Process for the preparation and use of quinoxaline-2,3(4H)-diones substituted in position 3 by a cyanoalkyl group

Abstract

The application belongs to the field of electrochemistry and green synthesis, and particularly relates to a preparation method and application of a quinoxaline ketone substituted with a cyanoalkyl at a C3 position. The preparation method is to use quinoxaline ketone and acrylonitrile as reaction raw materials, add electrolyte, organic solvent and additive, and perform electrolysis reaction to obtain the quinoxaline ketone substituted with a cyanoalkyl at the C3 position. The application first reports a method for electrolytically synthesizing the quinoxaline ketone substituted with a cyanoalkyl at the C3 position. The preparation method uses cheap and readily available acrylonitrile as an alkyl source, does not need to perform pre-activation of a substrate, is simple to operate, has low cost, has high atom utilization rate, does not need to participate in chemical oxidation-reduction reagents, has a room temperature reaction temperature, can efficiently and greenly synthesize the quinoxaline ketone substituted with a cyanoalkyl at the C3 position; the quinoxaline ketone substituted with a cyanoalkyl at the C3 position has good anticancer activity, can be used for preparing anticancer drugs, and has important application value.

Description

Technical Field

[0001] The present invention belongs to the field of electrochemistry and green synthesis, and particularly relates to a preparation method and application of a C3-cyanoalkyl-substituted quinoxalinone. Background Art

[0002] C3-alkyl-substituted quinoxalinones (quinoxalin-2(1H)-ones) are an important class of drug molecules and bioactive molecular scaffolds. For example, these molecular scaffolds can be used as drug antagonists (J. Med. Chem. 2001, 44, 594–601). Furthermore, cyanoalkyl groups can significantly improve the physicochemical properties, pharmacodynamics, and pharmacokinetic properties of drug molecules. For example, verapamil, used to treat angina pectoris, and saxagliptin, used for hypoglycemia, both contain cyanoalkyl structures. Therefore, modifying bioactive molecules with cyano groups is an important approach in drug development.

[0003] Given the important applications of C3-alkyl-substituted quinoxalinones and cyanoalkyl groups in drug development, the introduction of cyanoalkyl groups into the C3 position of quinoxalinones, enabling the efficient synthesis of structurally diverse C3-cyanoalkyl-substituted quinoxalinones, holds significant research significance and potential application value. However, the synthesis of C3-cyanoalkyl-substituted quinoxalinones remains a challenging problem, with no relevant literature or patent reports to date. Summary of the Invention

[0004] In view of the shortcomings of the prior art, the first object of the present invention is to provide a method for preparing a C3-cyanoalkyl-substituted quinoxalinone; the preparation method has the advantages of simple operation, low cost and environmental protection.

[0005] The second object of the present invention is to provide the use of the C3 cyanoalkyl-substituted quinoxalinone prepared by the above method. The C3 cyanoalkyl-substituted quinoxalinone has good anticancer activity and can be used to prepare anticancer drugs.

[0006] To achieve the above object, the technical solution adopted by the present invention is as follows:

[0007] A method for preparing a C3-cyanoalkyl-substituted quinoxalinone is disclosed. The method comprises using a quinoxalinone (quinoxaline-2(1H)-one) represented by Formula I and acrylonitrile as reaction raw materials, adding an electrolyte, an organic solvent, and an additive, and conducting an electrolytic reaction to obtain a C3-cyanoalkyl-substituted quinoxalinone represented by Formula II. The reaction scheme is as follows:

[0008]

[0009] Among them, R 1is methyl, benzyl, isopropyl, 3-methoxypropyl, 3-phenoxypropyl, 3-benzyloxypropyl, alkoxy, difluoroisopropyl, chloroalkyl, methyl propionate, methyl valerate, 3-tert-butoxycarbonyl, dimethyl-tert-butylsilyloxyethyl, diphenyl-tert-butylsilyloxypropyl, allyl, 1,1-dimethylallyl, butylallyl, propargyl, 1-methylpropargyl, butylynyl, alkyl propionate or aryl propyl acetate; R 2 is hydrogen, methyl, chlorine or fluorine; R 2 The benzene ring is singly substituted or polysubstituted.

