反应详情

温度

90 °C

To a solution of 5,6-dichloro-1-methyl-3-tributylstannyl-1H-indazole (crude from Step 5, 218 mg, 0.44 mmol) and 2-bromo-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid [(R)-2-(4-cyano-piperidin-1-yl)-1-cyclopropyl-2-oxo-ethyl]-amide (125 mg, 0.22 mmol) in DMF (2 mL) were added Pd(PPh3)4 (12.9 mg, 0.011 mmol) and copper(I) iodide (8 mg, 0.044 mmol). The yellow reaction mixture was heated at 90° C. for 1.5 h then cooled to room temperature, quenched with water and extracted with EtOAc (2×). The combined organics were washed with water (3×) and brine then dried over MgSO4 and concentrated. The crude residue was purified by silica gel chromatography with 50% to 100% EtOAc/hexanes to isolate 130 mg (86%) of 2-(5,6-dichloro-1-methyl-1H-indazol-3-yl)-5-(2-trimethylsilanylethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid [(R)-2-(4-cyano-piperidin-1-yl)-1-cyclopropyl-2-oxo-ethyl]-amide as a pale yellow foamy solid.

1. temperaturethen cooled to room temperature
2. customquenched with water
3. extractionextracted with EtOAc (2×)
4. washThe combined organics were washed with water (3×) and brine
5. dry with materialthen dried over MgSO4
6. concentrationconcentrated
7. customThe crude residue was purified by silica gel chromatography with 50% to 100% EtOAc/hexanes