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

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Reaction Steps

1-[2-Fluoro-4-(2-{[4-(4-methylpiperazin-1-yl)piperidine-1-carbonyl]amino}pyridin-4-yloxy)phenylcarbamoyl]cyclopropanecarboxylic acid benzyl ester (500 mg) was dissolved in a mixed solvent of tetrahydrofuran (2.5 ml), ethanol (2.5 ml) and water (1.5 ml), palladium on carbon (100 mg) was added, and the mixture was stirred at room temperature under a hydrogen atmosphere (0.15 MPa) for 3 hours. The reaction mixture was filtered, and the residue was washed with a 90% aqueous ethanol (1 ml), and the filtrate was concentrated. Addition of ethanol to the residue and subsequent concentration were repeated three times. Ethanol (2.5 ml), tetrahydrofuran (2.5 ml) and the seed crystals obtained in (Method 1) were added to the residue, and the mixture was stirred at room temperature for 1 hour. Ethyl acetate (5 ml) was added, and the mixture was further stirred for 1 hour. The crystals were filtered and dried to give the title compound (420 mg) as white crystals.

Provenance & Evidence