A vial was charged with 2-chloro-N-(5-(difluoromethyl)-1H-pyrazol-3-yl)pyrimidin-4-amine (80 mg, 0.33 mmol), the bis HCl salt of 1-(4-chloro-1-(tetrahydro-2H-pyran-2-yl)-1H-benzo[d]imidazol-5-yl)-N-methylmethanamine (138 mg, 0.39 mmol), DIPEA (0.29 mL, 1.63 mmol) and n-BuOH (1.5 mL), sealed and heated at 90° C. for 8 h. The reaction mixture was then cooled to RT, and 4N HCl/dioxane (0.81 mL, 3.26 mmol) was added. The mixture was stirred at 40° C. for 3 h and then concentrated in vacuo. The crude mixture was purified by preparative HPLC to afford 15.1 Mg9 12%) of N2-((4-chloro-1H-benzo[d]imidazol-5-yl)methyl)-N4-(5-(difluoromethyl)-1H-pyrazol-3-yl)-N2-methylpyrimidine-2,4-diamine (II-81).
