反应详情

To a solution of N-{3-[(2-amino[1,3]thiazolo[5,4-b]pyridin-5-yl)oxy]phenyl}-1,3-dimethyl-1H-pyrazole-5-carboxamide (1.03 g, 2.71 mmol) and triethylamine (563 μL, 4.07 mmol) in tetrahydrofuran (15 mL) was added with stirring under ice-cooling cyclopropanecarbonyl chloride (295 μL, 3.25 mmol), and the mixture was stirred at room temperature for 2 hr. Cyclopropanecarbonyl chloride (500 μL, 5.51 mmol) was further added thereto, and the mixture was stirred for 2 hr. The reaction mixture was diluted with water and extracted with ethyl acetate. The organic layer was washed with water and saturated brine, dried over anhydrous magnesium sulfate and filtrated. The filtrate was concentrated under reduced pressure, sodium carbonate (750 mg), methanol (15 mL) and water (100 μL) were added to the residue, and the mixture was stirred at 70° C. for 2 hr. The reaction mixture was diluted with water and extracted with ethyl acetate. The organic layer was washed with water and saturated brine, dried over anhydrous magnesium sulfate and filtrated. The filtrate was concentrated under reduced pressure, and the residue was purified by column chromatography (silica gel, hexane/ethyl acetate=60/40→0/100) and recrystallized from ethanol-ethyl acetate-hexane to give the title compound (675 mg, 56%) as a white solid.

1. stirringthe mixture was stirred at room temperature for 2 hr
2. stirringthe mixture was stirred for 2 hr
3. extractionextracted with ethyl acetate
4. washThe organic layer was washed with water and saturated brine
5. dry with materialdried over anhydrous magnesium sulfate
6. filtrationfiltrated
7. concentrationThe filtrate was concentrated under reduced pressure, sodium carbonate (750 mg), methanol (15 mL) and water (100 μL)
8. additionwere added to the residue
9. stirringthe mixture was stirred at 70° C. for 2 hr
10. additionThe reaction mixture was diluted with water
11. extractionextracted with ethyl acetate
12. washThe organic layer was washed with water and saturated brine
13. dry with materialdried over anhydrous magnesium sulfate
14. filtrationfiltrated
15. concentrationThe filtrate was concentrated under reduced pressure
16. customthe residue was purified by column chromatography (silica gel, hexane/ethyl acetate=60/40→0/100)
17. customrecrystallized from ethanol-ethyl acetate-hexane