Methyl iodide → 4-Ethyl-5-({[4-methoxy-6-(trifluoromethyl)pyrimidin-2-yl]sulfanyl}methyl)-1,3-thiazole

Participants

Reaction Conditions

Reaction Steps

To a solution of 2-{[(4-ethyl-1,3-thiazol-5-yl)methyl]sulfanyl}-6-(trifluoromethyl)pyrimidin-4-ol (500 mg, 1.56 mmol) in anhydrous methanol (10 mL) was added dropwise a solution of 30% sodium methoxide in methanol (310 μL, 1.71 mmol) at 0° C. The mixture was heated to 65° C. for 1 hour. Iodomethane (220 μL, 3.43 mmol) was added at room temperature, and the reaction was heated overnight at 65° C. The solvent was evaporated, and the residue was extracted three times with dichloromethane/water. The combined organic phases were washed with brine, dried over magnesium sulfate, and evaporated to afford a crude oil. The residue was dissolved in DCM and purified on silica gel using DCM/MeOH (0 to 10%) to afford 4-ethyl-5-({[4-methoxy-6-(trifluoromethyl)pyrimidin-2-yl]sulfanyl}methyl)-1,3-thiazole (315 mg, 60% yield). 1H NMR (500 MHz, MeOH-d4): δ 1.21 (t, J=7.5 Hz, 3H), 2.79 (q, J=7.5 Hz, 2H), 3.40 (s, 3H), 4.74 (s, 2H), 6.76 (s, 1H), 8.89 (s, 1H). LRMS (ES+) m/z 336 (100%, M+1).

Provenance & Evidence