1-Aminopiperidine → 1-(4-chlorophenyl)-2-(2,4-dichlorophenyl)-5-methylsulfanyl-N-(piperidin-1-yl)-1H-imidazole-4-carboxamide

Participants

Reaction Steps

To a magnetically stirred suspension of 1-(4-chlorophenyl)-2-(2,4-dichlorophenyl)-5-methylsulfanyl-1H-imidazole-4-carboxylic acid (1.72 g, 4.16 mmol) in anhydrous CH3CN (45 ml) was successively added N,N-diisopropylethylamine (Hunig's base) (1.60 ml, 9.20 mmol), O-benzotriazol-1-yl-N,N,N′,N′-tetramethyluronium hexafluorophosphate (HBTU) (1.89 g, 4.99 mmol) and 1-aminopiperidine (0.54 ml, 5.01 mmol). After stirring for 40 h, water was added and the resulting mixture was extracted with dichloromethane. the dichloromethane layer was successively twice washed with an 1N HCl solution and water, dried over MgSO4, filtered and concentrated to give a crude oil. This oil was further purified by flash chromatography (silicagel, EtOAc) and triturated with diethyl ether to give 1-(4-chlorophenyl)-2-(2,4-dichlorophenyl)-5-methylsulfanyl-N-(piperidin-1-yl)-1H-imidazole-4-carboxamide in 72% yield, mp 170° C. (dec); 1H-NMR (600 MHz, DMSO-d6) δ 1.35–1.42 (m, 2H), 1.62–1.67 (m, 4H), 2.35 (s, 3H), 2.80–2.84 (m, 4H), 7.29 (d, J=8 Hz, 2H), 7.42 (dd, J=8 and 2 Hz, 1H), 7.45 (d, J=8 Hz, 2H), 7.52 (d, J=2 Hz, 1H), 7.62 (d, J=8 Hz, 1H), 8.90 (s, 1H); 13C-NMR (150 MHz, DMSO-d6) δ 19.26, 23.32, 25.63, 55.98, 127.52, 128.61, 129.14, 129.23, 129.86, 130.12, 130.18, 133.86, 134.45, 134.66, 136.01, 137.12, 144.04, 158.98; HRMS (C22H22Cl3N4OS) [M+H]+: found m/z 495.0592, calcd 495.0580.

Provenance & Evidence