反应详情

In a round-bottomed flask, 2-bromo-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carbaldehyde (1.56 g, 4.38 mmol) and 4,6-difluoro-3-tributylstannanyl-1H-indazole (1.94 g, 4.38 mmol) were dissolved in DMF (40 mL) and tetrakis(triphenylphosphine)palladium(0) (253 mg, 0.22 mmol) and copper(I) iodide (167 mg, 0.88 mmol) were added. The reaction mixture was purged with argon, stirred at room temperature for 4 h, then heated at 80° C. for 1 h. The reaction was cooled to room temperature, quenched with sat NH4Cl and extracted with EtOAc (2×). The combined organics were washed with sat LiCl and brine then dried over MgSO4 and concentrated. The crude residue was purified by silica gel chromatography with 50% to 100% EtOAc/heptane to provide 1.89 g of 2-(4,6-difluoro-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carbaldehyde as a brown solid.

1. customThe reaction mixture was purged with argon
2. temperatureheated at 80° C. for 1 h
3. temperatureThe reaction was cooled to room temperature
4. customquenched with sat NH4Cl
5. extractionextracted with EtOAc (2×)
6. washThe combined organics were washed with sat LiCl and brine
7. dry with materialthen dried over MgSO4
8. concentrationconcentrated
9. customThe crude residue was purified by silica gel chromatography with 50% to 100% EtOAc/heptane