1-Hydroxybenzotriazole → 5-Phenyl-[1,3,4]oxadiazole-2-carboxylic acid {2-oxo-2-[4-(2-trifluoromethyl-benzoyl)-piperazin-1-yl]-ethyl}-amide

HRID 1178105Notes

Reaction equation

HRID 1178105 reaction equation
CCN(C(C)C)C(C)C.C1C=CC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C.Cl.OC(C(F)(F)F)=O.[NH2:39][CH2:40][C:41]([N:43]1[CH2:48][CH2:47][N:46]([C:49](=[O:60])[C:50]2[CH:55]=[CH:54][CH:53]=[CH:52][C:51]=2[C:56]([F:59])([F:58])[F:57])[CH2:45][CH2:44]1)=[O:42].[Li+].[C:62]1([C:68]2[O:72][C:71]([C:73]([O-])=[O:74])=[N:70][N:69]=2)[CH:67]=[CH:66][CH:65]=[CH:64][CH:63]=1>CN(C=O)C.O>[O:42]=[C:41]([N:43]1[CH2:44][CH2:45][N:46]([C:49](=[O:60])[C:50]2[CH:55]=[CH:54][CH:53]=[CH:52][C:51]=2[C:56]([F:59])([F:57])[F:58])[CH2:47][CH2:48]1)[CH2:40][NH:39][C:73]([C:71]1[O:72][C:68]([C:62]2[CH:63]=[CH:64][CH:65]=[CH:66][CH:67]=2)=[N:69][N:70]=1)=[O:74]

Participants

8

Reactant 5

HCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 669534535-Phenyl-[1,3,4]oxadiazole-2-carboxylic acid lithium saltHCID 866340882-amino-1-[4-(2-trifluoromethyl-benzoyl)-piperazin-1-yl]-ethanone TFA salt

Product 1

HCID 578556405-Phenyl-[1,3,4]oxadiazole-2-carboxylic acid {2-oxo-2-[4-(2-trifluoromethyl-benzoyl)-piperazin-1-yl]-ethyl}-amideYield 22.8%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

DIPEA (106 mg, 0.142 mL, 0.82 mmol) followed by HOBT (40.8 mg, 0.30 mmol), EDCI.HCl (131.8 mg, 0.69 mmol) and 2-amino-1-[4-(2-trifluoromethyl-benzoyl)-piperazin-1-yl]-ethanone TFA salt (129 mg, 0.3 mmol) were added sequentially to a stirred solution of 5-phenyl-[1,3,4]oxadiazole-2-carboxylic acid lithium salt (52 mg, 0.27 mmol) in DMF (5 mL). The resulting mixture was maintained at room temperature for 6 hrs. Cold water was added and the product was extracted with ethyl acetate. The organic layer was washed with saturated brine solution, dried over sodium sulphate and concentrated. The crude residue was purified by column chromatography (using 60-120 mesh silica gel and 50% EtOAc in hexane as eluent) to afford 30 mg (22.4% yield) of 5-phenyl-[1,3,4]oxadiazole-2-carboxylic acid {2-oxo-2-[4-(2-trifluoromethyl-benzoyl)-piperazin-1-yl]-ethyl}-amide as a white solid, LCMS purity: 87.99%, 1H NMR: (DMSO) δ 9.2 (t, 1H), 8.1 (d, 2H), 7.9-7.72 (dd, 2H), 7.72-7.6 (m, 3H), 7.6-7.5 (t, 1H), 4.3-4.1 (dd, 2H), 3.8-3.5 (m, 4H), 3.3-3.0 (m, 4H).

Workup

  1. extractionthe product was extracted with ethyl acetate
  2. washThe organic layer was washed with saturated brine solution
  3. dry with materialdried over sodium sulphate
  4. concentrationconcentrated
  5. customThe crude residue was purified by column chromatography (using 60-120 mesh silica gel and 50% EtOAc in hexane as eluent)

Sources & evidence

ORD record
ord-ebeec8d430784e1a908ecf2e8124de65
Source dataset
uspto-grants-2010_11
Patent number
US07842696B2

Reaction notes

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