Reaction Steps
H2O2 (70%, 3.0 mL, ca. 60.4 mmol) was added dropwise to a stirred solution of TFM (8.4 mL, 60.4 mmol) in DCM (80 mL) at 0° C. The solution was stirred at 20° C. for 10 min, then cooled to 0° C., and added to a solution of 1-oxide 52 (2.0 g, 6.04 mmol) and TFA (1.0 mL, 13.0 mmol) in CHCl3 (80 mL) at 0° C. and the solution stirred at 20° C. for 18 h. The solution was made basic with dilute aqueous NH3 solution and extracted with CHCl3 (3×100 mL). The combined organic fraction was dried and the solvent evaporated. The residue was purified by chromatography, eluting with a gradient (2-18%) of MeOH/DCM, to give 1,4-dioxide 53 (99 mg, 5%) as a red solid: mp 77-79° C.; 1H NMR δ 8.12 (s, 1H, H-9), 8.10 (s, 1H, H-5), 7.26 (br s, 1H, NH), 3.66 (t, J=6.3 Hz, 2H, CH2), 3.59 (t, J=5.6 Hz, 2H, CH2), 3.36 (s, 3H, OCH3), 3.03-3.12 (m, 4H, H-6, H-8), 2.66-2.71 (m, 4H, 2×CH2), 2.39 (s, 3H, NCH3), 2.19 (p, J=7.4 Hz, 2H, H-7), 1.91 (p, J=6.6 Hz, 2H, CH2); 13C NMR δ 155.6, 149.5, 145.7, 138.0, 129.7, 115.8, 111.6, 70.5, 58.9, 56.8, 55.9, 42.5, 40.5, 33.4, 32.4, 25.9, 25.6; HRMS (FAB+) calcd for C17H26N5O3 (MH+) m/z 348.2036, found 348.2032.
