Dicyclohexylcarbodiimide → (+/-)-(3R,4R)-1-(2-chloro-5-cyano-3-((7-cyano-4-(ethylamino)imidazo[2,1-f][1,2,4]triazin-2-yl)amino)phenyl)-4-((methoxycarbonyl)amino)piperidin-3-yl 2-(phosphonooxy)propanoate

Participants

Reaction Steps

To a solution of methyl ((3R,4R)-1-(2-chloro-5-cyano-3-((7-cyano-4-(ethyl(4-methoxybenzyl)amino)imidazo[2,1-f][1,2,4]triazin-2-yl)amino)phenyl)-3-hydroxypiperidin-4-yl)carbamate (0.040 g, 0.063 mmol), 2-((bis(benzyloxy)phosphoryl)oxy)propanoic acid (0.067 g, 0.19 mmol) in DCM (2 mL) was added DCC (0.039 g, 0.190 mmol) followed DMAP (0.77 mg, 0.006 mmol) and stirred at room temperature for 30 min. After completion of starting material (by LC-MS), reaction mixture was diluted with DCM (50 mL), filtered through celite and filtrate was washed with water and brine solution (5 mL). Combined organic extracts were dried over anhydrous Na2SO4, concentrated and purified by flash chromatography on silica gel using an ISCO system (eluted with 1:1 Hexanes and EtOAc) to give diastereomeric mixture of (3R,4R) 1-(2-chloro-5-cyano-3-((7-cyano-4-(ethyl(4-methoxybenzyl)amino)imidazo[2,1-f][1,2,4]triazin-2-yl)amino)phenyl)-4((methoxycarbonyl)amino)piperidin-3-yl-2-((bis(benzyloxy)phosphoryl)oxy)propanoate (0.060 g) as gummy liquid.

Provenance & Evidence