Electrocatalytic preparation method of (indolizine-3-yl)-ethanedione derivative

Abstract

The present invention relates to the field of organic synthesis, and in particular to an electrocatalytic preparation method of an (indolizine-3-yl)-ethanedione derivative. The present invention uses indolizine derivatives and 2-oxo-2-aryl acetaldehyde derivatives as raw materials, does not use metal catalysts, photocatalysts and other high-cost, difficult-to-handle catalysts, and can obtain a series of (indolizine-3-yl)-ethanedione derivatives with good regioselectivity and high yield by electrification, which is more suitable for industrial scenarios.

Description

Technical Field

[0001] The invention relates to the field of organic synthesis, and in particular to an electrocatalytic preparation method of an (indolizine-3-yl)-ethanedione derivative. Background Art

[0002] (Indolizine-3-yl)-ethanedione derivatives have a wide range of applications in biochemistry, pharmaceuticals, agrochemicals, and functional organic materials. For example, Novel indolizine derivatives lowers blood glucose levels instreptozotocin-induced diabetic rats: A histopathological approach (Pharmacological Reports, 2019, vol. 71, #2, p. 233-242) reported a series of (indolizine-3-yl)-ethanedione derivatives with good hypoglycemic activity; CN101679410 A disclosed a series of (indolizine-3-yl)-ethanedione derivatives with antifungal activity; CN111269228A disclosed that (indolizine-3-yl)-ethanedione derivatives have certain fluorescence properties.

[0003] Regarding the preparation of (indolizine-3-yl)-ethanedione derivatives, CN1158121A discloses the use of oxalyl chloride derivatives and indolizine derivatives to prepare them by Friedel-Crafts acylation. The preparation of acyl chloride requires the use of acyl chloride reagents, which has problems such as difficulty in waste liquid treatment and safety; CN111269228A discloses the use of indolizine derivatives and 2-oxo-2-aryl acetaldehyde to prepare (indolizine-3-yl)-ethanedione derivatives under photocatalysis. Although the photocatalysis has good atom economy, it is difficult to treat the organic waste liquid after photocatalysts such as eosin, Bengal red, and rhodamine; Mechanochemical Synthesis of 1,2-Diketoindolizine Derivatives from Indolizines and Epoxides Using Piezoelectric Materials (Org. Lett. 2021, 23, 18, 7171-7176) reported the use of indolizine derivatives and ethylene oxide derivatives to prepare (indolizine-3-yl)-ethanedione derivatives under BaTiO3 catalysis. This reaction requires the use of heavy metals as catalysts, which is relatively costly.

[0004] Based on the existing technology for the preparation of (indolizine-3-yl)-ethanedione derivatives, it is necessary to develop a more environmentally friendly, quick and low-cost method for preparing (indolizine-3-yl)-ethanedione derivatives. Summary of the invention

[0005] The purpose of the present invention is to overcome the problems existing in the prior art and develop an electrocatalytic preparation method of (indolizine-3-yl)-ethanedione derivatives.

[0006] The purpose of the present invention is achieved through the following technical solutions.

[0007] A method for preparing an (indolizine-3-yl)-ethanedione derivative, comprising reacting the following formula:

[0008]

[0009] Wherein R, R1, and R2 are each independently selected from H, alkyl, alkoxy, halogen, and substituted or unsubstituted aryl;

[0010] n = 1, 2, 3, or 4;

[0011] When n is not 1, each R1 may be the same or different.

[0012] In some specific embodiments, n=1.

[0013] In some specific embodiments, the alkyl group is selected from C1-C6 alkyl groups, preferably C1-C3 alkyl groups.

[0014] In some specific embodiments, the alkoxy group is selected from C1-C6 alkoxy groups, preferably C1-C3 alkoxy groups.

[0015] In some specific embodiments, the halogen is selected from fluorine, chlorine, bromine or iodine.

[0016] In some specific embodiments, the aryl group is selected from 5-6 membered aryl groups.

[0017] In some specific embodiments, the aryl group contains 0, 1, 2, or 3 heteroatoms independently selected from O, N, or S.

