反应详情

A mixture of 3-[(3-amino-7-bromoquinolin-4-yl)amino]propan-1-ol (7.2 g, 24 mmol), pyridine hydrochloride (1.05 g, 9.09 mmol) and trimethyl orthobutyrate (4.05 mL, 25.5 mmol) in toluene (240 mL) was heated at reflux for two hours under an atmosphere of nitrogen. The solvent was removed under reduced pressure, and the residue was dissolved in methanol (100 mL). Aqueous sodium hydroxide (15 mL of 6 M) was added to the solution, and the resulting mixture was stirred for two hours at ambient temperature. A portion of the solvent was removed under reduced pressure, and the resulting mixture was adjusted to pH 7 with the addition of 6 N hydrochloric acid. The mixture was then extracted with chloroform (4×150 mL), and the combined extracts were washed sequentially with saturated aqueous sodium bicarbonate (40 mL) and brine (30 mL), dried over magnesium sulfate, filtered, and concentrated under reduced pressure. An analysis by nuclear magnetic resonance spectroscopy indicated the presence of starting material, and the procedure was repeated using 1 mL trimethyl orthobutyrate and heating at reflux for one hour. Following the work-up procedure, the resulting solid was triturated with ethyl acetate and isolated by filtration to provide 7.30 g of 3-(7-bromo-2-propyl-1H-imidazo[4,5-c]quinolin-1-yl)propan-1-ol.

1. temperaturewas heated
2. temperatureat reflux for two hours under an atmosphere of nitrogen
3. customThe solvent was removed under reduced pressure
4. dissolutionthe residue was dissolved in methanol (100 mL)
5. additionAqueous sodium hydroxide (15 mL of 6 M) was added to the solution
6. customA portion of the solvent was removed under reduced pressure
7. additionthe resulting mixture was adjusted to pH 7 with the addition of 6 N hydrochloric acid
8. extractionThe mixture was then extracted with chloroform (4×150 mL)
9. washthe combined extracts were washed sequentially with saturated aqueous sodium bicarbonate (40 mL) and brine (30 mL)
10. dry with materialdried over magnesium sulfate
11. filtrationfiltered
12. concentrationconcentrated under reduced pressure
13. temperatureheating
14. temperatureat reflux for one hour
15. customthe resulting solid was triturated with ethyl acetate
16. customisolated by filtration