A PROCESS FOR SYNTHESIS OF [6,7-BIS-(2-METHOXYETHOXY)-QUINAZOLIN-4- YL]-(3-ETHYNYLPHENYL)AMINE HYDROCHLORIDE

摘要

A process for synthesizing [6,7-bis(2-methoxyethoxy)quinazolin-4-yl]-(3-ethynylphenyl)amine hydrochloride (Erlitinib Hydrochloride) having the formula (I) comprising reacting 3,4-dihydroxy benzaldehyde with bromo derivative of ethyl methyl ether to obtain 3,4-bis(2-methoxyethoxy)benzaldehyde having formula (III). This is converted to give 3,4- bis (2-methoxyethoxy)-benzonitrile. On further nitration we obtain 4,5- bis (2-methoxyethoxy)-2-nitrobenzonitrile which on nitro reduction we get 2-amino-4,5-bis(2-methoxyethoxy)benzonitrile and reacting this with N'-(3-ethynylphenyl)-N,N-dimethyl formamidine gives erlotinib free base. On further treatment of this free base with methanolic/ethanolic hydrochloric acid gives us erlotinib hydrochloride.