Dimethyl Sulfoxide → Erlotinib Hydrochloride

Participants

Reaction Conditions

Reaction Steps

4-Chloro-6,7-bis-(2-methoxyethoxy)-quinazoline (50 gm) and dimethyl sulfoxide (250 ml) are added to methanol (500 ml) while stirred at 25-30° C., 3-ethynylaniline (20.5 gm) is added to the reaction mixture at 25-30° C. and then the contents are heated to 85° C. The reaction mass is stirred for 2 hours at 80-85° C., the mass is cooled to 25-30° C. and then stirred for 1 hour. The material is filtered, washed with a mixture of dimethyl sulfoxide (50 ml) and methanol (100 ml), and then dried at 60° C. under vacuum for 4 hours to give 60 gm of erlotinib hydrochloride [HPLC purity: 99.65%; Content of N-methoxyethyl impurity: 0.09% (at 1.14 RRT)].

Provenance & Evidence