Water → HCID 67403343, compound

Participants

Reaction Steps

2-Amino-5-fluoropyridine (2.5 g) and 2-bromo-4′-cyanoacetophenone (5.0 g) were dissolved in ethanol (100 mL), and sodium hydrogencarbonate (1.9 g) was added to the solution, followed by refluxing for 16 hours. Water (10 mL) was added to the reaction mixture. After the reaction mixture had been left to cool, the precipitated matter was recovered through filtration and dried, to thereby yield 4-(6-fluoroimidazo[1,2-a]pyridin-2-yl)benzonitrile (2.1 g). Subsequently, the thus-obtained 4-(6-fluoroimidazo[1,2-a]pyridin-2-yl)benzonitrile was dissolved in anhydrous tetrahydrofuran solution (30 mL), and diisobutylaluminum hydride (9.0 mL, 0.93M hexane solution) was added dropwise to the solution at −78° C., followed by stirring under a stream of argon at room temperature for 2 hours. Saturated aqueous ammonium chloride solution (10 mL) was added dropwise to the reaction mixture, and the mixture was stirred at room temperature for 1 hour. Anhydrous magnesium sulfate and diethyl ether were added to the resultant mixture, followed by further stirring for 1 hour. The solvent was evaporated, and the residue was purified, to thereby yield 4-(6-fluoroimidazo[1,2-a]pyridin-2-yl)benzaldehyde (0.6 g). Subsequently, this product was dissolved in anhydrous tetrahydrofuran solution (30 mL), and methyl magnesium bromide (0.78 mL, 3M hexane solution) was added dropwise to the mixture under a stream of argon at −78° C., followed by stirring under ice cooling for 15 minutes and then at room temperature for 3 hours. Saturated aqueous ammonium chloride solution (10 mL) was added dropwise to the reaction mixture, followed by stirring at room temperature for 1 hour. The mixture was extracted with dichloromethane-methanol, and purified through silica gel chromatography (dichloromethane:methanol=95:5), to thereby yield 1-[4-(6-fluoroimidazo[1,2-a]pyridin-2-yl)phenyl]-1-ethanol (530 mg). The thus-obtained 1-[4-(6-fluoroimidazo[1,2-a]pyridin-2-yl)phenyl]-1-ethanol (530 mg) was dissolved in chloroform solution (50 mL), and manganese dioxide (721 mg) was added to the solution, followed by refluxing for 4 hours. After the reaction mixture had been filtered through Celite, the filtrate was concentrated, and the residue was purified through silica gel chromatography (dichloromethane:methanol=98:2), to thereby yield the title compound (410 mg).

Provenance & Evidence