Methanol → Lapatinib

Participants

Reaction Steps

The suspension of 5-[4-((3-chloro-4-((3-fluorobenzyl)oxy)phenyl)amino)-quinazolin-6-yl]-2-furaldehyde (20 g, 42.2 mmoL) in methanol (100 mL) and dichloromethane (60 mL) was charged with 2-aminoethylmethylsulfone (5.8 g, 46.4 mmoL) slowly under constant stirring at room temperature and then the reaction mixture was stirred for 2-4 hours until reaction completion. The reaction mixture was charged with 5% Pd—C (1 g) and stirred under hydrogen atmosphere (after evacuation) for 16-24 hours until reaction completion. The obtained mixture was filtered, washed with 3:1 mixture of methanol (40 mL) and dichloromethane (20 mL). The filtrate was distilled to low volume whereupon the obtained solution was slowly charged with a solution of p-toluenesulfonic acid monohydrate (8.8 g, 46.4 mmoL) in methanol (20 mL). The yellow solid which precipitated out was filtered and washed with 1:3 mixture of methanol (10 mL) and dichloromethane (30 mL). The solid obtained was dried under vacuum at 40-45° C. to furnish the monotosylate salt of Lapatinib (23.7 g, Yield=75%, HPLC purity>99%).

Provenance & Evidence