Triphenylphosphine → 1-Aminoisoquinoline-7-carbonitrile

HRID 1279074Notes

Reaction equation

HRID 1279074 reaction equation
[NH2:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[C:9](OS(C(F)(F)F)(=O)=O)[CH:10]=2)[CH:5]=[CH:4][N:3]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[CH3:39][N:40]1CCCC1=O>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.[C-]#N.[Zn+2].[C-]#N>[NH2:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[C:9]([C:39]#[N:40])[CH:10]=2)[CH:5]=[CH:4][N:3]=1

Participants

6

Reactant 3

HCID 11776TriphenylphosphineHCID 13387N-methyl-2-pyrrolidoneHCID 54109345Trifluoromethanesulfonic acid 1-amino-isoquinolin-7-yl ester

Product 1

HCID 226658481-Aminoisoquinoline-7-carbonitrileYield 94%

Reagents, catalysts & solvents 2

HCID 11186Zinc cyanide (Zn(CN)2)CatalystHCID 167845palladium(II) acetateCatalyst

Procedure

Palladium acetate (0.9 g) was added to a heated mixture of trifluoromethanesulfonic acid 1-amino-isoquinolin-7-yl ester (5.8 g), zinc cyanide (2.3 g) and triphenylphosphine (1.0 g) in 75 mL of N-methyl-pyrrolidone at 190° C. (exothermic!). Stirring was continued at 190° C. for 2 h. Precipitated material was removed by filtration and discarded. Ethyl acetate was added and the organic mixture washed with 2N aqueous ammonia, water and brine and dried (Na2SO4). Filtration and concentration afforded a brownish oil, which was purified by silica chromatography (ethyl acetate/isohexane=3/7, 4/6, 515, 6/4, 7/3, 8/2) to give 3.2 g (94%) of the title compound as yellow crystals. M.p. 183-186° C.

Workup

  1. customPrecipitated material was removed by filtration
  2. additionEthyl acetate was added
  3. washthe organic mixture washed with 2N aqueous ammonia, water and brine
  4. dry with materialdried (Na2SO4)
  5. filtrationFiltration and concentration
  6. customafforded a brownish oil, which
  7. customwas purified by silica chromatography (ethyl acetate/isohexane=3/7, 4/6, 515, 6/4, 7/3, 8/2)

Sources & evidence

ORD record
ord-e1c7c192519b43a0af28eaeb69931efd
Source dataset
uspto-grants-2002_09
Patent number
US06444672B1

Reaction notes

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