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 (1.2 g, 3.0 mmol), 3-(hydroxymethyl)benzeneboronic acid (0.555 g, 3.65 mmol), potassium carbonate (1.4 g, 10.0 mmol), dichlorobis(triphenylphosphine)palladium(II)(0.021 g, 0.030 mmol), DME (13 mL), and water (7 mL) was stirred under a nitrogen atmosphere in a pressure vessel. The vessel was then sealed and heated at 110° C. for 16.5 hours and allowed to cool to room temperature. The volatiles were removed under reduced pressure. The residue was diluted with methanol, and silica gel was added. The mixture was concentrated under reduced pressure. The residue was purified by automated flash chromatography (FLASH 40+M silica cartridge, eluting with 5% to 20% methanol in ethyl acetate) followed by trituration with acetonitrile. The resulting solid was isolated by filtration, washed with acetonitrile, and dried in a vacuum oven at 65° C. to provide 449 mg of 1-{4-amino-2-(ethoxymethyl)-7-[3-(hydroxymethyl)phenyl]-1H-imidazo[4,5-c][1,5]naphthyridin-1-yl]-2-methylpropan-2-ol as a white solid, mp 186-187° C.

1. customThe vessel was then sealed
2. temperatureto cool to room temperature
3. customThe volatiles were removed under reduced pressure
4. additionThe residue was diluted with methanol, and silica gel
5. additionwas added
6. concentrationThe mixture was concentrated under reduced pressure
7. customThe residue was purified by automated flash chromatography (FLASH 40+M silica cartridge, eluting with 5% to 20% methanol in ethyl acetate)
8. customThe resulting solid was isolated by filtration
9. washwashed with acetonitrile
10. customdried in a vacuum oven at 65° C.