2-Fluorobenzoic acid → Biphenyl-4-carboxylicacid {2-[4-(2-fluoro-benzoyl)-piperazin-1-yl]-2-oxo-ethyl}-amide

HRID 1178011Notes

Reaction equation

HRID 1178011 reaction equation
CCN(C(C)C)C(C)C.OC(C(F)(F)F)=O.[O:17]=[C:18]([N:35]1[CH2:40][CH2:39][NH:38][CH2:37][CH2:36]1)[CH2:19][NH:20][C:21]([C:23]1[CH:28]=[CH:27][C:26]([C:29]2[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=2)=[CH:25][CH:24]=1)=[O:22].C1C=CC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C.Cl.[F:63][C:64]1[CH:72]=[CH:71][CH:70]=[CH:69][C:65]=1[C:66](O)=[O:67]>CN(C=O)C.O>[F:63][C:64]1[CH:72]=[CH:71][CH:70]=[CH:69][C:65]=1[C:66]([N:38]1[CH2:39][CH2:40][N:35]([C:18](=[O:17])[CH2:19][NH:20][C:21]([C:23]2[CH:24]=[CH:25][C:26]([C:29]3[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=3)=[CH:27][CH:28]=2)=[O:22])[CH2:36][CH2:37]1)=[O:67]

Participants

8

Reactant 5

HCID 99352-Fluorobenzoic acidHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 131728551biphenyl-4-carboxylic acid (2-oxo-2-piperazin-1-yl-ethyl)-amide TFA salt

Product 1

HCID 25166105Biphenyl-4-carboxylicacid {2-[4-(2-fluoro-benzoyl)-piperazin-1-yl]-2-oxo-ethyl}-amideYield 42.2%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

DIPEA (77.35 mg, 0.598 mmol) was added to a stirred solution of biphenyl-4-carboxylicacid (2-oxo-2-piperazin-1-yl-ethyl)-amide TFA salt (70 mg, 0.16 mmol) in DMF (2 mL). HOBT (19.8 mg, 0.15 mmol) and EDCI.HCl (63.74 mg, 0.33 mmol) were then added. After 2 minutes 2-fluorobenzoic acid (18.6 mg, 0.133 mmol) was added and the resulting mixture was stirred overnight. The reaction mixture was diluted with cold water and the product was precipitated and isolated by filtration to afford crude product, which was purified by column chromotography (using silica gel of 160-120 mesh and 50% EtOAc in hexane as eluent) to afford 25 mg (41.4% yield) of Biphenyl-4-carboxylicacid {2-[4-(2-fluoro-benzoyl)-piperazin-1-yl]-2-oxo-ethyl}-amide. LC-MS purity: 94.8%, 1H NMR: (CDCl3) δ 7.9 (d, 2H), 7.6 (dd, 4H), 7.4 (m, 4H), 7.2 (s, 1H), 7.1 (t, 1H), 4.4 (dd, 2H), 3.8 (t, 2H), 3.6 (t, 4H), 3.4 (s, 2H).

Workup

  1. customthe product was precipitated
  2. customisolated by filtration
  3. customto afford crude product, which
  4. customwas purified by column chromotography (using silica gel of 160-120 mesh and 50% EtOAc in hexane as eluent)

Sources & evidence

ORD record
ord-030eaf54243b420cafc8317faadf9f1c
Source dataset
uspto-grants-2010_11
Patent number
US07842696B2

Reaction notes

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