1-Hydroxybenzotriazole → N-biphenyl-4-yl-3-[4-(2-bromo-benzoyl)-piperazin-1-yl]-2-methyl-3-oxo-propionamide

HRID 1665677Notes

Reaction equation

HRID 1665677 reaction equation
C1C=CC2N(O)N=NC=2C=1.CCN(C(C)C)C(C)C.CCN=C=NCCCN(C)C.Cl.Cl.[Br:33][C:34]1[CH:39]=[CH:38][CH:37]=[CH:36][C:35]=1[C:40]([N:42]1[CH2:47][CH2:46][NH:45][CH2:44][CH2:43]1)=[O:41].[C:48]1([C:62]2[CH:67]=[CH:66][CH:65]=[CH:64][CH:63]=2)[CH:53]=[CH:52][C:51]([NH:54][C:55](=[O:61])[CH:56]([CH3:60])[C:57](O)=[O:58])=[CH:50][CH:49]=1>CN(C=O)C.O>[C:48]1([C:62]2[CH:63]=[CH:64][CH:65]=[CH:66][CH:67]=2)[CH:53]=[CH:52][C:51]([NH:54][C:55](=[O:61])[CH:56]([CH3:60])[C:57]([N:45]2[CH2:44][CH2:43][N:42]([C:40](=[O:41])[C:35]3[CH:36]=[CH:37][CH:38]=[CH:39][C:34]=3[Br:33])[CH2:47][CH2:46]2)=[O:58])=[CH:50][CH:49]=1

Participants

8

Reactant 5

HCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 57875794N-biphenyl-4-yl-2-methyl-malonamic acidHCID 66625832(2-Bromo-phenyl)-piperazin-1-yl-methanone hydrochloride

Product 1

HCID 44231681N-biphenyl-4-yl-3-[4-(2-bromo-benzoyl)-piperazin-1-yl]-2-methyl-3-oxo-propionamideYield 73%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

HOBt (60 mg, 0.44 mmol), DIPEA (140 mg, 1.1 mmol), EDCI.HCl (85 mg, 0.44 mmol) followed by (2-bromo-phenyl)-piperazin-1-yl-methanone hydrochloride (136 mg, 0.44 mmol), were added to a stirred solution of N-biphenyl-4-yl-2-methyl-malonamic acid (100 mg, 0.37 mmol) in DMF (2.0 mL). The resulting mixture was stirred at ambient temperature overnight then diluted with water. The product was extracted with ethyl acetate. The ethyl acetate layer was washed with brine and concentrated under reduced pressure to afford 140 mg (73%) of N-biphenyl-4-yl-3-[4-(2-bromo-benzoyl)-piperazin-1-yl]-2-methyl-3-oxo-propionamide. LCMS: 520.12 (M+1)+, 97.32%, 1H NMR (DMSO-d6): δ 10.2 (d, 1H), 7.8-7.3 (m, 13H), 4.0-3.4 (m, 7H), 3.2-3.0 (m, 2H), 1.3 (m, 3H).

Workup

  1. extractionThe product was extracted with ethyl acetate
  2. washThe ethyl acetate layer was washed with brine
  3. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-4a600e8a4f1a4b0cabceebb5b2e4653b
Source dataset
uspto-grants-2011_10
Patent number
US08039463B2

Reaction notes

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