[0018] In some specific embodiments, in the substituted aryl group, the substituent is 1, 2, or 3, and the substituent is independently selected from C1-C6 alkyl, C1-C6 fluoroalkyl, C1-C6 alkoxy or halogen; preferably C1-C3 alkyl, C1-C3 alkoxy, C1-C3 fluoroalkyl or halogen.

[0019] The present invention does not particularly limit the amounts of compound 1 and compound 2, but for economic and conversion considerations, the molar ratio of compound 1 to compound 2 is preferably 1:0.6-3; preferably 1:0.7-2.9; more preferably 1:0.8-2.8; further preferably 1:0.9-2.7; further preferably 1:1.0-2.6; further preferably 1:1.1-2.5; further preferably 1:1.2-2.4; further preferably 1:1.3-2.3; further preferably 1:1.4-2.2; further preferably 1:1.5-2.1; further preferably 1:1.6-2.0; further preferably 1:1.7-1.9; further preferably 1:1.7-1.8.

[0020] The present invention does not impose any particular limitation on the conditions for conducting the reaction, and the reaction can occur as long as current flows.

[0021] In some specific embodiments, the current of the power supply is 5-20 mA, preferably 10 mA.

[0022] In some specific embodiments, the voltage of the power supply is 5-30V, preferably 15V.

[0023] In some specific embodiments, the reaction is carried out in the presence of an electrolyte and a solvent.

[0024] The present invention does not impose any specific limitation on the electrolyte, as long as it plays a role in transmitting current in the reaction of the present invention.

[0025] In some specific embodiments, the electrolyte is at least one of a quaternary ammonium salt and an alkali metal salt.

[0026] In some specific embodiments, the quaternary ammonium salt is a tetraalkylammonium halide, wherein the alkyl groups are each independently selected from C1-C20 alkyl groups, and the halogen is selected from fluorine, chlorine, bromine or iodine.

[0027] In some specific embodiments, in the tetraalkylammonium halide, the alkyl group is selected from C1-C4 alkyl.

[0028] In some specific embodiments, the quaternary ammonium salt is tetrabutylammonium iodide.

[0029] In some specific embodiments, the alkali metal salt is selected from alkali metal halide salts, wherein the alkali metal is selected from Li, Na, K, Ru, Cs, and the halogen is selected from fluorine, chlorine, bromine or iodine.

[0030] In some specific embodiments, in the alkali metal salt, the alkali metal is selected from Na or K, and the halogen is selected from bromine or iodine.

[0031] The present invention does not impose any particular limitation on the amount of the electrolyte, and only needs to ensure that the current transfer of the electrolytic reaction system is carried out. However, considering the current transfer efficiency, the molar ratio of the amount of the electrolyte to the reactant 1 in the electrolytic reaction system of the present invention is 0.001-7:1; preferably 1-5:1; more preferably 2-7:1; further preferably 3-7:1; and further preferably 4-7:1.

[0032] In some specific embodiments, the solvent is a mixed solvent of an aprotic solvent and water.

[0033] The present invention does not limit the selection of the aprotic solvent and the volume ratio of the aprotic solvent to water, as long as the reaction substrate and the electrolyte can be well dissolved to form a uniform solution.

[0034] In some specific embodiments, the volume ratio of the aprotic solvent to water is 0.5-10:1, specifically 0.5:1, 0.7:1, 0.9:1, 1:1, 2:1, 4:1, 6:1, 8:1, 10:1, preferably 3-6:1.

[0035] In some specific embodiments, the aprotic solvent is selected from at least one of acetonitrile, dimethyl sulfoxide, N,N-dimethylformamide, N,N-dimethylacetamide, acetone, tetrahydrofuran, dioxane, N-methylpyrrolidone, 1,2-dichloroethane, and dichloromethane.

[0036] In some specific embodiments, the aprotic solvent is selected from at least one of acetonitrile, dimethyl sulfoxide, and N,N-dimethylformamide, preferably acetonitrile.

