To a 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 (500 mg, 0.901 mmol) in THF (2.5 mL) and MeOH (2.5 mL) was added tert-butyl 3-oxoazetidine-1-carboxylate (185 mg, 1.081 mmol), acetic acid (0.052 rnL, 0.901 mmol). The reaction mixture was stirred at room temperature for overnight. The reaction mixture was cooled to 0° C., added sodium cyanoborohydride (113 mg, 1.802 mmol) and the reaction mixture was allowed to come to room temperature and stirred for 5 h at the same temperature. The solvent was removed completely under vacuum, the resultant residue was dissolved in ethyl acetate (100 ml), washed it with 10% NaHCO3 solution, brine, dried over anhydrous Na2SO4 and concentrated. The crude material was purified via ISCO (12 gm silica Redisep, 0 to 10% CH3OH—CHC13 gradient elution). The fractions were concentrated to get the tert-butyl 3-(4-(2-chloro-5-cyano-3-((7-cyano-4-(cyclopropyl(4-methoxybenzyl)amino)imidazo[2,1-f][1,2,4]triazin-2-yl)amino)phenyl)piperazin-1-yl)azetidine-1-carboxylate (500 mg) as a off white solid.
