反应详情

温度

100 °C

A pressure tube was charged with 2-(5-difluoromethoxy-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid tert-butylamide (180 mg, 0.34 mmol), tert-butyl 4-bromopiperidine-1-carboxylate (179 mg, 0.68 mmol), cesium carbonate (332 mg, 1.02 mmol) and DMF (1.5 ml). The tube was flushed with argon, sealed and stirred at 100° C. in an oil bath overnight. The reaction was cooled to room temperature and additional tert-butyl 4-bromopiperidine-1-carboxylate (179 mg, 0.68 mmol) and cesium carbonate (332 mg, 1.02 mmol) were added. The tube was again flushed with argon, sealed and stirred at 100° C. in an oil bath for 6 h. The reaction mixture 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 25 g silica gel with EtOAc/hexanes (gradient: 0-30% EtOAc) to afford 197 mg (81%) of 4-{3-[7-tert-butylcarbamoyl-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazin-2-yl]-5-difluoromethoxy-indazol-1-yl}-piperidine-1-carboxylic acid tert-butyl ester as an off-white solid.

1. customThe tube was flushed with argon
2. customsealed
3. temperatureThe reaction was cooled to room temperature
4. customThe tube was again flushed with argon
5. customsealed
6. stirringstirred at 100° C. in an oil bath for 6 h
7. temperatureThe reaction mixture was cooled to room temperature
8. customquenched with water
9. extractionextracted with diethyl ether (2×)
10. washThe combined organic layers were washed twice with water and once with brine
11. dry with materialthen dried over sodium sulfate
12. filtrationfiltered
13. concentrationconcentrated
14. customThe residue was chromatographed over 25 g silica gel with EtOAc/hexanes (gradient: 0-30% EtOAc)