Cesium carbonate → HCID 89922727, compound

Participants

Reaction Conditions

Reaction Steps

To 2-chloro-4-(cyclopropyl(4-methoxybenzyl)amino)imidazo[2,1-f][1,2,4]triazine-7-carbonitrile (53.2 mg, 0.15 mmol), cesium carbonate (98 mg, 0.300 mmol), palladium(II) acetate (10.10 mg, 0.045 mmol), DPPF (8.32 mg, 0.015 mmol) and Xantphos (8.68 mg, 0.015 mmol) was added a solution of 5-amino-4-chloro-2-(4-morpholinobutyl)benzonitrile (48.5 mg, 0.165 mmol) in dioxane (1 mL). The reaction was heated at 100° C. for 1.5 h at which point LCMS showed full conversation. The reaction was cooled to room temperature and diluted with EtOAc, filtered through a pad of celite, concentrated and purified by flash column chromatography. The intermediate was then treated with TFA/DCManisole (0.25 mL, 0.25 mL, 0.25 mL) and stirred overnight at room temperature. The reaction mixture was concentrated in vacuo and then diluted with MeOH (3 ml), loaded onto an SCX column, washed with MeOH (3×4 mL), and then 7N NH3/MeOH (4 mL). The ammonia filtrate was collected, concentrated in vacuo, and purified by preparative HPLC to give 2-((2-chloro-5-cyano-4-(4-morpholinobutyl)phenyl)amino)-4-(cyclopropylamino)imidazo[2,1-f][1,2,4]triazine-7-carbonitrile (10.5 mg) as an off-white solid.

Provenance & Evidence