2,5-Dichlorobenzoic acid → Biphenyl-4-carboxylicacid {2-[4-(2,5-dichloro-benzoyl)-piperazin-1-yl]-2-oxo-ethyl}-amide

HRID 1178010Notes

Reaction equation

HRID 1178010 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.[Cl:63][C:64]1[CH:72]=[CH:71][C:70]([Cl:73])=[CH:69][C:65]=1[C:66](O)=[O:67]>CN(C=O)C.O>[Cl:63][C:64]1[CH:72]=[CH:71][C:70]([Cl:73])=[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 57842,5-Dichlorobenzoic 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 25166106Biphenyl-4-carboxylicacid {2-[4-(2,5-dichloro-benzoyl)-piperazin-1-yl]-2-oxo-ethyl}-amideYield 31.8%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

DIPEA (110 mg, 0.85 mmol) was added to a stirred solution of biphenyl-4-carboxylic acid (2-oxo-2-piperazin-1-yl-ethyl)-amide TFA salt (100 mg, 0.22 mmol) in DMF (3 mL). HOBT (28.3 mg, 0.2 mmol) and EDCI.HCl (91.25 mg, 0.47 mmol) were then added. After 2 minutes 2,5-dichlorobenzoic acid (36.4 mg, 0.19 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 preparative HPLC (Column: Zorbax-XDB-9.4×250 mm, 5 μm, mobile phase: A-0.1% Trifluoroacetic acid, B-Acetonitrile, Flow: 7 ml/min). The product obtained was extracted with ethyl acetate and the ethyl acetate layer was washed with NaHCO3 solution, saturated brine solution, dried over sodium sulphate and concentrated to afford 30 mg (26.5% yield) of biphenyl-4-carboxylicacid {2-[4-(2,5-dichloro-benzoyl)-piperazin-1-yl]-2-oxo-ethyl}-amide. LC-MS purity: 99.5%, 1H NMR: (DMSO) δ 8.6 (t, 1H), 8.0 (d, 2H), 7.7 (q, 4H), 7.5 (m, 5H), 7.4 (t, 1H), 4.25-4.1 (m, 2H), 3.8-3.6 (m, 4H), 3.5-3.4 (m, 2H), 3.25 (m, 2H).

Workup

  1. customthe product was precipitated
  2. customisolated by filtration
  3. customto afford crude product, which
  4. customwas purified by preparative HPLC (Column
  5. customThe product obtained
  6. extractionwas extracted with ethyl acetate
  7. washthe ethyl acetate layer was washed with NaHCO3 solution, saturated brine solution
  8. dry with materialdried over sodium sulphate
  9. concentrationconcentrated

Sources & evidence

ORD record
ord-718ea68bd3e543459a4d18e098591b0a
Source dataset
uspto-grants-2010_11
Patent number
US07842696B2

Reaction notes

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