Aldoxime → HCID 66607086, compound

HRID 1910892Notes

Reaction equation

HRID 1910892 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]([C:34]#[N:35])=[CH:4][N:3]=1.C(=N[OH:39])C.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>C1(C)C=CC=CC=1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[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:34]([NH2:35])=[O:39])=[CH:4][N:3]=1

Participants

6

Reactant 3

HCID 7863Aldoxime2×HCID 11776Triphenylphosphine2×HCID 54673226HCID 54673226, compound

Product 1

HCID 66607086HCID 66607086, compound

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalyst2×HCID 1140TolueneSolvent

Conditions

Temperature
80 °C

Procedure

To a solution of (S)-2-amino-4-((1-(8-(1-methyl-1H-pyrazol-4-yl)-1-oxo-2-phenyl-1,2-dihydroisoquinolin-3-yl)ethyl)amino)pyrimidine-5-carbonitrile (69) (30.4 mg, 0.066 mmol) in anhydrous toluene (1 mL), acetaldoxime (10 μL, 0.13 mmol), palladium acetate (2 mg, 0.0066 mmol) and triphenyl phosphine (4 mg, 0.013 mmol) were added and the resulting mixture was stirred at 80° C. for 2 h. Additional amounts of acetaldoxime (10 μL, 0.13 mmol), palladium acetate (2 mg, 0.0066 mmol) and triphenyl phosphine (4 mg, 0.013 mmol) were added and stirring was continued at 80° C. for 2 h. The mixture was allowed to cool to RT, quenched with water (30 mL), and then extracted with ethyl acetate (30 mL×2). The combined organic layers were washed with brine, dried over Na2SO4 and filtered. The filtrate was concentrated in vacuo and the residue was purified by ISCO column chromatography (silica gel cartridge, 0-8.5% MeOH-DCM) to afford the desired product, (S)-2-amino-4-((1-(8-(1-methyl-1H-pyrazol-4-yl)-1-oxo-2-phenyl-1,2-dihydroisoquinolin-3-yl)ethyl)amino)pyrimidine-5-carboxamide (79) as a white solid. ESI-MS m/z: 481.2 [M+H]+.

Workup

  1. stirringstirring
  2. waitwas continued at 80° C. for 2 h
  3. temperatureto cool to RT
  4. customquenched with water (30 mL)
  5. extractionextracted with ethyl acetate (30 mL×2)
  6. washThe combined organic layers were washed with brine
  7. dry with materialdried over Na2SO4
  8. filtrationfiltered
  9. concentrationThe filtrate was concentrated in vacuo
  10. customthe residue was purified by ISCO column chromatography (silica gel cartridge, 0-8.5% MeOH-DCM)

Sources & evidence

ORD record
ord-e67227985d46431eaf77455b88b15f03
Source dataset
uspto-grants-2013_12
Patent number
US08604032B2

Reaction notes

Loading…