反应详情

Potassium carbonate (772 mg) was added to a mixture of 1-[2-fluoro-4-(2-phenoxycarbonylaminopyridin-4-yloxy)phenylcarbamoyl]cyclopropanecarboxylic acid benzyl ester (2.75 g) and N,N-dimethylformamide (13.8 ml) was added, followed by stirring. 1-Methyl-4-(piperidin-4-yl)piperazine (1.02 g) was added, followed by stirring for 6 hours. The reaction mixture was partitioned after the addition of ethyl acetate (41 ml) and water (27.5 ml). The resultant organic layer was washed with water (13.8 ml, three times), dried over sodium sulfate, and filtered, and the filtrate was concentrated. The resultant residue was purified by silica gel column chromatography (Fuji Silysia NH, eluent; ethyl acetate:methanol=30:1). The eluate was concentrated under reduced pressure, and the precipitate appeared by the addition of tert-butyl methyl ether (3 ml) and the application of a stimulus. tert-Butyl methyl ether (40 ml) was further added, followed by stirring overnight. The resultant precipitate was collected by filtration, washed with tert-butyl methyl ether (3 ml), and dried under aeration to give the target title compound (1.61 g).

1. additionwas added
2. stirringby stirring for 6 hours
3. customThe reaction mixture was partitioned
4. additionafter the addition of ethyl acetate (41 ml) and water (27.5 ml)
5. washThe resultant organic layer was washed with water (13.8 ml, three times)
6. dry with materialdried over sodium sulfate
7. filtrationfiltered
8. concentrationthe filtrate was concentrated
9. customThe resultant residue was purified by silica gel column chromatography (Fuji Silysia NH, eluent; ethyl acetate:methanol=30:1)
10. concentrationThe eluate was concentrated under reduced pressure
11. additionthe precipitate appeared by the addition of tert-butyl methyl ether (3 ml)
12. additiontert-Butyl methyl ether (40 ml) was further added
13. stirringby stirring overnight
14. filtrationThe resultant precipitate was collected by filtration
15. washwashed with tert-butyl methyl ether (3 ml)
16. customdried under aeration