1-[2-Fluoro-4-(2-{[4-(4-methylpiperazin-1-yl)piperidine-1-carbonyl]amino}pyridin-4-yloxy)phenylcarbamoyl]cyclopropanecarboxylic acid benzyl ester trihydrochloride → 1-[2-Fluoro-4-(2-{[4-(4-methylpiperazin-1-yl)piperidine-1-carbonyl]amino}pyridin-4-yloxy)phenylcarbamoyl]cyclopropanecarboxylic acid trihydrochloride

Participants

Reaction Steps

1-[2-Fluoro-4-(2-{[4-(4-methylpiperazin-1-yl)piperidine-1-carbonyl]amino}pyridin-4-yloxy)phenylcarbamoyl]cyclopropanecarboxylic acid benzyl ester trihydrochloride (5 g) was dissolved in a mixed solvent of water (10 ml) and ethanol (20 ml), and palladium on carbon (250 mg) was added, and the mixture was stirred at room temperature under a hydrogen atmosphere (0.2 MPa) for 7 hours and 50 minutes. The reaction mixture was filtered, and the residue was washed with a mixed solvent of water (6 ml) and ethanol (10 ml). Ethanol (50 ml) was added to the filtrate, which was azeotropically distilled off and concentrated, and water (0.6 g) and ethanol (8.3 ml) were added. 2-Propanol (10 ml) was added to the solution, followed by stirring at room temperature for 5 minutes. 1-[2-Fluoro-4-(2-{[4-(4-methylpiperazin-1-yl)piperidine-1-carbonyl]amino}pyridin-4-yloxy)phenylcarbamoyl]cyclopropanecarboxylic acid trihydrochloride (150 mg) was added, followed by stirring for 13 hours and 45 minutes. 2-Propanol (50 ml) was further added, and the mixture was stirred at room temperature for 24 hours and 35 minutes. The crystals were filtered and dried to give the title compound (4.26 g) as a white solid.

Provenance & Evidence