Boron tribromide → 3-((4-amino-3-(3-hydroxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)methyl)-8-methyl-2-o-tolylisoquinolin-1(2H)-one

HRID 2368817Notes

Reaction equation

HRID 2368817 reaction equation
[NH2:1][C:2]1[N:7]=[CH:6][N:5]=[C:4]2[N:8]([CH2:19][C:20]3[N:21]([C:32]4[CH:37]=[CH:36][CH:35]=[CH:34][C:33]=4[CH3:38])[C:22](=[O:31])[C:23]4[C:28]([CH:29]=3)=[CH:27][CH:26]=[CH:25][C:24]=4[CH3:30])[N:9]=[C:10]([C:11]3[CH:16]=[CH:15][CH:14]=[C:13]([O:17]C)[CH:12]=3)[C:3]=12.B(Br)(Br)Br>C(Cl)Cl>[NH2:1][C:2]1[N:7]=[CH:6][N:5]=[C:4]2[N:8]([CH2:19][C:20]3[N:21]([C:32]4[CH:37]=[CH:36][CH:35]=[CH:34][C:33]=4[CH3:38])[C:22](=[O:31])[C:23]4[C:28]([CH:29]=3)=[CH:27][CH:26]=[CH:25][C:24]=4[CH3:30])[N:9]=[C:10]([C:11]3[CH:16]=[CH:15][CH:14]=[C:13]([OH:17])[CH:12]=3)[C:3]=12

Participants

4

Reactant 2

HCID 25134Boron tribromideHCID 580086943-((4-amino-3-(3-methoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)methyl)-8-methyl-2-o-tolylisoquinolin-1(2H)-one

Product 1

HCID 580087113-((4-amino-3-(3-hydroxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)methyl)-8-methyl-2-o-tolylisoquinolin-1(2H)-oneYield 91%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
-78 °C

Procedure

To a solution of 3-((4-amino-3-(3-methoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)methyl)-8-methyl-2-o-tolylisoquinolin-1(2H)-one (1702) (100 mg, 0.2 mmol) in CH2Cl2 (20 mL) at −78° C. under a nitrogen atmosphere, BBr3 (1 mL) was added and the resulting mixture was stirred at −78° C. for 3 h. The mixture was allowed to warm to RT, poured into ice-water (200 mL) and extracted with ethyl acetate (3×50 mL). The combined organic layer was washed with brine (20 mL), dried over Na2SO4 and filtered. The filtrate was concentrated in vacuo and the residue was purified by flash column chromatography on silica gel (10-50% MeOH/CH2Cl2) to afford the desired product, 3-((4-amino-3-(3-hydroxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)methyl)-8-methyl-2-o-tolylisoquinolin-1(2H)-one (1610) (87 mg, 91% yield) as a white solid.

Workup

  1. temperatureto warm to RT
  2. extractionextracted with ethyl acetate (3×50 mL)
  3. washThe combined organic layer was washed with brine (20 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 (10-50% MeOH/CH2Cl2)

Sources & evidence

ORD record
ord-302ee22e390240caa0a276c625fbfc0e
Source dataset
uspto-grants-2014_04
Patent number
US08703777B2

Reaction notes

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