Benzenamine, 3-ethynyl- → Erlotinib Hydrochloride

Participants

Reaction Conditions

Reaction Steps

4-chloro-6,7-bis-(2-methoxyethoxy)quinazoline (50 g, 0.1598 mol) was added to methanol (900 ml, 18 vol.) and the mixture was heated to 35-40° C. to obtain a uniform suspension. 3-Ethynylaniline (20.6 g, 0.1758 mol) was mixed with 100 ml (2 vol.) of methanol and added drop wise into the uniform suspension of 4-chloro-6,7-bis-(2-methoxyethoxy)quinazoline over a period of 15 min at 35-40° C. The temperature of the reaction mixture was slowly raised to 60-65° C. and maintained for 2-3 hours. The reaction was monitored by TLC as well as HPLC. When the 4-chloro-6,7-bis-(2-methoxyethoxy)-quinazoline content in the reaction mixture was not more than 3%, the reaction mixture was cooled to 25-30° C. and crude erlotinib hydrochloride was isolated by filtration. The cake was washed with 100 ml (2 vol.) of methanol and suck dried.

Provenance & Evidence