Sodium Carbonate → 3-((4-amino-3-(3-hydroxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)methyl)-2-isopropyl-8-methylisoquinolin-1(2H)-one

HRID 217117Notes

Reaction equation

HRID 217117 reaction equation
[NH2:1][C:2]1[N:7]=[CH:6][N:5]=[C:4]2[N:8]([CH2:12][C:13]3[N:14]([CH:25]([CH3:27])[CH3:26])[C:15](=[O:24])[C:16]4[C:21]([CH:22]=3)=[CH:20][CH:19]=[CH:18][C:17]=4[CH3:23])[N:9]=[C:10](I)[C:3]=12.CC1(C)C(C)(C)OB([C:36]2[CH:37]=[C:38]([OH:42])[CH:39]=[CH:40][CH:41]=2)O1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C([O-])([O-])=O.[Na+].[Na+]>CN(C=O)C.C(O)C.O.CC([O-])=O.CC([O-])=O.[Pd+2]>[NH2:1][C:2]1[N:7]=[CH:6][N:5]=[C:4]2[N:8]([CH2:12][C:13]3[N:14]([CH:25]([CH3:27])[CH3:26])[C:15](=[O:24])[C:16]4[C:21]([CH:22]=3)=[CH:20][CH:19]=[CH:18][C:17]=4[CH3:23])[N:9]=[C:10]([C:36]3[CH:41]=[CH:40][CH:39]=[C:38]([OH:42])[CH:37]=3)[C:3]=12

Participants

7

Reactant 4

HCID 10340Sodium CarbonateHCID 11776TriphenylphosphineHCID 27346233-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)phenolHCID 580088813-((4-Amino-3-iodo-1H-pyrazolo[3,4-d]pyrimidin-1-yl)methyl)-2-isopropyl-8-methylisoquinolin-1(2H)-one

Product 1

HCID 580089843-((4-amino-3-(3-hydroxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)methyl)-2-isopropyl-8-methylisoquinolin-1(2H)-oneYield 61%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 86633292ethanol water DMFSolvent

Conditions

Temperature
100 °C

Procedure

To a stirred mixture of 3-((4-Amino-3-iodo-1H-pyrazolo[3,4-d]pyrimidin-1-yl)methyl)-2-isopropyl-8-methylisoquinolin-1(2H)-one (2008) (95 mg, 0.2 mmol) and 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenol (66 mg, 0.3 mmol) in DMF-EtOH-H2O (3:1:1, 20 mL), Pd(OAc)2 (16 mg, 0.075 mmol), PPh3 (39.3 mg 0.15 mmol) and Na2CO3 (132 mg, 1.25 mmol) were added sequentially. The resulting mixture was degassed and back-filled with argon three times and then stirred at 100° C. for 1 h. The mixture was allowed to cool to RT, filtered through silica gel (10 g) and concentrated in vacuo. The residue was purified by flash column chromatography on silica gel (2-20% MeOH/DCM) to afford the product, 3-((4-amino-3-(3-hydroxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)methyl)-2-isopropyl-8-methylisoquinolin-1(2H)-one (2009) (53 mg, 61% yield) as a slightly yellow solid.

Workup

  1. additionwere added sequentially
  2. customThe resulting mixture was degassed
  3. additionback-filled with argon three times
  4. temperatureto cool to RT
  5. filtrationfiltered through silica gel (10 g)
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified by flash column chromatography on silica gel (2-20% MeOH/DCM)

Sources & evidence

ORD record
ord-3b5a3b6e6e1e498fb188b6a34dfa6ed7
Source dataset
uspto-grants-2012_06
Patent number
US08193182B2

Reaction notes

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