反应详情

The 3-[({[1,6-diethyl-4-(tetrahydro-2H-pyran-4-ylamino)-1H-pyrazolo[3,4-b]pyridin-5-yl]methyl}amino)carbonyl]-5-methylbenzoic acid (931 mg, 2 mmol) was partially dissolved in dichloromethane (50 mL), and HBTU (758 mg, 2.000 mmol) was added followed sequentially by [(3-bromo-4-fluorophenyl)methyl]amine hydrochloride (481 mg, 2.000 mmol), and TEA (0.836 mL, 6.00 mmol). The mixture was allowed to stir under argon overnight at room temperature. The solvent was removed on a rotavap. The residue was taken up in EtOAc (100 mL) and washed 3× with water (50 mL) (emulsion, a few drops of 1N NaOH helps break emulsion), 1× with brine, dried over anhydrous Na2SO4, filtered and evaporated to give the crude residue. It was taken up in methylene chloride and absorbed on Isolute® Sorbent and purified by Combiflash using an 80 g silica column eluted with 0-10% DCM/MeOH. The product fractions were combined and concentrated to give N-[(3-bromo-4-fluorophenyl)methyl]-N′-{[1,6-diethyl-4-(tetrahydro-2H-pyran-4-ylamino)-1H-pyrazolo[3,4-b]pyridin-5-yl]methyl}-5-methyl-1,3-benzenedicarboxamide (875 mg, 1.329 mmol, 66.5% yield) as a white solid. LC-MS m/z 651.3 (M+H)+, 0.98 min (ret time).

1. customThe solvent was removed on a rotavap
2. washwashed 3× with water (50 mL) (emulsion, a few drops of 1N NaOH helps break emulsion), 1× with brine
3. dry with materialdried over anhydrous Na2SO4
4. filtrationfiltered
5. customevaporated
6. customto give the crude residue
7. customabsorbed on Isolute® Sorbent
8. custompurified by Combiflash
9. washeluted with 0-10% DCM/MeOH
10. concentrationconcentrated