反应详情

N-{4-[(2-Aminopyridin-4-yl)oxy]-2-fluorophenyl}-N′-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide (1.5 g) was dissolved in tetrahydrofuran (15 ml) under a nitrogen atmosphere, and triethylamine (0.987 ml) and phenyl chloroformate (0.978 ml) were added dropwise at room temperature in this order, followed by stirring for 30 min. The reaction mixture was stirred after addition of ethyl acetate and a saturated aqueous solution of sodium hydrogencarbonate. The organic layer was separated, washed with brine, and dried over anhydrous sodium sulfate. The solvent was concentrated under reduced pressure. The residue was dissolved in N,N-dimethylformamide (7.5 ml). Triethylamine (4.92 ml) and azetidine hydrochloride (1.33 g) were added at room temperature, followed by stirring for 7.5 hr. The reaction mixture was partitioned between ethyl acetate and a saturated aqueous solution of sodium hydrogencarbonate. The organic layer was washed with water (three times) and brine in this order, and dried over anhydrous sodium sulfate. The solvent was concentrated under reduced pressure. To the resultant residue were added ethyl acetate (5 ml) and heptane (5 ml) to precipitate a solid. The solid was collected by filtration and dried under aeration to provide the titled compound as white powder (1.29 g, 72%).

1. stirringThe reaction mixture was stirred
2. customThe organic layer was separated
3. washwashed with brine
4. dry with materialdried over anhydrous sodium sulfate
5. concentrationThe solvent was concentrated under reduced pressure
6. dissolutionThe residue was dissolved in N,N-dimethylformamide (7.5 ml)
7. additionTriethylamine (4.92 ml) and azetidine hydrochloride (1.33 g) were added at room temperature
8. stirringby stirring for 7.5 hr
9. customThe reaction mixture was partitioned between ethyl acetate
10. washThe organic layer was washed with water (three times) and brine in this order
11. dry with materialdried over anhydrous sodium sulfate
12. concentrationThe solvent was concentrated under reduced pressure
13. additionTo the resultant residue were added ethyl acetate (5 ml) and heptane (5 ml)
14. customto precipitate a solid
15. filtrationThe solid was collected by filtration
16. customdried under aeration