Ammonium Hydroxide → 6-Chloroimidazo[1,5-A]pyridine

Participants

Reaction Conditions

Reaction Steps

To a mixture of N-((5-chloropyridin-2-yl)methyl)formamide (740 mg, 4.34 mmol) in toluene (18.4 mL) was added phosphorus oxychloride (1.21 g, 736 μL, 7.89 mmol) and the mixture heated at to 100° C. After 16 h ice was added to the reaction mixture followed by the slow addition of 25% aqueous ammonium hydroxide until pH˜9 was reached. The mixture was diluted with dichloromethane and extracted into dichloromethane (2×). The organic layers were washed with water and brine, dried (MgSO4) and filtered. Purification of the filtrate by chromatography (silica, MeOH/DCM gradient) gave 6-chloroimidazo[1,5-a]pyridine (417 mg, 2.73 mmol, 63.0%) as a brown oil. MS (M+H)+=152.8; 1H NMR (CDCl3) δ: 8.10 (s, 1H), 8.01 (m, 1H), 7.47 (s, 1H), 7.43 (d, J=9.5 Hz, 1H), 6.69 (dd, J=9.5 Hz, 1.5 Hz, 1H).

Provenance & Evidence