A kind of preparation method of silodosin intermediate

Abstract

The invention discloses a method for preparing a silodosin intermediate: subjecting a 5-bromoindoline solution and triethylamine to an alkylation reaction to obtain a substance A; preparing a solution of the substance A, ethyl acetoacetate, a catalyst, The acid binding agent is subjected to substitution reaction to obtain substance B; the solution of substance B and Lewis acid are subjected to decarboxylation reaction to obtain substance C; the solution of substance C, R-tert-butylsulfinamide, catalyst and reducing agent are subjected to amination reaction to obtain substance D; the solution of substance D and N-bromosuccinimide solution are subjected to bromination reaction to obtain substance E; the solution of substance E and cuprous cyanide are subjected to cyanation reaction to obtain substance F; the solution of substance F, cuprous cyanide is subjected to cyanation reaction to obtain substance F; The acid is subjected to acid hydrolysis to obtain substance G; the substance G is converted into tartrate to obtain silodosin intermediate. The preparation method of the invention has the advantages of simple preparation method, high yield, low energy consumption, environmental protection and good quality of the prepared silodosin intermediate, which is suitable for large-scale industrial production.

Description

technical field [0001] The invention relates to the technical field of pharmaceutical preparation, in particular to a preparation method of a silodosin intermediate. Background technique [0002] Silodosin is an α-adrenergic receptor antagonist invented by Kissei Pharmaceutical Company of Japan, which has a very good therapeutic effect on urination disorders related to benign prostatic hyperplasia. [0003] At present, the synthesis of silodosin is mainly synthesized from the intermediate described in compound 1 through a multi-step reaction, as shown in reaction formula 1. [0004] [0005] There are many synthetic routes for silodosin intermediate compound 1, and the literature reports mainly include the following: First, Japanese patent JP2001199956 reported the synthetic route with benzoic acid, indoline, etc. as starting materials, such as reaction formula two shown. [0006] [0007] This route is long, the yield is low, and the phosphide produced has a great i...

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Problems solved by technology

[0014] Although this route is relatively novel in the design of the route, the total yield of the route is low. During the azidation reaction, there are potential safety hazards in industrial production. In addition, palladium- Barium sulfate is used as a catalyst, and the cost is relatively high

[0015] In summary, the current synthesis of silodosin intermediate compound 1 is either due to serious production pollution, high production costs due to production yield, or difficult to achieve industrialization due to the use of expensive chemical reagents. Production, therefore the preparation method of the synthetic silodosin intermediate compound 1 that develops green, environmental protection, strong maneuverability has broad prospect

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