反应详情

Triethyl orthoformate (0.80 mL, 4.80 mmol) and pyridine hydrochloride (0.092 g, 0.80 mmol) were sequentially added to a solution of N4-[(5-butylisoxazol-3-yl)methyl]quinoline-3,4-diamine (1.19 g, 4.00 mmol) in acetonitrile (100 mL), and the solution was heated gently at reflux overnight. An analysis by HPLC indicated the presence of starting material, and additional triethyl orthoformate and pyridine hydrochloride were added. The solution was heated at reflux for an additional 24 hours. The solvents were removed under reduced pressure, and the residue was partitioned between dichloromethane and saturated aqueous sodium bicarbonate. The aqueous layer was separated and extracted with dichloromethane, and the combined organic fractions were washed with brine, dried over magnesium sulfate, filtered, and concentrated under reduced pressure. The crude product was purified by flash column chromatography on silica gel (eluting with 3% to 8% methanol in dichloromethane) to provide 1.06 g of 1-[(5-butylisoxazol-3-yl)methyl]-1H-imidazo[4,5-c]quinoline as an orange solid.

1. temperaturethe solution was heated gently
2. temperatureat reflux overnight
3. additionwere added
4. temperatureThe solution was heated
5. temperatureat reflux for an additional 24 hours
6. customThe solvents were removed under reduced pressure
7. customthe residue was partitioned between dichloromethane and saturated aqueous sodium bicarbonate
8. customThe aqueous layer was separated
9. extractionextracted with dichloromethane
10. washthe combined organic fractions were washed with brine
11. dry with materialdried over magnesium sulfate
12. filtrationfiltered
13. concentrationconcentrated under reduced pressure
14. customThe crude product was purified by flash column chromatography on silica gel (eluting with 3% to 8% methanol in dichloromethane)