To a round-bottomed flask containing 2-((3-fluoro-4-nitrophenoxy)methyl)-5-methylpyridine (68.0 g, 259 mmol) and 4-bromobenzylamine (58 g, 259 mmol) in acetonitrile (680 mL) was added DIPEA (113 mL, 648 mmol). The stirred mixture was then heated to 80° Celsius. After 14.5 h, the mixture was cooled to RT and was concentrated to 261 g. The resulting residue was added to i-PrOH (900 mL) and heated to 70° Celsius until homogeneous. The solution was cooled to RT and the crystalline solids were isolated through filtration. The filter cake was washed with cold i-PrOH (200 mL), the solids were collected and dried in a vacuum oven at 40° Celsius for 3 days to give the title compound (78.4 g, 71%). MS (ESI): mass calcd. for C20H18BrN3O3, 427.1; m/z found, 428.0 [M+H]+. 1H NMR (400 MHz, CDCl3) δ 8.66 (t, J=5.9, 1H), 8.36 (d, J=2.1, 1H), 8.16 (d, J=9.5, 1H), 7.57-7.37 (m, 3H), 7.27-7.23 (d incident with solvent signal, 1H), 7.22-7.13 (m, 2H), 6.34 (dd, J=9.5, 2.6, 1H), 6.18 (d, J=2.6, 1H), 5.12 (s, 2H), 4.44 (d, J=5.8, 2H), 2.35 (s, 3H).
