Diisopropylethylamine → HCID 42633093, compound

HRID 417979Notes

Reaction equation

HRID 417979 reaction equation
[C:1](=[O:22])(OC1C=CC([N+]([O-])=O)=CC=1)[O:2][CH2:3][CH2:4][N:5]1[CH2:10][CH2:9][N:8]([CH3:11])[CH2:7][CH2:6]1.CCN(C(C)C)C(C)C.[C:32]1([CH:38]2[CH2:42][CH2:41][NH:40][CH2:39]2)[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=1>CN(C=O)C>[C:32]1([CH:38]2[CH2:42][CH2:41][N:40]([C:1]([O:2][CH2:3][CH2:4][N:5]3[CH2:6][CH2:7][N:8]([CH3:11])[CH2:9][CH2:10]3)=[O:22])[CH2:39]2)[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=1

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 31467433-PhenylpyrrolidineHCID 574450072-(4-Methylpiperazin-1-yl)ethyl 4-nitrophenyl carbonate2×

Product 1

HCID 42633093HCID 42633093, compoundYield 48%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

2-(4-Methylpiperazin-1-yl)ethyl 4-nitrophenyl carbonate (Intermediate 4; 2.10 g, 6.79 mmol) was dissolved in DMF (30 mL). DIPEA (2.37 mL, 13.59 mmol) and 3-phenylpyrrolidine (1.00 g, 6.79 mmol) were added and the reaction mixture was stirred at room temperature for 4 hours, and the reaction mixture was then concentrated in vacuo. The resulting residue was dissolved in EtOAc (300 mL) and washed with 1M aq Na2CO3 solution (6×200 mL), brine (50 mL), dried (MgSO4) and concentrated in vacuo. The residue was dissolved in DCM (100 mL) and methyl isocyanate resin (2.0 g) was added, the reaction mixture shaken for 14 h, filtered and then concentrated in vacuo. The 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 (60 mL) and stirred with solid K2CO3 for 20 minutes, filtered and concentrated in vacuo, to give 2-(4-methylpiperazin-1-yl)ethyl 3-phenylpyrrolidine-1-carboxylate (1.03 g, 48.0%) as a pale yellow oil.

Workup

  1. concentrationthe reaction mixture was then concentrated in vacuo
  2. dissolutionThe resulting residue was dissolved in EtOAc (300 mL)
  3. washwashed with 1M aq Na2CO3 solution (6×200 mL), brine (50 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. stirringthe reaction mixture shaken for 14 h
  9. filtrationfiltered
  10. concentrationconcentrated in vacuo
  11. customThe residue was purified by reverse phase chromatography (gradient
  12. washeluting with MeOH in water, with 1% formic acid in each solvent, 0-30%)
  13. dissolutionThe resulting residue was dissolved in DCM (60 mL)
  14. stirringstirred with solid K2CO3 for 20 minutes
  15. filtrationfiltered
  16. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-ba09491b73aa4ed4a032f8e4435069be
Source dataset
uspto-grants-2012_01
Patent number
US08093248B2

Reaction notes

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