[0037] The present invention does not limit the concentrations of compound 1 and compound 2 in the reaction, as long as the molar ratio of the two amounts described above is satisfied. However, considering the reaction efficiency and conversion rate, the substrate concentration of the reaction of the present invention is 0.01-1 mol / L, preferably 0.01-0.05 mol / L.

[0038] The present invention also provides a use of compound 3, which is use in preparing cancer-related products.

[0039] In some specific embodiments, the cancer is liver cancer or cervical cancer.

[0040] The advantages of the present invention are:

[0041] 1. The electrocatalytic preparation method of (indolizine-3-yl)-ethanedione derivatives of the present invention does not use metal catalysts, photocatalysts and other catalysts that are costly and difficult to handle. By applying electricity, a series of (indolizine-3-yl)-ethanedione derivatives can be obtained with good regioselectivity and high yield, which is more suitable for industrial scenarios. DETAILED DESCRIPTION

[0042] The above features mentioned in the present invention or the features mentioned in the embodiments can be combined in any way. All the features explained in the specification of this case can be used in combination with any method form, and each feature disclosed in the specification can be replaced by any alternative feature that can provide the same, equal or similar purpose. Therefore, unless otherwise specified, the disclosed features are only general examples of equal or similar features.

[0043] The present invention will be further described below in conjunction with specific examples. These examples are only used to illustrate the present invention and are not intended to limit the scope of the present invention. In the following examples, the implementation methods for specifying specific conditions are usually based on conventional conditions or the conditions recommended by the manufacturer. Unless otherwise specified, all percentages and fractions are by weight.

[0044] Unless otherwise defined, all professional and scientific terms used herein have the same meanings as those known to those skilled in the art. In addition, any methods and materials similar or equivalent to those described herein can be applied to the methods of the present invention. The preferred implementation methods and materials described herein are for demonstration purposes only.

[0045] Embodiment 1:

[0046] 19.3 mg (0.1 mmol) of 2-phenylindoleazine, 147.6 mg-258.3 mg (0.4 mmol) of tetrabutylammonium iodide, and 40.2 mg (0.3 mmol) of phenylglyoxal were placed in a 25 ml test tube with a stirring bar. A mixed solution of 4 mL of acetonitrile and 1 mL of water was added at room temperature. The mixture was stirred for 6 hours at 10 mA. After being spin-dried, the target product was obtained by rapid column chromatography with a yield of 91%.

[0047]

[0048] 1 H NMR (400MHz, CDCl3) δppm 10.09(d,J=6.9Hz,1H),7.67-7.62(m,2H),7.59(d,J=8.7Hz,1H),7.50(t,J=7.3Hz,1H),7.33(q,J =8.7,8.0Hz,3H),7.14(d,J=7.3Hz,1H),7.07(t,J=8.7Hz,3H),7.00(t,J=7.5Hz,2H),6.53(s,1H).

[0049] 13C NMR(100MHz,CDCl3)δppm 192.4,183.2,142.2,139.4,134.2,134.0,133.6,130.4,129.6,129.6,128.4,128.0,127.6,126.6,118.8,118.5,114.9,106.1.

[0050] HRMS MALDI(m / z):calcd for C 22 H 15 NO2[M+Na] + :348.0995,found:348.0996.

[0051] Embodiment 2:

[0052] 20.7 mg (0.1 mmol) of 8-methyl-2-phenylindoleazine, 258.3 mg (0.7 mmol) of tetrabutylammonium iodide and 10.4 mg (0.1 mmol) of phenylglyoxal were placed in a 25 ml test tube with a stirring bar. A mixed solution of 3 mL of acetonitrile and 2 mL of water was added at room temperature. The mixture was stirred for 6 hours at 15 mA. After being spin-dried, the target product was obtained by rapid column chromatography with a yield of 83%.

[0053]

[0054] 1 H NMR (400MHz, CDCl3) δppm 9.96(d,J=6.8Hz,1H),7.64(d,J=7.2Hz,2H),7.49(t,J=7.4Hz,1H),7.30(d,J=7.8Hz,2H),7.17 -7.08(m,4H),7.00(t,J=7.6Hz,2H),6.96(t,J=7.0Hz,1H),6.53(d,J=0.7Hz,1H),2.50(s,3H).

