反应详情

To a round bottom flask charged with tert-butyl (1-(2-chloro-5-cyano-3-((7-cyano-4-(cyclopropyl(4-methoxybenzyl)amino)imidazo[2,1-f][1,2,4]triazin-2-yl)amino)phenyl)piperidin-4-yl)carbamate (I12C) (0.517 g, 0.773 mmol) in dichloromethane (5.15 ml) was added anisole (1.688 ml, 15.45 mmol), followed by the slow addition of trifluoroacetic acid (2.381 ml, 30.9 mmol). The reaction mixture was stirred at room temperature 2 d. The reaction mixture was warmed to 45° C. for 1 h. The reaction mixture was cooled to room temperature and concentrated in vacuo. After cooling to room temperature, 25 mL 2 N ammonia/methanol was added and a white solid crashed out of solution. The slurry was stirred for 30 min and the solid was isolated by vacuum filtration washing with cold methanol. 2-((3-(4-Aminopiperidin-1-yl)-2-chloro-5-cyanophenyl)amino)-4-(cyclopropylamino)imidazo[2,1-f][1,2,4]triazine-7-carbonitrile (0.1563 g) was isolated as a white solid. Material used as is in subsequent transformations.

1. temperatureThe reaction mixture was warmed to 45° C. for 1 h
2. temperatureThe reaction mixture was cooled to room temperature
3. concentrationconcentrated in vacuo
4. temperatureAfter cooling to room temperature
5. addition25 mL 2 N ammonia/methanol was added
6. stirringThe slurry was stirred for 30 min
7. customthe solid was isolated by vacuum filtration
8. washwashing with cold methanol