[0010] Furthermore, the structural formula of the C3-cyanoalkyl-substituted quinoxalinone is any one of the following:

[0011]

[0012] Furthermore, the molar ratio of the quinoxalinone, acrylonitrile, electrolyte and additive is 1:10:1:1: the molar volume ratio of the quinoxalinone and the organic solvent is 0.3 mmol:5 mL.

[0013] Furthermore, the electrolyte is tetraethylammonium chloride (Et4NCl); the additive is acetic acid (HOAc); and the organic solvent is acetonitrile.

[0014] Furthermore, the anode of the electrolysis is a graphite sheet, the cathode is a zinc sheet, and the current density is 5 mA / cm 2 ; The reaction temperature is room temperature and the time is 8h.

[0015] Furthermore, after the reaction is completed, the reaction solution needs to be extracted, dried, distilled under reduced pressure and purified by column chromatography.

[0016] Furthermore, ethyl acetate is used in the extraction.

[0017] The preparation method provided by the present invention is based on the coupling reaction of quinoxalinone and acrylonitrile, and can prepare C3-cyanoalkyl-substituted quinoxalinone efficiently and greenly without the need for adding an external chemical redox reagent.

[0018] The C3-cyanoalkyl-substituted quinoxalinone prepared by the above method can be used to prepare anticancer drugs.

[0019] Furthermore, the C3-cyanoalkyl-substituted quinoxalinone can be used to prepare anti-breast cancer drugs.

[0020] Beneficial effects

[0021] (1) The present invention uses quinoxalinone and acrylonitrile as reaction raw materials to carry out electrolytic reaction to efficiently and greenly synthesize C3 cyanoalkyl-substituted quinoxalinone. The present invention reports for the first time a preparation method for electrolytic synthesis of C3 cyanoalkyl-substituted quinoxalinone.

[0022] (2) The present invention directly uses cheap and readily available acrylonitrile as the alkyl source, and does not require pre-activation of the substrate. Therefore, the preparation process provided by the present invention has the advantages of low cost and high atomic utilization rate. The present invention does not require the participation of chemical redox reagents, and the reaction temperature is room temperature. Therefore, the process has the significant advantages of being economical and green.

[0023] (3) The C3-cyanoalkyl-substituted quinoxalinone prepared by the present invention has good anticancer activity and can be used to prepare anticancer drugs, which has important application value. DETAILED DESCRIPTION

[0024] The following description further elaborates on the specific details of the present invention for a full understanding of the present invention. The terms used in the description of the present invention are only used to illustrate the advantages and features of the present invention and are not intended to limit the present invention.

[0025] Unless otherwise defined, all technical and scientific terms used herein have the same meanings as those understood by those skilled in the art within the technical field of the present invention. Unless otherwise specified, the drugs and reagents used herein were used in accordance with the product instructions or conventional methods in the art. The process of the present invention is now further described based on the specification and specific embodiments.

[0026] The route for synthesizing C3 cyanoalkyl-substituted quinoxalinone of the present invention is:

[0027]

[0028] Among them, R 1 is methyl, benzyl, isopropyl, 3-methoxypropyl, 3-phenoxypropyl, 3-benzyloxypropyl, alkoxy, difluoroisopropyl, chloroalkyl, methyl propionate, methyl valerate, 3-tert-butoxycarbonyl, dimethyl-tert-butylsilyloxyethyl, diphenyl-tert-butylsilyloxypropyl, allyl, 1,1-dimethylallyl, butylallyl, propargyl, 1-methylpropargyl, butylynyl, alkyl propionate or aryl propyl acetate; R 2 is hydrogen, methyl, chlorine or fluorine; R 2 The benzene ring is singly substituted or polysubstituted.

