Cesium carbonate → tert-butyl (3R)-3-((6-(5-(6-(1-methylethoxy)-2-pyrazinyl)-1-(tetrahydro-2H-pyran-2-yl)-1H-indazol-3-yl)-2-pyrazinyl)oxy)-1-piperidinecarboxylate

Participants

Reaction Conditions

Reaction Steps

To a 50 mL round bottom flask was added CuCl (0.035 g, 0.36 mmol), Cs2CO3 (0.467 g, 1.43 mmol), 1,1′-bis(diphenylphosphino)ferrocene (0.020 g, 0.04 mmol), tert-butyl (3R)-3-((6-(5-bromo-1-(tetrahydro-2H-pyran-2-yl)-1H-indazol-3-yl)-2-pyrazinyl)oxy)-1-piperidinecarboxylate 10a (0.200 g, 0.36 mmol), Pd(OAc)2 (4.02 mg, 0.02 mmol), and 2-isopropoxy-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrazine (0.189 g, 0.72 mmol, CombiPhos Catalysis). The flask was sealed and evacuated under vacuum and backfilled with N2. DMF (2.7 mL) was added, and the reaction mixture was stirred at 80° C. for 18 h. The reaction was filtered through a 0.45 M filter and then diluted in water and extracted with EtOAc (3×). The combined organic layers were dried over anhydrous Na2SO4, filtered and concentrated. The crude material was absorbed onto a plug of silica gel and purified by chromatography through a Redi-Sep pre-packed silica gel column (12 g), eluting with a gradient of 0% to 50% EtOAc in hexane, to provide tert-butyl (3R)-3-((6-(5-(6-(1-methylethoxy)-2-pyrazinyl)-1-(tetrahydro-2H-pyran-2-yl)-1H-indazol-3-yl)-2-pyrazinyl)oxy)-1-piperidinecarboxylate (0.130 g, 0.21 mmol, 59% yield) as a light-yellow oil. MS (ESI, pos. ion) m/z: 616.2 (M+1).

Provenance & Evidence