Phenyl isocyanate → N-phenyl-4-(3-{[5-(trifluoromethyl)pyridin-2-yl]oxy}benzylidene)piperidine-1-carboxamide

Participants

Reaction Steps

A solution of 2-(3-piperidin-4-ylidenemethyl-phenoxy)-5-trifluoromethyl-pyridine hydrochloride (0.371 g, 1.00 mmol) (from Example 1, Step 5) and phenylisocyanate (0.143 g, 1.2 mmol) in dichloromethane (20 mL) was treated with diisopropylethylamine (0.155 g, 1.2 mmol) and stirred at RT for 18 h. The reaction mixture was stirred with 10% K2CO3 for 1 h and then partitioned after diluting with additional dichloromethane (200 mL). The combined organic layer was washed with brine and dried over sodium sulfate, filtered and concentrated. The residue was purified by silica gel chromatography (1% of the 1N NH3 in MeOH, in dichloromethane) to afford the title compound (100 mg, 22%) as a white solid after trituration with diethyl ether. MS (APCI 10V) AP+ 454.28; 1H NMR (400 MHz, DMSO-d6) δ ppm 2.34 (t, J=5.46 Hz, 2H) 2.46 (t, J=5.46 Hz, 2H) 3.29 (s, 3H) 3.46 (t, J=5.46 Hz, 2H) 3.54 (t, J=5.46 Hz, 2H) 6.37 (s, 1H) 6.89 (t, J=8.60 Hz, 1H) 7.03 (m, 2H) 7.12 (d, J=7.60 Hz, 1H) 7.19-7.22 (m, 3H) 7.38 (d, J=7.8 Hz, 1H) 7.41 (d, J=8.77 Hz, 2H) 8.20 (dd, J=8.8 Hz, 2.8 Hz, 1H) 8.50 (s, 1H) 8.55 (s, 1H).

Provenance & Evidence