反应详情

A solution of sodium carbonate (572 mg, 5.4 mmol) in deionized water (6 mL) was added to a solution of 5-iodo-1-(2-methylpropyl)-2-propyl-1H-imidazole-4-carbonitrile (634 mg, 2.0 mmol) and 4-aminopyridin-3-ylboronic acid hydrochloride salt (383 mg, 2.2 mmol) in n-propanol (15 mL), and nitrogen was bubbled through the resultant solution for 15 minutes. Palladium (II) acetate (22 mg, 0.1 mmol) and triphenylphosphine (79 mg, 0.3 mmol) were added. The reaction was evacuated and purged with nitrogen several times and then heated at reflux for 18 hours. The reaction mixture was partitioned between saturated aqueous sodium bicarbonate and ethyl acetate. The aqueous layer was separated and extracted several times with ethyl acetate. The combined organic fractions were washed with brine, dried over magnesium sulfate, filtered, and concentrated under reduced pressure. The crude product was purified by column chromatography on silica gel (eluting with 7% methanol in dichloromethane) to provide 210 mg of 1-(2-methylpropyl)-2-propyl-1H-imidazo[4,5-c][1,6]naphthyridin-4-amine as a tan solid.

1. customwas bubbled through the resultant solution for 15 minutes
2. customThe reaction was evacuated
3. custompurged with nitrogen several times
4. temperatureheated
5. temperatureat reflux for 18 hours
6. customThe reaction mixture was partitioned between saturated aqueous sodium bicarbonate and ethyl acetate
7. customThe aqueous layer was separated
8. extractionextracted several times with ethyl acetate
9. washThe combined organic fractions were washed with brine
10. dry with materialdried over magnesium sulfate
11. filtrationfiltered
12. concentrationconcentrated under reduced pressure
13. customThe crude product was purified by column chromatography on silica gel (eluting with 7% methanol in dichloromethane)