Environment-friendly preparation method of amifostine

Abstract

The invention relates to the field of drug synthesis, and discloses an environment-friendly technology for preparing medicinal amifostine. The technology is as follows: mixing a N-bromoethyl-1,3-propanediamine dihydrobromide solution with sodium thiophosphate at the concentration of a aqueous solution of 10-70%, keeping mol ratio within the range of 1.0:0.8-1.2, and reaction temperature at 5.0-60 DEG C, using a lower alcohol or a polyhydric alcohol as an accelerant to generate the amifostine product, directly filtering the product to obtain the crude product of amifostine, and carrying out recrystallization and purification to the crude product to obtain medicinal amifostine trihydrate, wherein the amifostine content is larger than or equal to 99.5%, the content of sodium thiophosphate is smaller than 0.1%, the content of other related single substances is smaller than 0.1%, and the content of the whole related substances is lower than 0.3%. The preparation method is free from high boiling point aprotic solvent residual; the medicinal safety is improved; the filtrated stock can be recovered by distilling at normal pressure; the accelerant can be recycled. Amifostine prepared by the method is high in the quality, free from high boiling point aprotic solvent residual, environment-friendly, efficient, easy to operate, low in cost, and suitable for industrial scale production.

Description

technical field [0001] The invention belongs to the field of drug synthesis, and more specifically relates to a clean preparation method for preparing medicinal amifostine trihydrate. Background technique [0002] Amifostine is a broad-spectrum cytoprotective agent, which was first screened out by the Walter Reed Army Medical Research Institute of the United States in the 1960s. It is a radiation protective agent with high anti-radiation effect and safe use. The codename used by the Institute is WR-2721. It is currently used clinically to reduce the toxic and side effects caused by radiation and drugs during radiotherapy and chemotherapy, and was approved by the FDA in 1996 as the first cytoprotective agent. The chemical structure is H 2 N-(CH 2 ) 3 -NH-(CH 2 ) 2 -SPO 3 h 2 , is an organophosphorylated aminothio-based prodrug, which is hydrolyzed by alkaline phosphatase into an active metabolite in normal tissues, code-named WR-1065, namely H 2 N-(CH 2 ) 3 -NH-(CH...

AI Technical Summary

Problems solved by technology

However, such polar aprotic solvents such as DMSO and DMF have very high boiling points and are difficult to recycle; in addition, such solvents are not conventional green solvents and have certain pollution to the environment. The key is the residual high boiling point solvents in amifostine products need control

The standards achieved by the pure products purified by the methods in the relevant literatures vary. Except for the patent CN200810146538.8 mentioning that it meets the requirements of the USP29 version, there are no relevant literatures and patents reporting the quality of refined amifostine.

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