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

Participants

Reaction Conditions

Reaction Steps

3-amino-4-chloro-5-(3-(4-methylpiperazin-1-yl)propyl)benzonitrile, TFA (104 mg) was converted to the free base by dissolving in MeOH and passing through an SCX column, first rinsing with MeOH, then 2N NH3 in MeOH to release the material. To this aniline (38.8 mg, 0.132 mmol) in a 2 dram vial was added 2-chloro-4-(cyclopropyl(4-methoxybenzyl)amino)imidazo[2,1-f][1,2,4]triazine-7-carbonitrile (47 mg, 0.132 mmol), palladium(II) acetate (8.92 mg, 0.040 mmol), DPPF (7.34 mg, 0.013 mmol), Xantphos (7.67 mg, 0.013 mmol), cesium carbonate (86 mg, 0.265 mmol) and dioxane (Iml). The vial was evacuated and backfilled with N2 3×, then heated at 100° C. for 1 h. The reaction was cooled to room temperature and filtered through celite, rinsing with EtOAc. The solvent was removed in vacuo and the material purified by flash column chromatography (0-10% MeOH/DCM; 24 g column). 2-((2-chloro-5-cyano-3-(3-(4-methylpiperazin-1-yl)propyl)phenyl)amino)-4-(cyclopropyl(4-methoxybenzyl)amino)imidazo[2,1-f][1,2,4]triazine-7-carbonitrile (48 mg) was obtained as a yellow glass.

Provenance & Evidence