反应详情

DIPEA (230 mg, 0.33 mL, 1.8 mmol) was added to a stirred solution of 2-bromo-5-nitro-benzoic acid (114 mg, 0.46 mmol) in DMF (2 mL). HOBT (93 mg, 0.69 mmol) and EDCI (220 mg, 1.15 mmol) were then added at room temperature. After 2 minutes, Biphenyl-4-carboxylic acid (2-oxo-2-piperazin-1-yl-ethyl)-amide (150 mg, 0.46 mmol) was added and the resulting mixture was stirred at room temperature overnight. Cold water was then added and the product was extracted with EtOAc and the organic layer was washed with brine. The organic phase was dried over Na2SO4 and concentrated under reduced pressure to get the residue. The obtained residue was purified by column chromatography (using basic alumina and 10% MeOH in CHCl3 as eluent) to afford 100 mg (39.5% yield) of biphenyl-4-carboxylic acid {2-[4-(2-bromo-5-nitro-benzoyl)-piperazin-1-yl]-2-oxo-ethyl}-amide. LCMS Purity: 96.4%. 1H NMR (CDCl3): δ 8.4 (bs, 1H), 8.2 (m, 2H), 7.9 (d, 2H), 7.6 (m, 5H), 7.5 (m, 3H), 7.4 (m, 1H), 6.0 (d, 1H), 4.4 (m, 2H), 4.0 (m, 2H), 3.8 (m, 3H), 3.6 (m, 3H), 3.5-(m, 2H).

1. extractionthe product was extracted with EtOAc
2. washthe organic layer was washed with brine
3. dry with materialThe organic phase was dried over Na2SO4
4. concentrationconcentrated under reduced pressure
5. customto get the residue
6. customThe obtained residue was purified by column chromatography (using basic alumina and 10% MeOH in CHCl3 as eluent)