A mixture of 2-((2-chloro-5-cyano-3-(hexahydro-1H-pyrrolo[3,2-c]pyridin-5(6H)-yl)phenyl)amino)-4-(cyclopropyl(4-methoxybenzyl)amino)imidazo[2,1-f][1,2,4]triazine-7-carbonitrile (Example 443F, 29 mg, 0.049 mmol) and 2-(=/−)-methyloxirane (14.15 mg, 0.244 mmol) in ethanol (0.8 mL)/THF (0.2 mL) in a sealed 1-dram vial was heated at 80° C. overnight. A clear solution was observed and LCMS showed completion of reaction. Solvent was evaporated and to the crude intermediate were added anisole (0.027 ml, 0.244 mmol) and 25% TFA in dichloroethane (2 ml, 6.49 mmol) and the resulting solution was stirred at 35° C. overnight. Solvent was evaporated and the crude was purified by prep-HPLC to give the title compound (9.8 mg) as a white solid.