[0055] 13 C NMR(100MHz,CDCl3)δppm 192.5,183.2,141.7,139.8,134.3,134.0,133.6,130.4,129.5,128.3,127.9,127.7,127.5,127.3,126.0,119.1,114.9,104.6,18.1.

[0056] HRMS MALDI(m / z):calcd for C 23 H 17 NO2[M+H] +:340.1332,found:340.1338.

[0057] Embodiment 3:

[0058] 20.7 mg (0.1 mmol) of 7-methyl-2-phenylindoleazine, 184.5 mg (0.5 mmol) of tetrabutylammonium iodide and 26.8 mg (0.2 mmol) of phenylglyoxal were placed in a 25 ml test tube with a stirrer. A mixed solution of 2.5 mL of acetonitrile and 2.5 mL of water was added at room temperature. The mixture was stirred for 12 hours at 5 mA. After being spin-dried, the target product was obtained by rapid column chromatography with a yield of 87%.

[0059]

[0060] 1 H NMR (400MHz, CDCl3) δppm 9.97(d,J=7.1Hz,1H),7.64(d,J=7.0Hz,2H),7.48(t,J=7.4Hz,1H),7.35-7.28(m,3H),7.14(t,J=7.3 Hz,1H),7.07(d,J=6.8Hz,2H),6.99(t,J=7.5Hz,2H),6.87(d,J=6.9Hz,1H),6.39(s,1H),2.44(s,3H).

[0061] 13 C NMR(100MHz,CDCl3)δppm 192.6,182.3,142.5,139.9,138.1,134.3,134.1,133.5,130.3,129.5,129.0,128.3,127.9,127.5,118.4,117.3,117.2,105.2,21.5.

[0062] HRMS MALDI(m / z):calcd for C 23 H 17 NO2[M+H] + :340.1332,found:340.1327.

[0063] Embodiment 4:

[0064] 22.3 mg (0.1 mmol) 7-methoxy-2-phenylindoleazine, 99.6 mg (0.5 mmol) potassium iodide, and 10.7 mg (0.08 mmol) phenylglyoxal were placed in a 25 ml test tube with a stirring bar. A mixed solution of 4 mL acetonitrile and 1 mL water was added at room temperature. The mixture was stirred for 6 hours at 10 mA. After being spin-dried, the target product was obtained by rapid column chromatography with a yield of 73%.

[0065]

[0066] 1 H NMR (400MHz, CDCl3) δppm 9.97(d,J=7.5Hz,1H),7.64(d,J=7.4Hz,2H),7.48(t,J=7.2Hz,1H),7.32(d,J=7.4Hz,2H),7.16-7.12(m,1H) ,7.07(d,J=7.2Hz,2H),7.00(d,J=7.3Hz,2H),6.85(s,1H),6.73(d,J=7.2Hz,1H),6.34(s,1H),3.92(s,3H).

[0067] 13 C NMR(100MHz,CDCl3)δppm 192.7,181.6,158.9,143.5,141.8,134.3,134.3,133.5,131.2,130.3,129.6,128.3,128.0,127.6,118.0,108.4,105.1,96.6,55.7.

[0068] HRMS MALDI(m / z):calcd for C 23 H 17 NO3[M+Na] + :378.1101,found:378.1103.

[0069] Embodiment 5:

[0070] 20.7 mg (0.1 mmol) of 2-p-tolylindolizine, 51.5 mg (0.5 mmol) of sodium bromide and 20.1 mg (0.15 mmol) of phenylglyoxal were placed in a 25 ml test tube with a stirring bar. A mixed solution of 4 mL of acetonitrile and 1 mL of water was added at room temperature. The mixture was stirred for 6 hours at 20 mA. After being spin-dried, the target product was obtained by rapid column chromatography with a yield of 77%.

