Reaction Steps
Morpholine (0.22 mL, 2.52 mmol) was added to a solution of aldehyde 214 (220 mg, 0.90 mmol) in MeOH (10 mL) and DMF (10 ml), and the solution stirred for 30 min. NaCNBH3 (176 mg, 2.80 mmol) was added, followed by HOAc (0.12 mL) and the mixture stirred at 20° C. for 30 min. The solvent was evaporated and the residue partitioned between DCM (40 mL) and water (40 mL). The aqueous phase was extracted with DCM (2×40 mL), the combined organic phase was dried and the solvent evaporated. The residue was purified by chromatography, eluting with 10% MeOH/EtOAc, to give 1-oxide 215 (210 mg, 74%) as a pale brown solid, mp 96-99° C.; 1H NMR δ 8.27 (t, J=1.6 Hz, 1H, H-9), 7.11 (s, 1H, H-5), 4.80 (t, J=8.4 Hz, 2H, H-8), 3.59 (t, J=4.6 Hz, 4H, 2×CH2O), 3.43 (dt, J=8.4, 1.6 Hz, 2H, H-7), 2.97-3.01 (m, 2H, CH2), 2.44-2.48 (m, 2H, CH2), 2.41 (t, J=4.5 Hz, 4H, 2×CH2N), 2.03-2.11 (m, 2H, CH2); 13C NMR δ 167.1, 166.4, 150.5, 134.8, 128.9, 116.2, 103.9, 73.0, 67.0 (2), 58.3, 53.5 (2), 53.4, 27.0, 24.9. Anal. calcd for C16H20N4O3: C, 60.8; H, 6.4; N, 17.7. Found: C, 60.7; H, 6.5; N, 17.7%.
