3-Bromobenzylamine hydrochloride → N-[(3-bromophenyl)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

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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-bromophenyl)methyl]amine hydrochloride (464 mg, 2.000 mmol), and TEA (0.558 mL, 4.00 mmol). The mixture was allowed to stir under argon overnight at room temperature. The solvent was removed on a rotavap and 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. The residue 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-bromophenyl)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 (962 mg, 1.476 mmol, 73.8% yield) as a white solid. LC-MS m/z 633.6 (M+H)+, 0.97 min (ret time); mp 116-118° C.

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