Participants
| Role | Name | HCID | Charge |
|---|
| Reactant | Triethylamine | HCID 8471 | — |
| Reactant | Carbon tetrabromide | HCID 11205 | — |
| Reactant | Diethylphosphite | HCID 3780918 | — |
| Reactant | Aluminum | HCID 5359268 | — |
| Reactant | HCID 58008590 | HCID 58008590 | — |
| Solvent | Tetrahydrofuran | HCID 8028 | — |
| Product | HCID 58008960 | HCID 58008960 | 124.5% |
| Product | HCID 58009045 | HCID 58009045 | — |
Reaction Steps
3-((4-Amino-3-(3-fluoro-5-hydroxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)methyl)-8-methyl-2-o-tolylisoquinolin-1(2H)-one 4301 (250 mg, 0.5 mmol) was dissolved in anhydrous THF (15 mL) in a round bottom flask in dark (covered by aluminum foil) and cooled to 0° C. under an argon atmosphere. CBr4 (498 mg, 1.5 mmol) was added followed by diethylphosphite (129 μL, 1.0 mmol) and triethylamine (417 μL, 1.5 mmol). The resulting mixture was stirred in dark from 0° C. to RT for 16 h. The mixture was then partitioned between ethyl acetate and brine. The organic layer was dried over Na2SO4, filtered and concentrated in vacuo. The residue was purified by column chromatography on silica gel eluting with methanol and dichloromethane to afford the desired product, 3-(4-amino-1-((8-methyl-1-oxo-2-o-tolyl-1,2-dihydroisoquinolin-3-yl)methyl)-1H-pyrazolo[3,4-d]pyrimidin-3-yl)-5-fluorophenyl diethyl phosphate 4302 (200 mg, 62% yield) as an off-white solid.
Provenance & Evidence
| DOI | 10.6084/m9.figshare.5104873.v1 |
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| Patent number | US08193182B2 |
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| Source dataset | uspto-grants-2012_06 |
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| ORD ID | ord-4efdd4daa9834b309ae0466fb69b16c6 |
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| Source note | uspto-grants-2012_06 |
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