Reaction Steps
H2O2 (70%, 2.0 mL, ca. 40 mmol) was added dropwise to a stirred solution of TFM (5.6 mL, 40 mmol) in DCM (50 mL) at 0° C. The solution was stirred at 20° C. for 10 min, then cooled to 0° C., added to a solution of 1-oxide 54 (1.3 g, 4.0 mmol) and TFA (1.5 mL, 20 mmol) in DCM (50 mL) at 0° C. The solution was stirred at 20° C. for 26 h, diluted with dilute aqueous NH3 solution (80 mL) and extracted with DCM (4×125 mL). The combined organic fraction was dried and the solvent evaporated. The residue was purified by chromatography, eluting with a gradient (0-15%) of MeOH/DCM, to give 1,4-dioxide 55 (400 mg, 30%) as a red solid: mp 150-152° C.; 1H NMR δ 8.12 (s, 1H, H-9), 8.10 (s, 1H, H-5), 8.06 (br s, 1H, NH), 4.18 (p, J=5.9 Hz, 1H, CHO), 3.91 (br s, 2H, CH2N), 3.64 (t, J=6.4 Hz, 2H, CH2N), 3.28 (s, 3H, OCH3), 2.98-3.13 (m, 6H, H-6, H-8, CH2N), 2.80 (t, J=6.3 Hz, 2H, CH2N), 2.20 (p, J=7.5 Hz, 2H, H-7), 1.82 (p, J=6.4 Hz, 2H, CH2); 13C NMR δ 155.7, 149.4, 145.7, 138.0, 129.7, 115.8, 111.6, 69.3, 61.4 (2), 57.3, 56.2, 40.4, 33.4, 32.4, 26.0, 25.6; MS (APCI) m/z 346 (MH+, 100%); HRMS (FAB+) calcd for C17H24N5O3 (MH+) m/z 346.1879, found 346.1878.
