反应详情

4-(4,6-Dimethoxy[1,3,5]triazin-2-yl)-4-methylmorpholinium chloride hydrate (164 mg) was added to a suspension of 1-[2-fluoro-4-(2-{[4-(4-methylpiperazin-1-yl)piperidine-1-carbonyl]amino}pyridin-4-yloxy)phenylcarbamoyl]cyclopropanecarboxylic acid (100 mg) in mixture of tetrahydrofuran (1 ml), N,N-dimethylformamide (0.2 ml) and 4-fluoroaniline (0.0526 ml), followed by stirring at room temperature for 2.5 hours. A 5% aqueous solution of sodium hydrogencarbonate was added to the reaction mixture to quench the reaction, and ethyl acetate was added and the layers were separated. The organic layer was washed with water and concentrated. The residue was purified by silica gel column chromatography (Fuji Silysia NH, eluent; ethyl acetate, ethyl acetate:methanol=95:5). The eluate was concentrated. Ethyl acetate (2 ml) was added to the resultant residue, followed by stirring at room temperature for 30 minutes. Heptane (2 ml) was added, and the mixture was stirred for 30 minutes. The crystals were collected by filtration and dried to give the title compound (74 mg) as white crystals.

1. customto quench
2. customthe reaction, and ethyl acetate
3. additionwas added
4. customthe layers were separated
5. washThe organic layer was washed with water
6. concentrationconcentrated
7. customThe residue was purified by silica gel column chromatography (Fuji Silysia NH, eluent; ethyl acetate, ethyl acetate:methanol=95:5)
8. concentrationThe eluate was concentrated
9. additionEthyl acetate (2 ml) was added to the resultant residue
10. stirringby stirring at room temperature for 30 minutes
11. additionHeptane (2 ml) was added
12. stirringthe mixture was stirred for 30 minutes
13. filtrationThe crystals were collected by filtration
14. customdried