1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → 4-imidazol-1-yl-N-{2-oxo-2-[4-(2-trifluoromethyl-benzoyl)-piperazin-1-yl]-ethyl}-benzamide

HRID 1177914Notes

Reaction equation

HRID 1177914 reaction equation
CCN(C(C)C)C(C)C.Cl.[NH2:11][CH2:12][C:13]([N:15]1[CH2:20][CH2:19][N:18]([C:21](=[O:32])[C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][C:23]=2[C:28]([F:31])([F:30])[F:29])[CH2:17][CH2:16]1)=[O:14].C1C=CC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C.[N:54]1([C:59]2[CH:67]=[CH:66][C:62]([C:63](O)=[O:64])=[CH:61][CH:60]=2)[CH:58]=[CH:57][N:56]=[CH:55]1>CN(C=O)C.O>[N:54]1([C:59]2[CH:60]=[CH:61][C:62]([C:63]([NH:11][CH2:12][C:13](=[O:14])[N:15]3[CH2:16][CH2:17][N:18]([C:21](=[O:32])[C:22]4[CH:27]=[CH:26][CH:25]=[CH:24][C:23]=4[C:28]([F:31])([F:29])[F:30])[CH2:19][CH2:20]3)=[O:64])=[CH:66][CH:67]=2)[CH:58]=[CH:57][N:56]=[CH:55]1

Participants

8

Reactant 5

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 7365294-(1-Imidazolyl)benzoic AcidHCID 669531782-Amino-1-[4-(2-trifluoromethyl-benzoyl)-piperazin-1-yl]-ethanone hydrochloride

Product 1

HCID 251665034-imidazol-1-yl-N-{2-oxo-2-[4-(2-trifluoromethyl-benzoyl)-piperazin-1-yl]-ethyl}-benzamideYield 33.8%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

DIPEA (247.2 mg, 0.33 mL, 1.9 mmol) was added to a stirred solution of 2-amino-1-[4-(2-trifluoromethyl-benzoyl)-piperazin-1-yl]-ethanone hydrochloride salt (164.3 mg, 0.46 mmol) in DMF (2 mL). HOBT (63.1 mg, 0.46 mmol) and EDCI (179.2 mg, 0.93 mmol) were then added at room temperature. After 2 minutes, 4-imidazol-1-yl-benzoic acid (80 mg, 0.42 mmol) was added and 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 column chromatography (using silica gel of 60-120 mesh and 50% EtOAc in Hexane as eluent) to afford 69 mg (33.4% yield) 4-imidazol-1-yl-N-{2-oxo-2-[4-(2-trifluoromethyl-benzoyl)-piperazin-1-yl]-ethyl}-benzamide. LCMS Purity: 94.26%. 1H NMR (DMSO-d6): δ 8.8-8.7 (s, 1H), 8.4 (s, 1H), 8.1-8.0 (d, 2H), 7.9-7.7 (m, 5H), 7.7-7.62 (m, 1H), 7.62-7.5 (t, 1H), 7.2-7.1 (s, 1H), 4.3-4.1 (d, 2H), 3.8-3.5 (m, 4H), 3.5-3.4 (m, 2H), 3.24-3.0 (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
  5. customto get the residue
  6. 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-82133b328c2e4d4596be07a032770cac
Source dataset
uspto-grants-2010_11
Patent number
US07842696B2

Reaction notes

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