(1,1'-Biphenyl)-3-carboxylic acid → Biphenyl-3-carboxylic acid {2-oxo-2-[4-(2-trifluoromethyl-benzoyl)-piperazin-1-yl]-ethyl}-amide

HRID 1177967Notes

Reaction equation

HRID 1177967 reaction equation
CCN(C(C)C)C(C)C.OC(C(F)(F)F)=O.[NH2:17][CH2:18][C:19]([N:21]1[CH2:26][CH2:25][N:24]([C:27](=[O:38])[C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][C:29]=2[C:34]([F:37])([F:36])[F:35])[CH2:23][CH2:22]1)=[O:20].C1C=CC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C.Cl.[C:61]1([C:67]2[CH:68]=[C:69]([CH:73]=[CH:74][CH:75]=2)[C:70](O)=[O:71])[CH:66]=[CH:65][CH:64]=[CH:63][CH:62]=1>CN(C=O)C.O>[O:20]=[C:19]([N:21]1[CH2:22][CH2:23][N:24]([C:27](=[O:38])[C:28]2[CH:33]=[CH:32][CH:31]=[CH:30][C:29]=2[C:34]([F:37])([F:35])[F:36])[CH2:25][CH2:26]1)[CH2:18][NH:17][C:70]([C:69]1[CH:68]=[C:67]([C:61]2[CH:66]=[CH:65][CH:64]=[CH:63][CH:62]=2)[CH:75]=[CH:74][CH:73]=1)=[O:71]

Participants

8

Reactant 5

HCID 12854(1,1'-Biphenyl)-3-carboxylic acidHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 866340882-amino-1-[4-(2-trifluoromethyl-benzoyl)-piperazin-1-yl]-ethanone TFA salt

Product 1

HCID 25164725Biphenyl-3-carboxylic acid {2-oxo-2-[4-(2-trifluoromethyl-benzoyl)-piperazin-1-yl]-ethyl}-amideYield 70.6%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

DIPEA (78 mg, 0.61 mmol) was added to a stirred solution of 2-amino-1-[4-(2-trifluoromethyl-benzoyl)-piperazin-1-yl]-ethanone TFA salt (104 mg, 0.24 mmol) in DMF (1 mL). HOBT (33 mg, 0.24 mmol) and EDCI.HCl (46 mg, 0.24 mmol) were then added at room temperature. After 2 minutes, 3-phenyl benzoic acid (40 mg, 0.20 mmol) was added and the resulting mixture was stirred at room temperature for 4 hrs. 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 afford 70 mg (70% yield) of biphenyl-3-carboxylic acid {2-oxo-2-[4-(2-trifluoromethyl-benzoyl)-piperazin-1-yl]-ethyl}-amide. LCMS Purity: 95.7%, 1H NMR (DMSO-d6): δ 8.8 (t, 1H), 8.2 (s, 1H), 7.9-7.8 (m, 3H), 7.8-7.6 (m, 4H), 7.6-7.4 (m, 4H), 7.4 (m, 1H), 4.2 (m, 2H), 3.8-3.6 (m, 4H), 3.5-3.4 (m, 2H), 3.2-3.0 (m, 2H).

Workup

  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

Sources & evidence

ORD record
ord-50f6b9c4533d4be385e1b5bb307b059f
Source dataset
uspto-grants-2010_11
Patent number
US07842696B2

Reaction notes

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