Potassium tert-butoxide → 3-((4-amino-3-(3-methoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)methyl)-8-methyl-2-o-tolylisoquinolin-1(2H)-one

HRID 1502486Notes

Reaction equation

HRID 1502486 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]([C:9]2[C:17]3[C:12](=[N:13][CH:14]=[N:15][C:16]=3[NH2:18])[NH:11][N:10]=2)[CH:6]=[CH:7][CH:8]=1.CC(C)([O-])C.[K+].Br[CH2:26][C:27]1[N:28]([C:39]2[CH:44]=[CH:43][CH:42]=[CH:41][C:40]=2[CH3:45])[C:29](=[O:38])[C:30]2[C:35]([CH:36]=1)=[CH:34][CH:33]=[CH:32][C:31]=2[CH3:37]>CN(C=O)C>[NH2:18][C:16]1[N:15]=[CH:14][N:13]=[C:12]2[N:11]([CH2:26][C:27]3[N:28]([C:39]4[CH:44]=[CH:43][CH:42]=[CH:41][C:40]=4[CH3:45])[C:29](=[O:38])[C:30]4[C:35]([CH:36]=3)=[CH:34][CH:33]=[CH:32][C:31]=4[CH3:37])[N:10]=[C:9]([C:5]3[CH:6]=[CH:7][CH:8]=[C:3]([OH:2])[CH:4]=3)[C:17]=12.[NH2:18][C:16]1[N:15]=[CH:14][N:13]=[C:12]2[N:11]([CH2:26][C:27]3[N:28]([C:39]4[CH:44]=[CH:43][CH:42]=[CH:41][C:40]=4[CH3:45])[C:29](=[O:38])[C:30]4[C:35]([CH:36]=3)=[CH:34][CH:33]=[CH:32][C:31]=4[CH3:37])[N:10]=[C:9]([C:5]3[CH:6]=[CH:7][CH:8]=[C:3]([O:2][CH3:1])[CH:4]=3)[C:17]=12

Participants

6

Reactant 3

HCID 23665647Potassium tert-butoxideHCID 580086503-(Bromomethyl)-8-methyl-2-o-tolylisoquinolin-1(2H)-oneHCID 1784899393-(3-Methoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine

Product 2

HCID 580086943-((4-amino-3-(3-methoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)methyl)-8-methyl-2-o-tolylisoquinolin-1(2H)-oneYield 139.3%HCID 580087113-((4-amino-3-(3-hydroxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)methyl)-8-methyl-2-o-tolylisoquinolin-1(2H)-one

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

3-(3-Methoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine (1701) (964 mg, 4 mmol) and potassium tert-butoxide (0.44 g, 4 mmol) were dissolved in anhydrous DMF (150 mL) and stirred at RT for 30 min. 3-(Bromomethyl)-8-methyl-2-o-tolylisoquinolin-1(2H)-one (1610) (1.37 g, 4.0 mmol) was added. The resulting mixture was stirred at RT for 30 min, poured into ice water (30 mL) and then extracted with ethyl acetate (3×50 mL). The combined organic layer was washed with brine (25 mL), dried over Na2SO4 and filtered. The filtrate was concentrated in vacuo and the residue was purified by flash column chromatography on silica gel (2-20% MeOH/DCM) to afford the desired product, 3-((4-amino-3-(3-methoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)methyl)-8-methyl-2-o-tolylisoquinolin-1(2H)-one (1702) (1.4 g, 70% yield) as a white solid.

Workup

  1. stirringThe resulting mixture was stirred at RT for 30 min
  2. extractionextracted with ethyl acetate (3×50 mL)
  3. washThe combined organic layer was washed with brine (25 mL)
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationThe filtrate was concentrated in vacuo
  7. customthe residue was purified by flash column chromatography on silica gel (2-20% MeOH/DCM)

Sources & evidence

ORD record
ord-10f743d319ef438396f4df7954aaa809
Source dataset
uspto-grants-2015_12
Patent number
US09206182B2

Reaction notes

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