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 (2 g) was dissolved in a mixed solvent of water (4 ml) and ethanol (8 ml), palladium on carbon (100 mg) was added, and the mixture was stirred at room temperature under a hydrogen atmosphere (ca. 1 atmospheric pressure) for 5 hours and 10 minutes. The reaction mixture was filtered, and the residue was washed with a mixed solvent of water (1 ml) and ethanol (2 ml). Ethanol (20 ml) was added to the filtrate, which was concentrated. Addition of ethanol (10 ml) to the residue and subsequent concentrate were repeated four times. The mixture was filtered with heating and ethyl acetate (40 ml) was added dropwise with stirring at the same time. After stirring at room temperature for 25 hours and 30 minutes, the crystals were filtered with washing with a mixed solvent of ethanol (2 ml) and ethyl acetate (2 ml) and dried to give the title compound (1.56 g) as a white solid.

Provenance & Evidence