反应详情

To a solution of 4-(4-aminophenoxy)-2-{[4-(azetidin-1-yl)piperidin-1-yl]carbonylamino}pyridine (67.8 mg) in tetrahydrofuran (2.5 ml) was added a solution of 2-(4-fluorophenyl)acetyl isocyanate in tetrahydrofuran (0.25 M, 2.2 ml) at room temperature, followed by stirring for 2 hours. A solution of 2-(4-fluorophenyl)acetyl isocyanate in tetrahydrofuran (0.25 M, 1.5 ml) was further added thereto at room temperature. After 6 hours, a solution of 2-(4-fluorophenyl)acetyl isocyanate in tetrahydrofuran (0.25 M, 1.85 ml) and diisopropylethylamine (0.322 ml) were added thereto at room temperature, followed by stirring for 2 days. The reaction mixture was partitioned between ethyl acetate and a saturated aqueous solution of sodium hydrogencarbonate. The organic layer was washed with brine and dried over anhydrous sodium sulfate. The solvent was evaporated to give a residue, which was then purified by silica gel column chromatography (Fuji Silysia NH, eluent; ethyl acetate, then ethyl acetate:methanol=97:3). Fractions containing the target compound were concentrated to give a residue, which was then suspended in ethyl acetate (1 ml). The solid was filtered off and dried under aeration to provide the titled compound (17.0 mg, 17%) as white powder.

1. customat room temperature
2. waitAfter 6 hours
3. customat room temperature
4. stirringby stirring for 2 days
5. customThe reaction mixture was partitioned between ethyl acetate
6. washThe organic layer was washed with brine
7. dry with materialdried over anhydrous sodium sulfate
8. customThe solvent was evaporated
9. customto give a residue, which
10. customwas then purified by silica gel column chromatography (Fuji Silysia NH, eluent
11. additionFractions containing the target compound
12. concentrationwere concentrated
13. customto give a residue, which
14. filtrationThe solid was filtered off
15. customdried under aeration