Reaction Steps
H2O2 (70%, 1.6 mL, ca. 32 mmol) was added dropwise to a stirred solution of TFM (4.5 mL, 32 mmol) in DCM (40 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 199 (1.06 g, 3.2 mmol) and TFA (1.25 mL, 16 mmol) in DCM (40 mL) at 0° C. The solution was stirred at 20° C. for 4.5 h, diluted with dilute aqueous NH3 solution (50 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 (0-10%) of MeOH/DCM to give 1,4-dioxide 200 (150 mg, 14%) as a red solid: mp 145-148° C.; 1H NMR δ 8.26 (br s, 1H, NH), 8.14 (s, 1H, H-9), 7.53 (s, 1H, H-5), 4.74 (t, J=8.3 Hz, 2H, H-7), 3.83 (t, J=4.6 Hz, 4H, 2×CH2O), 3.65 (br q, J=5.9 Hz, 2H, CH2N), 3.43 (dt, J=8.3, 1.2 Hz, 2H, H-6), 2.58 (br t, J=6.1 Hz, 2H, CH2), 2.53 (br s, 4H, 2×CH2N), 1.88 (p, J=6.2 Hz, 2H, CH2); 13C NMR δ 159.8, 149.0, 141.5, 135.2, 130.8, 113.1, 97.4, 72.4, 66.8 (2), 57.7, 53.8 (2), 41.6, 29.7, 24.5; MS (APCI) m/z 348 (MH+, 100%); HRMS (FAB+) calcd for C16H22N5O4 (MH+) m/z 348.1672, found 348.1666. Anal. calcd for C16H21N5O4.0.4CH2Cl2: C, 51.7; H, 5.8; N, 18.4. Found: C, 51.7; H, 5.4; N, 18.1%.
