Hydrochloric Acid → 4-[1,3,4]oxadiazol-2-yl-N-{2-oxo-2-[4-(2-trifluoromethyl-benzoyl)-piperazin-1-yl]-ethyl}-benzamide

HRID 1177896Notes

Reaction equation

HRID 1177896 reaction equation
CCN(C(C)C)C(C)C.[O:10]1[CH:14]=[N:13][N:12]=[C:11]1[C:15]1[CH:23]=[CH:22][C:18]([C:19]([OH:21])=O)=[CH:17][CH:16]=1.CCN=C=NCCCN(C)C.C1C=CC2N(O)N=NC=2C=1.[NH2:45][CH2:46][C:47]([N:49]1[CH2:54][CH2:53][N:52]([C:55](=[O:66])[C:56]2[CH:61]=[CH:60][CH:59]=[CH:58][C:57]=2[C:62]([F:65])([F:64])[F:63])[CH2:51][CH2:50]1)=[O:48].Cl>CN(C=O)C.O>[O:10]1[CH:14]=[N:13][N:12]=[C:11]1[C:15]1[CH:16]=[CH:17][C:18]([C:19]([NH:45][CH2:46][C:47](=[O:48])[N:49]2[CH2:50][CH2:51][N:52]([C:55](=[O:66])[C:56]3[CH:61]=[CH:60][CH:59]=[CH:58][C:57]=3[C:62]([F:63])([F:65])[F:64])[CH2:53][CH2:54]2)=[O:21])=[CH:22][CH:23]=1

Participants

9

Reactant 6

HCID 313Hydrochloric AcidHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 71310554-(1,3,4-oxadiazol-2-yl)benzoic AcidHCID 595596292-Amino-1-[4-(2-trifluoromethyl-benzoyl)-piperazin-1-yl]-ethanone

Product 1

HCID 251671224-[1,3,4]oxadiazol-2-yl-N-{2-oxo-2-[4-(2-trifluoromethyl-benzoyl)-piperazin-1-yl]-ethyl}-benzamideYield 33%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

DIPEA (80 mg, 0.1 mL, 0.64 mmol) was added drop wise to 4-[1,3,4]Oxadiazol-2-yl-benzoic acid (40 mg, 0.2 mmol) in DMF (2 mL). EDCI (45 mg, 0.24 mmol) and HOBT (32 mg, 0.24 mmol) were added consecutively and, after 10 minutes, 2-Amino-1-[4-(2-trifluoromethyl-benzoyl)-piperazin-1-yl]-ethanone in its HCl salt form (70 mg, 0.2 mmol) was added. 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 10% EtOAc in Hexane as eluent) to afford 30 mg (33% yield) of 4-[1,3,4]oxadiazol-2-yl-N-{2-oxo-2-[4-(2-trifluoromethyl-benzoyl)-piperazin-1-yl]-ethyl}-benzamide. LCMS Purity: 93.4%. 1H NMR (CDCl3): δ 8.5 (s, 1H), 8.2 (d, 2H), 8.0 (d, 2H), 7.8 (m, 3H), 7.3 (m, 2H), 4.2 (m, 2H), 3.8 (m, 5H), 3.4 (m, 1H), 3.2 (m, 3H).

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 10% EtOAc in Hexane as eluent)

Sources & evidence

ORD record
ord-e4ff8a4c85354c0c92245a4d52153d8e
Source dataset
uspto-grants-2010_11
Patent number
US07842696B2

Reaction notes

Loading…