反应详情

温度

80 °C

In a round-bottomed flask, methanesulfonic acid 2-((R)-1-{[2-(6-fluoro-1-methyl-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carbonyl]-amino}-ethyl)-oxazol-4-ylmethyl ester (146 mg, 0.18 mmol) was dissolved in DMF (0.5 ml). Sodium cyanide (27 mg, 0.55 mmol) was added and the reaction mixture was stirred at 80° C. overnight. The reaction was 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 EtOAc/hexanes (gradient 0-60% EtOAc) to isolate 37 mg (36%) of 2-(6-fluoro-1-methyl-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid [(R)-1-(4-cyanomethyl-oxazol-2-yl)-ethyl]-amide as a yellow solid.

1. temperatureThe reaction was cooled to room temperature
2. customquenched 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 EtOAc/hexanes (gradient 0-60% EtOAc)