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

1-[2-Fluoro-4-(2-{[4-(4-methylpiperazin-1-yl)piperidine-1-carbonyl]amino}pyridin-4-yloxy)phenylcarbamoyl]cyclopropanecarboxylic acid benzyl ester hydrochloride (2 g) was dissolved in water (20 ml) and ethyl acetate (20 ml), and a 2N aqueous solution of sodium hydroxide (4 ml) was added, and the layers were separated. The organic layer was washed with water and concentrated. Addition of tetrahydrofuran and subsequent concentration was repeated three times. The residue was dissolved in a mixed solvent of tetrahydrofuran (8 ml) and water (1.6 ml), and palladium on carbon (200 mg) was added, and the mixture was stirred at room temperature under a hydrogen atmosphere (0.2 MPa) for 5 hours. Tetrahydrofuran (4 ml) and methanol (6 ml) were added to the reaction mixture, which was filtered. The residue was washed with 90% aqueous methanol (3 ml). Tetrahydrofuran (12 ml) and the seed crystals obtained in (Method 1) were added to the filtrate, and the mixture was stirred at room temperature for 1 hour. Ethyl acetate (32 ml) was added, and the mixture was stirred for 14 hours. The crystals were filtered and dried to give the title compound (1.2 g) as white crystals.

1. customthe layers were separated
2. washThe organic layer was washed with water
3. concentrationconcentrated
4. additionAddition of tetrahydrofuran and subsequent concentration
5. dissolutionThe residue was dissolved in a mixed solvent of tetrahydrofuran (8 ml) and water (1.6 ml), and palladium on carbon (200 mg)
6. additionwas added
7. additionTetrahydrofuran (4 ml) and methanol (6 ml) were added to the reaction mixture, which
8. filtrationwas filtered
9. washThe residue was washed with 90% aqueous methanol (3 ml)
10. customTetrahydrofuran (12 ml) and the seed crystals obtained in (Method 1)
11. additionwere added to the filtrate
12. stirringthe mixture was stirred at room temperature for 1 hour
13. stirringthe mixture was stirred for 14 hours
14. filtrationThe crystals were filtered
15. customdried

ORDレコード

ord-6ab44b900cbb44f6b80260df3f55dfa5

出典データセット

uspto-grants-2013_02

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US08377938B2