反应详情

To a solution of 4-(4-amino-3-fluorophenoxy)pyridin-2-ylamine (500 mg) in tetrahydrofuran (23 ml) was added triethylamine (0.318 ml), and then phenyl chloroformate (0.357 ml, 2.28 mmol) was added thereto while stirring in an ice bath, followed by stirring under a nitrogen atmosphere for 1 hr and 20 min. The reaction mixture was concentrated under a reduced pressure to give a residue, to which N,N-dimethylformamide (20 ml) and morpholine (0.994 ml) were added, followed by stirring at room temperature for 8 hrs. The reaction mixture was partitioned between ethyl acetate (100 ml) and water (100 ml). The organic layer was washed with a saturated aqueous solution of sodium hydrogencarbonate, and dried over anhydrous sodium sulfate. The solvent was evaporated to give a residue, which was then purified by silica gel column chromatography (eluent; hexane:ethyl acetate=1:1, ethyl acetate, then ethyl acetate:methanol=10:1). The resultant solid was suspended in ethyl acetate:diethyl ether (1:10), filtered, washed with diethyl ether, and dried under aeration to provide the titled compound (48 mg, 6.3%) as pale red powder.

1. stirringby stirring under a nitrogen atmosphere for 1 hr and 20 min
2. concentrationThe reaction mixture was concentrated under a reduced pressure
3. customto give a residue
4. stirringby stirring at room temperature for 8 hrs
5. customThe reaction mixture was partitioned between ethyl acetate (100 ml) and water (100 ml)
6. washThe organic layer was washed with a saturated aqueous solution of sodium hydrogencarbonate
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 (eluent
11. filtrationfiltered
12. washwashed with diethyl ether
13. customdried under aeration