3-Pyrroline → HCID 178469896, compound

HRID 1375648Notes

Reaction equation

HRID 1375648 reaction equation
[CH2:1]([O:3][C:4]([C:6]1[N:7]=[C:8]([C:11]([O:13][CH2:14][C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)=[O:12])[NH:9][CH:10]=1)=[O:5])[CH3:2].[H][H].C1N=CN(C(N2C=NC=C2)=O)C=1.[NH:35]1[CH2:39][CH:38]=[CH:37][CH2:36]1>CCO.CC(N(C)C)=O.[Pd].O>[CH2:1]([O:3][C:4]([C:6]1[N:7]=[C:8]([C:11]([O:13][CH2:14][C:15]2[CH:16]=[CH:17][CH:18]=[CH:19][CH:20]=2)=[O:12])[NH:9][CH:10]=1)=[O:5])[CH3:2].[CH2:1]([O:3][C:4]([C:6]1[N:7]=[C:8]([C:11]([N:35]2[CH2:39][CH:38]=[CH:37][CH2:36]2)=[O:13])[NH:9][CH:10]=1)=[O:5])[CH3:2]

Participants

10

Reactant 4

HCID 660593-PyrrolineHCID 682631,1'-CarbonyldiimidazoleHCID 178418361HCID 178418361, compoundHCID 178469897HCID 178469897, compound

Product 2

HCID 178469896HCID 178469896, compoundYield 66.8%HCID 178469897HCID 178469897, compound

Reagents, catalysts & solvents 4

HCID 23938PalladiumCatalystHCID 702EthanolSolventHCID 962WaterSolventHCID 31374DimethylacetamideSolvent

Procedure

1H-Imidazole-2,4-dicarboxylic acid 2-benzyl ester 4-ethyl ester was prepared in a manner substantially similar to that described by Branco, P. S.; Prabhakar, S.; Lobo, A. M.; Williams, D. Tetrahedron, 1992, 48, 6335. To a solution of 1H-imidazole-2,4-dicarboxylic acid 2-benzyl ester 4-ethyl ester (380 mg, 1.4 mmol) in EtOH (10 mL) was added Pd/C (10%) (40 mg) under N2 atmosphere. The suspension was then treated with hydrogen under 50 psi for 3 hours. The catalyst was removed by filtration through Celite® and the filtrate was evaporated. To a solution of the crude acid (140 mg, 0.76 mmol) in DMA (2 mL) was added CDI (140 mg, 0.86 mmol). The mixture was stirred at ambient temperature for 1 hour and then 2,5-dihydro-1H-pyrrole (110 mg, 1.59 mmol) was added. After stirring at ambient temperature for 2 hours, the reaction mixture was poured into water (5 mL). The aqueous solution was extracted with EtOAc (2×10 mL) and the combined organic layers dried over MgSO4, filtered, and evaporated. The crude product was purified by flash column eluting with 50% EtOAc in hexane to afford the title compound as a white solid (110 mg, 61%). MS (ES+): m/e=236.2 (M+H); Rt=2.04 minutes.

Workup

  1. customThe catalyst was removed by filtration through Celite®
  2. customthe filtrate was evaporated
  3. stirringAfter stirring at ambient temperature for 2 hours
  4. extractionThe aqueous solution was extracted with EtOAc (2×10 mL)
  5. dry with materialthe combined organic layers dried over MgSO4
  6. filtrationfiltered
  7. customevaporated
  8. customThe crude product was purified by flash column
  9. washeluting with 50% EtOAc in hexane

Sources & evidence

ORD record
ord-45d53962ba6e410c934faaad06113b6e
Source dataset
uspto-grants-2007_01
Patent number
US07169800B2

Reaction notes

Loading…