1-Hydroxybenzotriazole → 3-[4-(2-bromo-benzoyl)-piperazin-1-yl]-3-oxo-N-(3-phenyl-isoxazol-5-yl)-propionamide

HRID 1665683Notes

Reaction equation

HRID 1665683 reaction equation
CCN(C(C)C)C(C)C.[C:10]1([C:16]2[CH:20]=[C:19]([NH:21][C:22](=[O:27])[CH2:23][C:24]([OH:26])=O)[O:18][N:17]=2)[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1.C1C=CC2N(O)N=NC=2C=1.Cl.[Br:39][C:40]1[CH:45]=[CH:44][CH:43]=[CH:42][C:41]=1[C:46]([N:48]1[CH2:53][CH2:52][NH:51][CH2:50][CH2:49]1)=[O:47]>CN(C=O)C.O>[Br:39][C:40]1[CH:45]=[CH:44][CH:43]=[CH:42][C:41]=1[C:46]([N:48]1[CH2:49][CH2:50][N:51]([C:24](=[O:26])[CH2:23][C:22]([NH:21][C:19]2[O:18][N:17]=[C:16]([C:10]3[CH:11]=[CH:12][CH:13]=[CH:14][CH:15]=3)[CH:20]=2)=[O:27])[CH2:52][CH2:53]1)=[O:47]

Participants

7

Reactant 4

HCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 57875817N-(3-phenyl-isoxazol-5-yl)-malonamic acidHCID 66625832(2-Bromo-phenyl)-piperazin-1-yl-methanone hydrochloride

Product 1

HCID 442316833-[4-(2-bromo-benzoyl)-piperazin-1-yl]-3-oxo-N-(3-phenyl-isoxazol-5-yl)-propionamideYield 43.5%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

DIPEA (69.2 mg, 0.55 mmol) was added to a stirred solution of N-(3-phenyl-isoxazol-5-yl)-malonamic acid (45 mg, 0.18 mmol) in DMF (2 mL) followed by HOBt (29 mg, 0.22 mmol). After 2 minutes of stirring, (2-bromo-phenyl)-piperazin-1-yl-methanone hydrochloride (67 mg, 0.22 mmol) was added and stirring was continued at ambient temperature overnight. The reaction mixture was diluted with water and extracted with ethyl acetate. The organic layer was washed with brine solution, dried over Na2SO4 and concentrated to afford 38.9 mg (43.22% Yield) of 3-[4-(2-bromo-benzoyl)-piperazin-1-yl]-3-oxo-N-(3-phenyl-isoxazol-5-yl)-propionamide. LC/MS [M+1]+: 497.07, 97.0%. 1H NMR: (300 MHz, DMSO-d6): δ 11.8 (bs, 1H), 7.92-7.8 (m, 2H), 7.5 (d, 1H), 7.6-7.3 (m, 6H), 6.8-6.7 (d, 1H), 3.8-3.4 (m, 8H), 3.24-3.04 (m, 2H).

Workup

  1. stirringstirring
  2. waitwas continued at ambient temperature overnight
  3. extractionextracted with ethyl acetate
  4. washThe organic layer was washed with brine solution
  5. dry with materialdried over Na2SO4
  6. concentrationconcentrated

Sources & evidence

ORD record
ord-db137e823b9a477d9af9d5844aee295d
Source dataset
uspto-grants-2011_10
Patent number
US08039463B2

Reaction notes

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