1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → 3-[4-(2-bromo-benzoyl)-piperazin-1-yl]-N-[5-(4-fluoro-phenyl)-isoxazol-3-yl]-3-oxo-propionamide

HRID 1665689Notes

Reaction equation

HRID 1665689 reaction equation
CCN(C(C)C)C(C)C.[F:10][C:11]1[CH:16]=[CH:15][C:14]([C:17]2[O:21][N:20]=[C:19]([NH:22][C:23](=[O:28])[CH2:24][C:25]([OH:27])=O)[CH:18]=2)=[CH:13][CH:12]=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[CH2:65][CH2:64][NH:63][CH2:62][CH2:61]1)=[O:59]>CN(C=O)C>[Br:51][C:52]1[CH:57]=[CH:56][CH:55]=[CH:54][C:53]=1[C:58]([N:60]1[CH2:61][CH2:62][N:63]([C:25](=[O:27])[CH2:24][C:23]([NH:22][C:19]2[CH:18]=[C:17]([C:14]3[CH:13]=[CH:12][C:11]([F:10])=[CH:16][CH:15]=3)[O:21][N:20]=2)=[O:28])[CH2:64][CH2:65]1)=[O:59]

Participants

7

Reactant 5

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 57875816N-[5-(4-fluoro-phenyl)-isoxazol-3-yl]-malonamic acidHCID 66625832(2-Bromo-phenyl)-piperazin-1-yl-methanone hydrochloride

Product 1

HCID 442317963-[4-(2-bromo-benzoyl)-piperazin-1-yl]-N-[5-(4-fluoro-phenyl)-isoxazol-3-yl]-3-oxo-propionamideYield 28.5%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

DIPEA (57 mg, 0.078 mL, 0.45 mmol) was added dropwise to N-[5-(4-fluoro-phenyl)-isoxazol-3-yl]-malonamic acid (40 mg, 0.15 mmol) in DMF (2 mL) followed by EDCI (35 mg, 0.18 mmol) and HOBT (24 mg, 0.18 mmol). After 2 minutes, (2-bromo-phenyl)-piperazin-1-yl-methanone hydrochloride (55 mg, 0.18 mmol) was added and stirring was continued at room temperature overnight. The reaction mixture was quenched with cold water and was then extracted with ethyl acetate, washed with brine, dried over Na2SO4, and concentrated under reduced pressure. Purification by preparative HPLC afforded 22 mg (28.27% yield) of 3-[4-(2-bromo-benzoyl)-piperazin-1-yl]-N-[5-(4-fluoro-phenyl)-isoxazol-3-yl]-3-oxo-propionamide. LC/MS [M+H]+: 515.07, 96.02%. 1H NMR (300 MHz, DMSO-d6): δ 11.4-11.2 (m, 1H), 7.8 (m, 2H), 7.6 (d, 1H), 7.4-7.2 (m, 5H), 7.1 (t, 2H), 6.6 (d, 1H), 4.1-3.9 (m, 2H), 3.8-3.2 (m, 10H).

Workup

  1. waitwas continued at room temperature overnight
  2. customThe reaction mixture was quenched with cold water
  3. extractionwas then extracted with ethyl acetate
  4. washwashed with brine
  5. dry with materialdried over Na2SO4
  6. concentrationconcentrated under reduced pressure
  7. customPurification by preparative HPLC

Sources & evidence

ORD record
ord-479f1968a072435c865a863edd8dad3b
Source dataset
uspto-grants-2011_10
Patent number
US08039463B2

Reaction notes

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