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

HRID 417991ノート

反応式

HRID 417991 の反応式
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

参加物

5

反応物 2

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

生成物 1

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

試薬・触媒・溶媒 2

HCID 6344Dichloromethane溶媒HCID 13387N-methyl-2-pyrrolidone溶媒

反応条件

温度
200 °C

実験手順

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.

後処理

  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

出典と根拠

ORDレコード
ord-6f0f8f75ea3844ce93de8098bbb352e6
出典データセット
uspto-grants-2012_01
特許番号
US08093248B2

反応ノート

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