Chloroform → Benzenamine, 3-ethynyl-

Participants

Reaction Steps

The U.S. Pat. No. 5,747,498 (herein after referred to as the '498 patent) makes no reference to the existence of specific polymorphic forms of erlotinib hydrochloride. In this patent, it is disclosed that the compound is isolated according to conventional techniques; more precisely, according to the embodiments exemplified, crude erlotinib hydrochloride residue (obtained by reaction of 4-chloro-6,7-bis-(2-methoxyethoxy)-quinazoline with 3-ethynylaniline or its hydrochloride salt in a solvent such as a C1-C6-alcohol, dimethylformamide, N-methylpyrrolidin-2-one, chloroform, acetonitrile, tetrahydrofuran, 1,4-dioxane, pyridine or other aprotic solvents, preferably isopropanol) is basified with saturated aqueous NaHCO3 in the presence of methanol and chloroform followed by flash chromatography on silica using 30% acetone in hexane to afford erlotinib free base, which is further treated with hydrochloric acid in the presence of diethyl ether and chloroform to give erlotinib hydrochloride (melting point: 228°-230° C.).

Provenance & Evidence