反应详情

温度

125 °C

To a stirred solution of 2-bromo-N-tert-butyl-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide (136 mg, 318 μmol), 3-chloro-1H-indazole (48.6 mg, 318 mmol) in dioxane (3.5 mL) was added sodium tert-butoxide (67.3 mg, 700 μmol) and bis(tri-tert-butylphosphine)palladium(0) (16.3 mg, 31.8 μmol). The mixture was degassed then heated in sealed tube at 125° C. for two days. The mixture was cooled, filtered through celite, the cake washed with ethyl acetate, and the combined filtrates were concentrated in vacuo. Purification by chromatography (silica, 24 g Analogix column, 0-40% ethyl acetate in hexanes) gave N-tert-butyl-2-(3-chloro-1H-indazol-1-yl)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide. 1H NMR (CDCl3) δ: 9.12 (s, 1H), 8.61 (d, J=8.5 Hz, 1H), 8.36 (s, 1H), 7.82 (d, J=8.0 Hz, 1H), 7.70 (s, 1H), 7.58 (ddd, J=8.5, 7.2, 1.1 Hz, 1H), 7.42 (ddd, J=8.1, 7.1, 0.9 Hz, 1H), 5.72 (s, 2H), 3.55-3.62 (m, 2H), 1.61 (s, 9H), 0.95 (d, J=16.6 Hz, 2H), −0.03 (s, 9H).

1. customThe mixture was degassed
2. temperatureThe mixture was cooled
3. filtrationfiltered through celite
4. washthe cake washed with ethyl acetate
5. concentrationthe combined filtrates were concentrated in vacuo
6. customPurification by chromatography (silica, 24 g Analogix column, 0-40% ethyl acetate in hexanes)