反应详情

温度

100 °C

5-Bromo-1,2-dimethyl-1H-imidazole-4-carbonitrile (2.00 g, 10.0 mmol), palladium (II) acetate (112 mg, 0.499 mmol), triphenylphosphine (393 mg, 1.50 mmol), and water (3.5 mL) were added to a solution of 4-aminopyridin-3-ylboronic acid hydrochloride salt (3.5 g, 0.020 mol), aqueous sodium carbonate (17.5 mL of 2 M), and n-propanol (17.5 mL). The vessel was evacuated and filled with nitrogen three times. The reaction was sealed and heated under a nitrogen atmosphere at 100° C. for two hours and allowed to cool to room temperature. An analysis by high-performance liquid chromatography (HPLC) indicated the presence of starting material, and additional aqueous sodium carbonate (2.5 mL of 2M), palladium (II) acetate (56 mg), triphenylphosphine (197 mg), and 4-aminopyridin-3-ylboronic acid hydrochloride salt (872 mg) were added. The reaction was heated again at reflux for two hours, allowed to cool to room temperature, and further cooled with ice. A precipitate was present and was isolated by filtration and washed with water to provide 865 mg of 1,2-dimethyl-1H-imidazo[4,5-c][1,6]naphthyridin-4-amine. The product was purified by column chromatography on silica gel (eluting with 25% to 40% CMA in chloroform) to provide an analytically pure sample, mp 330-335° C.

1. customThe vessel was evacuated
2. additionfilled with nitrogen three times
3. customThe reaction was sealed
4. temperatureto cool to room temperature
5. additionwere added
6. temperatureThe reaction was heated again
7. temperatureat reflux for two hours
8. temperatureto cool to room temperature
9. temperaturefurther cooled with ice
10. customwas isolated by filtration
11. washwashed with water