反应详情

温度

70 °C

Under an argon gas flow, to a mixture of 10.4 g of 5-amino-2,2-dimethyl-1,3-dioxane-5-carbonitrile, 27.8 ml of triethylamine, and 280 ml of dichloroethane were added 27.2 g of 8-[(2,6-difluorobenzyl)oxy]-2-methylimidazo[1,2-a]pyridine-3-carbonyl chloride hydrochloride and 12 ml of dichloroethane at room temperature, followed by stirring at 70° C. for 2 hours. After leaving to be cooled to room temperature, the insoluble materials were separated by filtration and washed with dichloroethane. The filtrate was washed with a 10% aqueous citric acid solution three times, and the aqueous layer was extracted with chloroform. The organic layer was combined, washed with water, a saturated aqueous sodium hydrogen carbonate solution, 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 azeotropic distilled with ethyl acetate twice. To the obtained residue was added THF, and the insoluble materials were separated by filtration and washed with THF. The filtrate was concentrated and the residue was purified by silica gel column chromatography to obtain 27.7 g of N-(5-cyano-2,2-dimethyl-1,3-dioxan-5-yl)-8-[(2,6-difluorobenzyl)oxy]-2-methylimidazo[1,2-a]pyridine-3-carboxamide.

1. customAfter leaving
2. temperatureto be cooled to room temperature
3. customthe insoluble materials were separated by filtration
4. washwashed with dichloroethane
5. washThe filtrate was washed with a 10% aqueous citric acid solution three times
6. extractionthe aqueous layer was extracted with chloroform
7. washwashed with water
8. dry with materiala saturated aqueous sodium hydrogen carbonate solution, and a saturated aqueous sodium chloride solution, and dried over anhydrous magnesium sulfate
9. customthe solvent was then evaporated under reduced pressure
10. distillationThe obtained residue was azeotropic distilled with ethyl acetate twice
11. additionTo the obtained residue was added THF
12. customthe insoluble materials were separated by filtration
13. washwashed with THF
14. concentrationThe filtrate was concentrated
15. customthe residue was purified by silica gel column chromatography