[0071]

[0072] 1 H NMR (400MHz, CDCl3) δppm 10.07(d,J=6.8Hz,1H),7.64(d,J=7.2Hz,2H),7.57(d,J=9.2Hz,1H),7.50(t,J=7.4Hz,1H),7.32(t,J=7 .8Hz,3H),7.02(t,J=6.9Hz,1H),6.96(d,J=8.0Hz,2H),6.80(d,J=7.6Hz,2H),6.51(s,1H),2.24(s,3H).

[0073] 13 C NMR(100MHz,CDCl3)δppm 192.5,183.2,142.3,139.4,137.8,134.0,133.6,131.1,130.3,129.5,129.5,128.3,128.2,126.6,118.9,118.4,114.7,106.0,21.2.

[0074] HRMS MALDI(m / z):calcd for C 23 H 17 NO2[M+Na] + :362.1152,found:362.1153.

[0075] Embodiment 6:

[0076] 27.2 mg (0.1 mmol) of 2-p-bromophenylindolizine, 147.6 mg (0.4 mmol) of tetrabutylammonium iodide and 13.4 mg (0.1 mmol) of phenylglyoxal were placed in a 25 ml test tube with a stirring bar. A mixed solution of 4 mL of acetonitrile and 1 mL of water was added at room temperature. The mixture was stirred for 6 hours at 15 mA. After being spin-dried, the target product was obtained by rapid column chromatography with a yield of 82%.

[0077]

[0078] 1 H NMR (400MHz, CDCl3) δppm 10.06(d,J=6.9Hz,1H),7.62(dd,J=8.4,1.3Hz,2H),7.58(d,J=8.8Hz,1H),7.52(t,J=7.4Hz,1H) ,7.37-7.32(m,3H),7.10(d,J=8.3Hz,2H),7.07-7.03(m,1H),6.90(d,J=8.5Hz,2H),6.49(s,1H).

[0079] 13 C NMR(100MHz,CDCl3)δppm 192.7,183.0,140.6,139.3,134.0,133.9,133.0,132.0,130.6,129.5,129.5,128.4,126.8,122.4,118.6,118.5,115.1,106.0.

[0080] HRMS MALDI(m / z):calcd for C 22 H 14 BrNO2[M+H] + :404.0281,found:404.0277.

[0081] Embodiment 7:

[0082] 21.1 mg (0.1 mmol) of 2-p-fluorophenylindoleazine, 147.6 mg (0.4 mmol) of tetrabutylammonium iodide, and 13.4 mg (0.1 mmol) of phenylglyoxal were placed in a 25 ml test tube with a stirring bar. A mixed solution of 4 mL of acetonitrile and 1 mL of water was added at room temperature. The mixture was stirred for 6 hours at 10 mA. After being spin-dried, the target product was obtained by rapid column chromatography with a yield of 89%.

[0083]

[0084] 1 H NMR (400MHz, CDCl3) δppm 10.06(d,J=6.9Hz,1H),7.64(d,J=7.4Hz,2H),7.57(d,J=9.0Hz,1H),7.50(t,J=7.4H z,1H),7.32(t,J=7.8Hz,3H),7.05-6.99(m,3H),6.67(t,J=8.7Hz,2H),6.48(s,1H).

[0085] 1 3 C NMR(100MHz,CDCl3)δppm 192.6,183.0,162.6(J=248.2Hz),140.8,139.3,133.8,132.0(J=8.3Hz),130.0 (J=3.3Hz),129.4,128.4,126.7,118.8,118.5,115.0,114.3(J=21.7Hz),106.2.

[0086] HRMS MALDI(m / z):calcd for C 22 H14 FNO2[M+H] + :366.0901,found:366.0901.

[0087] Embodiment 8:

[0088] 26.1 mg (0.1 mmol) of 2-(4-trifluoromethylphenyl)indolizine, 147.6 mg (0.4 mmol) of tetrabutylammonium iodide and 13.4 mg (0.1 mmol) of phenylglyoxal were placed in a 25 ml test tube with a stirrer. A mixed solution of 4 mL of acetonitrile and 1 mL of water was added at room temperature. The mixture was stirred for 6 hours at 10 mA. After being spin-dried, the target product was obtained by rapid column chromatography with a yield of 80%.