[0029] Example 1

[0030] Into an electrolysis cell were added raw material N-methyl quinolinone (0.3 mmol), acrylonitrile (3 mmol), acetonitrile (5 mL), tetraethyl ammonium chloride (0.3 mmol) and HOAc (0.3 mmol), respectively. Then, graphite sheet and zinc sheet were inserted into the electrolysis cell as anode and cathode, respectively. The above mixed solution was electrolyzed at a current density of 5 mA / cm 2 at room temperature for 8 h. Subsequently, the above solution was transferred into a separatory funnel, 15 mL of water was added, extracted with ethyl acetate (20 mL x 3), dried, and the solvent was removed by distillation under reduced pressure. Finally, the target product was obtained by column chromatography. Yield: 75%.

[0031]

[0032] Example 2

[0033] Into an electrolysis cell were added raw material 6,7-dimethyl-N-methyl quinolinone (0.3 mmol), acrylonitrile (3 mmol), acetonitrile (5 mL), tetraethyl ammonium chloride (0.3 mmol) and HOAc (0.3 mmol), respectively. Then, graphite sheet and zinc sheet were inserted into the electrolysis cell as anode and cathode, respectively. The above mixed solution was electrolyzed at a current density of 5 mA / cm 2 at room temperature for 8 h. Subsequently, the above solution was transferred into a separatory funnel, 15 mL of water was added, extracted with ethyl acetate (20 mL x 3), dried, and the solvent was removed by distillation under reduced pressure. Finally, the target product was obtained by column chromatography. Yield: 71%.

[0034]

[0035] Example 3

[0036] Into an electrolysis cell were added raw material 6,7-dimethyl-N-methyl quinolinone (0.3 mmol), acrylonitrile (3 mmol), acetonitrile (5 mL), tetraethyl ammonium chloride (0.3 mmol) and HOAc (0.3 mmol), respectively. Then, graphite sheet and zinc sheet were inserted into the electrolysis cell as anode and cathode, respectively. The above mixed solution was electrolyzed at a current density of 5 mA / cm 2 at room temperature for 8 h. Subsequently, the above solution was transferred into a separatory funnel, 15 mL of water was added, extracted with ethyl acetate (20 mL x 3), dried, and the solvent was removed by distillation under reduced pressure. Finally, the target product was obtained by column chromatography. Yield: 64%.

[0037]

[0038] Example 4

[0039] The raw materials 6-methyl-N-methylquinoxalinone (0.3 mmol), acrylonitrile (3 mmol), acetonitrile (5 mL), tetraethylammonium chloride (0.3 mmol) and HOAc (0.3 mmol) were added to the electrolytic cell. Then, a graphite sheet and a zinc sheet were inserted into the electrolytic cell as the anode and cathode, respectively. At room temperature, the above mixed solution was heated at 5 mA / cm 2 Electrolysis was performed at a current density of 100 nm for 8 h. Subsequently, the solution was transferred to a separatory funnel, 15 mL of water was added, and extraction was performed with ethyl acetate (20 mL x 3). The mixture was dried and the solvent was removed by vacuum distillation. Finally, column chromatography was used for separation and purification to obtain the desired product, with the structural formula shown below. Yield: 74%.

[0040]

[0041] Example 5

[0042] The raw materials N-benzylquinoxalinone (0.3 mmol), acrylonitrile (3 mmol), acetonitrile (5 mL), tetraethylammonium chloride (0.3 mmol) and HOAc (0.3 mmol) were added to the electrolytic cell. Then, a graphite sheet and a zinc sheet were inserted into the electrolytic cell as the anode and cathode, respectively. At room temperature, the above mixed solution was heated at 5 mA / cm 2 Electrolysis was performed at a current density of 100 nm for 8 h. Subsequently, the solution was transferred to a separatory funnel, 15 mL of water was added, and extraction was performed with ethyl acetate (20 mL x 3). The mixture was dried and the solvent was removed by vacuum distillation. Finally, column chromatography was used for separation and purification to obtain the desired product, with the structural formula shown below. Yield: 73%.

