A preparation method of androsta-17β-n-(2,5-bis(trifluoromethyl))benzamide

Abstract

The invention provides a preparation method of androstane-17beta-N-(2,5-bis (trifluoromethyl)) benzamide. The preparation method comprises the following steps: (1) in the presence of an acid-binding agent, carrying out acyl chloride forming reaction between androstane-17beta carboxylic acid and thionyl chloride to obtain androstane-17beta acyl chloride; (2) enabling the androstane-17beta acyl chloride and 2,5-bis(trifluoromethyl) aniline to generate amide forming reaction in the presence of a hydrogen stripping agent to obtain androstane-17beta-N-(2,5-bis (trifluoromethyl)) benzamide, wherein the acid-binding agent is anhydrous potassium carbonate fine powder. The preparation method disclosed by the invention can be used for simply preparing the androstane-17beta-N-(2,5-bis (trifluoromethyl)) benzamide with low toxicity, high quality, high yield and low cost.

Description

technical field

[0001] The invention relates to a preparation method of a pharmaceutical intermediate, in particular to a preparation method of androsta-17β-N-(2,5-bis(trifluoromethyl))benzamide. Background technique

[0002] Dutasteride is a drug for the treatment of benign prostatic hyperplasia and alopecia developed by Glaxo, with definite curative effect and few side effects. Its important intermediate androst-17β-N-(2,5-bis(trifluoromethyl))benzamide is amide formed from 2,5-bis(trifluoromethyl)aniline and androsta-17β-carboxylic acid Then, the general reaction formula is as follows:

[0003]

[0004] The current traditional production method is: use aromatic hydrocarbons or chlorinated hydrocarbons or DMF or pyridine as a solvent, a large amount of pyridine catalyzes and binds acids, and after forming acid chlorides, add a large excess of 2,5-bis(trifluoromethyl)aniline, high temperature Form amides, post-treatment is anhydrous concentration under reduced pressure...

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