887115-56-2

875781-17-2

74-88-4

887115-56-2

Step 1 Synthesis of 5-bromo-1-methyl-1H-pyrazolo[3,4-b]pyridine (compound 4-2): sodium hydride (720 mg, 30 mmol) and anhydrous tetrahydrofuran (40 mL) were added to a 100 mL reaction flask. After stirring at 0 °C for 5 min, 5-bromo-1H-pyrazolo[3,4-b]pyridine (4.0 g, 20 mmol, commercially available) was dissolved in tetrahydrofuran (20 mL) and slowly added dropwise to the reaction flask through a constant pressure dropping funnel, and stirring was continued for 30 min. Subsequently, iodomethane (1.6 mL, 26 mmol) was added dropwise to the reaction system. After the dropwise addition, the reaction solution was slowly warmed to room temperature and stirred overnight. The reaction process was monitored by thin layer chromatography (TLC). Upon completion of the reaction, the reaction was quenched by the addition of 10 mL of ice water and the tetrahydrofuran was removed by concentration under reduced pressure. The residue was extracted with dichloromethane (60 mL) and water (20 mL x 3). The organic layer was dried with anhydrous sodium sulfate and concentrated under reduced pressure to give 4.1 g of brown solid. The crude product was separated and purified by Combi-flash chromatography [petroleum ether: ethyl acetate = 10:90-40:60] to afford the target compound 5-bromo-1-methyl-1H-pyrazolo[3,4-b]pyridine (4-2) (3.1 g, 73% yield). Mass spectrum (ESI) m/z: 211.9 [M + H]+.