[0043]

[0044] Example 6

[0045] The raw materials N-isopropylquinoxalinone (0.3 mmol), acrylonitrile (3 mmol), acetonitrile (5 mL), tetraethylammonium chloride (0.3 mmol) and HOAc (0.3 mmol) were added to the electrolytic cell. Then, a graphite sheet and a zinc sheet were inserted into the electrolytic cell as the anode and cathode, respectively. At room temperature, the above mixed solution was heated at 5 mA / cm 2 Electrolysis was performed at a current density of 100 nm for 8 h. Subsequently, the solution was transferred to a separatory funnel, 15 mL of water was added, and extraction was performed with ethyl acetate (20 mL x 3). The mixture was dried and the solvent was removed by vacuum distillation. Finally, column chromatography was used for separation and purification to obtain the desired product, with the structural formula shown below. Yield: 68%.

[0046]

[0047] Example 7

[0048] The raw materials N-3-methoxypropylquinoxalinone (0.3 mmol), acrylonitrile (3 mmol), acetonitrile (5 mL), tetraethylammonium chloride (0.3 mmol) and HOAc (0.3 mmol) were added to the electrolytic cell. Then, a graphite sheet and a zinc sheet were inserted into the electrolytic cell as the anode and cathode, respectively. At room temperature, the above mixed solution was heated at 5 mA / cm 2 Electrolysis was performed at a current density of 100 nm for 8 h. Subsequently, the solution was transferred to a separatory funnel, 15 mL of water was added, and extraction was performed with ethyl acetate (20 mL x 3). The mixture was dried and the solvent was removed by vacuum distillation. Finally, column chromatography was used for separation and purification to obtain the desired product, with the structural formula shown below. Yield: 63%.

[0049]

[0050] Example 8

[0051] The raw materials N-3-phenoxypropylquinoxalinone (0.3 mmol), acrylonitrile (3 mmol), acetonitrile (5 mL), tetraethylammonium chloride (0.3 mmol) and HOAc (0.3 mmol) were added to the electrolytic cell. Then, a graphite sheet and a zinc sheet were inserted into the electrolytic cell as the anode and cathode, respectively. At room temperature, the above mixed solution was heated at 5 mA / cm 2 Electrolysis was performed at a current density of 100 nm for 8 h. Subsequently, the solution was transferred to a separatory funnel, 15 mL of water was added, and extraction was performed with ethyl acetate (20 mL x 3). The mixture was dried and the solvent was removed by vacuum distillation. Finally, column chromatography was used for separation and purification to obtain the desired product, with the structural formula shown below. Yield: 61%.

[0052]

[0053] Example 9

[0054] The raw materials N-3-benzyloxypropylquinoxalinone (0.3 mmol), acrylonitrile (3 mmol), acetonitrile (5 mL), tetraethylammonium chloride (0.3 mmol) and HOAc (0.3 mmol) were added to the electrolytic cell. Then, a graphite sheet and a zinc sheet were inserted into the electrolytic cell as the anode and cathode, respectively. At room temperature, the above mixed solution was heated at 5 mA / cm 2 Electrolysis was performed at a current density of 100 nm for 8 h. Subsequently, the solution was transferred to a separatory funnel, 15 mL of water was added, and extraction was performed with ethyl acetate (20 mL x 3). The mixture was dried and the solvent was removed by vacuum distillation. Finally, column chromatography was used for separation and purification to obtain the desired product, with the structural formula shown below. Yield: 63%.

[0055]

[0056] Example 10

[0057] The raw materials N-alkoxyquinoxalinone (0.3 mmol), acrylonitrile (3 mmol), acetonitrile (5 mL), tetraethylammonium chloride (0.3 mmol) and HOAc (0.3 mmol) were added to the electrolytic cell. Then, a graphite sheet and a zinc sheet were inserted into the electrolytic cell as the anode and cathode, respectively. At room temperature, the mixed solution was heated at 5 mA / cm 2 Electrolysis was performed at a current density of 100 nm for 8 h. Subsequently, the solution was transferred to a separatory funnel, 15 mL of water was added, and extraction was performed with ethyl acetate (20 mL x 3). The mixture was dried and the solvent was removed by vacuum distillation. Finally, column chromatography was used for separation and purification to obtain the desired product, with the structural formula shown below. Yield: 67%.

