Reaction Steps
4-(4-Morpholinyl)butylamine (306) (2.02 g, 12.8 mmol) was added to a stirred solution of chloride 21 (1.89 g, 8.5 mmol) and Et3N (1.8 mL, 12.8 mmol) in DME (80 mL) and the solution stirred at reflux temperature for 16 h. The solvent was evaporated and the residue was partitioned between DCM (100 mL) and dilute aqueous NH3 solution (50 mL). The organic fraction was dried and the solvent evaporated. The residue was purified by chromatography, eluting with a gradient (0-10%) of MeOH/DCM, to give 1-oxide 62 (2.57 g, 88%) as pale yellow solid: mp (MeOH/EtOAc) 151-152° C.; 1H NMR δ 8.07 (s, 1H, H-9), 7.38 (s, 1H, H-5), 5.78 (br s, 1H, NH), 3.78 (br t, J=4.6 Hz, 4H, 2×CH2O), 3.50 (br dd, J=6.6, 5.9 Hz, 2H, CH2N), 2.95-3.02 (m, 4H, H-6, H-8), 2.45 (br t, J=4.4 Hz, 4H, 2×CH2N), 2.40 (t, J=7.0 Hz, 2H, CH2N), 2.15 (p, J=7.5 Hz, 2H, H-7), 1.67-1.74 (m, 2H, CH2), 1.58-1.64 (m, 2H, CH2); 13C NMR δ 158.8, 154.5, 148.8, 143.2, 129.8, 120.5, 114.7, 66.9 (2), 58.5, 53.7 (2), 41.3, 33.1, 32.3, 27.4, 25.7, 24.0. Anal. Calcd for C18H25N5O2: C, 63.0; H, 7.3; N, 20.4. Found: C, 62.9; H, 7.2; N, 20.5%.