[0089]

[0090] 1 H NMR (400MHz, CDCl3) δppm 10.01(d,J=6.9Hz,1H),7.55(d,J=8.8Hz,1H),7.51(d,J=8.4Hz,2H),7.45(t,J=7.4Hz,1H),7.33-7.28(m ,1H),7.24(t,J=7.8Hz,2H),7.17(d,J=8.0Hz,2H),7.10(d,J=7.9Hz,2H),7.04-6.99(m,1H),6.47(s,1H).

[0091] 13 C NMR(100MHz,CDCl3)δppm 192.8,183.0,140.2,139.3,137.9,134.0,133.8,130.8,129.8(J=32.6Hz),129.5,12 9.4,128.5,126.9,125.4,124.3(J=3.7Hz),122.7(J=272.5Hz),118.6,115.3,106.1.

[0092] HRMS MALDI(m / z):calcd for C 23 H 14 F3NO2[M+H] + :394.1049,found:394.1052.

[0093] Embodiment 9:

[0094] 19.3 mg (0.1 mmol) of 2-phenylindolizine, 147.6 mg (0.4 mmol) of tetrabutylammonium iodide and 14.8 mg (0.1 mmol) of 4-methylphenylglyoxal were placed in a 25 ml test tube with a stirrer. A mixed solution of 4 mL of acetonitrile and 1 mL of water was added at room temperature. The mixture was stirred for 6 hours at 10 mA. After being spin-dried, the target product was obtained by rapid column chromatography with a yield of 85%.

[0095]

[0096] 1 H NMR (400MHz, CDCl3) δppm 10.08(d,J=5.9Hz,1H),7.60-7.53(m,3H),7.33(d,J=6.9Hz,1H),7.14(d,J=8.3 Hz,3H),7.09(d,J=9.7Hz,2H),7.02(d,J=6.8Hz,3H),6.52(s,1H),2.38(s,3H).

[0097] 13 C NMR(100MHz,CDCl3)δppm 192.2,183.5,144.6,142.1,139.3,134.3,131.7,130.4,129.8,129.6,129.1,127.9,127.6,126.5,118.8,118.5,114.8,106.0,21.9.

[0098] HRMS MALDI(m / z):calcd for C 23 H 17 NO2[M+Na] + :362.1152,found:362.1152.

[0099] Embodiment 10:

[0100] 19.3 mg (0.1 mmol) of 2-phenylindolizine, 147.6 mg (0.4 mmol) of tetrabutylammonium iodide and 14.8 mg (0.1 mmol) of 3-methylphenylglyoxal were placed in a 25 ml test tube with a stirrer. A mixed solution of 4 mL of acetonitrile and 1 mL of water was added at room temperature. The mixture was stirred for 6 hours at 10 mA. After being spin-dried, the target product was obtained by rapid column chromatography with a yield of 83%.

[0101]

[0102] 1H NMR (400MHz, CDCl3) δppm 10.84(d,J=7.0Hz,1H),8.31(d,J=8.4Hz,1H),8.23-8.17(m,2H),8.05(d,J=5.4Hz,2H), 7.93(dt,J=13.7,7.5Hz,3H),7.84(d,J=6.8Hz,2H),7.76(t,J=7.4Hz,3H),3.05(s,3H).

[0103] 13 C NMR(100MHz,CDCl3)δppm 192.7,183.2,142.0,139.2,138.0,134.4,134.1,134.0,130.3,129.7,12 9.3,128.1,127.7,127.5,126.8,126.5,118.6,118.4,114.8,106.0,21.2.

[0104] HRMS MALDI(m / z):calcd for C 23 H 17 NO2[M+H] + :340.1332,found:340.1336.

[0105] Embodiment 11:

[0106] 19.3 mg (0.1 mmol) of 2-phenylindolizine, 147.6 mg (0.4 mmol) of tetrabutylammonium iodide and 21.3 mg (0.1 mmol) of 3-bromophenylglyoxal were placed in a 25 ml test tube with a stirring bar. A mixed solution of 4 mL of acetonitrile and 1 mL of water was added at room temperature. The mixture was stirred for 6 hours at 10 mA. After being spin-dried, the target product was obtained by rapid column chromatography with a yield of 88%.

