反应详情

温度

60 °C

In a 15 ml round-bottomed flask, 2-[6-fluoro-1-(2-morpholin-4-yl-2-oxo-ethyl)-1H-indazol-3-yl]-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid (110 mg, 0.20 mmol) was suspended in THF (3 ml) and 1,1′-carbonyldiimidazole (39 mg, 0.24 mmol) was added. The light yellow suspension was stirred at 60° C. for 45 min during which time all solids dissolved. The reaction mixture was cooled to room temperature, tert-butylamine (0.20 ml, 1.9 mmol) was added, and the reaction was stirred at room temperature overnight. The reaction mixture was quenched with water and extracted with EtOAc (2×). The combined organic layers were washed with water and brine then dried over sodium sulfate, filtered and concentrated. The residue was chromatographed over silica gel with EtOAc/hexanes (gradient: 0-80% EtOAc) to afford 84 mg (70%) of 2-[6-fluoro-1-(2-morpholin-4-yl-2-oxo-ethyl)-1H-indazol-3-yl]-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid tert-butylamide as an off-white solid.

1. dissolutiondissolved
2. temperatureThe reaction mixture was cooled to room temperature
3. stirringthe reaction was stirred at room temperature overnight
4. customThe reaction mixture was quenched with water
5. extractionextracted with EtOAc (2×)
6. washThe combined organic layers were washed with water and brine
7. dry with materialthen dried over sodium sulfate
8. filtrationfiltered
9. concentrationconcentrated
10. customThe residue was chromatographed over silica gel with EtOAc/hexanes (gradient: 0-80% EtOAc)