Dimethyl Sulfoxide → N-(pyridazin-4-yl)-4-(3-{[5-(trifluoromethyl)pyridin-2-yl]oxy}benzylidene)piperidine-1-carboxamide

Participants

Reaction Conditions

Reaction Steps

A solution of 2-(3-piperidin-4-ylidene-methyl-phenoxy)-5-trifluoromethyl-pyridine hydrochloride (0.371 g, 1.00 mmol) (from Example 1, Step 5) and phenyl pyridazin-4-ylcarbamate (0.215 g, 1.00 mmol, from Step 1) in DMSO (2.5 mL) was treated with diisopropylethylamine (0.155 g, 1.2 mmol) and heated to 60° C. After 3 h, the reaction mixture was partitioned between water and ethyl acetate. The organic layer was separated and the aqueous layer was extracted again with ethyl acetate. The combined organic layers were washed with brine and dried over sodium sulfate, filtered and concentrated. The residue was crystallized in a 1:1 mix of hexanes and ethyl ether to afford the title compound (335 mg, 73%) as white crystals. MS (APCI 10V) AP+ 456.16; 1H NMR (400 MHz, DMSO-d6) δ ppm 2.36 (t, J=5.46 Hz, 2H) 2.44 (t, J=5.46 Hz, 2H+DMSO) 3.49 (t, J=5.46 Hz, 2H) 3.56 (t, J=5.46 Hz, 2H) 6.39 (s, 1H) 7.03-7.04 (m, 2H) 7.12 (d, J=7.81 Hz, 1H) 7.21 (d, J=8.79 Hz, 1H) 7.39 (t, J=8.77 Hz, 1H) 7.74 (dd, J=5.86 Hz, 2.73 Hz, 1H) 8.20 (dd, J=8.60 Hz, 2.15 Hz, 1H) 8.54 (s, 1H) 8.58 (s, 1H) 8.85 (d, J=5.86 Hz, 1H) 9.20 (s, 1H) 9.25 (d, J=2.93 Hz, 1H).

Provenance & Evidence