[0107]

[0108] 1 H NMR (400MHz, CDCl3) δppm 10.03(d,J=6.9Hz,1H),7.68(t,J=1.8Hz,1H),7.61-7.54(m,3H),7.33(d ,J=6.9Hz,1H),7.17(t,J=7.9Hz,2H),7.04(d,J=6.9Hz,5H),6.51(s,1H).

[0109] 13C NMR(100MHz,CDCl3)δppm 191.0,181.8,142.0,139.4,136.3,135.7,133.9,131.9,130.3,129.8, 129.3,128.0,127.9,127.6,126.8,122.5,118.5,118.4,115.0,106.2.

[0110] HRMS MALDI(m / z):calcd for C 22 H 14 BrNO2[M+H] + :404.0281,found:404.0283.

[0111] Effect example

[0112] By selecting 4 examples for MTT test, osimertinib (AZD-9291) was used as the positive control drug, and cells were selected as HepG2 (human liver cancer cells) and HeLa (cervical cancer cells). The IC50 values ​​of the compounds were analyzed and showed that the series of compounds had certain inhibitory activity against the above cell lines. The results are shown in the following table:

[0113] Table 1 In vitro antiproliferative activity of some compounds

[0114]

[0115]

[0116] Finally, it should be noted that the above content is only used to illustrate the technical solution of the present invention, rather than to limit the scope of protection of the present invention. Simple modifications or equivalent substitutions of the technical solution of the present invention by ordinary technicians in this field do not deviate from the essence and scope of the technical solution of the present invention.

Claims

1. A method for preparing an (indolizine-3-yl)-ethanedione derivative, characterized in that: The reaction is carried out by the following formula: Wherein, R1 is selected from H, alkyl, halogen; R and R2 are independently selected from substituted or unsubstituted 6-membered aryl groups; in the substituted aryl group, the number of substituents is 1, 2, or 3, and the substituents are independently selected from C1-C6 alkyl, C1-C6 fluoroalkyl, C1-C6 alkoxy or halogen; The electrolyte is at least one of a quaternary ammonium salt and an alkali metal salt; The quaternary ammonium salt is a tetraalkylammonium halide, wherein the alkyl groups are independently selected from C1-C4 alkyl groups, and the halogen group is selected from fluorine, chlorine, bromine or iodine; The alkali metal salt is selected from alkali metal halide salts, wherein the alkali metal is selected from Li, Na, K, and the halogen is selected from fluorine, chlorine, bromine or iodine; The solvent is a mixed solvent of acetonitrile and water; n=4； Each R1 may be the same or different.

2. The preparation method according to claim 1, characterized in that: The alkyl in R1 is selected from C1-C6 alkyl, and the halogen in R1 is selected from fluorine, chlorine, bromine or iodine.

3. The preparation method according to claim 2, characterized in that: The alkyl group in R1 is a C1-C3 alkyl group.

4. The preparation method according to claim 1, characterized in that: The molar ratio of compound 1 to compound 2 is 1:0.6-3.

5. The preparation method according to claim 1, characterized in that: The current of the power supply is 5-20mA.

6. The preparation method according to claim 1, characterized in that: The volume ratio of acetonitrile to water is 0.5-10:1; the initial reaction concentration of the compound 1 in the reaction is 0.01-1 mol / L.

7. The preparation method according to claim 1, characterized in that: In the tetraalkylammonium halide, the alkyl group is selected from C1-C4 alkyl; In the alkali metal salt, the alkali metal is selected from Na or K, and the halogen is selected from bromine or iodine; The molar ratio of the electrolyte to compound 1 is 0.001-7:

1.

8. A use of a compound of formula 3, characterized in that: The use is for preparing products related to the prevention and / or treatment of liver cancer and cervical cancer, and the structure of the compound of formula 3 is selected from the following structures: , or .

Images