Preparation method of silodosin intermediate

Abstract

The invention discloses a preparation method of a silodosin intermediate. The preparation method includes: allowing 5-bromoindoline solution and triethylamine to be in alkylation reaction to obtain asubstance A; allowing a solution of the substance A, ethyl acetoacetate, catalyst and acid-binding agent to be in substitution reaction to obtain a substance B; allowing a solution of the substance Band Lewis acid to be in decarboxylic reaction to obtain a substance C; allowing a solution of the substance C, R-tert butyl sulfonamide, catalyst and reducer to be in amination reaction to obtain a substance D; allowing a solution of the substance D and N-bromosuccinimide solution to be in bromination reaction to obtain a substance E; allowing a solution of the substance E and cuprous cyanide to be in cyanation reaction to obtain a substance F; allowing a solution of the substance F and acid to be in acidolysis reaction to obtain a substance G; preparing the substance G into tartrate to obtainthe silodosin intermediate. The preparation method is simple, high in yield, low in energy consumption and environment-friendly; the silodosin intermediate prepared by the method is high in quality and suitable for large-scale industrial production.

Description

technical field [0001] The invention relates to the technical field of medicine preparation, in particular to a preparation method of a silodosin intermediate. Background technique [0002] Silodosin is an α-adrenoceptor antagonist invented by Kissei Pharmaceutical Company of Japan, which has a very good therapeutic effect on urinary disorders related to benign prostatic hyperplasia. [0003] At present, the synthesis of silodosin is mainly synthesized from the intermediate described in compound 1 through multi-step reactions, as shown in Reaction Formula 1. [0004] [0005] There are many synthetic routes about the silodosin intermediate compound 1, and the literature reports mainly contain the following types: One, Japanese Patent JP2001199956 reports a synthetic route using benzoic acid, indoline, etc. as starting materials, such as reaction formula 2 shown. [0006] [0007] The route is long, the yield is low, and the phosphides produced have a great impact on ...

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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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