl or alkyl; R 3 is selected from one of aryl, substituted aryl or heteroaryl; R 4 One selected from an alkyl group, an aryl group or a substituted aryl group.

2. The method for preparing a pyrazolone amino acid ester derivative according to claim 1, characterized in that: R 1 is phenyl, methyl substituted phenyl, methoxy substituted phenyl, halogen substituted phenyl or tert-butyl; R 2 is phenyl, methyl substituted phenyl, methoxy substituted phenyl, halogen substituted phenyl, methyl, ethyl or butyl; R 3 is phenyl, methyl substituted phenyl, methoxy substituted phenyl, halogen substituted phenyl, thienyl or indomethacin; R 4 The phenyl group is substituted with a methyl, ethyl, butyl, cyclopentyl, cyclohexyl, phenethyl, phenylpropyl or acetyl group.

3. The method for preparing a pyrazolone amino acid ester derivative according to claim 1, characterized in that: The reaction temperature was 0°C, the reaction environment was air atmosphere, and stirring was performed under ice bath conditions.

4. The method for preparing a pyrazolone amino acid ester derivative according to claim 1, characterized in that: The molar ratio of the pyrazolone imine, alcohol and pentafluorophenyl acetate is 1:10-20:1-2.

5. The method for preparing a pyrazolone amino acid ester derivative according to claim 1, characterized in that: The organic base is diisopropylethylamine or triethylamine.

6. The method for preparing a pyrazolone amino acid ester derivative according to claim 1, characterized in that: The solvent is selected from one of the alcohols of the structure shown in formula III or dichloromethane.

7. The method for preparing a pyrazolone amino acid ester derivative according to claim 1, characterized in that: The structural formula of the chiral isothiourea catalyst is:

8. The method for preparing a pyrazolone amino acid ester derivative according to claim 1, characterized in that: The reaction time of the reaction system is 10min-180min.

9. The method for preparing a pyrazolone amino acid ester derivative according to claim 1, characterized in that: The post-treatment method is column chromatography separation.

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