Sodium Bicarbonate → 6-(2-bromo-5H-pyrrolo[2,3-b]pyrazin-7-yl)-5,5-dimethyl-6-oxo-hexanenitrile

HRID 1677521Notes

Reaction equation

HRID 1677521 reaction equation
[Cl-].C([Al+]CC)C.[Br:7][C:8]1[N:9]=[C:10]2[CH:16]=[CH:15][NH:14][C:11]2=[N:12][CH:13]=1.[C:17]([CH2:19][CH2:20][CH2:21][C:22]([CH3:27])([CH3:26])[C:23](Cl)=[O:24])#[N:18].C([O-])(O)=O.[Na+]>ClCCl.C(OCC)(=O)C>[Br:7][C:8]1[N:9]=[C:10]2[C:16]([C:23](=[O:24])[C:22]([CH3:27])([CH3:26])[CH2:21][CH2:20][CH2:19][C:17]#[N:18])=[CH:15][NH:14][C:11]2=[N:12][CH:13]=1

Participants

7

Reactant 4

HCID 516892Sodium BicarbonateHCID 16686102Diethyl aluminum chlorideHCID 250673082-bromo-5H-pyrrolo[2,3-b]pyrazineHCID 59540530HCID 59540530, compound

Product 1

HCID 595407676-(2-bromo-5H-pyrrolo[2,3-b]pyrazin-7-yl)-5,5-dimethyl-6-oxo-hexanenitrileYield 20%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolvent2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
2.5 °C

Procedure

Diethylaluminum chloride (1.0 M in CH2Cl2, 3.6 mL, 3.6 mmol) was added to a 0-5° C. mixture of 2-bromo-5H-pyrrolo[2,3-b]pyrazine (0.237 g, 1.20 mmol) and 5 mL of dichloromethane in a sealed tube, and the mixture was stirred at 0-5° C. for 30 min. Crude 5-cyano-2,2-dimethyl-pentanoyl chloride from the previous step (“2.98 mmol”) dissolved in 3 mL of dichloromethane was added, and the mixture was stirred at 60° C. for 16 h. A sat. aq. NaHCO3 solution (50 mL) was carefully added, followed by 50 mL of ethyl acetate. The mixture was filtered through Celite, and the layers separate. The aqueous layer was extracted with 50 mL of ethyl acetate. The combined organic layers were dried over MgSO4, filtered and concentrated to a residue. Column chromatography (0→80% EtOAc/hexanes) afforded 0.079 g (20%) of 6-(2-bromo-5H-pyrrolo[2,3-b]pyrazin-7-yl)-5,5-dimethyl-6-oxo-hexanenitrile as a yellow liquid.

Workup

  1. additionwas added
  2. stirringthe mixture was stirred at 60° C. for 16 h
  3. filtrationThe mixture was filtered through Celite
  4. customthe layers separate
  5. extractionThe aqueous layer was extracted with 50 mL of ethyl acetate
  6. dry with materialThe combined organic layers were dried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated to a residue

Sources & evidence

ORD record
ord-41c8531f383a4ac28aac61a3cdaa7564
Source dataset
uspto-grants-2011_08
Patent number
US08008298B2

Reaction notes

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