Diisopropylethylamine → 4-Phenyl-pyrazole-1-carboxylic acid {2-[4-(5-fluoro-2-trifluoromethyl-benzoyl)-piperazin-1-yl]-2-oxo-ethyl}-amide

HRID 1178110Notes

Reaction equation

HRID 1178110 reaction equation
Cl.[C:2]1([C:8]2[CH:9]=[N:10][NH:11][CH:12]=2)[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.CCN(C(C)C)C(C)C.Cl[C:23](Cl)([O:25]C(=O)OC(Cl)(Cl)Cl)Cl.Cl.[NH2:35][CH2:36][C:37]([N:39]1[CH2:44][CH2:43][N:42]([C:45](=[O:57])[C:46]2[CH:51]=[C:50]([F:52])[CH:49]=[CH:48][C:47]=2[C:53]([F:56])([F:55])[F:54])[CH2:41][CH2:40]1)=[O:38]>C(Cl)Cl.O>[F:52][C:50]1[CH:49]=[CH:48][C:47]([C:53]([F:54])([F:56])[F:55])=[C:46]([CH:51]=1)[C:45]([N:42]1[CH2:41][CH2:40][N:39]([C:37](=[O:38])[CH2:36][NH:35][C:23]([N:10]2[CH:9]=[C:8]([C:2]3[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=3)[CH:12]=[N:11]2)=[O:25])[CH2:44][CH2:43]1)=[O:57]

Participants

7

Reactant 4

HCID 81531Diisopropylethylamine2×HCID 94429TriphosgeneHCID 665923304-phenyl-1H-pyrazole hydrochlorideHCID 669531292-Amino-1-[4-(5-fluoro-2-trifluoromethyl-benzoyl)-piperazin-1-yl]ethanone hydrochloride

Product 1

HCID 251655344-Phenyl-pyrazole-1-carboxylic acid {2-[4-(5-fluoro-2-trifluoromethyl-benzoyl)-piperazin-1-yl]-2-oxo-ethyl}-amideYield 45.6%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent3×

Procedure

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).

Workup

  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)

Sources & evidence

ORD record
ord-bfb8a5ff9ff34001b48e354a40ad9240
Source dataset
uspto-grants-2010_11
Patent number
US07842696B2

Reaction notes

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