4-(Trifluoromethyl)benzoic acid → Biphenyl-4-carboxylicacid {2-[4-(4-trifluoromethyl-benzoyl)-piperazin-1-yl]-2-oxo-ethyl}-amide

HRID 1178089Notes

Reaction equation

HRID 1178089 reaction equation
CCN(C(C)C)C(C)C.[F:10][C:11]([F:22])([F:21])[C:12]1[CH:20]=[CH:19][C:15]([C:16]([OH:18])=O)=[CH:14][CH:13]=1.C1C=CC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C.Cl.[O:45]=[C:46]([N:63]1[CH2:68][CH2:67][NH:66][CH2:65][CH2:64]1)[CH2:47][NH:48][C:49]([C:51]1[CH:56]=[CH:55][C:54]([C:57]2[CH:62]=[CH:61][CH:60]=[CH:59][CH:58]=2)=[CH:53][CH:52]=1)=[O:50]>CN(C=O)C.O>[F:21][C:11]([F:10])([F:22])[C:12]1[CH:13]=[CH:14][C:15]([C:16]([N:66]2[CH2:65][CH2:64][N:63]([C:46](=[O:45])[CH2:47][NH:48][C:49]([C:51]3[CH:56]=[CH:55][C:54]([C:57]4[CH:62]=[CH:61][CH:60]=[CH:59][CH:58]=4)=[CH:53][CH:52]=3)=[O:50])[CH2:68][CH2:67]2)=[O:18])=[CH:19][CH:20]=1

Participants

8

Reactant 5

HCID 99664-(Trifluoromethyl)benzoic acidHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 57855677Biphenyl-4-carboxylicacid (2-oxo-2-piperazin-1-yl-ethyl)-amide

Product 1

HCID 55586253Biphenyl-4-carboxylicacid {2-[4-(4-trifluoromethyl-benzoyl)-piperazin-1-yl]-2-oxo-ethyl}-amideYield 25.9%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

DIPEA (149.8 mg, 1.15 mmol) was added to a stirred solution of 4-trifluoromethyl-benzoic acid (48.9 mg, 0.26 mmol) in DMF (3 mL), HOBt (38.2 mg, 0.28 mmol) and EDCI.HCl (123.4 mg, 0.64 mmol) at room temperature. After 2 minutes biphenyl-4-carboxylicacid (2-oxo-2-piperazin-1-yl-ethyl)-amide (100 mg, 0.31 mmol) was added and the resulting mixture was stirred at room temperature overnight. Cold water was then added, and the resulting precipitate was filtered. The residue was purified by column chromatography (using 60-120 mesh silica gel and 60% EtOAc in hexane as eluent) to afford 33 mg (25.9% yield) of biphenyl-4-carboxylicacid {2-[4-(4-trifluoromethyl-benzoyl)-piperazin-1-yl]-2-oxo-ethyl}-amide, LC-MS purity: 98.96%, 1H NMR: (DMSO) δ 8.65 (t, 1H), 8.0 (d, 2H), 7.9-7.7 (m, 6H), 7.7-7.64 (d, 2H), 7.56-7.46 (t, 2H), 7.46-7.38 (t, 1H) 4.2 (s, 3H), 3.6 (d, 7H).

Workup

  1. filtrationthe resulting precipitate was filtered
  2. customThe residue was purified by column chromatography (using 60-120 mesh silica gel and 60% EtOAc in hexane as eluent)

Sources & evidence

ORD record
ord-cb6ddc870c7d4fec8374848d96d95f23
Source dataset
uspto-grants-2010_11
Patent number
US07842696B2

Reaction notes

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