1-Methylpiperazine → 1-[2,2-Dimethyl-3-(4-methylpiperazin-1-yl)propanoyl]-4-(4-fluorophenyl)piperazine

HRID 417994Notes

Reaction equation

HRID 417994 reaction equation
Br[CH:2]1[NH:7][CH2:6][CH2:5][N:4]([C:8]2[CH:13]=[CH:12][C:11]([F:14])=[CH:10][CH:9]=2)[CH2:3]1.[CH3:15][C:16]([CH3:20])([CH3:19])[CH:17]=[O:18].[CH3:21][N:22]1[CH2:27][CH2:26][NH:25][CH2:24][CH2:23]1>CN1CCCC1=O.C(Cl)Cl>[CH3:15][C:16]([CH3:20])([CH2:19][N:25]1[CH2:26][CH2:27][N:22]([CH3:21])[CH2:23][CH2:24]1)[C:17]([N:7]1[CH2:6][CH2:5][N:4]([C:8]2[CH:13]=[CH:12][C:11]([F:14])=[CH:10][CH:9]=2)[CH2:3][CH2:2]1)=[O:18]

Participants

5

Reactant 2

HCID 531671-MethylpiperazineHCID 866357803-Bromo-1-(4-fluorophenyl)piperazine 2,2-dimethylpropan-1-one

Product 1

HCID 579554711-[2,2-Dimethyl-3-(4-methylpiperazin-1-yl)propanoyl]-4-(4-fluorophenyl)piperazineYield 21.3%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
200 °C

Procedure

3-Bromo-1-(4-fluorophenyl)piperazine-2,2-dimethylpropan-1-one (2.00 g, 5.83 mmol) was dissolved in N-methylpyrrolidinone (10 mL). N-Methylpiperazine (1.30 mL, 11.7 mmol) was added. The reaction mixture was split into four batches and each was heated at 200° C. for 15 minutes in a Biotage Initiator microwave at high absorption. The reaction mixtures were combined and dissolved in DCM (100 mL), and washed with water (2×80 mL), dried (MgSO4) and concentrated in vacuo. The resulting residue was purified by reverse phase column chromatography (gradient eluting with MeOH in water, with 1% formic acid in each solvent, 0-30%). The resulting residue was dissolved in DCM (100 mL) and stirred with solid Na2CO3 for 20 minutes, filtered and concentrated in vacuo, to give 1-[2,2-dimethyl-3-(4-methylpiperazin-1-yl)propanoyl]-4-(4-fluorophenyl)piperazine (451 mg, 21%) as a yellow oil.

Workup

  1. customThe reaction mixture was split into four batches
  2. customThe reaction mixtures
  3. washwashed with water (2×80 mL)
  4. dry with materialdried (MgSO4)
  5. concentrationconcentrated in vacuo
  6. customThe resulting residue was purified by reverse phase column chromatography (gradient
  7. washeluting with MeOH in water, with 1% formic acid in each solvent, 0-30%)
  8. dissolutionThe resulting residue was dissolved in DCM (100 mL)
  9. filtrationfiltered
  10. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-a1f3e5134fd049eeb886a0b9cd9a94d3
Source dataset
uspto-grants-2012_01
Patent number
US08093248B2

Reaction notes

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