Reaction Steps
To a warm (70° C.), stirred, solution of N-(3,5-Dimethyl-pyridin-2-ylmethyl)-N1-isoquinolin-1-ylmethyl-butane-1,4-diamine (0.130 g, 0.37 mmol) and DIPEA (0.39 mL, 2.24 mmol) in DMF (4 mL) was added freshly prepared imidazole-1-carboxylic acid (1H-imidazol-2-yl)-amide (2 equiv). After 1 hour, the mixture was cooled to room temperature, diluted with brine (5 mL) and extracted with CH2Cl2 (4×10 mL). The combined organic extracts were washed with water (5×10 mL), dried (Na2SO4) and concentrated. Purification of the crude material by column chromatography on silica gel (20:1:1 CH2Cl2-MeOH—NH4OH) provided 75 mg (42%) of COMPOUND 154 as a white solid. 1H NMR (CDCl3) δ 1.32-1.36 (m, 2H), 1.56-1.72 (m, 2H), 2.18 (s, 3H), 2.29 (s, 3H), 2.68-2.77 (m, 4H), 3.80 (s, 2H), 4.—(s, 2H), 6.72 (s, 2H), 7.24-7.26 (m, 1H), 7.39-7.44 (m, 1H), 7.57-7.63 (m, 2H), 7.74-7.78 (m, 2H), 7.86 (d, 1H, J=8.4 Hz), 8.46 (s, 1H), 8.50 (d, 1H, J=5.7 Hz); 13C NMR (CDCl3) δ 18.33, 18.72, 23.45, 27.95, 38.86, 55.10, 58.91, 59.22, 121.06, 126.47, 127.09, 127.31, 128.06, 130.36, 132.61, 133.16, 136.57, 139.42, 141.66, 144.62, 147.15, 153.65, 156.21, 158.75; ES-MS m/z 480 (M+23). Anal. Calcd. For C26H31N7O.0.8CH3OH: C, 66.62; H, 7.13; N, 20.29. Found: C, 66.84; H, 6.93; N, 20.23.
