Sodium Iodide → 5-(2,5-dimethyl-2H-1,2,4-triazol-3-yl)-3-ethyl-6-methyl-1H-pyridin-2-one

Participants

Reaction Conditions

Reaction Steps

To a mixture of 3-(2,5-dimethyl-2H-1,2,4-triazol-3-yl)-5-ethyl-6-methoxy-2-methylpyridine (76 mg, 0.309 mmol) and sodium iodide (139 mg, 0.927 mmol) under a nitrogen atmosphere is added anhydrous acetonitrile (5 mL) followed by drop-wise addition of chlorotrimethylsilane (116 μL, 0.924 mmol). The reaction mixture is stirred at 60° C. under nitrogen for 12 hr. LC/MS shows the reaction is incomplete. A further amount of chlorotrimethylsilane (100 μL) is added and the reaction is reheat at 60° C. for 9 hr. The reaction mixture is allowed to cool and then quenched with water (0.7 mL). After stirring for 30 min the mixture is partitioned between water and dichloromethane and the mixture treated with little sodium bisulfite to decolorize. The dichloromethane layer is separated and the aqueous layer is extracted with six further portions of dichloromethane. The combined dichloromethane layer is dried over magnesium sulfate and evaporated. The crude product is purified by flash chromatography on a 5-gram silica gel cartridge by elution with dichloromethane:methanol (1:0, increasing to 19:1). Fractions containing the product are combined, the solvent evaporated and triturated with ether to give 5-(2,5-dimethyl-2H-1,2,4-triazol-3-yl)-3-ethyl-6-methyl-1H-pyridin-2-one (47 mg, 66% yield) as a cream solid. LC/MS: RT: 1.88 min, MS: m/e=233 (M+H); 1H NMR (400 MHz, d6-DMSO, δ, ppm): 11.85 (1H, s), 7.20 (1H, s), 3.61 (3H, s), 2.36 (2H, q), 2.20 (3H, s), 2.07 (3H, s), 1.07 (3H, t).

Provenance & Evidence