反应详情

温度

90 °C

In a round-bottomed flask, 2-bromo-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid ((R)-2-hydroxy-1,2-dimethyl-propyl)-amide (120 mg, 0.26 mmol) and 6-chloro-1-methyl-3-tributylstannyl-1H-indazole (319 mg, 0.42 mmol) were dissolved in DMF (2.5 ml). The flask was evacuated and backfilled with argon then tetrakis(triphenylphosphine)palladium(0) (16 mg, 0.014 mmol) and copper(I) iodide (10 mg, 0.053 mmol) were added. The reaction mixture was stirred at 90° C. in an oil bath overnight then cooled to room temperature, quenched with water and extracted with diethyl ether (2×). The combined organic layers were washed twice with water and once with brine then dried over sodium sulfate, filtered and concentrated. The residue was chromatographed over silica gel with MeOH/CH2Cl2/0.5% NH4OH (gradient 0-2% MeOH) to afford 122 mg (86%) of 2-(6-chloro-1-methyl-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid ((R)-2-hydroxy-1,2-dimethyl-propyl)-amide as an off-white solid.

1. customThe flask 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 once with brine
6. dry with materialthen dried over sodium sulfate
7. filtrationfiltered
8. concentrationconcentrated
9. customThe residue was chromatographed over silica gel with MeOH/CH2Cl2/0.5% NH4OH (gradient 0-2% MeOH)