Hydrochloric Acid → 1-(piperidin-4-yl)-1H,2H,3H-imidazo[4,5-b]pyridin-2-one dihydrochloride

Participants

Reaction Steps

A 50 mL 3-necked round bottom flask fitted with a thermometer, was charged with 30 mL of methanol (HPLC grade), and tert-butyl 4-(2-oxo-2,3-dihydro-1H-imidazo[4,5-b]pyridin-1-yl)piperidine-1-carboxylate (1.71 g, 5.37 mmol) was then added over a period of 5 minutes. The resulting brown suspension was stirred at room temperature for 30 minutes. Hydrogen chloride gas (Reagent Plus, steel cylinder, Aldrich) was carefully bubbled into the reaction mixture, resulting in a dark brown solution (Note: the temperatures of the reaction mixture rises to 38° C.). The flow of gas was stopped when the reaction mixture was saturated with hydrogen chloride. After 20 minutes a solid precipitated out of solution, and the resulting slurry was cooled to room temperature. The progress of the reaction was monitored by LCMS. The reaction was complete in 6 hours. The reaction mixture was diluted with isopropyl acetate (25 mL) and stirred for an additional 30 minutes; the solids were then collected by vacuum filtration. The resulting brown solid was washed with isopropyl acetate (5 mL), and dried to constant weight to give 1.32 g (84% yield) of 1-piperidin-4-yl-1,3-dihydro-2H-imidazo[4,5-b]pyridin-2-one dihydrochloride. This material was submitted to the next step without further purification. 1H NMR (400 MHz, DMSO-d6): δ 11.77 (broad s, 1H), 8.32 (broad s, 3H), 7.95 (d, 1H), 7.93 (s, 1H), 7.06 (dd, 1H), 4.60 (m, 1H), 3.39 (d, 2H), 3.07 (q, 2H), 3.65 (dq, 2H), 1.86 (d, 2H). MS (EI) for C11H14N4; 219 (MH+)

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