Reaction Steps
A solution of chloride 21 (1.33 g, 6.0 mmol), Et3N (1.7 mL, 12 mmol) and 3-(3-methoxy-1-azetidinyl)propylamine (299) (1.2 g, 8.4 mmol) in DME (30 mL) was heated at reflux temperature for 18 h. The solution was cooled, the solvent evaporated and the residue partitioned between dilute aqueous NH3 solution (50 mL) and DCM (50 mL). The aqueous layer was extracted with DCM (2×25 mL), the combined organic fraction dried and the solvent evaporated. The residue was purified by chromatography, eluting with a gradient (0-15%) of MeOH/DCM, to give 1-oxide 54 (1.32 g, 66%) as a yellow solid: mp 101-102° C.; 1H NMR δ 8.07 (s, 1H, H-9), 7.39 (s, 1H, H-5), 6.18 (br s, 1H, NH), 4.07 (p, J=5.9 Hz, 1H, CHO), 3.65-3.71 (m, 2H, CH2N), 3.54 (dt, J=6.2, 5.8 Hz, 2H, CH2N), 3.26 (s, 3H, OCH3), 2.94-3.04 (m, 4H, H-6, H-8), 2.82-2.88 (m, 2H, CH2N), 2.63 (t, J=6.4 Hz, 2H, CH2N), 2.14 (p, J=7.1 Hz, 2H, H-7), 1.70 (p, J=6.4 Hz, 2H, CH2); 13C NMR δ 158.8, 154.5, 148.8, 143.1, 129.8, 120.6, 114.7, 69.7, 61.5 (2), 58.6, 56.0, 40.8, 33.1, 32.3, 26.6, 25.8; MS (APCI) m/z 330 (MH+, 100%). Anal. calcd for C17H23N5O2: C, 62.0; H, 7.0; N, 21.3. Found: C, 61.7; H, 7.2; N, 21.2%.
