Synthesis
Potassium acetate (4.73 g, 48.3 mmol) and Pd(dppf)Cl2 (0.66 g, 0.81 mmol) in anhydrous DMF (60 mL) were added to tert-butyl 5-bromo-3-methyl-1H-indazole-1-carboxylate (5.00 g, 16.1 mmol) and pinacol ester of bisboronic acid (4.49 g, 17.7 mmol). The mixture was placed in a vial with a rubber-lined screw cap and degassed by three vacuum/nitrogen cycles. Subsequently, the suspension was heated with stirring at 100 °C for 2 h under nitrogen protection. Upon completion of the reaction, the mixture was cooled to room temperature, mixed with saturated aqueous sodium bicarbonate solution (100 mL) and extracted with ethyl acetate (2 x 150 mL). The organic phases were combined, dried over anhydrous sodium sulfate and concentrated to give the crude product. The crude product was purified by silica gel column chromatography using gradient elution with ethyl acetate/hexane (0% to 15%) to afford the target product tert-butyl 3-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indazole-1-carboxylate as an oil (5.55 g, 96% yield).LCMS (+APCI) m/z. 499 (M+H).
References
[1] Patent: US2008/153813, 2008, A1. Location in patent: Page/Page column 24
[2] Patent: WO2005/85227, 2005, A1. Location in patent: Page/Page column 37; 76
[3] Bioorganic and Medicinal Chemistry Letters, 2010, vol. 20, # 2, p. 673 - 678
[4] Patent: US2008/153813, 2008, A1. Location in patent: Page/Page column 22-23
[5] Patent: US2008/153813, 2008, A1. Location in patent: Page/Page column 23
