反应详情

温度

80 °C

To a suspension of N-[4-({2-[(cyclopropylcarbonyl)amino]imidazo[1,2-a]pyridin-6-yl}oxy)-3-fluorophenyl]-6-(4-fluorophenyl)-5-methylpyridine-2-carboxamide 1-oxide (1.54 g, 2.77 mmol) in ethanol (15 mL) was added and dissolved therein 6N hydrochloric acid (554 μL, 3.32 mmol), and the mixture was left standing at room temperature overnight. The precipitate was collected by filtration and washed with ethanol to give a white powder. The white powder was dissolved in ethyl acetate, tetrahydrofuran and saturated aqueous sodium hydrogen carbonate solution, and the mixture was extracted twice with ethyl acetate. The combined organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate and filtered, and the solvent was evaporated under reduced pressure. The residue was suspended in ethanol (30 mL) and heated to 80° C. 6N Hydrochloric acid (370 μL, 2.22 mmol) was added dropwise and dissolved therein. The solution was allowed to gradually cool to 50° C., and the mixture was stirred for 6 hr. The precipitate was collected by filtration and washed with ethanol to give a white solid. The white solid was suspended in methyl ethyl ketone (10 mL), and the suspension was stirred at 50° C. overnight. The precipitate was collected by filtration and washed with methyl ethyl ketone to give the title compound (747 mg, 46%) as white crystals.

1. additionwas added
2. dissolutiondissolved
3. filtrationThe precipitate was collected by filtration
4. washwashed with ethanol
5. customto give a white powder
6. extractiontetrahydrofuran and saturated aqueous sodium hydrogen carbonate solution, and the mixture was extracted twice with ethyl acetate
7. washThe combined organic layer was washed with saturated brine
8. dry with materialdried over anhydrous magnesium sulfate
9. filtrationfiltered
10. customthe solvent was evaporated under reduced pressure
11. dissolutiondissolved
12. temperatureto gradually cool to 50° C.
13. filtrationThe precipitate was collected by filtration
14. washwashed with ethanol
15. customto give a white solid
16. stirringthe suspension was stirred at 50° C. overnight
17. filtrationThe precipitate was collected by filtration
18. washwashed with methyl ethyl ketone