1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → N-biphenyl-4-yl-3-[4-(2-bromo-benzoyl)-[1,4]diazepan-1-yl]-3-oxo-propionamide

HRID 1665686

Reaction equation

HRID 1665686 reaction equation
CCN(C(C)C)C(C)C.[C:10]1([C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)[CH:15]=[CH:14][C:13]([NH:16][C:17](=[O:22])[CH2:18][C:19]([OH:21])=O)=[CH:12][CH:11]=1.CCN=C=NCCCN(C)C.C1C=CC2N(O)N=NC=2C=1.Cl.[Br:51][C:52]1[CH:57]=[CH:56][CH:55]=[CH:54][C:53]=1[C:58]([N:60]1[CH2:66][CH2:65][CH2:64][NH:63][CH2:62][CH2:61]1)=[O:59]>CN(C=O)C.O>[C:10]1([C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)[CH:11]=[CH:12][C:13]([NH:16][C:17](=[O:22])[CH2:18][C:19]([N:63]2[CH2:64][CH2:65][CH2:66][N:60]([C:58](=[O:59])[C:53]3[CH:54]=[CH:55][CH:56]=[CH:57][C:52]=3[Br:51])[CH2:61][CH2:62]2)=[O:21])=[CH:14][CH:15]=1

Participants

8

Reactant 5

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 55049154N-biphenyl-4-yl-malonamic acidHCID 66625409(2-Bromophenyl)(1,4-diazepan-1-yl)methanone hydrochloride

Product 1

HCID 44231685N-biphenyl-4-yl-3-[4-(2-bromo-benzoyl)-[1,4]diazepan-1-yl]-3-oxo-propionamideYield 54.2%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

DIPEA (146 mg, 0.2 mL, 1.17 mmol) was added dropwise to N-biphenyl-4-yl-malonamic acid (100 mg, 0.39 mmol) in DMF (2 mL) followed by EDCI (90 mg, 0.47 mmol) and HOBT (63 mg, 0.47 mmol). After 2 minutes, (2-bromo-phenyl)-[1,4]diazepan-1-yl-methanone hydrochloride (150 mg, 0.47 mmol) was added and stirring was continued at room temperature overnight. Cold water was then added and extracted with ethyl acetate. The organic layer was washed with brine, dried over Na2SO4, and concentrated under reduced pressure to afford 110 mg (54.18% yield) of N-biphenyl-4-yl-3-[4-(2-bromo-benzoyl)-[1,4]diazepan-1-yl]-3-oxo-propionamide. LC/MS [M+H]+: 520.12, 96.67%. 1H NMR (300 MHz, DMSO-d6): δ 10.3-10.2 (m, 1H), 7.8-6.7 (m, 13H), 4.1-3.4 (m, 9H), 3.3-3.0 (m, 2H), 2.0-1.8 (m, 1H), 1.7-1.5 (m, 1H).

Workup

  1. waitwas continued at room temperature overnight
  2. extractionextracted with ethyl acetate
  3. washThe organic layer was washed with brine
  4. dry with materialdried over Na2SO4
  5. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-755284caf33f424ea1545ed90c125c35
Source dataset
uspto-grants-2011_10
Patent number
US08039463B2

Linked notes

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