Aldoxime → HCID 71269998, compound

HRID 1626914Notes

Reaction equation

HRID 1626914 reaction equation
[NH2:1][C:2]1[N:7]=[C:6]([NH:8][C@H:9]([C:11]2[N:12]([C:30]3[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=3)[C:13](=[O:29])[C:14]3[C:19]([CH:20]=2)=[CH:18][CH:17]=[CH:16][C:15]=3[C:21]2[CH:22]=[N:23][C:24]([O:27][CH3:28])=[N:25][CH:26]=2)[CH3:10])[C:5]([C:36]#[N:37])=[CH:4][N:3]=1.C(=N[OH:41])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:30]3[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=3)[C:13](=[O:29])[C:14]3[C:19]([CH:20]=2)=[CH:18][CH:17]=[CH:16][C:15]=3[C:21]2[CH:26]=[N:25][C:24]([O:27][CH3:28])=[N:23][CH:22]=2)[CH3:10])[C:5]([C:36]([NH2:37])=[O:41])=[CH:4][N:3]=1

Participants

6

Reactant 3

HCID 7863AldoximeHCID 11776TriphenylphosphineHCID 71270387HCID 71270387, compound

Product 1

HCID 71269998HCID 71269998, compound

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 1140TolueneSolvent

Conditions

Temperature
80 °C

Procedure

To a solution of (S)-2-amino-4-((1-(8-(2-methoxypyrimidin-5-yl)-1-oxo-2-phenyl-1,2-dihydroisoquinolin-3-yl)ethyl)amino)pyrimidine-5-carbonitrile 5 (34 mg, 0.070 mmol) in anhydrous toluene (4 mL) under argon, acetaldoxime (13 μL, 0.21 mmol), palladium(II) acetate (5 mg, 0.01 mmol) and triphenyl phosphine (5 mg, 0.017 mmol) were added and the resulting mixture was stirred at 80° C. for 3 h. The mixture was allowed to cool to RT and partitioned between water and ethyl acetate. The organic layer was washed with brine, dried with Na2SO4 and filtered. The filtrate was concentrated in vacuo and the residue was purified by ISCO column chromatography (silica gel cartridge, 0-10% MeOH/DCM) to afford the product, (S)-2-amino-4-((1-(8-(2-methoxypyrimidin-5-yl)-1-oxo-2-phenyl-1,2-dihydroisoquinolin-3-yl)ethyl)amino)pyrimidine-5-carboxamide 11. ESI-MS m/z: 509.2 [M+H]+.

Workup

  1. temperatureto cool to RT
  2. custompartitioned between water and ethyl acetate
  3. washThe organic layer was washed with brine
  4. dry with materialdried with Na2SO4
  5. filtrationfiltered
  6. concentrationThe filtrate was concentrated in vacuo
  7. customthe residue was purified by ISCO column chromatography (silica gel cartridge, 0-10% MeOH/DCM)

Sources & evidence

ORD record
ord-a42b6459a27c411c9b4dfee33f7139e6
Source dataset
uspto-grants-2014_07
Patent number
US08785470B2

Reaction notes

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