反应详情

温度

80 °C

A 5 ml microwave vial was loaded with 2-chloro-4-(ethyl(4-methoxybenzyl)amino)imidazo[2,1-f][1,2,4]triazine-7-carbonitrile (71.8 mg, 0.209 mmol), 3-amino-4-chloro-5-((1S,4S)-5-methyl-2,5-diazabicyclo[2.2.1]heptan-2-yl)benzonitrile (50 mg, 0.190 mmol), Pd(OAc)2 (6.41 mg, 0.029 mmol), XANTPHOS (17.62 mg, 0.030 mmol) and Potassium phosphate (145 mg, 0.685 mmol). The vial was evacuated and back-filled with nitrogen 4 times. Toluene (2 ml) was added and the flask was again evacuated and back-filled with nitrogen 4 times, and then heated with stirring to 80° C. for 5 hours. The reaction mixture was cooled to room temperature, filtered through Celite and solids washed with dichloromethane. Evaporation to dryness gave 163 mg crude product 2-((2-chloro-5-cyano-3-((1S,4S)-5-methyl-2,5-diazabicyclo[2.2.1]heptan-2-yl)phenyl)amino)-4-(ethyl(4-methoxybenzyl)amino)imidazo[2,1-f][1,2,4]triazine-7-carbonitrile, which was used “as is” in the following deprotection reaction.

1. customThe vial was evacuated
2. additionback-filled with nitrogen 4 times
3. additionToluene (2 ml) was added
4. customthe flask was again evacuated
5. additionback-filled with nitrogen 4 times
6. temperatureheated
7. temperatureThe reaction mixture was cooled to room temperature
8. filtrationfiltered through Celite and solids
9. washwashed with dichloromethane
10. customEvaporation to dryness