反应详情

To a solution of N-{5-[(2-amino[1,3]thiazolo[5,4-b]pyridin-5-yl)oxy]-2,4-difluorophenyl}-2-chloro-3-(1-cyanocyclopropyl)benzamide (0.17 g, 0.33 mmol) and N,N-dimethylpyridine-4-amine (0.12 g, 1.00 mmol) in pyridine (2 mL) was added dropwise cyclopropanecarbonyl chloride (0.11 g, 1.00 mmol) under ice-cooling, and the mixture was stirred at room temperature for 2 hr. To the reaction mixture was added water (50 mL), and the mixture was extracted with ethyl acetate (50 mL×2). The ethyl acetate layers were combined, and dried over anhydrous magnesium sulfate. The insoluble material was filtered off, and the filtrate was concentrated under reduced pressure. The obtained residue was dissolved in methanol (5 mL), 8N aqueous sodium hydroxide solution (1 mL) was added, and the mixture was stirred at room temperature for 1 hr. The reaction mixture was poured into water (50 mL), and the mixture was extracted with ethyl acetate (50 mL×2). The ethyl acetate layers were combined, and dried over anhydrous sodium sulfate. The insoluble material was filtered off, and the filtrate was concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography (ethyl acetate/hexane=0/100→100/0), and recrystallized from methanol to give the title compound (88 mg, 47%) as white crystals.

1. temperaturecooling
2. extractionthe mixture was extracted with ethyl acetate (50 mL×2)
3. dry with materialdried over anhydrous magnesium sulfate
4. filtrationThe insoluble material was filtered off
5. concentrationthe filtrate was concentrated under reduced pressure
6. dissolutionThe obtained residue was dissolved in methanol (5 mL)
7. addition8N aqueous sodium hydroxide solution (1 mL) was added
8. stirringthe mixture was stirred at room temperature for 1 hr
9. additionThe reaction mixture was poured into water (50 mL)
10. extractionthe mixture was extracted with ethyl acetate (50 mL×2)
11. dry with materialdried over anhydrous sodium sulfate
12. filtrationThe insoluble material was filtered off
13. concentrationthe filtrate was concentrated under reduced pressure
14. customThe obtained residue was purified by silica gel column chromatography (ethyl acetate/hexane=0/100→100/0)
15. customrecrystallized from methanol