反应详情

A solution of 1-{[(3-amino[1,5]naphthyridin-4-yl)amino]methyl}cyclohexanol (prepared as described in Part B, 15.1 mmol), trimethyl orthobutyrate (2.63 mL, 16.6 mmol), and pyridine hydrochloride (0.650 g, 5.64 mmol) in toluene (100 mL) was heated at reflux overnight. The solution was allowed to cool to rt, then was concentrated under reduced pressure. The residue was partitioned between chloroform (200 mL) and saturated aqueous sodium bicarbonate (75 mL). The aqueous layer was extracted with chloroform (2×50 mL). The combined organic layers were washed with brine (50 mL), dried over MgSO4, filtered, and concentrated under reduced pressure. The resulting solid was triturated with ethyl acetate and isolated by filtration. The filtrate was concentrated and the solid was again triturated with ethyl acetate; this procedure was repeated two more times. The white solids were combined and dried under vacuum to yield 1-[(2-propyl-1H-imidazo[4,5-c][1,5]naphthyridin-1-yl)methyl]cyclohexanol (3.40 g, 70% over two steps).

1. temperatureat reflux overnight
2. concentrationwas concentrated under reduced pressure
3. customThe residue was partitioned between chloroform (200 mL) and saturated aqueous sodium bicarbonate (75 mL)
4. extractionThe aqueous layer was extracted with chloroform (2×50 mL)
5. washThe combined organic layers were washed with brine (50 mL)
6. dry with materialdried over MgSO4
7. filtrationfiltered
8. concentrationconcentrated under reduced pressure
9. customThe resulting solid was triturated with ethyl acetate
10. customisolated by filtration
11. concentrationThe filtrate was concentrated
12. customthe solid was again triturated with ethyl acetate
13. customdried under vacuum