Dimethylformamide → Isoquinoline-8-carbonitrile

HRID 1861678Notes

Reaction equation

HRID 1861678 reaction equation
Br[C:2]1[CH:3]=[CH:4][CH:5]=[C:6]2[C:11]=1[CH:10]=[N:9][CH:8]=[CH:7]2.[CH3:12][N:13](C=O)C>C1(C)C=CC=CC=1.[C-]#N.[Zn+2].[C-]#N.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>[CH:10]1[C:11]2[C:6](=[CH:5][CH:4]=[CH:3][C:2]=2[C:12]#[N:13])[CH:7]=[CH:8][N:9]=1

Participants

6

Reactant 2

HCID 6228DimethylformamideHCID 98591348-Bromoisoquinoline

Product 1

HCID 12018698Isoquinoline-8-carbonitrile

Reagents, catalysts & solvents 3

HCID 11186Zinc cyanide (Zn(CN)2)CatalystHCID 178418397HCID 178418397, compoundCatalystHCID 1140TolueneSolvent

Procedure

To a solution of 0.5035 g (2.42 mmol) 24 in 10 mL DMF was added 0.1713 g (1.45 mmol) zinc cyanide and 0.1687 g (0.15 mmol) tetrakis(triphenylphosphine)palladium(0). After 70.5 h under argon at 80° C., the reaction mixture was cooled to room temperature, diluted with 50 mL toluene and washed with 15 mL 2N NH4H. The aqueous layer was extracted with 15 mL toluene. The combined organic layers were washed with 15 mL brine, dried over Na2SO4, filtered and concentrated in vacuo. Purification by flash chromatography (40×105 mm silica gel, linear gradient 1-4% MeOH:CH2Cl2) yielded 25. 1H NM (CDCl3, 400 MHz) δ 9.679 (s, 1H, ArH); 8.732 (d, 1H, J=5.67 Hz, ArH); 8.097 (d, 1H, J=8.41 Hz, ArH); 8.031 (d, 1H, J=7.13, ArH); 7.771 (dd, 2H, J=6.81, 10.47 Hz, ArH); MS (Electrospray): m/z 155.0 (M+H).

Workup

  1. washwashed with 15 mL 2N NH4H
  2. extractionThe aqueous layer was extracted with 15 mL toluene
  3. washThe combined organic layers were washed with 15 mL brine
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customPurification by flash chromatography (40×105 mm silica gel, linear gradient 1-4% MeOH:CH2Cl2)

Sources & evidence

ORD record
ord-5d525415fdf8489e831536ff7455ccae
Source dataset
uspto-grants-2003_03
Patent number
US06534510B2

Reaction notes

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