Diisopropylethylamine → N-(5-methylpyridin-3-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-ylidenemethyl-phenoxy)-5-trifluoromethyl-pyridine hydrochloride (0.371 g, 1.00 mmol) (from Example 1, Step 5) and phenyl 5-methylpyridin-3-ylcarbamate (0.274 g, 1.2 mmol, prepared according to the procedure described in Synthesis, 1997, 1189-1194 from 3-amino-5-methylpyridine) in DMSO (2.5 mL) was treated with diisopropylethylamine (0.155 g, 1.2 mmol) and the mixture was heated to 60° C. After 4 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 organic layers were combined and were washed with brine and dried over sodium sulfate, filtered and concentrated to form a residue. The residue was purified by silica gel chromatography (10% of the 1N NH3 in MeOH, in dichloromethane) to afford the title compound as a white foam (300 mg, 64%). MS (APCI 10V) AP+ 458.16; 1H NMR (400 MHz, DMSO) 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) 6.38 (s, 1H) 7.03 (m, 2H) 7.13 (d, J=7.80 Hz, 1H) 7.21 (d, J=8.58 Hz, 1H) 7.4 (dd, J=7.8 Hz, 2 Hz, 1H) 7.70 (s, 1H) 7.96 (d, J=2 Hz, 1H) 8.20 (dd, J=8.8 Hz, 2.5 Hz, 1H) 8.41 (d, J=2.2 Hz, 1H) 8.55 (s, 1H) 8.64 (s, 1H).

Provenance & Evidence