反应详情

A suspension of 1-[4-amino-7-bromo-2-(ethoxymethyl)-1H-imidazo[4,5-c][1,5]naphthyridin-1-yl]-2-methylpropan-2-ol (1.55 g, 3.93 mmol), phenylboronic acid (0.575 g, 4.72 mmol), potassium carbonate (1.79 g, 13.0 mmol), dichlorobis(triphenylphosphine)palladium(II)(0.028 g, 0.039 mmol), DME (13 mL), and water (7 mL) was stirred under a nitrogen atmosphere and then heated at reflux for 61 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 chromatography according to the method described in Example 59. The resulting foamy solid (1.55 g) was concentrated twice from acetonitrile and then triturated with acetonitrile (25 mL) to provide a solid. The solid was isolated by filtration, washed with acetonitrile, and dried in a vacuum oven at 65° C. to provide 887 mg of 1-[4-amino-2-(ethoxymethyl)-7-phenyl-1H-imidazo[4,5-c][1,5]naphthyridin-1-yl]-2-methylpropan-2-ol as an off-white solid, mp 158-159° C.

1. temperatureheated
2. temperatureat reflux for 61 hours
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 chromatography
8. concentrationThe resulting foamy solid (1.55 g) was concentrated twice from acetonitrile
9. customtriturated with acetonitrile (25 mL)
10. customto provide a solid
11. customThe solid was isolated by filtration
12. washwashed with acetonitrile
13. customdried in a vacuum oven at 65° C.