Method for producing adefovir

Abstract

The invention provides a method for industrially producing adefovir. The method has a synthesis route that: 2-chloroethanol is subjected to cholromethylation and then reacted with triisopropyl phosphite to generate side chain of adefovir; and the side chain and adenine are subjected to condensation and hydrolysis to prepare the adefovir product. The method has the advantages of simple process, easy operation, safety, environmental protection, the most basic raw materials and common agents, mild reaction conditions, low cost, high purity of the product, and industrial production. The adefovir provided by the method can be used as a raw material medicament for producing adefovir dipivoxil.

Description

technical field

[0001] The invention relates to an industrial production method of adefovir, which belongs to the field of pharmaceutical chemistry. Background technique

[0002] Adefovir (Adefovir, 9-(2-phosphomethoxyethyl) adenine) is a purine derivative with biological activity against hepatitis B virus, and its prodrug adefovir dipivoxil 9-[2 -[bis(pivaloyloxymethyl)phosphonomethoxy]ethyl]adenine is a new type of open-chain nucleotide developed by GileadSciences in the United States and approved by the FDA in September 2002 for the treatment of New drugs for hepatitis B. In China, there are currently many manufacturers approved by the State Food and Drug Administration.

[0003] According to the chemical structure characteristics of adefovir, it is decomposed, and there are currently six synthetic routes, all of which use adenine as the starting material. The difference is that there is a change in the synthesis of the side chain.

[0004] There are three existing in...