Dimethylacetamide → 1-((2-(Trimethylsilyl)ethoxy)methyl)-1H-pyrrolo[2,3-b]pyridine-5-carbonitrile

HRID 389110Notes

Reaction equation

HRID 389110 reaction equation
C1(C2C=CC=CC=2)C=CC=CC=1P(C(C)(C)C)C(C)(C)C.Br[C:23]1[CH:24]=[C:25]2[CH:31]=[CH:30][N:29]([CH2:32][O:33][CH2:34][CH2:35][Si:36]([CH3:39])([CH3:38])[CH3:37])[C:26]2=[N:27][CH:28]=1.C[C:41]([N:43](C)C)=O>[C-]#N.[Zn+2].[C-]#N.[Zn]>[CH3:37][Si:36]([CH3:39])([CH3:38])[CH2:35][CH2:34][O:33][CH2:32][N:29]1[C:26]2=[N:27][CH:28]=[C:23]([C:41]#[N:43])[CH:24]=[C:25]2[CH:31]=[CH:30]1

Participants

6

Reactant 3

HCID 31374DimethylacetamideHCID 27342152-(Di-tert-butylphosphino)biphenylHCID 598250161H-Pyrrolo[2,3-B]pyridine, 5-bromo-1-[[2-(trimethylsilyl)ethoxy]methyl]-

Product 1

HCID 582437901-((2-(Trimethylsilyl)ethoxy)methyl)-1H-pyrrolo[2,3-b]pyridine-5-carbonitrile

Reagents, catalysts & solvents 2

HCID 11186Zinc cyanide (Zn(CN)2)CatalystHCID 23994ZincCatalyst

Procedure

Zinc cyanide (900 mg), biphenyl-2-yl(di-tert-butyl)phosphine (610 mg) and zinc (67 mg) were added to a solution of 5-bromo-1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-pyrrolo[2,3-b]pyridine (1.917 g) in DMA (25 ml), followed by stirring for 5 minutes while degassing under ice cooling, and palladium (II) trifluoroacetate (338 mg) was added thereto, followed by stirring at 80° C. overnight after making it under an argon atmosphere. Ethyl acetate was added thereto, an insoluble substance was separated by celite filtration, and water was added to the filtrate, followed by extraction. The organic layer was washed with a 3M aqueous ammonia solution and then saturated brine in this order and was dried over anhydrous sodium sulfate, and the solvent was then evaporated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate:hexane=0:100 to 0:100) to obtain, as a colorless amorphous solid, 1-{[2-(trimethylsilyl)ethoxy]methyl}-1H-pyrrolo[2,3-b]pyridine-5-carbonitrile (377 mg).

Workup

  1. customwhile degassing under ice cooling
  2. additionpalladium (II) trifluoroacetate (338 mg) was added
  3. stirringby stirring at 80° C. overnight
  4. additionEthyl acetate was added
  5. customan insoluble substance was separated by celite filtration, and water
  6. additionwas added to the filtrate
  7. extractionfollowed by extraction
  8. washThe organic layer was washed with a 3M aqueous ammonia solution
  9. dry with materialsaturated brine in this order and was dried over anhydrous sodium sulfate
  10. customthe solvent was then evaporated under reduced pressure
  11. customThe residue was purified by silica gel column chromatography (ethyl acetate:hexane=0:100 to 0:100)

Sources & evidence

ORD record
ord-eda98cefadc54d45bcb623578f93350d
Source dataset
uspto-grants-2013_02
Patent number
US08377923B2

Reaction notes

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