反应详情

To a mixture of 5-bromo-6-chloro-1H-indazole-3-carboxylic acid (100 mg, 0.36 mmol) and 2-[4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenyl]-propan-2-ol (114 mg, 0.44 mmol) in toluene (1.5 mL) and EtOH (1.5 mL) was added 2 N aqueous potassium carbonate solution (0.7 mL, 1.4 mmol). The reaction mixture was degassed with N2 for 10 minutes, treated with [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II) (15.0 mg, 0.018 mmol), and heated to reflux for 16 hours. After cooling to room temperature, the reaction was quenched with 1 N NaOH (1 mL). The mixture was stirred for 30 minutes, acidified with 1 N HCl to pH 5 and extracted with EtOAc. The organic layer was washed with brine, dried over Na2SO4 and concentrated in vacuo. The crude material was purified by reverse phase chromatography (Biotage C18 column, 0-40% MeCN/water) to give the title compound (42 mg, 35% yield) as a solid. MS (ES−) 329.1 (M−H)+. 1H NMR (400 MHz, CD3OD) δ 8.06 (s, 1H), 7.74 (s, 1H), 7.55 (d, J=8.20 Hz, 2H), 7.37 (d, J=8.20 Hz, 2H), 1.57 (s, 6H).

1. customThe reaction mixture was degassed with N2 for 10 minutes
2. temperatureheated
3. temperatureto reflux for 16 hours
4. customthe reaction was quenched with 1 N NaOH (1 mL)
5. extractionextracted with EtOAc
6. washThe organic layer was washed with brine
7. dry with materialdried over Na2SO4
8. concentrationconcentrated in vacuo
9. customThe crude material was purified by reverse phase chromatography (Biotage C18 column, 0-40% MeCN/water)