1-Methylpiperazine → 1-{2,2-Dimethyl-3-[4-(4-methylphenyl)-piperazin-1-yl]-3-oxopropyl}-4-methylpiperazine

HRID 417991

Reaktionsgleichung

Reaktionsgleichung von HRID 417991
Br[CH:2]1[NH:7][CH2:6][CH2:5][N:4]([C:8]2[CH:13]=[CH:12][C:11]([CH3:14])=[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])([C:17]([N:7]1[CH2:6][CH2:5][N:4]([C:8]2[CH:13]=[CH:12][C:11]([CH3:14])=[CH:10][CH:9]=2)[CH2:3][CH2:2]1)=[O:18])[CH2:19][N:25]1[CH2:26][CH2:27][N:22]([CH3:21])[CH2:23][CH2:24]1

Komponenten

5

Edukt 2

HCID 531671-MethylpiperazineHCID 866357783-Bromo-1-(4-methylphenyl)piperazine 2,2-dimethylpropan-1-one

Produkt 1

HCID 579554731-{2,2-Dimethyl-3-[4-(4-methylphenyl)-piperazin-1-yl]-3-oxopropyl}-4-methylpiperazineAusbeute 23,2 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 6344DichloromethaneLösungsmittelHCID 13387N-methyl-2-pyrrolidoneLösungsmittel

Reaktionsbedingungen

Temperatur
200 °C

Versuchsvorschrift

3-Bromo-1-(4-methylphenyl)piperazine-2,2-dimethylpropan-1-one (6.00 g, 17.68 mmol) was dissolved in N-methylpyrrolidinone (12 mL). N-Methylpiperazine (4.12 mL, 37.94 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 (300 mL), and washed with a 0.5M aq KOH solution (100 mL), water (100 mL), brine (100 mL), and then dried (MgSO4) and concentrated in vacuo. The residue was dissolved in DCM (100 mL) and methyl isocyanate resin (2.0 g) was added, and the reaction mixture was shaken for 48 hours, filtered and then concentrated in vacuo. The resulting residue was purified by reverse phase 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 K2CO3 for 20 minutes, filtered and concentrated in vacuo, to give a pale brown oil which was recrystallised from heptane to give 1-{2,2-dimethyl-3-[4-(4-methylphenyl)-piperazin-1-yl]-3-oxopropyl}-4-methylpiperazine (1.47 g, 23.2%) as a white solid.

Aufarbeitung

  1. customThe reaction mixture was split into four batches
  2. customThe reaction mixtures
  3. washwashed with a 0.5M aq KOH solution (100 mL), water (100 mL), brine (100 mL)
  4. dry with materialdried (MgSO4)
  5. concentrationconcentrated in vacuo
  6. dissolutionThe residue was dissolved in DCM (100 mL)
  7. additionmethyl isocyanate resin (2.0 g) was added
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo
  10. customThe resulting residue was purified by reverse phase chromatography (gradient
  11. washeluting with MeOH in water, with 1% formic acid in each solvent, 0-30%)
  12. dissolutionThe resulting residue was dissolved in DCM (100 mL)
  13. stirringstirred with solid K2CO3 for 20 minutes
  14. filtrationfiltered
  15. concentrationconcentrated in vacuo
  16. customto give a pale brown oil which
  17. customwas recrystallised from heptane

Quellen und Nachweise

ORD-Eintrag
ord-6f0f8f75ea3844ce93de8098bbb352e6
Quelldatensatz
uspto-grants-2012_01
Patentnummer
US08093248B2

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