Nitrogen → 4-Isoquinolinecarbonitrile

HRID 1470479Notes

Reaction equation

HRID 1470479 reaction equation
Br[C:2]1[N:3]=[CH:4][C:5]2[C:10]([CH:11]=1)=[CH:9][CH:8]=[CH:7][CH:6]=2.N#N.[CH3:14][N:15](C=O)C>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.[C-]#N.[C-]#N.[Zn+2]>[CH:4]1[C:5]2[C:10](=[CH:9][CH:8]=[CH:7][CH:6]=2)[C:11]([C:14]#[N:15])=[CH:2][N:3]=1

Participants

6

Reactant 3

HCID 947NitrogenHCID 6228DimethylformamideHCID 6409693-Bromoisoquinoline

Product 1

HCID 964504-IsoquinolinecarbonitrileYield 27.4%

Reagents, catalysts & solvents 2

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

Conditions

Temperature
120 °C

Procedure

To a stirred solution of 3-bromoisoquinoline (Intermediate-12) (9.2 g, 44.2 mmol) in DMF (15 mL) were added, Pd(PPh3)4 (10.2 g, 8.84 mmol) and Zn(CN)2 (10.34 g, 88.44 mmol, 2.0 eq) and the solution was degassed with N2 for 20 min. It was then heated to 120° C. overnight. After the completion (TLC), reaction mixture was cooled to RT, filtered and concentrated under reduced pressure. The crude product obtained was purified by flash column chromatography (10% EtOAc:Hexanes) to afford the desired compound (3.4 g, 27.4%) as pale yellow solid.

Workup

  1. customAfter the completion (TLC), reaction mixture
  2. temperaturewas cooled to RT
  3. filtrationfiltered
  4. concentrationconcentrated under reduced pressure
  5. customThe crude product obtained
  6. customwas purified by flash column chromatography (10% EtOAc:Hexanes)

Sources & evidence

ORD record
ord-bcda7d7fa6fa4218b3098cdbb0913636
Source dataset
uspto-grants-2015_04
Patent number
US09006442B2

Reaction notes

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