Diisopropylethylamine → 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) and 2-aminoethylmethylsulfone hydrochloride (3 g, 19 mmoL) in methanol (10 mL) and dichloromethane (25 mL) was charged with N,N-diisopropylethylamine (1.6 g, 12.7 mmoL) 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 (after evacuation) for 16-24 hours until reaction completion. The reaction mixture was further charged with methanol (25 mL) and dichloromethane (25 mL) and stirred for 12-16 hours. The obtained mixture was filtered, washed with 1:1 mixture of methanol (20 mL) and dichloromethane (20 mL). The yellow filtrate thus obtained was charged slowly with a solution of p-toluenesulfonic acid monohydrate (2 g, 10.6 mmoL) in methanol (5 mL). The yellow solid which precipitated out was filtered and washed with 1:1 mixture of methanol (20 mL) and dichloromethane (20 mL). The solid obtained was dried under vacuum at 40-45° C. to provide the monotosylate salt of Lapatinib (4.8 g, Yield=60%, HPLC purity>99%).

Provenance & Evidence