Sodium Iodide → 3-ethyl-5-imidazol-1-yl-6-methyl-1H-pyridin-2-one

Participants

Reaction Conditions

Reaction Steps

To a mixture of 3-ethyl-5-imidazol-1-yl-2-methoxy-6-methyl-pyridine (76 mg, 0.350 mmol) and sodium iodide (158 mg, 1.05 mmol) under a N2 atmosphere is added anhydrous acetonitrile (4 mL) followed by drop-wise addition of chlorotrimethylsilane (132 μL, 1.05 mmol). The reaction mixture is stirred at 65° C. under nitrogen for 17 h. LC/MS shows the reaction is incomplete. Further sodium iodide (158 mg) and chlorotrimethylsilane (132 μL) are added and the heating is continued for 2 h. Further sodium iodide (158 mg) and chlorotrimethylsilane (132 μL) are added and heating is continued for 45 min. LC/MS indicates the reaction is complete. The reaction mixture is allowed to cool, diluted with water, treated with solid sodium bicarbonate and the resulting mixture is extracted with 10 portions of dichloromethane. The combined extracts are dried over magnesium sulfate and evaporated to leave an orange residue. The crude product is triturated with ether/acetonitrile, then the solid is suspended in dichloromethane:ethyl acetate (1:1) and filtered. The filtrate is evaporated and the residue is triturated with ether to give 3-ethyl-5-imidazol-1-yl-6-methyl-1H-pyridin-2-one (52 mg, 73% yield) as a light orange powder. This material (38 mg) is suspended in dichloromethane (2 mL) and treated with ethereal hydrochloric acid (2.0M, 0.38 mL). The heterogeneous mixture is stirred for 1.5 h, evaporated and the residue is triturated with ether to give 3-ethyl-5-(imidazol-1-yl)-6-methyl-1H-pyridin-2-one hydrochloride (29 mg) as an orange solid. LC/MS: RT: 0.45 min, MS: m/e=204 (M+H); 1H NMR (δ ppm): 12.09 (1H, s), 9.36 (1H, d), 7.91 (1H, t), 7.88 (1H, d), 7.40 (1H, s), 2.40 (2H, q), 2.06 (3H, s), 1.10 (3H, t).

Provenance & Evidence