Water → N-(5-ethyl-1,3,4-thiadiazol-2-yl)-4-(3-{[5-(trifluoromethyl)pyridin-2-yl]oxy}benzylidene)piperidine-1-carboxamide

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Reaction Steps

A solution of 2-(3-(piperidin-4-ylidenemethyl)phenoxy)-5-(trifluoromethyl)pyridine hydrochloride (0.100 g; Example 1a, Step 5), phenyl 5-ethyl-1,3,4-thiadiazol-2-ylcarbamate (0.081 g, 1.2 equiv), and triethylamine (0.045 mL, 1.2 equiv) in dimethyl sulfoxide (1 mL, 0.3 M) was heated to 65° C. for 2 h. The reaction was cooled to room temperature. Water was added and then the solution was extracted with ethyl acetate (2×). The organic extracts were dried over magnesium sulfate, filtered, and concentrated. The residue was purified on a 12 g silica gel column using 10-30% ethyl acetate/dichloromethane over 30 minutes as the eluent to give the title compound as a white foam. 0.056 g, 42% yield. 1H NMR (400 MHz, CDCl3) δ ppm 1.36 (3H, t, J=7.6 Hz), 2.46 (2H, t, J=5.7 Hz), 2.61 (2H, t, J=5.7 Hz), 2.95 (2H, q, J=7.8 Hz), 3.67 (2H, t, J=5.8 Hz), 3.77 (2H, t, J=5.8 Hz), 6.40 (1H, s), 6.96-7.05 (3H, m), 7.08 (1H, d, J=7.8 Hz), 7.37 (1H, t, J=8.0 Hz), 7.89 (1H, dd, J=8.8, 2.5 Hz), 8.43 (1H, s).

Provenance & Evidence