反应详情

To a solution of N-{3-[(2-amino[1,2,4]triazolo[1,5-a]pyridin-6-yl)oxy]phenyl}-3-(1-cyano-1-methylethyl)benzamide (219 mg, 0.531 mmol) in pyridine (10 mL) was added 2-chloro-2-oxoethyl acetate (171 μL, 1.59 mmol), and the mixture was stirred at room temperature for 18 hr. The reaction solution was concentrated under reduced pressure, and the residue was dissolved in methanol (10 mL). Potassium carbonate (147 mg, 1.06 mmol) was added thereto, and the mixture was stirred at room temperature for 19 hr. Water (30 mL) was added to the reaction mixture, and the mixture was extracted with ethyl acetate (50 mL, 2×10 mL). The combined organic layer was washed with saturated brine (10 mL) 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 (NH silica gel, ethyl acetate/methanol=100/0→90/10), and fractions containing the desired product were concentrated under reduced pressure. Ethyl acetate and diisopropyl ether were added to the obtained residue. The obtained precipitate was collected by filtration, and dried to give the title compound (140 mg, 56%) as a pale-yellow powder.

1. concentrationThe reaction solution was concentrated under reduced pressure
2. dissolutionthe residue was dissolved in methanol (10 mL)
3. stirringthe mixture was stirred at room temperature for 19 hr
4. extractionthe mixture was extracted with ethyl acetate (50 mL, 2×10 mL)
5. washThe combined organic layer was washed with saturated brine (10 mL)
6. dry with materialdried over anhydrous sodium sulfate
7. filtrationThe insoluble material was filtered off
8. concentrationthe filtrate was concentrated under reduced pressure
9. customThe obtained residue was purified by silica gel column chromatography (NH silica gel, ethyl acetate/methanol=100/0→90/10), and fractions
10. additioncontaining the desired product
11. concentrationwere concentrated under reduced pressure
12. additionEthyl acetate and diisopropyl ether were added to the obtained residue
13. filtrationThe obtained precipitate was collected by filtration
14. customdried