Pyridine → 1-[4-(Piperidin-1-yl)pyrimidin-2-yl]ethanone

Participants

Reaction Conditions

Reaction Steps

To a stirred solution of 2-acetylpyrimidin-4(3H)-one (Intermediate 51, 500 mg, 3.62 mmol) in dichloromethane (10 mL) cooled to 0° C., pyridine (860 mg, 10.87 mmol) was added and stirred for 10 min at 0° C., followed by the addition of methane sulfonyl chloride (830 mg, 7.23 mmol) at 0° C. The above reaction mixture was stirred at room temperature for overnight. The reaction mixture was washed with water (50 mL), the aqueous layer was extracted with dichloromethane (50 mL). The combined organic layer was washed with brine solution, dried over anhydrous sodium sulphate and concentrated under reduced pressure. The crude residue was dissolved in acetonitrile; piperidine (616 mg, 7.24 mmol) was added and the reaction mixture was stirred for 2 h at room temperature. The reaction mixture was concentrated under reduced pressure; water (50 mL) was added and extracted with ethyl acetate (2×30 mL). The combined organic layer was washed with brine and dried over anhydrous sodium sulphate and concentrated under reduced pressure to yield the crude product, which was purified by column chromatography over silica gel (10-50% ethyl acetate/pet ether) to obtain 1-[4-(piperidin-1-yl)pyrimidin-2-yl]ethanone 200 mg (46.8%).

Provenance & Evidence