[0058]

[0059] Example 11

[0060] The raw materials N-difluoroisopropylquinoxalinone (0.3 mmol), acrylonitrile (3 mmol), acetonitrile (5 mL), tetraethylammonium chloride (0.3 mmol) and HOAc (0.3 mmol) were added to the electrolytic cell. Then, a graphite sheet and a zinc sheet were inserted into the electrolytic cell as the anode and cathode, respectively. At room temperature, the above mixed solution was heated at 5 mA / cm 2 Electrolysis was performed at a current density of 100 nm for 8 h. Subsequently, the solution was transferred to a separatory funnel, 15 mL of water was added, and extraction was performed with ethyl acetate (20 mL x 3). The mixture was dried and the solvent was removed by vacuum distillation. Finally, column chromatography was used for separation and purification to obtain the desired product, with the structural formula shown below. Yield: 59%.

[0061]

[0062] Example 12

[0063] The raw materials N-chloroalkylquinoxalinone (0.3 mmol), acrylonitrile (3 mmol), acetonitrile (5 mL), tetraethylammonium chloride (0.3 mmol) and HOAc (0.3 mmol) were added to the electrolytic cell. Then, a graphite sheet and a zinc sheet were inserted into the electrolytic cell as the anode and cathode, respectively. At room temperature, the above mixed solution was heated at 5 mA / cm 2 Electrolysis was performed at a current density of 100 nm for 8 h. Subsequently, the solution was transferred to a separatory funnel, 15 mL of water was added, and extraction was performed with ethyl acetate (20 mL x 3). The mixture was dried and the solvent was removed by vacuum distillation. Finally, column chromatography was used for separation and purification to obtain the desired product, with the structural formula shown below. Yield: 69%.

[0064]

[0065] Example 13

[0066] The raw materials N-methylpropionate quinoxalinone (0.3 mmol), acrylonitrile (3 mmol), acetonitrile (5 mL), tetraethylammonium chloride (0.3 mmol) and HOAc (0.3 mmol) were added to the electrolytic cell. Then, a graphite sheet and a zinc sheet were inserted into the electrolytic cell as the anode and cathode, respectively. At room temperature, the above mixed solution was heated at 5 mA / cm 2 Electrolysis was performed at a current density of 100 nm for 8 h. Subsequently, the solution was transferred to a separatory funnel, 15 mL of water was added, and extraction was performed with ethyl acetate (20 mL x 3). The mixture was dried and the solvent was removed by vacuum distillation. Finally, column chromatography was used for separation and purification to obtain the desired product, with the structural formula shown below. Yield: 67%.

[0067]

[0068] Example 14

[0069] The raw materials N-methylpentanoate quinoxalinone (0.3 mmol), acrylonitrile (3 mmol), acetonitrile (5 mL), tetraethylammonium chloride (0.3 mmol) and HOAc (0.3 mmol) were added to the electrolytic cell. Then, a graphite sheet and a zinc sheet were inserted into the electrolytic cell as the anode and cathode, respectively. At room temperature, the above mixed solution was heated at 5 mA / cm 2 Electrolysis was performed at a current density of 100 nm for 8 h. Subsequently, the solution was transferred to a separatory funnel, 15 mL of water was added, and extraction was performed with ethyl acetate (20 mL x 3). The mixture was dried and the solvent was removed by vacuum distillation. Finally, column chromatography was used for separation and purification to obtain the desired product, with the structural formula shown below. Yield: 70%.

[0070]

[0071] Example 15

[0072] The raw materials N-3-tert-butyloxycarbonylpropylamine protected quinoxalinone (0.3 mmol), acrylonitrile (3 mmol), acetonitrile (5 mL), tetraethylammonium chloride (0.3 mmol) and HOAc (0.3 mmol) were added to the electrolytic cell. Then, a graphite sheet and a zinc sheet were inserted into the electrolytic cell as the anode and cathode, respectively. At room temperature, the above mixed solution was heated at 5 mA / cm 2 Electrolysis was performed at a current density of 100 nm for 8 h. Subsequently, the solution was transferred to a separatory funnel, 15 mL of water was added, and extraction was performed with ethyl acetate (20 mL x 3). The mixture was dried and the solvent was removed by vacuum distillation. Finally, column chromatography was used for separation and purification to obtain the desired product, with the structural formula shown below. Yield: 69%.

