反应详情

DIPEA (77.35 mg, 0.598 mmol) was added to a stirred solution of biphenyl-4-carboxylicacid (2-oxo-2-piperazin-1-yl-ethyl)-amide TFA salt (70 mg, 0.16 mmol) in DMF (2 mL). HOBT (19.8 mg, 0.15 mmol) and EDCI.HCl (63.74 mg, 0.33 mmol) were then added. After 2 minutes 2-fluorobenzoic acid (18.6 mg, 0.133 mmol) was added and the resulting mixture was stirred overnight. The reaction mixture was diluted with cold water and the product was precipitated and isolated by filtration to afford crude product, which was purified by column chromotography (using silica gel of 160-120 mesh and 50% EtOAc in hexane as eluent) to afford 25 mg (41.4% yield) of Biphenyl-4-carboxylicacid {2-[4-(2-fluoro-benzoyl)-piperazin-1-yl]-2-oxo-ethyl}-amide. LC-MS purity: 94.8%, 1H NMR: (CDCl3) δ 7.9 (d, 2H), 7.6 (dd, 4H), 7.4 (m, 4H), 7.2 (s, 1H), 7.1 (t, 1H), 4.4 (dd, 2H), 3.8 (t, 2H), 3.6 (t, 4H), 3.4 (s, 2H).

1. customthe product was precipitated
2. customisolated by filtration
3. customto afford crude product, which
4. customwas purified by column chromotography (using silica gel of 160-120 mesh and 50% EtOAc in hexane as eluent)