反应详情

N,N,N′,N′-Tetramethylazodicarboxamide(TMAD) (189 mg, 1.1 mmol) and tri-n-butyl phosphine (0.28 ml, 1.1 mmol) were added to a THF solution (5 ml) of 7-hydroxy-1-isobutyl-3,3,5-trimethyl-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione (213 mg, 0.73 mmol) and 3-[(2-pyridin-3-ylethyl)pyridin-4-ylmethylamino]propan-1-ol (199 mg, 0.73 mmol), and stirred at room temperature overnight. Water was added to the reaction mixture, and extraction with dichloromethane was performed. The organic layer was dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate:methanol=20:1→10:1). The purified product was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography (dichloromethane:methanol=40:1→10:1) again. The purified product was concentrated under reduced pressure. A 4N-hydrogen chloride ethyl acetate solution (0.57 ml) was added to the residue (ethyl acetate solution), stirred at room temperature for 30 minutes, and concentrated to dryness under reduced pressure to thereby obtain 480 mg (yield: quantitative) of 1-isobutyl-3,3,5-trimethyl-7-{3-[(2-pyridin-3-ylethyl)pyridin-4-ylmethylamino]propoxy}-1,5-dihydrobenzo[b][1,4]diazepine-2,4-dione trihydrochloride as a white amorphous solid.

1. dry with materialThe organic layer was dried over anhydrous sodium sulfate
2. concentrationconcentrated under reduced pressure
3. customThe residue was purified by silica gel column chromatography (ethyl acetate:methanol=20:1→10:1)
4. concentrationThe purified product was concentrated under reduced pressure
5. customthe residue was purified by silica gel column chromatography (dichloromethane:methanol=40:1→10:1) again
6. concentrationThe purified product was concentrated under reduced pressure
7. additionA 4N-hydrogen chloride ethyl acetate solution (0.57 ml) was added to the residue (ethyl acetate solution)
8. stirringstirred at room temperature for 30 minutes
9. concentrationconcentrated to dryness under reduced pressure