反应详情

温度

50 °C

7-(Benzyloxy)-2-(chloromethyl)-1-(tetrahydro-2H-pyran-4-ylmethyl)-1H-imidazo[4,5-c]quinolin-4-amine (2.3 g, 5.26 mmol) and triethylamine (1.6 g, 15.78 mmol) were added to a solution of methoxylamine hydrochloride (0.88 g, 10.52 mmol) in N,N-dimethylformamide (DMF) (11 mL). The reaction was heated with stirring for 40 hours at 50° C., allowed to cool to ambient temperature, and partitioned between dichloromethane (50 mL) and water (50 mL). The aqueous layer was extracted with another portion of dichloromethane (50 mL). The combined organic layers were dried over sodium sulfate, filtered and concentrated under reduced pressure. The crude material was purified by column chromatography using a HORIZON HPFC system equipped with a FLASH 40+M silica cartridge eluting with dichloromethane:methanol in a gradient from 100:0 to 90:10. The resulting product (1.0 g) was recrystallized from acetonitrile, and the crystals were isolated by filtration, washed with acetonitrile, and dried overnight in a vacuum oven at 65° C. to provide 0.85 g of 7-(benzyloxy)-2-[(methoxyamino)methyl]-1-(tetrahydro-2H-pyran-4-ylmethyl)-1H-imidazo[4,5-c]quinolin-4-amine as a yellow, crystalline solid, mp 190-193° C.

1. temperatureThe reaction was heated
2. temperatureto cool to ambient temperature
3. custompartitioned between dichloromethane (50 mL) and water (50 mL)
4. extractionThe aqueous layer was extracted with another portion of dichloromethane (50 mL)
5. dry with materialThe combined organic layers were dried over sodium sulfate
6. filtrationfiltered
7. concentrationconcentrated under reduced pressure
8. customThe crude material was purified by column chromatography
9. customequipped with a FLASH 40+M silica cartridge
10. washeluting with dichloromethane
11. customThe resulting product (1.0 g) was recrystallized from acetonitrile
12. customthe crystals were isolated by filtration
13. washwashed with acetonitrile
14. customdried overnight in a vacuum oven at 65° C.