[0073]

[0074] Example 16

[0075] The raw materials N-dimethyl-tert-butylsilyloxyethyl protected quinoxalinone (0.3 mmol), acrylonitrile (3 mmol), acetonitrile (5 mL), tetraethylammonium chloride (0.3 mmol) and HOAc (0.3 mmol) were added to the electrolytic cell. Then, a graphite sheet and a zinc sheet were inserted into the electrolytic cell as the anode and cathode, respectively. At room temperature, the above mixed solution was heated at 5 mA / cm 2 Electrolysis was performed at a current density of 100 nm for 8 h. Subsequently, the solution was transferred to a separatory funnel, 15 mL of water was added, and extraction was performed with ethyl acetate (20 mL x 3). The mixture was dried and the solvent was removed by vacuum distillation. Finally, column chromatography was used for separation and purification to obtain the desired product, with the structural formula shown below. Yield: 70%.

[0076]

[0077] Example 17

[0078] The raw materials N-diphenyl-tert-butylsilyloxypropyl protected quinoxalinone (0.3 mmol), acrylonitrile (3 mmol), acetonitrile (5 mL), tetraethylammonium chloride (0.3 mmol) and HOAc (0.3 mmol) were added to the electrolytic cell. Then, a graphite sheet and a zinc sheet were inserted into the electrolytic cell as the anode and cathode, respectively. At room temperature, the above mixed solution was heated at 5 mA / cm 2 Electrolysis was performed at a current density of 100 nm for 8 h. Subsequently, the solution was transferred to a separatory funnel, 15 mL of water was added, and extraction was performed with ethyl acetate (20 mL x 3). The mixture was dried and the solvent was removed by vacuum distillation. Finally, column chromatography was used for separation and purification to obtain the desired product, with the structural formula shown below. Yield: 64%.

[0079]

[0080] Example 18

[0081] The raw materials N-allylquinoxalinone (0.3 mmol), acrylonitrile (3 mmol), acetonitrile (5 mL), tetraethylammonium chloride (0.3 mmol) and HOAc (0.3 mmol) were added to the electrolytic cell. Then, a graphite sheet and a zinc sheet were inserted into the electrolytic cell as the anode and cathode, respectively. At room temperature, the above mixed solution was heated at 5 mA / cm 2 Electrolysis was performed at a current density of 100 nm for 8 h. Subsequently, the solution was transferred to a separatory funnel, 15 mL of water was added, and extraction was performed with ethyl acetate (20 mL x 3). The mixture was dried and the solvent was removed by vacuum distillation. Finally, column chromatography was used for separation and purification to obtain the desired product, with the structural formula shown below. Yield: 68%.

[0082]

[0083] Example 19

[0084] Into an electrolysis cell were added the starting material N-1,1-dimethylallyl protected quinoxalinone (0.3 mmol), acrylonitrile (3 mmol), acetonitrile (5 mL), tetraethylammonium chloride (0.3 mmol) and HOAc (0.3 mmol). Then, graphite and zinc sheets were inserted into the electrolysis cell as anode and cathode, respectively. The above mixture solution was electrolyzed at room temperature for 8 h at a current density of 5 mA / cm 2 The solution was then transferred to a separatory funnel, 15 mL of water was added, and the solution was extracted with ethyl acetate (20 mL x 3), dried, and the solvent removed by distillation under reduced pressure. The target product was finally isolated and purified by column chromatography. Yield: 70%.

[0085]

[0086] Example 20

[0087] Into an electrolysis cell were added the starting material N-1,1-dimethylallyl protected quinoxalinone (0.3 mmol), acrylonitrile (3 mmol), acetonitrile (5 mL), tetraethylammonium chloride (0.3 mmol) and HOAc (0.3 mmol). Then, graphite and zinc sheets were inserted into the electrolysis cell as anode and cathode, respectively. The above mixture solution was electrolyzed at room temperature for 8 h at a current density of 5 mA / cm 2 The solution was then transferred to a separatory funnel, 15 mL of water was added, and the solution was extracted with ethyl acetate (20 mL x 3), dried, and the solvent removed by distillation under reduced pressure. The target product was finally isolated and purified by column chromatography. Yield: 70%.

