反应详情

温度

110 °C

To a stirred solution of 2-bromo-N-tert-butyl-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide (150 mg, 351 μmol) in toluene (1 mL) was added copper (I) iodide (3.52 mg, 39.3 μmol), sodium iodide (105 mg, 702 μmol) and trans-N,N′-dimethylcyclohexane-1,2-diamine (12.7 mg, 89.5 μmol). The reaction mixture was sealed under nitrogen and the mixture heated at 110° C. for 15 h then 5-chloro-1H-indazole (53.5 mg, 351 μmol) and potassium phosphate tribasic (156 mg, 737 μmol) were added. The mixture was degassed, filled with nitrogen, and the mixture heated at in sealed tube at 110° C. for 15 h. The mixture was filtered, the cake washed with ethyl acetate, and the filtrate concentrated in vacuo. Purification by chromatography (silica, 24 g Analogix column, 0-40% ethyl acetate in hexanes) gave N-tert-butyl-2-(5-chloro-1H-indazol-1-yl)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide (150 mg, 86%). 1H NMR (CDCl3) δ: 9.17 (s, 1H), 8.56 (d, J=8.9 Hz, 1H), 8.37 (s, 1H), 8.24 (s, 1H), 7.83 (s, 1H), 7.68 (s, 1H), 7.46 (dd, J=8.9, 1.6 Hz, 1H), 5.72 (s, 2H), 3.51-3.65 (m, 2H), 1.61 (s, 9H), 0.87-1.03 (m, 2H), −0.03 (s, 9H).

1. customThe reaction mixture was sealed under nitrogen
2. customThe mixture was degassed
3. additionfilled with nitrogen
4. temperaturethe mixture heated at in sealed tube at 110° C. for 15 h
5. filtrationThe mixture was filtered
6. washthe cake washed with ethyl acetate
7. concentrationthe filtrate concentrated in vacuo
8. customPurification by chromatography (silica, 24 g Analogix column, 0-40% ethyl acetate in hexanes)