Dimethylformamide → 1H-Pyrrolo[2,3-b]pyridine-5-carbonitrile

HRID 2114055Notes

Reaction equation

HRID 2114055 reaction equation
Br[C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][N:6]=[CH:5]2.[CH3:11][N:12](C=O)C>[Cl-].[Cl-].[Zn+2].C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[NH:12]1[C:11]2=[N:7][CH:8]=[C:4]([C:5]#[N:6])[CH:3]=[C:2]2[CH:10]=[CH:9]1

Participants

5

Reactant 2

HCID 6228DimethylformamideHCID 7619295-bromo-1H-indazole

Product 1

HCID 117883551H-Pyrrolo[2,3-b]pyridine-5-carbonitrileYield 75%

Reagents, catalysts & solvents 2

HCID 3007855ZincchlorideCatalystHCID 178418397HCID 178418397, compoundCatalyst

Conditions

Temperature
80 °C

Procedure

A mixture of bromide 24 (10.0 g, 50.8 mmol), ZnCl2 (3.58 g, 30.5 mmol), and Pd(PPh3)4 (3.52 g, 3.05 mmol) in DMF (110 mL) was heated at 80° C. overnight. The solvent was evaporated and the residue separated by silicagel chromatography (100 g column) using hexane:ethyl acetate as eluent (gradient elution). The resulting solid was partitioned between water (200 mL)/CH2Cl2 (100 mL) and the aqueous phase extracted with more CH2Cl2 (4×100 mL). The combined organic extracts were dried (MgSO4) and concentrated to give the product as a white solid (5.48 g, 75%), which was used for subsequent reactions without further purification.

Workup

  1. customThe solvent was evaporated
  2. customthe residue separated by silicagel chromatography (100 g column)
  3. washethyl acetate as eluent (gradient elution)
  4. customThe resulting solid was partitioned between water (200 mL)/CH2Cl2 (100 mL)
  5. extractionthe aqueous phase extracted with more CH2Cl2 (4×100 mL)
  6. dry with materialThe combined organic extracts were dried (MgSO4)
  7. concentrationconcentrated

Sources & evidence

ORD record
ord-9ed682214c4146bc9514781a888c7847
Source dataset
uspto-grants-2008_10
Patent number
US07432375B2

Reaction notes

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