反应详情

To a mixture of 200 mg of 8-[(2,6-difluorobenzyl)oxy]-2-methylimidazo[1,2-a]pyridine-3-carboxylic acid, 6 ml of dichloromethane, and one droplet of DMF was added 110 μl of oxalyl chloride under ice-cooling, followed by stirring at room temperature for 30 minutes. The reaction mixture was concentrated under reduced pressure, and to the obtained residue were added 10 ml of THF, 300 μl of diisopropylethylamine, and a solution of 170 mg of 1-[2-(2,2-dimethyl-1,3-dioxolan-4-yl)phenyl]methanamine in 5 ml of THF under ice-cooling, followed by stirring at room temperature for 24 hours. To the reaction mixture was added water, followed by extraction with ethyl acetate. The organic layer was washed with a 10% aqueous citric acid solution, a saturated aqueous sodium hydrogen carbonate solution, water, and a saturated aqueous sodium chloride solution, and dried over anhydrous magnesium sulfate, and the solvent was then evaporated under reduced pressure. The obtained residue was purified by silica gel column chromatography to obtain 278 mg of 8-[(2,6-difluorobenzyl)oxy]-N-[2-(2,2-dimethyl-1,3-dioxolan-4-yl)benzyl]-2-methylimidazo[1,2-a]pyridine-3-carboxamide.

1. temperaturecooling
2. concentrationThe reaction mixture was concentrated under reduced pressure
3. additionto the obtained residue were added 10 ml of THF, 300 μl of diisopropylethylamine
4. temperaturea solution of 170 mg of 1-[2-(2,2-dimethyl-1,3-dioxolan-4-yl)phenyl]methanamine in 5 ml of THF under ice-cooling
5. stirringby stirring at room temperature for 24 hours
6. additionTo the reaction mixture was added water
7. extractionfollowed by extraction with ethyl acetate
8. washThe organic layer was washed with a 10% aqueous citric acid solution
9. dry with materiala saturated aqueous sodium hydrogen carbonate solution, water, and a saturated aqueous sodium chloride solution, and dried over anhydrous magnesium sulfate
10. customthe solvent was then evaporated under reduced pressure
11. customThe obtained residue was purified by silica gel column chromatography