2-(Methylsulfonyl)ethanamine → Lapatinib

Participants

Reaction Steps

The suspension of 5-[4-((3-chloro-4-((3-fluorobenzyl)oxy)phenyl)amino)quinazolin-6-yl]-2-furaldehyde (5 g, 10.6 mmoL) in dichloromethane (50 mL) was charged with a solution of 2-aminoethylmethylsulfone (3.2 g, 11.7 mmoL) in methanol (25 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 (750 mg) 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 (5 mL) and dichloromethane (15 mL) mixture. The filtrate was distilled to low volume and the solution was charged with dichloromethane (25 mL) followed by addition of the solution of p-toluenesulfonic acid monohydrate (4.4 g, 23.3 mmoL) in methanol (10 mL). The yellow solid which precipitated out was filtered after 2-8 hours and washed with 1:1 mixture of methanol and dichloromethane (20 mL). The solid obtained was dried under vacuum at 40-45° C. to provide Lapatinib (11.4 g, Yield=93%, HPLC purity>99%).

Provenance & Evidence