Methanesulfonic Acid → 1-(4-(5-bromopent-1-yn-1-yl)phenyl)-3-((1,6-diethyl-4-((tetrahydro-2H-pyran-4-yl)amino)-1H-pyrazolo[3,4-b]pyridin-5-yl)methyl)urea

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A suspension of Intermediate 24 methanesulfonic acid salt (1.4 g, 4.2 mmol) in dichloromethane (50 mL) was treated with triethylamine (8.8 mL, 63 mmol) and then the mixture was cooled in an ice-water bath and treated with triphosgene (0.93 g, 3.2 mmol), followed by 5-(aminomethyl)-1,6-diethyl-N-(tetrahydro-2H-pyran-4-yl)-1H-pyrazolo[3,4-b]pyridin-4-amine dihydrochloride (1.3 g, 3.4 mmol). The mixture was quenched by the addition of methanol and concentrated under reduced pressure. The residue was partitioned between ethyl acetate and water. The aqueous phase was extracted twice with ethyl acetate. The combined organics were washed with a 5% aqueous potassium hydrogen sulfate solution and saturated aqueous sodium chloride solution and then concentrated under reduced pressure. The crude residue was purified via automated flash silica gel chromatography, using a SiliSep flash column (dichloromethane/methanol/ammonium hydroxide). Concentration of the desired fractions under reduced pressure provided the title compound as a pale tan foam. ES/MS calcd. for C28H36BrN6O2+ 567.2. found m/z=567.2 (M+H)+.

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