Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1) → N-{[3-Bromo-4-(methyloxy)phenyl]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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Reaction Steps

3-[({[1,6-Diethyl-4-(tetrahydro-2H-pyran-4-ylamino)-1H-pyrazolo[3,4-b]pyridin-5-yl]methyl}amino)carbonyl]-5-methylbenzoic acid (0.931 g, 2 mmol) was partially dissolved in the dichloromethane (DCM) (50 mL), and then HBTU (0.758 g, 2.000 mmol) was added followed sequentially by {[3-bromo-4-(methyloxy)phenyl]methyl}amine (0.432 g, 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 to give the crude product. The residue was taken up in EtOAc (100 mL) and washed 3× with water (50 mL), 1× with brine, dried over anhydrous Na2SO4 filtered and the solvent concentrated. The residue was taken up in methylene chloride and absorbed on Isolute® Sorbent and purified by CombiFlash on an 80 g silica column eluted with 0-10% DCM/MeOH to give the title compound as a white solid. LC-MS m/z 663.0 (M+H)+, 0.91 min (ret time); mp 123-126° C.; analytical HPLC shows 97.6% purity, (ret time 13.411 min).

Provenance & Evidence