Sodium hydride → tert-butyl 4-(5-bromo-1-(4-methoxybenzyl)-1H-pyrazolo[3,4-b]pyridin-4-yl)piperazine-1-carboxylate

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A solution of 5-bromo-1-(4-methoxybenzyl)-1H-pyrazolo[3,4-b]pyridin-4-ol (10.85 g, 32.5 mmol) in DMF (130 mL) was added dropwise to a stirred suspension of sodium hydride (60% in mineral oil, 1.56 g, 39 mmol) in DMF (70 mL) at room temperature. Once the addition was complete, the mixture was stirred at 40° C. for 30 minutes. The resulting solution was cooled to room temperature and treated with 1,1,1-trifluoro-N-phenyl-N-(trifluoromethylsulfonyl)methanesulfonamide (13.92 g, 38.96 mmol). After 1 hour, solid tert-butyl piperazine-1-carboxylate (13.3 g, 71.43 mmol) was added in 2 portions with stirring, and the mixture was stirred at 80° C. for 1.5 hours. The resulting mixture was allowed to cool to room temperature overnight. Saturated NH4Cl solution (100 mL), water (50 mL) and EtOAc (250 mL) were then added to the reaction mixture. The phases were separated, and the aqueous layer was extracted with EtOAc (2×50 mL). The combined organic phases were washed with water (1×50 mL), dried (MgSO4), filtered, and concentrated in vacuo. The residue obtained was crystallized from boiling EtOAc (˜30 mL) and hexane (˜10 mL). The solid formed was filtered, washed with additional hexane (2×10 mL), and dried to provide tert-butyl 4-(5-bromo-1-(4-methoxybenzyl)-1H-pyrazolo[3,4-b]pyridin-4-yl)piperazine-1-carboxylate (14.8 g, 91% yield) as a solid. LCMS (APCI+) m/z 504 (M+H)+, Retention time=4.56 minutes.

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