反应详情

温度

0 °C

In a round-bottomed flask, 2-(6-chloro-1H-indazol-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, 0.155 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 1-bromo-2-methoxyethane (22 μl, 0.23 mmol) was added. The reaction mixture was stirred at 0° C. for 3 h and then at room temperature overnight. The reaction mixture was 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 0-3% MeOH) to afford 51 mg (52%) of 2-[6-chloro-1-(2-methoxy-ethyl)-1H-indazol-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 3 h
2. customat room temperature
3. customovernight
4. customThe reaction mixture was quenched with water
5. extractionextracted with diethyl ether (2×)
6. washThe combined organic layers were washed twice with water and once with brine
7. dry with materialthen dried over sodium sulfate
8. filtrationfiltered
9. concentrationconcentrated
10. customThe residue was chromatographed over silica gel with MeOH/CH2Cl2/0.5% NH4OH (gradient 0-3% MeOH)