反应详情

温度

110 °C

A suspension of 1-[4-amino-7-bromo-2-(ethoxymethyl)-1H-imidazo[4,5-c][1,5]naphthyridin-1-yl]-2-methylpropan-2-ol (1.4 g, 3.55 mmol), 6-fluoropyridine-3-boronic acid (0.597 g, 4.26 mmol), potassium carbonate (1.62 g, 11.7 mmol), dichlorobis(triphenylphosphine)palladium(II)(0.025 g, 0.036 mmol), DME (13 mL), and water (7 mL) was stirred under a nitrogen atmosphere and then heated at 110° C. for 17.5 hours and allowed to cool to room temperature. The volatiles were removed under reduced pressure, and the residue was partitioned between water (25 mL) and dichloromethane (25 mL). A solid was present in the organic layer, and methanol was added to dissolve the solid. The aqueous layer was extracted with dichloromethane (3×20 mL). Silica gel was added to the combined organic fractions, and the mixture was concentrated under reduced pressure. The residue was purified by automated flash chromatography (40+M silica cartridge, eluting with 5% to 15% methanol in ethyl acetate) followed by recrystallization from acetonitrile. The crystals were isolated by filtration, washed with acetonitrile, and dried in a vacuum oven to provide 530 mg of 1-[4-amino-2-(ethoxymethyl)-7-(6-fluoropyridin-3-yl)-1H-imidazo[4,5-c][1,5]naphthyridin-1-yl]-2-methylpropan-2-ol as white crystals, mp 218-220° C.

1. temperatureto cool to room temperature
2. customThe volatiles were removed under reduced pressure
3. customthe residue was partitioned between water (25 mL) and dichloromethane (25 mL)
4. additionwas added
5. dissolutionto dissolve the solid
6. extractionThe aqueous layer was extracted with dichloromethane (3×20 mL)
7. additionSilica gel was added to the combined organic fractions
8. concentrationthe mixture was concentrated under reduced pressure
9. customThe residue was purified by automated flash chromatography (40+M silica cartridge, eluting with 5% to 15% methanol in ethyl acetate)
10. customfollowed by recrystallization from acetonitrile
11. customThe crystals were isolated by filtration
12. washwashed with acetonitrile
13. customdried in a vacuum oven