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

HRID 1177844Notes

Reaction equation

HRID 1177844 reaction equation
CCN(C(C)C)C(C)C.[C:10]1([S:16]([C:18]2[CH:26]=[CH:25][C:21]([C:22]([OH:24])=O)=[CH:20][CH:19]=2)=[O:17])[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=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>[C:10]1([S:16]([C:18]2[CH:19]=[CH:20][C:21]([C:22]([NH:48][CH2:49][C:50](=[O:51])[N:52]3[CH2:53][CH2:54][N:55]([C:58](=[O:69])[C:59]4[CH:64]=[CH:63][CH:62]=[CH:61][C:60]=4[C:65]([F:66])([F:68])[F:67])[CH2:56][CH2:57]3)=[O:24])=[CH:25][CH:26]=2)=[O:17])[CH:11]=[CH:12][CH:13]=[CH:14][CH:15]=1

Participants

9

Reactant 6

HCID 6422Trifluoroacetic acidHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 3438114-Benzenesulfinyl-benzoic acidHCID 595596292-Amino-1-[4-(2-trifluoromethyl-benzoyl)-piperazin-1-yl]-ethanone

Product 1

HCID 251671264-benzenesulfinyl-N-{2-oxo-2-[4-(2-trifluoromethyl-benzoyl)-piperazin-1-yl]-ethyl}-benzamideYield 51%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

DIPEA (0.084 mL, 0.49 mmol) was added drop wise to 4-benzenesulfinyl-benzoic acid (48 mg, 0.19 mmol) in DMF (4 mL). EDCI (78 mg, 0.41 mmol) and HOBT 26 mg, 0.19 mmol) were added consecutively and 2-amino-1-[4-(2-trifluoromethyl-benzoyl)-piperazin-1-yl]-ethanone in its TFA salt form (70 mg, 0.16 mmol) was added after a further 10 mins. The resulting mixture was allowed to stir at room temperature overnight. Water was then added and the product was extracted with EtOAc and washed with brine. The organic phase was dried over Na2SO4 and concentrated under reduced pressure to afford a crude product. Purification by column chromatography (using silica gel with a mesh size of 60-120 and 100% EtOAc as eluent) afforded 45 mg (51% yield) of 4-benzenesulfinyl-N-{2-oxo-2-[4-(2-trifluoromethyl-benzoyl)-piperazin-1-yl]-ethyl}-benzamide. LC-MS purity: 91.93%. 1H NMR (DMSO-D6): δ 8.7 (t, 1H), 8 (m, 3H), 7.8 (m, 6H), 7.5 (m, 3H), 7.2 (m, 1H), 4.2 (d, 2H), 3.6 (m, 6H), 3.1 (m, 2H).

Workup

  1. extractionthe product was extracted with EtOAc
  2. washwashed with brine
  3. dry with materialThe organic phase was dried over Na2SO4
  4. concentrationconcentrated under reduced pressure
  5. customto afford a crude product
  6. customPurification by column chromatography (

Sources & evidence

ORD record
ord-2578c01d2e5243ff8ae15ab14638c5d6
Source dataset
uspto-grants-2010_11
Patent number
US07842696B2

Reaction notes

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