N-methyl-2-pyrrolidone → 1H-Pyrrolo[2,3-c]pyridine-4-carbonitrile

HRID 2409054Notes

Reaction equation

HRID 2409054 reaction equation
Br[C:2]1[CH:7]=[N:6][CH:5]=[C:4]2[NH:8][CH:9]=[CH:10][C:3]=12.[CH3:11][N:12]1C(=O)CCC1>[C-]#N.[C-]#N.[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:8]1[C:4]2[CH:5]=[N:6][CH:7]=[C:2]([C:11]#[N:12])[C:3]=2[CH:10]=[CH:9]1

Participants

5

Reactant 2

HCID 13387N-methyl-2-pyrrolidoneHCID 125100554-Bromo-1H-pyrrolo(2,3-c)pyridine

Product 1

HCID 468357241H-Pyrrolo[2,3-c]pyridine-4-carbonitrileYield 85.1%

Reagents, catalysts & solvents 2

HCID 11186Zinc cyanide (Zn(CN)2)CatalystHCID 178418397HCID 178418397, compoundCatalyst

Conditions

Temperature
100 °C

Procedure

To a solution of 4-bromo-1H-pyrrolo[2,3-c]pyridine (1.0 g, 5.08 mmol) in NMP (20 mL) under an argon atmosphere was added Zn(CN)2 (1.19 g, 10.15 mmol) and Pd(PPh3)4 (0) (590 mg, 0.51 mmol). The mixture was heated at 100° C. for 18 h. The reaction mixture was partitioned between EtOAc (300 mL) and water (50 mL). The organic layer was washed with brine, dried (MgSO4), filtered and concentrated under reduced pressure. The residue was purified by SiO2 chromatography eluting with petroleum ether:EtOAc (1:1) to afford 618 mg (85.1%) of 1H-pyrrolo[2,3-c]pyridine-4-carbonitrile as yellow solid. MS (ESI): m/z=144.3 [M+1]+.

Workup

  1. customThe reaction mixture was partitioned between EtOAc (300 mL) and water (50 mL)
  2. washThe organic layer was washed with brine
  3. dry with materialdried (MgSO4)
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure
  6. customThe residue was purified by SiO2 chromatography
  7. washeluting with petroleum ether:EtOAc (1:1)

Sources & evidence

ORD record
ord-384ae216e2ef4cdca07ed150c37ac308
Source dataset
uspto-grants-2014_08
Patent number
US08815877B2

Reaction notes

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