1-Hydroxybenzotriazole → 5-(3-Trifluoromethyl-phenyl)-furan-2-carboxylic acid {2-oxo-2-[4-(2-trifluoromethyl-benzoyl)-piperazin-1-yl]-ethyl}-amide

HRID 1178053Notes

Reaction equation

HRID 1178053 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.[F:61][C:62]([F:78])([F:77])[C:63]1[CH:64]=[C:65]([C:69]2[O:73][C:72]([C:74](O)=[O:75])=[CH:71][CH:70]=2)[CH:66]=[CH:67][CH:68]=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:74]([C:72]1[O:73][C:69]([C:65]2[CH:66]=[CH:67][CH:68]=[C:63]([C:62]([F:78])([F:61])[F:77])[CH:64]=2)=[CH:70][CH:71]=1)=[O:75]

Participants

8

Reactant 5

HCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 6882815-(3-(Trifluoromethyl)phenyl)-2-furoic acidHCID 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 251673275-(3-Trifluoromethyl-phenyl)-furan-2-carboxylic acid {2-oxo-2-[4-(2-trifluoromethyl-benzoyl)-piperazin-1-yl]-ethyl}-amideYield 37%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

DIPEA (75 mg, 0.1 mL, 0.59 mmol) was added to a stirred solution of 2-amino-1-[4-(2-trifluoromethyl-benzoyl)-piperazin-1-yl]-ethanone TFA salt (100 mg, 0.23 mmol) in DMF (1 mL). HOBT (32 mg, 0.23 mmol) and EDCI.HCl (44 mg, 0.23 mmol) were then added at room temperature. After 2 minutes, 5-(3-trifluoromethyl-phenyl)-furan-2-carboxylic acid (50 mg, 0.20 mmol) was added. The resulting mixture was stirred at room temperature for four hours. Water was then added, and the product was extracted with EtOAc. The organic layer was washed with brine, dried over Na2SO4 and concentrated under reduced pressure to afford 40 mg (37% yield) of 5-(3-trifluoromethyl-phenyl)-furan-2-carboxylic acid {2-oxo-2-[4-(2-trifluoromethyl-benzoyl)-piperazin-1-yl]-ethyl}-amide. LCMS Purity %: 86.88, HPLC 92.52%, 1H NMR (DMSO-d6): δ 8.8-8.7 (bt, 1H), 8.3 (s, 1H), 8.2 (bt, 1H), 7.9-7.6 (m, 5H), 7.6-7.5 (bt, 1H), 7.4-7.3 (d, 1H), 7.3-7.2 (m, 1H), 4.3-4.1 (m, 2H), 3.8-3.4 (m, 6H), 3.2-3.1 (m, 2H).

Workup

  1. extractionthe product was extracted with EtOAc
  2. washThe organic layer was washed with brine
  3. dry with materialdried over Na2SO4
  4. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-96cc432f08384d348d7acff97673a739
Source dataset
uspto-grants-2010_11
Patent number
US07842696B2

Reaction notes

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