反应详情

温度

0 °C

In a round-bottomed flask, 2-(6-chloro-1H-indol-3-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 (90 mg, 0.156 mmol) was dissolved in DMF (1 ml). The reaction mixture was cooled to 0° C. and sodium hydride (60% dispersion in mineral oil, 8 mg, 0.20 mmol) was added. The reaction mixture was stirred at 0° C. for 30 min then methyl iodide (10 μl, 0.16 mmol) was added. The reaction mixture was stirred at 0° C. for 1.5 h then 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 56 mg (61%) of 2-(6-chloro-1-methyl-1H-indol-3-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 yellow foam.

1. stirringThe reaction mixture was stirred at 0° C. for 1.5 h
2. customthen quenched with water
3. extractionextracted with diethyl ether (2×)
4. washThe combined organic layers were washed twice with water and once with brine
5. dry with materialthen dried over sodium sulfate
6. filtrationfiltered
7. concentrationconcentrated
8. customThe residue was chromatographed over silica gel with MeOH/CH2Cl2/0.5% NH4OH (gradient 0-2% MeOH)