Methanol → Lapatinib

Participants

Reaction Steps

The suspension of 5-[4-((3-chloro-4-((3-fluorobenzyl)oxy)phenyl)amino)quinazolin-6-yl]-2-furaldehyde (10 g, 21.1 mmoL) in dichloromethane (100 mL) was charged with a solution of 2-aminoethylmethylsulfone (5.8 g, 46.4 mmoL) in methanol (50 mL) slowly under constant stirring at room temperature. The reaction mixture was stirred for 2-4 hours until reaction completion. The reaction mixture was charged with 5% Pd—C (1.5 g) and stirred under hydrogen atmosphere using balloon pressure for 12-16 hours until reaction completion. The obtained mixture was filtered through Celite® pad and rinsed with methanol (30 mL) and dichloromethane (10 mL) mixture. The filtrate was distilled to a low volume and the solution was charged with toluene (50 mL) followed by addition of the solution of p-toluenesulfonic acid monohydrate (4.8 g, 25.3 mmoL) in methanol (25 mL). The yellow solid precipitated out was filtered after 2-8 hours and washed with 1:1 mixture of methanol and toluene (40 mL). The solid obtained was dried under vacuum at 40-45° C. to provide the monotosylate salt of Lapatinib (11.4 g, Yield=93%, HPLC purity>99%).

Provenance & Evidence