反应详情

N-{2,5-Difluoro-4-[(2-{[(3-hydroxyazetidin-1-yl)carbonyl]amino}pyridin-4-yl)oxy]phenyl}-N′-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide (38.9 mg) was dissolved in N,N-dimethylformamide (1.0 ml) under a nitrogen atmosphere, and N,N-dimethylglycine hydrochloride (20 mg), triethylamine (0.050 ml) and BOP reagent (63.5 mg) were added at room temperature, followed by stirring overnight. N,N-Dimethylglycine hydrochloride (20 mg), triethylamine (0.050 ml) and BOP reagent (63.5 mg) were added again at room temperature, and the reaction mixture was stirred for 5 hr. The reaction mixture was partitioned between ethyl acetate and water. The organic layer was separated, washed with a saturated aqueous solution of sodium hydrogencarbonate (twice) and brine, dried over anhydrous sodium sulfate. The solvent was concentrated under reduced pressure. The resultant residue was purified by silica gel column chromatography (Fuji Silysia NH, eluent; ethyl acetate), and fractions containing the target compound were concentrated under reduced pressure. To the resultant residue was added tert-butyl methyl ether (1 ml)-heptane (2 ml) to precipitate a solid. The solid was collected by filtration and dried under aeration to provide the titled compound as white powder (21.1 mg, 47%).

1. stirringthe reaction mixture was stirred for 5 hr
2. customThe reaction mixture was partitioned between ethyl acetate and water
3. customThe organic layer was separated
4. washwashed with a saturated aqueous solution of sodium hydrogencarbonate (twice) and brine
5. dry with materialdried over anhydrous sodium sulfate
6. concentrationThe solvent was concentrated under reduced pressure
7. customThe resultant residue was purified by silica gel column chromatography (Fuji Silysia NH, eluent; ethyl acetate), and fractions
8. additioncontaining the target compound
9. concentrationwere concentrated under reduced pressure
10. additionTo the resultant residue was added tert-butyl methyl ether (1 ml)-heptane (2 ml)
11. customto precipitate a solid
12. filtrationThe solid was collected by filtration
13. customdried under aeration