Novel preparation method of silodosin

Abstract

The invention discloses a novel method for preparing silodosin. In the invention, a complete silodosin synthesizing path is invented. By adopting brand new synthesis methods, intermediates synthesized in each step are brand new compounds, for example, if a Gabriel synthesis method is adopted, primary amine is introduced on the 2-site carbon atom, and chain extending reaction is carried out by utilizing benzyloxy-propyl, and the like. The invention provides the economic and safe path with high purity and high yield, and is suitable for industrial production.

Description

technical field [0001] The invention belongs to the technical field of medicine, and in particular relates to a new method for preparing silodosin. Background technique [0002] Background technology of the present invention is as follows: [0003] Silodosin (Silodosin) is an a1 adrenergic receptor antagonist, which is clinically used to treat dysuria caused by benign prostatic hyperplasia. [0004] According to the synthetic route of silodosin in the World New Drug Synthesis Database, starting from the starting material compound, the comprehensive conversion rate of the key intermediate 1-acetyl-7-amino-5-(2-aminopropyl)indoline is only 24%. %, and a large amount of toxic cyanide-containing compounds, azide compounds and organic solvents are used in the process, the process is complex, difficult to control and very polluting to the environment. At the same time, due to the use of relatively expensive tribromopyrrolidone and platinum oxide in the bromination and hydrogenat...

AI Technical Summary

Problems solved by technology

[0004] According to the synthetic route of silodosin in the World New Drug Synthesis Database, starting from the starting material compound, the comprehensive conversion rate of the key intermediate 1-acetyl-7-amino-5-(2-aminopropyl)indoline is only 24%. %, and a large amount of toxic cyanide-containing compounds, azide compounds and organic solvents are used in the process, the process is complex, difficult to control and very polluting to the environment

At the same time, due to the use of relatively expensive tribromopyrrolidone and platinum oxide in the bromination and hydrogenation reduction process, the cost is high and it is not easy to industrialized production

Another key intermediate, 2-[2-(2,2,2-trifluoroethoxy)phenoxy]bromoethane, proceeds from m-methoxyphenol, and undergoes two-step alkylation and one-step dehydrogenation, respectively. Methylation reaction, their reaction conversion rate is 72%, 65.5% and 40% respectively, and its comprehensive yield is only about 18%, and the industrialization value is not high