反应详情

Toluene (20 ml) was added to 2.0 g (4.3 mmol) of 2-(2'-cyanobiphenyl-4-yl)methylamino-3-cyclopropanecarboxamido-5-bromo-4-methylpyridine, p-toluenesulfonic acid monohydrate (200 mg) and Molecular Sieves 4A (500 mg), followed by heating under reflux with stirring for 3 hours. The reaction solution was brought to room temperature and filtered through Celite to remove insolubles. Chloroform (100 ml) and an aqueous solution (100 ml) of sodium hydrogencarbonate were added to the filtrate and the obtained mixture was caused liquid-liquid separation. The aqueous phase was further extracted with chloroform (50 ml) twice. The organic phases were combined, dried over anhydrous magnesium sulfate and subjected to vacuum concentration. The residue was purified by silica gel column chromatography (n-hexane/ethyl acetate) to give 1.7 g of 2-cyclopropyl-3-(2'-cyanobiphenyl-4-yl)methyl-6-bromo-7-methyl-3H-imidazo-[4,5-b]pyridine (yield 88%).

1. temperatureby heating
2. temperatureunder reflux
3. customwas brought to room temperature
4. filtrationfiltered through Celite
5. customto remove insolubles
6. additionChloroform (100 ml) and an aqueous solution (100 ml) of sodium hydrogencarbonate were added to the filtrate
7. customliquid-liquid separation
8. extractionThe aqueous phase was further extracted with chloroform (50 ml) twice
9. dry with materialdried over anhydrous magnesium sulfate
10. concentrationsubjected to vacuum concentration
11. customThe residue was purified by silica gel column chromatography (n-hexane/ethyl acetate)