A NOVEL PROCESS FOR THE PREPARATION OF ERLOTINIB

摘要

The present invention discloses an improved and novel process for the preparation of erlotinib (N-(3-ethynylphenyl)-6,7-bis(2-methoxyethoxy)-4-quinazolinamine) of formula (1), which comprises: (i) demethylation of commercially available 6,7-dimethoxy-4(3H)-quinazolinone of formula (8); acetylation using acetic anhydride; (iii) introduction of a leaving group at C-4 position in quinazolinone; (iv) condensation with 3-ethynylaniline to get novel compound of formula (12); (v) deacetylation to get novel dihydroxy compound of formula (13); and (vi) O-alkylation with 2-iodoethylmethyl ether to get the erlotinib base of formula (1). Erlotinib base is purified by recrystallization from ethyl acetate to get a HPLC purity of >99.5%. Salt formation of this base with hydrogen chloride gave pharmaceutically acceptable erlotinib hydrochloride of formula (1a) with a HPLC purity of >99.8%. Erlotinib hydrochloride is useful for the treatment of proliferative disorders, such as cancers, in humans.