Cesium carbonate → 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

참여 물질

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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.

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