反应详情

Part D: To a stirred solution of 5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-1H-1,2,4-triazole-3-carboxylic acid (1.48 gram, 4.0 mmol) in acetonitrile (20 mL) is successively added diisopropylethylamine (DIPEA) (1.5 mL, 2.1 molar equivalent), O-benzotriazol-1-yl-N,N, N′,N′-tetramethyluronium hexafluorophosphate (HBTU) (1.66 gram, 1.1 molar equivalent) and 1-aminopiperidine (0.44 gram, 1.1 molar equivalent). After stirring overnight an aqueous NaHCO3 solution is added. The resulting mixture is three times extracted with dichloromethane. The combined organic layers are washed with water, dried over Na2SO4, filtered and concentrated in vacuo to give a crude oil (3.6 gram). This oil is further purified by flash chromatography (silica gel; EtOAc/petroleum ether (40-60° C.)=7/3 (v/v)). The purified material is treated with ethanolic HCl (1M solution) to give 5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-N-(piperidin-1-yl)-1H-1,2,4-triazole-3-carboxamide hydrochloride (1.50 gram, 77% yield). Melting point: 238-240° C. (decomposition). 1H-NMR (400 MHz, DMSO-d6): δ 1.46-1.54 (m, 2H), 1.78-1.85 (m, 4H), 3.22-3.28 (m, 4H), 7.50 (s, 4H), 7.70 (dd, J=8 and 2 Hz, 1H), 7.85-7.87 (m, 1H), 7.91 (d, J=8 Hz, 1H), (NH not visible).

1. additionis added
2. extractionextracted with dichloromethane
3. washThe combined organic layers are washed with water
4. dry with materialdried over Na2SO4
5. filtrationfiltered
6. concentrationconcentrated in vacuo
7. customto give a crude oil (3.6 gram)
8. customThis oil is further purified by flash chromatography (silica gel; EtOAc/petroleum ether (40-60° C.)=7/3 (v/v))
9. additionThe purified material is treated with ethanolic HCl (1M solution)