Diisopropylethylamine → 4-(3-(5-bromopyridin-2-yloxy)benzylidene)-N-(3,4-dimethylisoxazol-5-yl)piperidine-1-carboxamide

Participants

Reaction Steps

5-Bromo-2-(3-(piperidin-4-ylidenemethyl)phenoxy)pyridine trifluoroacetate (0.584 mmol, from Step 5), in acetonitrile (1.75 mL) was treated with phenyl 3,4-dimethylisoxazol-5-ylcarbamate (100 mg, 0.467 mmol, prepared according to the procedure described in Synthesis, 1997, 1189-1194 from 3,4-dimethylisoxazol-5-amine) and diisopropylethylamine (0.305 mL, 1.75 mmol) and stirred at room temperature. After 2 h, the reaction was concentrated and the residue was purified by flash chromatography on silica gel (0-6% ethanol (containing 11% aq NH4OH):dichloromethane) to afford a clear oil which was evaporated from isopropyl ether/dichloromethane and evaporated again from diethyl ether/dichloromethane to give the title compound (0.200 g, 96% yield) as a white foam. MS (APCI) M+1=483.1; 1H NMR (400 MHz, CDCl3) δ ppm 1.89 (s, 3H) 2.20 (s, 3H) 2.43-2.49 (m, 2H) 2.56-2.62 (m, 2H) 3.45-3.52 (m, 2H) 3.56-3.62 (m, 2H) 6.41 (br. s, 1H) 6.61 (br. s, 1H) 6.86 (dd, J=8.68, 0.49 Hz, 1H) 6.95-7.02 (m, 2H) 7.04-7.09 (m, 1H) 7.37 (t, J=7.90 Hz, 1H) 7.79 (dd, J=8.58, 2.53 Hz, 1H) 8.22-8.24 (m, 1H).

Provenance & Evidence