Reaction Steps
Using General Procedure G: To a solution of N1-(3,5-Dimethyl-pyridin-2-ylmethyl)-N1-(5,6,7,8-tetrahydro-quinolin-8-yl)-butane-1,4-diamine (202 mg, 0.60 mmol) in dry DMF (3 mL) was added 6-hydroxy-nicotinic acid (108 mg, 0.78 mmol) followed by EDCI (149 mg, 0.78 mmol), HOBT (106 mg, 0.78 mmol), and DIPEA (0.21 mL, 1.21 mmol). Purification of the crude material by radial chromatography on silica gel (1 mm plate, 10:1:1 CH2Cl2-MeOH—NH4OH) provided 54 mg (20%) of the free base of the title compound as a white foam. Using General Procedure D: Conversion to the HBr salt gave COMPOUND 366 as a white solid. 1H NMR (D2O) δ 1.29-1.42 (m, 2H), 1.49-1.58 (m, 2H), 1.90-2.01 (m, 1H), 2.22-2.35 (m, 2H), 2.54 (s, 3H), 2.56 (s, 3H), 2.57-2.67 (m, 2H), 2.79-2.87 (m, 1H), 3.11-3.15 (m 2H), 3.29-3.40 (m, 2H), 4.33 (d, 1H, J=18.0 Hz), 4.52 (d, 1H, J=18.0 Hz), 4.63 (dd, 1H, J=10.8, 5.7 Hz), 6.82 (d, 1H, J=9.6 Hz), 7.96-8.01 (m, 2H), 8.10 (d, 1H, J=2.1 Hz), 8.23 (s, 1H), 8.46 (d, 1H, J=8.1 Hz), 8.55 (s, 1H), 8.73 (d, 1H, J=5.1 Hz); 13C NMR (D2O) δ 16.89, 17.47, 20.49, 20.74, 25.72, 26.63, 27.82, 39.10, 52.31, 52.90, 62.08, 115.63, 119.37, 125.79, 136.06, 137.16, 137.16, 137.29, 137.49, 139.30, 140.49, 140.88, 147.96, 148.85, 149.33, 151.25, 165.45, 166.46; ES-MS m/z 460 (M+H). Anal. Calcd. For C27H33N5O2.3.0HBr.3.5H2O: C, 42.37; H, 5.66; N, 9.15; Br, 31.32. Found: C, 42.16; H, 5.50; N, 9.26; Br, 31.61.
