Diisopropylethylamine → 2-((2-Chloro-5-cyano-3-(4-(2,2-difluoroethyl)piperazin-1-yl)phenyl)amino)-4-(cyclopropyl(4-methoxybenzyl)amino)imidazo[2,1-f][1,2,4]triazine-7-carbonitrile

Participants

Reaction Steps

To the stirred solution of 2-((2-chloro-5-cyano-3-(piperazin-1-yl)phenyl)amino)-4-(cyclopropyl(4-methoxybenzyl)amino)imidazo[2,1-f][1,2,4]triazine-7-carbonitrile (Intermediate 11) (0.100 g, 0.180 mmol) in DMF (2.0 mL) and N,N-diisopropylethylamine, (63 μL, 0.361 mmol) was added 2,2-difluoroethyl trifluoromethanesulfonate (0.046 g, 0.216 mmol) at room temperature. The reaction mixture was stirred at room temperature for overnight. On completion of the reaction, the reaction mixture was diluted with ethyl acetate and washed with water. The organic layer was separated and aqueous layer was extracted with ethyl acetate twice. The combined organic layers were dried over sodium sulfate, filtered and concentrated in vacuum to give off-white solid, which was purified by flash chromatography on silica gel using an automated ISCO system (12 g Redisep column, eluting with 0-5% methanol/chloroform) to get 2-((2-chloro-5-cyano-3-(4-(2,2-difluoroethyl)piperazin-1-yl)phenyl)amino)-4-(cyclopropyl(4-methoxybenzyl)amino)imidazo[2,1-f][1,2,4]triazine-7-carbonitrile (100 mg) as an off-white solid.

Provenance & Evidence