Reaction Steps
NaH (66 mg, 60% dispersion in oil, 1.7 mmol) was added to a stirred solution of fluoride 12 (261 mg, 1.0 mmol) and 2-methoxyethanol (0.12 mL, 1.6 mmol) in THF (10 mL) at 20° C. and the mixture stirred at reflux temperature for 2 h. More NaH (66 mg, 1.6 mmol) and 2-methoxyethanol (0.12 mL, 1.6 mmol) were added and the mixture stirred at reflux temperature for 16 h. The mixture was cooled to 20° C. and carefully quenched with water (5 mL). The solvent was evaporated and the residue partitioned between DCM (50 mL) and water (50 mL). The 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-oxide 13 (296 mg, 93%) as a yellow solid, mp (MeOH/EtOAc) 139-141° C.; 1H NMR δ 8.14 (d, J=9.4 Hz, 1 H, H-8), 6.91 (dd, J=9.4, 2.6 Hz, 1 H, H-7), 6.84 (d, J=2.6 Hz, 1 H, H-5), 5.91 (br s, 1 H, NH), 4.20-4.23 (m, 2 H, CH2O), 3.71-3.74 (m, 2 H, CH2O), 3.51-3.56 (m, 2 H, CH2N), 3.46 (s, 3 H, OCH3), 2.55 (br dd, J=6.0, 5.9 Hz, 2 H, CH2N), 2.28 [s, 6 H, (CH3)2]; 13C NMR δ 164.6, 159.6, 151.4, 126.1, 122.1, 118.0, 104.6, 70.5, 68.0, 59.3, 57.5, 45.1 (2), 38.7. Anal. Calcd for C14H21N5O3: C, 54.7; H, 6.9; N, 22.8. Found: C, 54.5; H, 6.7; N, 22.7%.
