Water → 4-((6-phenoxypyridin-2-yl)methylene)-N-(pyridazin-3-yl)piperidine-1-carboxamide

Participants

Reaction Steps

A solution of 2-(3-(piperidin-4-ylidenemethyl)phenoxy)pyridine trifluoroacetate (0.300 g), phenyl pyridazin-3-ylcarbamate (0.183 g, 1.40 equiv; Example 39, Step 2), and triethylamine (0.423 mL, 5.00 equiv) in dimethyl sulfoxide (2.0 mL, 0.30 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 (3×). The organic extracts were combined and washed with water, dried over magnesium sulfate, filtered, and concentrated. The residue was purified on a 12 g silica gel column using 20-50% ethyl acetate/dichloromethane over 60 minutes as the eluent. Combined product fractions and concentrated to give the title compound as a yellow foam. 0.071 g, 30% yield. 1H NMR (400 MHz, CDCl3) δ ppm 2.45 (2H, t, J=5.5 Hz), 2.59 (2H, t, J=5.5 Hz), 3.60 (2H, t, J=5.8 Hz), 3.70 (2H, t, J=5.8 Hz), 6.39 (1H, s), 6.90 (1H, d, J=8.2 Hz), 6.93-7.05 (4H, m), 7.34 (1H, t, J=8.0 Hz), 7.47 (1H, dd, J=9.4, 4.7 Hz), 7.63-7.72 (1H, m), 8.18 (1H, dd, J=1.9, 0.8 Hz), 8.45 (1H, d, J=9.0 Hz), 8.74 (1H, d, J=3.9 Hz).

Provenance & Evidence