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

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 (1613)(87 mg, 91% yield) as a white solid.

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)

ORD record

ord-8a1b9e9c48384b229d20cbb81fac209f

Source dataset

uspto-grants-2012_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08193182B2