[0088]

[0089] Example 21

[0090] Into an electrolysis cell were added the starting material N-1,1-dimethylallyl protected quinoxalinone (0.3 mmol), acrylonitrile (3 mmol), acetonitrile (5 mL), tetraethylammonium chloride (0.3 mmol) and HOAc (0.3 mmol). Then, graphite and zinc sheets were inserted into the electrolysis cell as anode and cathode, respectively. The above mixture solution was electrolyzed at room temperature for 8 h at a current density of 5 mA / cm 2 The solution was then transferred to a separatory funnel, 15 mL of water was added, and the solution was extracted with ethyl acetate (20 mL x 3), dried, and the solvent removed by distillation under reduced pressure. The target product was finally isolated and purified by column chromatography. Yield: 70%.

[0091]

[0092] Example 22

[0093] The raw materials N-1-methylpropargyl protected quinoxalinone (0.3 mmol), acrylonitrile (3 mmol), acetonitrile (5 mL), tetraethylammonium chloride (0.3 mmol) and HOAc (0.3 mmol) were added to the electrolytic cell. Then, a graphite sheet and a zinc sheet were inserted into the electrolytic cell as the anode and cathode, respectively. At room temperature, the above mixed solution was heated at 5 mA / cm 2 Electrolysis was performed at a current density of 100 nm for 8 h. Subsequently, the solution was transferred to a separatory funnel, 15 mL of water was added, and extraction was performed with ethyl acetate (20 mL x 3). The mixture was dried and the solvent was removed by vacuum distillation. Finally, column chromatography was used for separation and purification to obtain the desired product, with the structural formula shown below. Yield: 72%.

[0094]

[0095] Example 23

[0096] The raw materials N-acetyl butyl quinoxalinone (0.3 mmol), acrylonitrile (3 mmol), acetonitrile (5 mL), tetraethylammonium chloride (0.3 mmol) and HOAc (0.3 mmol) were added to the electrolytic cell. Then, a graphite sheet and a zinc sheet were inserted into the electrolytic cell as the anode and cathode, respectively. At room temperature, the above mixed solution was heated at 5 mA / cm 2 Electrolysis was performed at a current density of 100 nm for 8 h. Subsequently, the solution was transferred to a separatory funnel, 15 mL of water was added, and extraction was performed with ethyl acetate (20 mL x 3). The mixture was dried and the solvent was removed by vacuum distillation. Finally, column chromatography was used for separation and purification to obtain the desired product, with the structural formula shown below. Yield: 73%.

[0097]

[0098] Example 24

[0099] The raw materials N-alkyl propionate quinoxalinone (0.3 mmol), acrylonitrile (3 mmol), acetonitrile (5 mL), tetraethylammonium chloride (0.3 mmol) and HOAc (0.3 mmol) were added to the electrolytic cell. Then, a graphite sheet and a zinc sheet were inserted into the electrolytic cell as the anode and cathode, respectively. At room temperature, the above mixed solution was heated at 5 mA / cm 2 Electrolysis was performed at a current density of 100 nm for 8 h. Subsequently, the solution was transferred to a separatory funnel, 15 mL of water was added, and extraction was performed with ethyl acetate (20 mL x 3). The mixture was dried and the solvent was removed by vacuum distillation. Finally, column chromatography was used for separation and purification to obtain the desired product, with the structural formula shown below. Yield: 64%.

[0100]

[0101] Example 25

[0102] The raw materials N-alkyl propionate quinoxalinone (0.3 mmol), acrylonitrile (3 mmol), acetonitrile (5 mL), tetraethylammonium chloride (0.3 mmol) and HOAc (0.3 mmol) were added to the electrolytic cell. Then, a graphite sheet and a zinc sheet were inserted into the electrolytic cell as the anode and cathode, respectively. At room temperature, the above mixed solution was heated at 5 mA / cm 2 Electrolysis was performed at a current density of 100 nm for 8 h. Subsequently, the solution was transferred to a separatory funnel, 15 mL of water was added, and extraction was performed with ethyl acetate (20 mL x 3). The mixture was dried and the solvent was removed by vacuum distillation. Finally, column chromatography was used for separation and purification to obtain the desired product, with the structural formula shown below. Yield: 65%.

