1-Hydroxybenzotriazole → 2-(4-{2-[(Biphenyl-4-carbonyl)-amino]-acetyl}-piperazine-1-carbonyl)-benzoic acid methylester

Participants

Reaction Steps

DIPEA (233 mg, 1.80 mmol) was added to a stirred solution of [(biphenyl-4-carbonyl)-amino]-acetic acid (161 mg, 0.63 mmol) in DMF (5 mL), HOBt (85.6 mg, 0.63 mmol) and EDCI.HCl (276 mg, 1.44 mmol) at room temperature. After 2 minutes 2-(piperazine-1-carbonyl)-benzoic acid methyl ester (143 mg, 0.58 mmol) was and the resulting mixture was stirred at room temperature overnight. The mixture was then diluted with cold water and the product extracted with ethyl acetate. The organic layer was separated, washed with 10% HCl solution, NaHCO3 solution, and brine, dried over sodium sulphate and concentrated to afford 106 mg (37.9% yield) of 2-(4-{2-[(biphenyl-4-carbonyl)-amino]-acetyl}-piperazine-1-carbonyl)-benzoic acid methylester, LC-MS purity: 98.96%, 1H NMR: (DMSO) δ 8.6 (bs, 1H), 7.9 (d, 3H), 7.8-7.6 (m, 5H), 7.54 (t, 1H), 7.54-7.46 (t, 2H), 7.44-7.36 (t, 2H), 4.1 (d, 1H), 3.8 (s, 3H), 3.6 (d, 4H), 3.4 (bs, 2H), 3.1 (bd, 2H).

Provenance & Evidence