Trifluoroacetic acid → 4-(Methyl-phenyl-amino)-N-{2-oxo-2-[4-(2-trifluoromethyl-benzoyl)-piperazin-1-yl]-ethyl}-benzamide

HRID 1177854Notes

Reaction equation

HRID 1177854 reaction equation
CCN(C(C)C)C(C)C.[CH3:10][N:11]([C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1)[C:12]1[CH:20]=[CH:19][C:15]([C:16]([OH:18])=O)=[CH:14][CH:13]=1.CCN=C=NCCCN(C)C.C1C=CC2N(O)N=NC=2C=1.[NH2:48][CH2:49][C:50]([N:52]1[CH2:57][CH2:56][N:55]([C:58](=[O:69])[C:59]2[CH:64]=[CH:63][CH:62]=[CH:61][C:60]=2[C:65]([F:68])([F:67])[F:66])[CH2:54][CH2:53]1)=[O:51].C(O)(C(F)(F)F)=O>CN(C=O)C.O>[CH3:10][N:11]([C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1)[C:12]1[CH:13]=[CH:14][C:15]([C:16]([NH:48][CH2:49][C:50](=[O:51])[N:52]2[CH2:53][CH2:54][N:55]([C:58](=[O:69])[C:59]3[CH:64]=[CH:63][CH:62]=[CH:61][C:60]=3[C:65]([F:66])([F:68])[F:67])[CH2:56][CH2:57]2)=[O:18])=[CH:19][CH:20]=1

Participants

9

Reactant 6

HCID 6422Trifluoroacetic acidHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 232051694-(Methyl(phenyl)amino)benzoic acidHCID 595596292-Amino-1-[4-(2-trifluoromethyl-benzoyl)-piperazin-1-yl]-ethanone

Product 1

HCID 595596214-(Methyl-phenyl-amino)-N-{2-oxo-2-[4-(2-trifluoromethyl-benzoyl)-piperazin-1-yl]-ethyl}-benzamideYield 26%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

DIPEA (92 mg, 0.125 mL, 0.72 mmol) was added drop wise to 4-(Methyl-phenyl-amino)-benzoic acid (55 mg, 0.24 mmol) in DMF (5 mL). EDCI (115 mg, 0.6 mmol) and HOBT (39 mg, 0.28 mmol) were added consecutively and, after 10 minutes, 2-amino-1-[4-(2-trifluoromethyl-benzoyl)-piperazin-1-yl]-ethanone in its TFA salt form (124 mg, 0.289 mmol) was added. 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 Preparative HPLC [(Column-Zorbax XDB C18-21.2×150 mm, mobile phase-0.1% TFA in water (A)/acetonitrile (B), gradient: (Time): (% B)-0:20; 2:30; 8:70)]) to afford 34 mg (26% yield) of 4-(Methyl-phenyl-amino)-N-{2-oxo-2-[4-(2-trifluoromethyl-benzoyl)-piperazin-1-yl]-ethyl}-benzamide. LC-MS purity: 97.62%. 1H-NMR (CDCl3): δ 7.7 (m, 3H), 7.6 (m, 2H), 7.4 (q, 3H), 7.2 (m, 2H), 7.1 (m, 1H), 6.8 (d, 2H), 4.3 (dd, 1H), 4.2 (dd, 1H), 4.0 (m, 1H), 3.9 (m, 1H), 3.7 (m, 3H), 3.4 (m, 1H), 3.3 (s, 3H), 3.2 (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
  5. customto get the residue
  6. customThe obtained residue was purified by Preparative HPLC [(Column-Zorbax XDB C18-21.2×150 mm, mobile phase-0.1% TFA in water (A)/acetonitrile (B)

Sources & evidence

ORD record
ord-de49c3364a6d4d68855b6d3a82a85821
Source dataset
uspto-grants-2010_11
Patent number
US07842696B2

Reaction notes

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