反应详情

温度

80 °C

In a dry round-bottomed flask 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 (0.12 g, 0.21 mmol) and 1-methyl-3-tributylstannanyl-1H-indazole (117 mg, 0.28 mmol) were dissolved in DMF (2 ml). The reaction mixture was evacuated and backfilled with Argon then tetrakis(triphenylphosphine)palladium(0) (13 mg, 0.011 mmol) and copper(I) iodide (9 mg, 0.047 mmol) were added. The reaction mixture was stirred at 80° C. for 1.5 h then cooled to room temperature, quenched with water and extracted with diethyl ether (2×). The combined organic layers were washed twice with water and brine then dried over sodium sulfate, filtered and concentrated. The residue was purified by chromatography over silica gel with MeOH/CH2Cl2 (0.5% NH4OH) (gradient 0-3% MeOH) to afford 161 mg of 2-(1-methyl-1H-indazol-3-yl)-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 as a yellow oil.

1. customThe reaction mixture was evacuated
2. temperaturethen cooled to room temperature
3. customquenched with water
4. extractionextracted with diethyl ether (2×)
5. washThe combined organic layers were washed twice with water and brine
6. dry with materialthen dried over sodium sulfate
7. filtrationfiltered
8. concentrationconcentrated
9. customThe residue was purified by chromatography over silica gel with MeOH/CH2Cl2 (0.5% NH4OH) (gradient 0-3% MeOH)