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 and then was charged with 5% Pd—C (0.5 g) and stirred under hydrogen atmosphere at 25 psi pressure for 16-24 hours until reaction completion. The obtained mixture was filtered, washed with a 3:1 mixture of methanol (40 mL) and dichloromethane (20 mL). The filtrate was distilled to low volume, and the obtained solution was slowly charged with solution of p-toluenesulfonic acid monohydrate (4.4 g, 23.2 mmoL) in methanol (10 mL). The yellow solid which precipitated out was filtered and washed with a 1:1 mixture of methanol (20 mL) and dichloromethane (20 mL). The solid obtained was dried under vacuum at 40-45° C. to give the monotosylate salt of Lapatinib (11.4 g, Yield=72%, HPLC purity>99%).

Provenance & Evidence