反应详情

To a solution of phenyl N-[4-(3-fluoro-4-{[1-(4-fluorophenylcarbamoyl)cyclopropanecarbonyl]amino}phenoxy)pyridin-2-yl]-N-phenoxycarbonylcarbamate (50.0 mg) in N,N-dimethylformamide (1.0 ml) were added 4-(azetidin-1-yl)piperidine dihydrochloride (79.9 mg), triethylamine (0.105 ml) and water (0.050 ml), followed by stirring at room temperature for 24 hr. The reaction mixture was partitioned between ethyl acetate and a 1N aqueous solution of sodium hydroxide. The organic layer was washed with brine, and dried over anhydrous sodium sulfate. The solvent was removed, and the residue was purified by silica gel column chromatography (Fuji Silysia NH, ethyl acetate, then ethyl acetate:methanol=20:1). Fractions containing the target compound were concentrated. To the residue was added diethyl ether:hexane=1:3, and the precipitate was collected by filtration. This was washed with hexane and dried under aeration to provide the titled compound as white powder (22.9 mg, 51.7%).

1. customThe reaction mixture was partitioned between ethyl acetate
2. washThe organic layer was washed with brine
3. dry with materialdried over anhydrous sodium sulfate
4. customThe solvent was removed
5. customthe residue was purified by silica gel column chromatography (Fuji Silysia NH, ethyl acetate
6. additionFractions containing the target compound
7. concentrationwere concentrated
8. additionTo the residue was added diethyl ether
9. filtrationhexane=1:3, and the precipitate was collected by filtration
10. washThis was washed with hexane
11. customdried under aeration