反应详情

A mixture of 4-phenyl-1H-pyrazole hydrochloride salt (prepared by the method as described above)(45 mg, 0.2 mmol), DIPEA (80.5 mg, 0.11 ml, 0.625 mmol) and DCM (1 ml) was added to a stirred solution of triphosgene (40 mg, 0.1 mmol) in DCM (5 mL) at room temperature. After 30 minutes, to the above solution, a mixture of 2-amino-1-[4-(5-fluoro-2-trifluoromethyl-benzoyl)-piperazin-1-yl]-ethanone hydrochloride salt (prepared by the method as described above)(100 mg, 0.27 mmol), DIPEA (80.5 mg, 0.11 ml, 0.625 mmol) and DCM (1 ml) was added and the resulting mixture was stirred at room temperature for 30 minutes. Cold water was then added and the product was extracted with EtOAc and the organic layer was washed with 10% HCl solution, saturated sodium bicarbonate solution and 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 57 mg (45.6% yield) 4-phenyl-pyrazole-1-carboxylic acid {2-[4-(5-fluoro-2-trifluoromethyl-benzoyl)-piperazin-1-yl]-2-oxo-ethyl}-amide. LCMS Purity: 96.83%. 1H NMR (CDCl3): δ 8.5 (d, 1H), 8.02 (s, 1H), 7.94 (s, 1H), 7.8 (m, 1H), 7.56 (d, 2H), 7.44 (t, 2H), 7.14 (d, 2H), 7.1 (d, 1H), 4.38-4.2 (m, 2H), 4.08-3.8 (m, 1H), 3.8-3.6 (m, 4H), 3.46-3.36 (s, 1H), 3.34-3.18 (s, 2H).

1. customprepared by the method
2. customprepared by the method
3. additionwas added
4. extractionthe product was extracted with EtOAc
5. washthe organic layer was washed with 10% HCl solution, saturated sodium bicarbonate solution and brine
6. dry with materialThe organic phase was dried over Na2SO4
7. concentrationconcentrated under reduced pressure
8. customto get the residue
9. customThe obtained residue was purified by column chromatography (using silica gel of 60-120 mesh and 50% EtOAc in Hexane as eluent)