H2O2 (70%, 0.50 mL, ca. 10.0 mmol) was added to a stirred solution of 1-oxide 44 (3.00 g, 9.52 mmol) in a mixture of TFA (30 mL) and water (2 mL) at 20° C. Ten more aliquots of 70% H2O2 (0.5 mL) were added in 30 min intervals and the reaction mixture was stirred at 20° C. for 26 h. Water (100 mL) was added and the mixture made basic with Na2CO3. The mixture was extracted with DCM (4×200 mL) and the combined organic fraction was dried and the solvent evaporated. The residue was purified by chromatography, eluting with a gradient (0-5%) of MeOH/DCM, to give 1,4-dioxide 45 (1.13 g, 36%) as a red solid: 1H NMR δ 8.13 (s, 1H, H-9), 8.10 (s, 1H, H-5), 7.38 (br s, 1H, NH), 3.73 (t, J=4.5 Hz, 4H, CH2O), 3.67 (m, 2H, CH2N), 3.03-3.15 (m, 4H, H-6, H-8), 2.68 (t, J=6.0 Hz, 2H, CH2N), 2.53 (t, J=4.5 Hz, 4H, CH2N), 2.17-2.25 (m, 2H, H-7); 13C NMR δ 155.7, 149.4, 145.9, 137.9, 129.7, 115.8, 111.6, 65.9 (2), 56.8, 53.4 (2), 37.7, 33.4, 32.4, 25.6. The hydrochloride salt was crystallised as a red solid: mp (MeOH/DCM) 184-185° C. Anal. calcd for C16H21N5O3.¾HCl: C, 53.5; H, 6.2; N, 19.5. Found: C, 53.9; H, 6.3; N, 19.6%.
