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

HRID 417991

반응식

HRID 417991 반응식
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

참가 물질

5

반응물 2

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

생성물 1

HCID 579554731-{2,2-Dimethyl-3-[4-(4-methylphenyl)-piperazin-1-yl]-3-oxopropyl}-4-methylpiperazine수율 23.2%

시약·촉매·용매 2

HCID 6344Dichloromethane용매HCID 13387N-methyl-2-pyrrolidone용매

반응 조건

온도
200 °C

실험 절차

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.

후처리

  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

출처 및 근거

ORD 기록
ord-6f0f8f75ea3844ce93de8098bbb352e6
출처 데이터셋
uspto-grants-2012_01
특허 번호
US08093248B2

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