反应详情

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.

1. additionwas added
2. filtrationThe reaction mixture was filtered
3. washthe residue was washed with a 90% aqueous ethanol (1 ml)
4. concentrationthe filtrate was concentrated
5. additionAddition of ethanol
6. concentrationto the residue and subsequent concentration
7. customEthanol (2.5 ml), tetrahydrofuran (2.5 ml) and the seed crystals obtained in (Method 1)
8. additionwere added to the residue
9. stirringthe mixture was stirred at room temperature for 1 hour
10. stirringthe mixture was further stirred for 1 hour
11. filtrationThe crystals were filtered
12. customdried