Hydrochloric Acid → 1-(4-(2'-Chloro-5-methoxy-[1,1'-biphenyl]-3-carbonyl)piperazin-1-yl)prop-2-en-1-one

HRID 588810Notes

Reaction equation

HRID 588810 reaction equation
[C:1]([N:5]1[CH2:10][CH2:9][N:8]([C:11]([O:13]C(C)(C)C)=O)[CH2:7][CH2:6]1)(=[O:4])[CH:2]=[CH2:3].Cl.CO.[Cl:21][C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][C:23]=1[C:28]1[CH:29]=[C:30]([CH:34]=[C:35]([O:37][CH3:38])[CH:36]=1)C(O)=O.C1C=CC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C.Cl.CCN(CC)CC>C(Cl)Cl.CN(C=O)C>[Cl:21][C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][C:23]=1[C:28]1[CH:36]=[C:35]([O:37][CH3:38])[CH:34]=[C:30]([C:11]([N:8]2[CH2:7][CH2:6][N:5]([C:1](=[O:4])[CH:2]=[CH2:3])[CH2:10][CH2:9]2)=[O:13])[CH:29]=1

Participants

10

Reactant 7

HCID 313Hydrochloric AcidHCID 887MethanolHCID 8471TriethylamineHCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 532258043-(2-Chlorophenyl)-5-methoxybenzoic acidHCID 58593060tert-Butyl 4-acryloylpiperazine-1-carboxylate

Product 1

HCID 1176071631-(4-(2'-Chloro-5-methoxy-[1,1'-biphenyl]-3-carbonyl)piperazin-1-yl)prop-2-en-1-oneYield 52%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

To a solution of tert-butyl 4-acryloylpiperazine-1-carboxylate (260 mg, 1.07 mmol) in DCM (2 mL), a solution of HCl in MeOH (10 mL, 28.6 mmol) was added and the resulting mixture was stirred at room temperature for 1 h. The mixture was concentrated in vacuo. The residue was added to the solution of 3-(2-chlorophenyl)-5-methoxybenzoic acid (280 mg, 1.07 mmol), HOBt (290 mg, 2.17 mmol), EDCI.HCl (410 mg, 2.17 mmol) and Et3N (324 mg, 3.21 mmol) in DMF (10 mL). The resulting mixture was stirred at room temperature for 16 h and partitioned between DCM and saturated NaHCO3 solution. The organic layer was dried over MgSO4, filtered and concentrated in vacuo. The residue was purified by flash column chromatography on silica gel (dichloromethane/methanol=50:1) to afford the desired product (200 mg, 52% yield). ESI-MS m/z: 385.2[M+H]+.

Workup

  1. concentrationThe mixture was concentrated in vacuo
  2. stirringThe resulting mixture was stirred at room temperature for 16 h
  3. custompartitioned between DCM and saturated NaHCO3 solution
  4. dry with materialThe organic layer was dried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified by flash column chromatography on silica gel (dichloromethane/methanol=50:1)

Sources & evidence

ORD record
ord-7285c600060044cd938c36ed92417e48
Source dataset
uspto-grants-2016_01
Patent number
US09227978B2

Reaction notes

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