反应详情

DIPEA (198.6 mg, 0.26 mL, 1.5 mmol) was added to a stirred solution of 2-amino-1-[4-(2-trifluoromethyl-benzoyl)-piperazin-1-yl]-ethanone hydrochloride salt (144.1 mg, 0.4 mmol) in DMF (4 mL). HOBT (50.7 mg, 0.37 mmol) and EDCI (163.6 mg, 0.85 mmol) were then added at room temperature. After 2 minutes, 2′,6′-difluoro-biphenyl-4-carboxylic acid (80 mg, 0.34 mmol) (prepared by the method as described above) 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 50% EtOAc in Hexane as eluent) to afford 65 mg (35.8% yield) of 2′,6′-difluoro-biphenyl-4-carboxylic acid {2-oxo-2-[4-(2-trifluoromethyl-benzoyl)-piperazin-1-yl]-ethyl}-amide. LCMS Purity: 82.25%. 1H NMR (DMSO-d6): δ 8.8-8.7 (t, 1H), 8.0 (d, 2H), 7.9-7.7 (m, 2H), 7.7-7.6 (m, 1H), 7.6-7.5 (m, 4H), 7.3-7.2 (m, 2H), 4.2 (dd, 2H), 3.8-3.7 (m, 2H), 3.7-3.5 (m, 3H), 3.2-3.1 (m, 2H).

1. additionwas added
2. extractionthe product was extracted with EtOAc
3. washthe organic layer was washed with brine
4. dry with materialThe organic phase was dried over Na2SO4
5. concentrationconcentrated under reduced pressure
6. customto get the residue
7. customThe obtained residue was purified by column chromatography (using silica gel of 60-120 mesh and 50% EtOAc in Hexane as eluent)