1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → 3-[4-(2-bromo-benzoyl)-piperazin-1-yl]-3-oxo-N-(4-thiophen-3-yl-phenyl)-propionamide

HRID 1665697Notes

Reaction equation

HRID 1665697 reaction equation
[Br:1][C:2]1[CH:21]=[CH:20][CH:19]=[CH:18][C:3]=1[C:4]([N:6]1[CH2:11][CH2:10][N:9]([C:12](=[O:17])[CH2:13][C:14]([OH:16])=O)[CH2:8][CH2:7]1)=[O:5].CCN=C=NCCCN(C)C.C1C=CC2N(O)N=NC=2C=1.[S:43]1[CH:47]=[CH:46][C:45]([C:48]2[CH:53]=[CH:52][C:51]([NH2:54])=[CH:50][CH:49]=2)=[CH:44]1>CN(C1C=CN=CC=1)C.CN(C=O)C.O>[Br:1][C:2]1[CH:21]=[CH:20][CH:19]=[CH:18][C:3]=1[C:4]([N:6]1[CH2:7][CH2:8][N:9]([C:12](=[O:17])[CH2:13][C:14]([NH:54][C:51]2[CH:50]=[CH:49][C:48]([C:45]3[CH:46]=[CH:47][S:43][CH:44]=3)=[CH:53][CH:52]=2)=[O:16])[CH2:10][CH2:11]1)=[O:5]

Participants

8

Reactant 4

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 41303364-(Thiophen-3-yl)anilineHCID 578758013-[4-(2-Bromo-benzoyl)-piperazin-1-yl]-3-oxo-propionic acid

Product 1

HCID 442318003-[4-(2-bromo-benzoyl)-piperazin-1-yl]-3-oxo-N-(4-thiophen-3-yl-phenyl)-propionamideYield 19.2%

Reagents, catalysts & solvents 3

HCID 142844-(Dimethylamino)pyridineCatalystHCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

DMAP (104 mg, 0.85 mmol) was added to 3-[4-(2-bromo-benzoyl)-piperazin-1-yl]-3-oxo-propionic acid (167 mg, 0.47 mmol) in DMF (2 mL) followed by EDCI (90 mg, 0.47 mmol) and HOBT (63 mg, 0.47 mmol). After 2 minutes, 4-thiophen-3-yl-phenylamine (75 mg, 0.43 mmol) was added and stirring was continued at room temperature overnight. Cold water was added and the formed precipitate was collected. Purification by preparative HPLC afforded 42 mg (19.2% yield) of 3-[4-(2-bromo-benzoyl)-piperazin-1-yl]-3-oxo-N-(4-thiophen-3-yl-phenyl)-propionamide. LC/MS [M+H]+: 512.06, 93.02%. 1H NMR (300 MHz, CDCl3): δ 9.6 (d, 1H), 7.85-7.5 (m, 5H), 7.46-7.34 (m, 4H), 7.34-7.26 (m, 2H), 4.09-3.9 (m, 2H), 3.82-3.64 (m, 4H), 3.58-3.52 (s, 1H), 3.5-3.44 (s, 1H), 3.42-3.32 (m, 1H), 3.3-3.18 (m, 1H).

Workup

  1. waitwas continued at room temperature overnight
  2. customthe formed precipitate was collected
  3. customPurification by preparative HPLC

Sources & evidence

ORD record
ord-977753299297408abcc7e8d8c6c64c1d
Source dataset
uspto-grants-2011_10
Patent number
US08039463B2

Reaction notes

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