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

HRID 1178013Notes

Reaction equation

HRID 1178013 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][C:67]([C:68](O)=[O:69])=[CH:66][CH:65]=1>CN(C=O)C.O>[F:63][C:64]1[CH:72]=[CH:71][C:67]([C:68]([N:38]2[CH2:39][CH2:40][N:35]([C:18](=[O:17])[CH2:19][NH:20][C:21]([C:23]3[CH:24]=[CH:25][C:26]([C:29]4[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=4)=[CH:27][CH:28]=3)=[O:22])[CH2:36][CH2:37]2)=[O:69])=[CH:66][CH:65]=1

Participants

8

Reactant 5

HCID 99734-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 25166102Biphenyl-4-carboxylicacid {2-[4-(4-fluoro-benzoyl)-piperazin-1-yl]-2-oxo-ethyl}-amideYield 47.3%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

DIPEA (77.35 mg, 0.60 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, 0.14 mmol) and EDCI.HCl (63.74 mg, 0.33 mmol) were then added. After 2 minutes 4-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 filtered to afford 28 mg (46.7% yield) of biphenyl-4-carboxylicacid {2-[4-(4-fluoro-benzoyl)-piperazin-1-yl]-2-oxo-ethyl}-amide. LC-MS purity: 94.8%, 1H NMR Values: (CDCl3) δ 7.9 (d, 2H), 7.7-7.6 (q, 4H), 7.5-7.4 (m, 5H), 7.3 (t, 1H), 7.2-7.1 (t, 2H), 4.4 (d, 2H), 4.0-3.5 (d, 8H).

Workup

  1. customthe product was precipitated
  2. filtrationfiltered

Sources & evidence

ORD record
ord-60356ca351104d98811eccf82221174e
Source dataset
uspto-grants-2010_11
Patent number
US07842696B2

Reaction notes

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