1-Hydroxybenzotriazole → 4-benzyloxy-N-{2-[4-(2-bromo-5-methoxy-benzoyl)-piperazin-1-yl]-2-oxo-ethyl}-benzamide

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Reaction Steps

2-Bromo-5-methoxy benzoic acid (121 mg, 0.53 mmol) was added to 4-benzyloxy-N-(2-oxo-2-piperazin-1-yl-ethyl)-benzamide (155 mg, 0.44 mmol) in DMF (5 mL). EDCI.HCl (126 mg, 0.66 mmol), HOBT (71 mg, 0.53 mmol) and DIPEA (227 μL, 1.32 mmol) were added and the resulting mixture was stirred at room temperature for 4 hours. Water was then added and the product was extracted with EtOAc and washed with brine. The organic phase was dried over Na2SO4 and concentrated under reduced pressure. The crude product was purified twice by column chromatography using (i) silica gel of mesh size of 60-120 and 70:30 EtOAc:Hexane as the eluent (1st purification) and (ii) neutral alumina and 65:35 EtOAc:Hexane as the eluent (2nd purification) to afford 4-benzyloxy-N-{2-[4-(2-bromo-5-methoxy-benzoyl)-piperazin-1-yl]-2-oxo-ethyl}-benzamide in 43% yield. LC-MS purity: 99.6%. 1H NMR (CDCl3): δ 7.9 (d, 2H), 7.5 (m, 6H), 7.2 (s, 1H), 7 (d, 2H), 6.8 (d, 2H), 5.2 (s, 2H), 4.4 (d, 2H), 4 (m, 2H), 3.8 (s, 3H), 3.7 (t, 3H), 3.6 (t, 2H), 3.5 (m, 2H), 3.3 (m, 1H).

Provenance & Evidence