Method for synthesizing famciclovir

Abstract

The invention relates to a method for synthesizing famciclovir, which includes preparing sodium salt of diethyl malonate at the acting of sodium ethylate by taking diethyl malonate as raw charge and ethyl hydrate as dissolvent, preparing bromo ethyl group diethyl malonate by carrying out nucleophilic substitution reaction with 1, 2-dibromoethane and sodium salt of diethyl malonate, preparing bromo ethyl group propanediol by deoxidizing bromo ethyl group diethyl malonate at the acting of sodium borohydride, preparing 2-acetyl oxygen radicel methyl radicel -4-bromo butyl acetic ester by carrying out reaction with bromo ethyl group propanediol and acylating agent acetic oxide, preparing 2-(2-acetyl oxygen radicel-4-bromo butyl acetic ester)-6-chloropurine by carrying out condensation with 2-acetyl oxygen radicel methyl radical-4-bromo butyl acetic ester and 2-amidocyanogen-6-chloropurine, and then preparing famciclovir by carrying out dechlorination with 2-(2-acetyl oxygen radicel methyl radical -4-bromo butyl acetic ester)-6-chloropurine. This method is suitable for the industrial production with short production line, high yield and low cost.

Description

technical field [0001] The invention relates to a method for synthesizing antiviral drug faciclovir. Background technique [0002] Famciclovir is mainly used to treat herpes zoster, primary genital herpes. It has inhibitory effect on duck hepatitis B virus DNA. At present, there are mainly the following 3 reports about the synthetic route of famciclovir: [0003] 1. Condensation of 2-amino-6-chloropurine and 3-bromopropane-1,1,1-tricarboxylic acid triethyl ester to generate 2-amino-6-chloro-9-(2,2-diethoxycarbonyl butanoic acid Ethyl ester-4-base) purine prepares faciclovir through decarboxylation, reduction and esterification again, and 3-bromopropane 1 in this route, 1, 1-triethyl tricarboxylate needs to be self-made, and reaction route is relatively long, and cost higher. [0004] 2. Preparation by using 2,5-diamino4,6-dihydroxypyrimidine and N-alkyl chloride imine as raw materials. The disadvantage of this route is that the raw materials are more expensive and the yi...

AI Technical Summary

Problems solved by technology

[0003] 1. Condensation of 2-amino-6-chloropurine and 3-bromopropane-1,1,1-tricarboxylic acid triethyl ester to generate 2-amino-6-chloro-9-(2,2-diethoxycarbonyl butanoic acid Ethyl ester-4-base) purine prepares faciclovir through decarboxylation, reduction and esterification again, and 3-bromopropane 1 in this route, 1, 1-triethyl tricarboxylate needs to be self-made, and reaction route is relatively long, and cost higher

[0004] 2. Prepared with 2,5-diamino4,6-dihydroxypyrimidine and N-alkyl chloride imine as raw materials. The disadvantage of this route is that the raw materials are more expensive and the yield is lower

[0005] 3. Use 1,3-diacetoxyacetone and ethylene magnesium bromide as raw materials to prepare side chains, and then react with 2-amino 6-chloropurine to prepare faciclovir. This route has relatively few reaction steps, but The reaction needs to be carried out at a low temperature of -78°C, which is not suitable for industrial production