1-Hydroxybenzotriazole → Biphenyl-4-carboxylic acid (2-{4-[(2-chloro-phenyl)-methyl-amino]-piperidin-1-yl}-2-oxo-ethyl)-amide

Participants

Reaction Steps

To a stirred solution of [(biphenyl-4-carbonyl)-amino]-acetic acid (0.0659 g, 0.00025 mol) in DMF (1 mL), was added DIPEA (0.0911 g, 0.0007 mol), HOBt (0.0318 g, 0.00023 mol) and EDCI.HCl (0.054 g, 0.00028 mol) at ambient temperature. After 2 minutes (2-chloro-phenyl)-methyl-piperidin-4-yl-amine hydrochloride (0.07 g, 0.00023 mol) was added and the resulting mixture was stirred at the same temperature overnight. The reaction mixture was diluted with cold water and the product was extracted with ethyl acetate. The ethyl acetate layer was washed with aqueous sodium bicarbonate solution followed by brine solution, dried over sodium sulfate and concentrated under reduced pressure. The resulting residue obtained was purified by column chromatography using basic aluminium oxide (10-30% ethyl acetate in hexane) to afford 0.028 g (23%) of biphenyl-4-carboxylic acid (2-{4-[(2-chloro-phenyl)-methyl-amino]-piperidin-1-yl}-2-oxo-ethyl)-amide. LCMS: 462.1 (M+1)+, 96.19%, 1H NMR (DMSO-d6): δ 8.6 (t, 1H), 7.95 (d, 2H), 7.75 (m, 3H), 7.5 (t, 2H), 7.42 (m, 2H), 7.3-7.2 (m, 2H), 7.05 (m, 1H), 4.4 (d, 1H), 4.2 (m, 2H), 3.95 (d, 1H), 3.05 (t, 1H), 2.65 (s, 3H), 1.6 (bs, 3H), 1.6-1.4 (m, 1H).

Provenance & Evidence