Method for synthesizing axitinib

A technology of axitinib and coupling reagents, which is applied in the field of synthesizing axitinib, can solve the problems of production environment pollution, low yield, complex synthesis operation, etc., to avoid production environment pollution, high reaction yield, easy operation simple effect

Inactive Publication Date: 2019-03-22
南京天越星生物技术有限公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0003] In order to solve the above problems, the present invention discloses a method for synthesizing axitinib, the purpose of which is to solve the

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  • Method for synthesizing axitinib

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Embodiment 1

[0012] Example 1: A method for synthesizing axitinib provided by the present invention will now be described, including the following steps: (E)-6-nitro-3-[2-(2-pyridyl)vinyl]-1 -(2-Tetrahydropyranyl)-1H-indazole (2) is reduced, diazotized, Sandmeyer reaction, coupled with coupling reagent under the action of palladium catalyst, and finally deprotected and ester ammonia Solve the reaction to get Axitinib.

[0013] In this embodiment, a base is used as the reducing agent, and the base is cesium carbonate.

[0014] In this embodiment, the reaction temperature is -15°C.

[0015] In this embodiment, the coupling reagent is methyl thiosalicylate.

Embodiment 2

[0016] Example 2: Now a method for synthesizing axitinib provided by the present invention will be described, including the following steps: (E)-6-nitro-3-[2-(2-pyridyl)vinyl]-1 -(2-Tetrahydropyranyl)-1H-indazole (2) is reduced, diazotized, Sandmeyer reaction, coupled with coupling reagent under the action of palladium catalyst, and finally deprotected and ester ammonia Solve the reaction to get Axitinib.

[0017] In this embodiment, an alkali is used as the reducing agent, and the alkali is cesium hydroxide.

[0018] In this embodiment, the reaction temperature is 5°C.

[0019] In this embodiment, the coupling reagent is methyl thiosalicylate.

Embodiment 3

[0020] Example 3: The method for synthesizing axitinib provided by the present invention will now be described, including the following steps: (E)-6-nitro-3-[2-(2-pyridyl)vinyl]-1 -(2-Tetrahydropyranyl)-1H-indazole (2) is reduced, diazotized, Sandmeyer reaction, coupled with coupling reagent under the action of palladium catalyst, and finally deprotected and ester ammonia Solve the reaction to get Axitinib.

[0021] In this embodiment, a base is used as the reducing agent, and the base is diisopropylethylamine.

[0022] In this embodiment, the reaction temperature is 10°C.

[0023] In this embodiment, the coupling reagent is methyl thiosalicylate.

[0024] The present invention can also combine at least one of the technical features described in Examples 2 and 3 with Example 1 to form a new implementation.

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Abstract

The invention discloses a method for synthesizing axitinib, and belongs to the field of chemical pharmacy. (E)-6-nitro-3-[2-(2-pyridyl)vinyl]-1-(2-tetrahydropyranyl)-1H-carbazole(2) undergoes reduction, diazotization, Sandmeyer reaction and coupling with methyl thiosalicylate under the action of a palladium catalyst, and finally undergoes protection base removal and aminolysis of ester to obtain an antitumor drug axitinib. The method is simple and easy to operate, has high yield and low pollution and is suitable for industrial production.

Description

Technical field [0001] The invention relates to the field of chemical pharmacy, in particular to a method for synthesizing axitinib. Background technique [0002] Axitinib (axitinib, 1), the chemical name is N-methyl-2-((3-((1E)-2-(pyridin-2-yl)ethylene)-1H-indazol-6-yl) Sulfur) benzamide is a second-generation multi-target tyrosinase inhibitor. Developed by Pfizer in the United States, and approved by the FDA in January 2012, it is suitable for the treatment of advanced renal cell carcinoma after the failure of previous systemic treatments. Because the synthesis operation is relatively complicated and the yield is relatively low, causing pollution of the production environment, it is urgent for those skilled in the art to solve this problem. Summary of the invention [0003] In order to solve the above-mentioned problems, the present invention discloses a method for synthesizing axitinib, which aims to solve the problem of complicated synthesis operation and relatively low yiel...

Claims

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Application Information

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IPC IPC(8): C07D401/06C07D405/14
CPCC07D401/06C07D405/14
Inventor 吴学平陈耀
Owner 南京天越星生物技术有限公司
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