反应详情

DIPEA (179.7 mg, 0.24 mL, 1.39 mmol) was added to a stirred solution of 6-chloro-pyridine-3-carboxylic acid (48.6 mg, 0.37 mmol) in DMF (3 mL). HOBT (45.9 mg, 0.34 mmol) and EDCI (148.1 mg, 0.77 mmol) were then added at room temperature. After 2 minutes, Biphenyl-4-carboxylic acid (2-oxo-2-piperazin-1-yl-ethyl)-amide (120 mg, 0.37 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 silica gel of 60-120 mesh and 90% EtOAc in Hexane as eluent) to afford 58 mg (40.8% yield) of biphenyl-4-carboxylic acid {2-[4-(6-chloro-pyridine-3-carbonyl)-piperazin-1-yl]-2-oxo-ethyl}-amide. LCMS Purity: 95.92, 1H NMR (DMSO-d6): δ 8.7-8.6 (t, 1H), 8.5 (d, 1H), 8.0-7.9 (m, 3H), 7.84-7.7 (q, 4H), 7.68-7.6 (d, 1H), 7.54-7.46 (t, 2H), 7.46-7.36 (m, 1H), 4.2 (bs, 2H), 3.8-3.4 (m, 8H).

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 silica gel of 60-120 mesh and 90% EtOAc in Hexane as eluent)