Reaction Steps
To a solution of N1-(3,5-Dimethyl-pyridin-2-ylmethyl)-N1-{3-[1-(4-fluoro-phenyl)-1-methyl-ethyl]-pyridin-2-ylmethyl}-butane-1,4-diamine (0.210 g, 0.48 mmol) in dry THF (4 mL) was added 1,1′-carbonyldiimidazole (79 mg, 0.49 mmol), and the resultant solution was stirred room temperature for 30 minutes. The mixture was concentrated and the resultant oil was dissolved in DMF (2 mL), treated with DIPEA (0.50 mL, 2.87 mmol) and NH2OH.HCl (134 mg, 1.93 mmol), and heated at 60° C. overnight. The mixture was cooled to room temperature, diluted with CH2Cl2 (50 mL), washed with brine (3×10 mL), dried (Na2SO4) and concentrated. Purification of the crude material by column chromatography on silica gel (20:21:1 CH2Cl2-MeOH—NH4OH) provided 143 mg (59%) of COMPOUND 149 as a white solid. 1H NMR (CDCl3) δ 1.34 (br s, 4H), 1.65 (s, 6H), 1.93-2.25 (m, 8H), 3.09 (d, 2H, J=5.1 Hz), 3.32 (s, 2H), 3.45 (s, 2H), 6.87-7.09 (m, 5H), 7.21-7.38 (m, 3H), 7.89 (d, 1H, J=7.2 Hz), 8.14 (s, 1H), 8.53 (d, 1H, J=3.3 Hz), 10.27 (br s, 1H); 13C NMR (CDCl3) δ 18.26, 18.75, 23.87, 28.13, 31.51, 39.41, 42.50, 53.98, 57.19, 58.03, 115.56 (d, JC-F=21 Hz), 122.18, 127.72 (d, JC-F=7.5 Hz), 132.12, 132.87, 134.56, 139.50, 143.67, 145.71, 146.71, 146.97, 153.38, 157.78, 161.31 (d, JC-F=243 Hz), 162.84; ES-MS m/z 494 (M+H). Anal. Calcd. For C28H36N5O2F.0.7H2O: C, 66.43; H, 7.45; N, 13.83; F, 3.75. Found: C, 66.04; H, 7.29; N, 14.22; F, 3.85.
