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

HRID 1177880Notes

Reaction equation

HRID 1177880 reaction equation
CCN(C(C)C)C(C)C.[S:10]1[CH:14]=[CH:13][C:12]([C:15]2[CH:23]=[CH:22][C:18]([C:19]([OH:21])=O)=[CH:17][CH:16]=2)=[CH:11]1.C1C=CC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C.FC(F)(F)C(O)=O.[NH2:52][CH2:53][C:54]([N:56]1[CH2:61][CH2:60][N:59]([C:62](=[O:73])[C:63]2[CH:68]=[CH:67][CH:66]=[CH:65][C:64]=2[C:69]([F:72])([F:71])[F:70])[CH2:58][CH2:57]1)=[O:55]>CN(C=O)C.O>[O:55]=[C:54]([N:56]1[CH2:57][CH2:58][N:59]([C:62](=[O:73])[C:63]2[CH:68]=[CH:67][CH:66]=[CH:65][C:64]=2[C:69]([F:72])([F:71])[F:70])[CH2:60][CH2:61]1)[CH2:53][NH:52][C:19](=[O:21])[C:18]1[CH:17]=[CH:16][C:15]([C:12]2[CH:13]=[CH:14][S:10][CH:11]=2)=[CH:23][CH:22]=1

Participants

8

Reactant 5

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 7368624-(3-Thienyl)benzoic acidHCID 866340882-amino-1-[4-(2-trifluoromethyl-benzoyl)-piperazin-1-yl]-ethanone TFA salt

Product 1

HCID 59559628N-{2-oxo-2-[4-(2-trifluoromethyl-benzoyl)-piperazin-1-yl]-ethyl}-4-thiophen-3-yl-benzamideYield 48.3%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

DIPEA (74.9 mg, 0.09 mL, 0.58 mmol) was added to a stirred solution of 4-thiophen-3-yl-benzoic acid (40 mg, 0.19 mmol) in DMF (1 mL). HOBT (32 mg, 0.23 mmol) and EDCI (45 mg, 0.23 mmol) were then added at room temperature. After 2 minutes, 2-amino-1-[4-(2-trifluoromethyl-benzoyl)-piperazin-1-yl]-ethanone trifluoroacetic acid salt (100 mg, 0.23 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 afford 46 mg (46.9% yield) of N-{2-oxo-2-[4-(2-trifluoromethyl-benzoyl)-piperazin-1-yl]-ethyl}-4-thiophen-3-yl-benzamide. LCMS Purity: 97.5%. 1H NMR (DMSO-d6): δ 8.7-8.6 (m, 1H), 8.1-8.0 (s, 1H), 7.96-7.9 (m, 2H), 7.88-7.8 (m, 3H), 7.8-7.74 (m, 1H), 7.72-7.62 (m, 3H), 7.6-7.5 (bt, 1H), 4.24-4.08 (m, 2H), 3.78-3.56 (m, 4H), 3.5-3.4 (m, 2H), 3.2-3.06 (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-0cbea3ab9cff4136b7c49272adcdad17
Source dataset
uspto-grants-2010_11
Patent number
US07842696B2

Reaction notes

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