Sodium Carbonate → HCID 59130441, compound

Participants

Reaction Conditions

Reaction Steps

Under a nitrogen atmosphere, N-[3-(4-amino-7-bromo-2-propyl-1H-imidazo[4,5-c]quinolin-1-yl)propoxy]-2-methylpropanamide (300 mg, 0.67 mmol), phenylboronic acid (123 mg, 1.01 mmol), a solution of palladium (II) acetate (1.5 mg, 0.0067 mmol) in hot toluene (0.2 mL), triphenylphosphine (5.3 mg, 0.02 mmol), and 2 M aqueous sodium carbonate (0.4 mL, 0.8 mmol) were combined in 5:1 n-propanol:water (1.44 mL). The solution was placed under vacuum and back-filled with nitrogen gas three times and then heated at 100° C. for 16 hours. Additional phenylboronic acid (123 mg, 1.01 mmol), palladium (II) acetate (1.5 mg, 0.0067 mmol), and triphenylphosphine (5.3 mg, 0.02 mmol) were added, and the reaction was heated at 100° C. overnight. Again, additional phenylboronic acid (123 mg, 1.01 mmol), palladium (II) acetate (1.5 mg, 0.0067 mmol), and triphenylphosphine (5.3 mg, 0.02 mmol) were added, plus 2 M aqueous sodium carbonate (0.4 mL, 0.8 mmol), and the reaction was heated at 100° C. overnight. After cooling to room temperature, the reaction mixture was diluted with chloroform (60 mL) and washed with water (2×10 mL) and brine (10 mL). The organic layer was dried over sodium sulfate, filtered, and concentrated under reduced pressure. The crude product was purified by chromatography on a HORIZON HPFC system (silica gel, gradient elution with 0-35% CMA in chloroform) followed by recrystallization from acetonitrile. The final product was isolated and dried under vacuum at 100° C. to yield N-[3-(4-amino-7-phenyl-2-propyl-1H-imidazo[4,5-c]quinolin-1-yl)propoxy]-2-methylpropanamide as a white powder, mp 169.0-171.0° C.

Provenance & Evidence