Water → HCID 54673226, compound

HRID 709955Notes

Reaction equation

HRID 709955 reaction equation
[NH2:1][C:2]1[N:7]=[C:6]([NH:8][C@H:9]([C:11]2[N:12]([C:28]3[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=3)[C:13](=[O:27])[C:14]3[C:19]([CH:20]=2)=[CH:18][CH:17]=[CH:16][C:15]=3[C:21]2[CH:22]=[N:23][N:24]([CH3:26])[CH:25]=2)[CH3:10])[C:5](I)=[CH:4][N:3]=1.[C-:35]#[N:36].[Na+].O>C(#N)C.[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[Cu](I)I>[NH2:1][C:2]1[N:7]=[C:6]([NH:8][C@H:9]([C:11]2[N:12]([C:28]3[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=3)[C:13](=[O:27])[C:14]3[C:19]([CH:20]=2)=[CH:18][CH:17]=[CH:16][C:15]=3[C:21]2[CH:22]=[N:23][N:24]([CH3:26])[CH:25]=2)[CH3:10])[C:5]([C:35]#[N:36])=[CH:4][N:3]=1

Participants

7

Reactant 3

HCID 962WaterHCID 8929Sodium CyanideHCID 66608836HCID 66608836, compound

Product 1

HCID 54673226HCID 54673226, compoundYield 30.2%

Reagents, catalysts & solvents 3

HCID 83717Copper iodideCatalystHCID 11979704Tetrakis(triphenylphosphine)palladiumCatalystHCID 6342AcetonitrileSolvent

Conditions

Temperature
80 °C

Procedure

To a solution of (S)-3-(1-((2-amino-5-iodopyrimidin-4-yl)amino)ethyl)-8-(1-methyl-1H-pyrazol-4-yl)-2-phenylisoquinolin-1(2H)-one (65) (240 mg, 0.43 mmol) in anhydrous acetonitrile (12 mL) in a sealed tube, sodium cyanide (209 mg, 4.26 mmol), tetrakis(triphenylphosphine) palladium(0) (246 mg, 0.21 mmol), and copper iodide (57 mg, 0.30 mmol) were added and the resulting mixture was stirred at 80° C. for 16 h. The mixture was allowed to cool to RT, quenced with water and extracted with ethyl acetate (50 mL×2). The combined organic layer was washed with brine, dried over Na2SO4 and filtered. The filtrate was concentrated in vacuo and the residue was purified by ISCO (silica gel cartridge, 0-10% MeOH-DCM) to afford the product, (S)-2-amino-4-((1-(8-(1-methyl-1H-pyrazol-4-yl)-1-oxo-2-phenyl-1,2-dihydroiso-quinolin-3-yl)ethyl)amino)pyrimidine-5-carbonitrile (69) (60 mg, 30% yield). ESI-MS m/z: 463.2 [M+H]+.

Workup

  1. temperatureto cool to RT
  2. extractionextracted with ethyl acetate (50 mL×2)
  3. washThe combined organic layer was washed with brine
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationThe filtrate was concentrated in vacuo
  7. customthe residue was purified by ISCO (silica gel cartridge, 0-10% MeOH-DCM)

Sources & evidence

ORD record
ord-1e4dd23facc844fa8675d3c4505e566c
Source dataset
uspto-grants-2015_11
Patent number
US09181221B2

Reaction notes

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