[0103]

[0104] Example 26

[0105] The raw materials N-arylacetate propyl quinoxalinone (0.3 mmol), acrylonitrile (3 mmol), acetonitrile (5 mL), tetraethylammonium chloride (0.3 mmol) and HOAc (0.3 mmol) were added to the electrolytic cell. Then, a graphite sheet and a zinc sheet were inserted into the electrolytic cell as the anode and cathode, respectively. At room temperature, the above mixed solution was heated at 5 mA / cm 2 Electrolysis was performed at a current density of 100 nm for 8 h. Subsequently, the solution was transferred to a separatory funnel, 15 mL of water was added, and extraction was performed with ethyl acetate (20 mL x 3). The mixture was dried and the solvent was removed by vacuum distillation. Finally, column chromatography was used for separation and purification to obtain the desired product, with the structural formula shown below. Yield: 61%.

[0106]

[0107] Example 27

[0108] The raw materials N-arylacetate propyl quinoxalinone (0.3 mmol), acrylonitrile (3 mmol), acetonitrile (5 mL), tetraethylammonium chloride (0.3 mmol) and HOAc (0.3 mmol) were added to the electrolytic cell. Then, a graphite sheet and a zinc sheet were inserted into the electrolytic cell as the anode and cathode, respectively. At room temperature, the above mixed solution was heated at 5 mA / cm 2 Electrolysis was performed at a current density of 100 nm for 8 h. Subsequently, the solution was transferred to a separatory funnel, 15 mL of water was added, and extraction was performed with ethyl acetate (20 mL x 3). The mixture was dried and the solvent was removed by vacuum distillation. Finally, column chromatography was used for separation and purification to obtain the desired product, with the structural formula shown below. Yield: 62%.

[0109]

[0110] Performance testing:

[0111] In order to determine the anticancer properties of the C3 cyanoalkyl-substituted quinoxalinone synthesized in the present invention, we selected MCF-7 cells (human breast cancer cells) as the research object and tested the IC of the synthesized C3 cyanoalkyl-substituted quinoxalinone against MCF-7 cells. 50 The results show that the IC values ​​of the C3 cyanoalkyl-substituted quinoxalone synthesized in Examples 16, 18, 25 and 27 are 50 The values ​​were 83μM, 94μM, 77μM and 82μM respectively. The IC value of Vincristine, a widely used drug, was 50 The value is about 51 μM. From the above data, it can be found that the C3 cyanoalkyl-substituted quinoxalinone synthesized by the present invention has potential medicinal value.

Claims

1. A method for preparing a C3-cyanoalkyl-substituted quinoxalinone, characterized in that: The preparation method comprises using quinoxalinone and acrylonitrile as reaction raw materials, adding electrolyte, organic solvent and additives, and conducting electrolytic reaction to obtain C3 cyanoalkyl-substituted quinoxalinone as shown in Formula II. The reaction scheme is as follows: ； The structural formula of the C3 cyanoalkyl-substituted quinoxalinone is any one of the following: ； The electrolyte is tetraethylammonium chloride; the additive is acetic acid; and the organic solvent is acetonitrile.

2. The preparation method according to claim 1, characterized in that The molar ratio of the quinoxalinone, acrylonitrile, electrolyte and additive is 1:10:1:1: the molar volume ratio of the quinoxalinone and the organic solvent is 0.3 mmol:5 mL.

3. The preparation method according to claim 1, characterized in that The anode of the electrolysis was a graphite sheet, the cathode was a zinc sheet, and the current density was 5 mA / cm 2 ; The reaction temperature is room temperature and the reaction time is 8 h.

4. The preparation method according to claim 1, characterized in that After the reaction is completed, the reaction solution needs to be extracted, dried, distilled under reduced pressure and separated and purified by column chromatography.

5. The preparation method according to claim 4, characterized in that The extraction used ethyl acetate.

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