1-Hydroxybenzotriazole → 1-[4-(2-Bromo-benzoyl)-piperazine-1-carbonyl]-cyclopropanecarboxylic acid biphenyl-4-ylamide

HRID 1665681Notes

Reaction equation

HRID 1665681 reaction equation
[CH3:1][CH2:2]N(C(C)C)C(C)C.[C:10]1([C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)[CH:15]=[CH:14][C:13]([N:16](C)[C:17](=[O:22])[CH2:18][C:19]([OH:21])=O)=[CH:12][CH:11]=1.C1C=CC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C.Cl.Cl.[Br:53][C:54]1[CH:59]=[CH:58][CH:57]=[CH:56][C:55]=1[C:60]([N:62]1[CH2:67][CH2:66][NH:65][CH2:64][CH2:63]1)=[O:61]>CN(C=O)C.O>[C:10]1([C:24]2[CH:25]=[CH:26][CH:27]=[CH:28][CH:29]=2)[CH:11]=[CH:12][C:13]([NH:16][C:17]([C:18]2([C:19]([N:65]3[CH2:64][CH2:63][N:62]([C:60](=[O:61])[C:55]4[CH:56]=[CH:57][CH:58]=[CH:59][C:54]=4[Br:53])[CH2:67][CH2:66]3)=[O:21])[CH2:2][CH2:1]2)=[O:22])=[CH:14][CH:15]=1

Participants

8

Reactant 5

HCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 57875814N-biphenyl-4-yl-N-methyl-malonamic acidHCID 66625832(2-Bromo-phenyl)-piperazin-1-yl-methanone hydrochloride

Product 1

HCID 442315631-[4-(2-Bromo-benzoyl)-piperazine-1-carbonyl]-cyclopropanecarboxylic acid biphenyl-4-ylamideYield 12.95%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

DIPEA (140 mg, 1.1 mmol) was added to a stirred solution of N-biphenyl-4-yl-N-methyl-malonamic acid (100 mg, 0.37 mmol) in DMF (2.0 mL) followed by HOBt (60 mg, 0.44 mmol) and EDCI.HCl (85 mg, 0.44 mmol). After 2 minutes of stirring, (2-bromo-phenyl)-piperazin-1-yl-methanone hydrochloride (136 mg, 0.44 mmol) was added and stirring was continued at ambient temperature overnight. The reaction mixture was diluted with water, extracted with ethyl acetate, washed with brine and concentrated under reduced pressure to get the residue. Purification by column chromatography, (using silica gel 60-120, 100% EtOAc as eluent) to afford 14.8 mg (12.95%) of 1-[4-(2-bromo-benzoyl)-piperazine-1-carbonyl]-cyclopropanecarboxylic acid biphenyl-4-ylamide. LC/MS [M+H]+: 520.12, 89.73%. 1H NMR (300 MHz, CDCl3): δ 7.7-7.3 (m, 2H), 7.3-7.2 (m, 2H), 4.0-3.6 (m, 5H), 3.58-3.4 (m, 5H), 3.4-3.2 (m, 3H).

Workup

  1. stirringstirring
  2. waitwas continued at ambient temperature overnight
  3. extractionextracted with ethyl acetate
  4. washwashed with brine
  5. concentrationconcentrated under reduced pressure
  6. customto get the residue
  7. customPurification by column chromatography, (using silica gel 60-120, 100% EtOAc as eluent)

Sources & evidence

ORD record
ord-31990992e7c6486091f949140db51b0e
Source dataset
uspto-grants-2011_10
Patent number
US08039463B2

Reaction notes

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