反应详情

A solution of 1-{4-amino-7-[5-(tert-butyldimethylsilanyloxymethyl)pyridin-3-yl]-2-(ethoxymethyl)-1H-imidazo[4,5-c][1,5]naphthyridin-1-yl]-2-methylpropan-2-ol (1.37 g, 2.55 mmol) in acetic acid (10 mL), tetrahydrofuran (10 mL), and water (10 mL) was stirred at 60° C. for 18.5 hours and allowed to cool to room temperature. The solvent was removed under reduced pressure, and the residue was diluted with saturated aqueous sodium bicarbonate (30 mL). Dichloromethane was added, but an oil was present that remained insoluble in both phases. Both phases were decanted away from the oil, which was dissolved in methanol. The aqueous phase was then separated and extracted with dichloromethane (30 mL) and ethyl acetate (2×30 mL). Silica gel was added to the combined dichloromethane, ethyl acetate, and methanol fractions, and the solvent was removed under reduced pressure. The residue was purified by automated flash chromatography (FLASH 40+M silica cartridge, eluting with 5% to 20% methanol in dichloromethane). The resulting material was concentrated from acetonitrile to form a solid, which was triturated with acetonitrile (30 mL), isolated by filtration, washed with acetonitrile, and dried overnight in a vacuum oven to provide 530 mg of 1-{4-amino-2-(ethoxymethyl)-7-[5-(hydroxymethyl)pyridin-3-yl]-1H-imidazo[4,5-c][1,5]naphthyridin-1-yl}-2-methylpropan-2-ol as a light yellow solid, mp 212-214° C.

1. customThe solvent was removed under reduced pressure
2. additionthe residue was diluted with saturated aqueous sodium bicarbonate (30 mL)
3. additionDichloromethane was added
4. customBoth phases were decanted away from the oil, which
5. dissolutionwas dissolved in methanol
6. customThe aqueous phase was then separated
7. extractionextracted with dichloromethane (30 mL) and ethyl acetate (2×30 mL)
8. additionSilica gel was added to the combined dichloromethane, ethyl acetate, and methanol fractions
9. customthe solvent was removed under reduced pressure
10. customThe residue was purified by automated flash chromatography (FLASH 40+M silica cartridge, eluting with 5% to 20% methanol in dichloromethane)
11. concentrationThe resulting material was concentrated from acetonitrile
12. customto form a solid, which
13. customwas triturated with acetonitrile (30 mL)
14. customisolated by filtration
15. washwashed with acetonitrile
16. customdried overnight in a vacuum oven