Sodium Carbonate → 1,2-dimethyl-1H-imidazo[4,5-c][1,6]naphthyridin-4-amine

Participants

Reaction Conditions

Reaction Steps

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.

Provenance & Evidence