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-(3-cyano-azetidin-1-yl)-1-methyl-2-oxo-ethyl]-amide (100 mg, 0.20 mmol) and (6-Fluoro-1-tributylstannanyl-imidazo[1,5-a]pyridin-3-yl)-methanol (crude from Step 5) were dissolved in DMF (2 ml The flask was evacuated and backfilled with argon then tetrakis(triphenylphosphine)palladium (0) (12 mg, 0.010 mmol) and copper (I) iodide (8 mg, 0.042 mmol) were added. The reaction mixture was stirred at 90° C. in an oil bath for 3 h then cooled to room temperature, quenched with water and extracted with dichloromethane (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 absorbed on silica gel and chromatographed with MeOH/CH2Cl2/0.5% NH4OH (gradient 0-3% MeOH) to afford 83 mg (71%) of 2-(6-fluoro-3-hydroxymethyl-imidazo[1,5-a]pyridin-1-yl)-5-(2-trimethylsilanylethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid [(R)-2-(3-cyano-azetidin-1-yl)-1-methyl-2-oxo-ethyl]-amide as a light brown solid.

1. customwas evacuated
2. temperaturethen cooled to room temperature
3. customquenched with water
4. extractionextracted with dichloromethane (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 absorbed on silica gel
10. customchromatographed with MeOH/CH2Cl2/0.5% NH4OH (gradient 0-3% MeOH)