3-{[3-(aminomethyl)-6-chloro-2-fluorophenyl]oxy}-5-(1-methylethyl)benzonitrile (0.068 g, 0.213 mmol), 4-chloro-1H-imidazole-5-carboxylic acid (0.040 g, 0.273 mmol), and DIPEA (0.075 mL, 0.427 mmol) were combined in THF (6 mL) and treated with HATU (0.089 g, 0.235 mmol) at 25° C. overnight. The reaction mixture was concentrated to dryness and partitioned between DCM and water. The organic phase was isolated, dried over MgSO4, filtered and concentrated to dryness. The residue was purified by mass-directed HPLC on a SunFire prep C-18 column eluted with 30 to 85% CH3CN/H2O (0.1% formic acid buffer). Appropriate fractions were combined, concentrated to dryness, chased twice with ethanol and twice with toluene to remove residual water to give 4-chloro-N-[(4-chloro-3-{[3-cyano-5-(1-methylethyl)phenyl]oxy}-2-fluorophenyl)methyl]-1H-imidazole-5-carboxamide (0.0205 g, 0.046 mmol, 21.49% yield) as a clear oil. 1H NMR (400 MHz, DMSO-d6) δ ppm 13.15 (br. s., 1H), 8.23 (br. s., 1H), 7.77 (s, 1H), 7.43-7.55 (m, 2H), 7.36 (t, J=7.71 Hz, 1H), 7.24 (br. s., 1H), 7.13 (br. s., 1H), 4.54 (d, J=4.99 Hz, 2H), 2.95 (spt, 1H), 1.18 (d, J=6.96 Hz, 6H). LC-MS (ES−) m/z 445.09, 447.18 [M−1]. LC-MS (ES+) m/z 447.08, 449.06 [M+H].
