Reaction Steps
H2O2 (70%, 0.27 mL, ca. 5.4 mmol) was added dropwise to a stirred solution of TFM (0.8 mL, 5.4 mmol) in DCM (10 mL) at 0° C. The solution was stirred at 0° C. for 5 min, warmed to 20° C. for 10 min, then cooled to 0° C. and added to a stirred solution of 1-oxide 12 (170 mg, 0.5 mmol) and TFA (0.21 mL, 2.7 mmol) in DCM (15 mL) at 0° C. The solution was stirred at 20° C. for 16 h, diluted with dilute aqueous NH3 solution (10 mL) and extracted with CHCl3 (4×50 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 13 (89 mg, 50%) as a red solid: mp (MeOH/EtOAc) 138-141° C.; 1H NMR δ 8.12 (d, J=8.7 Hz, 1H, H-5), 7.70 (d, J=8.7 Hz, 1H, H-6), 7.44 (br s, 1H, NH), 3.70 (br t, J=7.6 Hz, 2H, H-9), 3.60-3.64 (m, 2H, CH2N), 3.04 (br t, J=7.7 Hz, 2H, H-7), 2.64 (br t, J=6.1 Hz, 2H, CH2N), 2.43-2.50 (m, 4H, 2×CH2), 2.21 (br p, J=7.7 Hz, 2H, H-8), 1.59-1.65 (m, 4H, 2×CH2), 1.42-1.48 (m, 2H, CH2); 13C NMR δ 149.1, 144.7, 138.6, 138.4, 132.7, 129.0, 115.7, 56.9, 54.4 (2), 38.1, 35.1, 32.9, 25.9 (2), 24.6, 24.3. Anal. calcd for C17H23N5O2.½H2O: C, 60.3; H, 7.2; N, 20.7. Found: C, 59.9; H, 7.0; N, 20.3%.
