Reaction Steps
A mixture of ethyl 11-(((benzyloxy)carbonyl)amino)-3-hydroxy-4-oxo-7,8,10,11-tetrahydro-4 H,6H-8,11-methanopyrimido[2,1-d][1,5]oxazocine-2-carboxylate (0.070 g, 0.163 mmol), (4-fluorophenyl)methanamine (0.125 g, 1 mmol) and Et3N (0.418 mL, 3 mmol) in EtOH (5 mL) was heated at reflux for 7 h. The reaction was cooled, concentrated and the residue purified by preparative-HPLC to afford title compound (0.0405 g, 0.080 mmol, 49%) as an off-white solid. 1H NMR (500 MHz, CDCl3) δ: 11.99 (0.6 H, brs), 11.92 (0.4 H, brs), 7.82 (0.4 H, t, J=5.8 Hz), 7.58 (0.6 H, t, J=5.8 Hz), 7.32-7.39 (3 H, m), 7.17-7.28 (2 H, m), 7.09 (1 H, dd, J=8.1, 5.6 Hz), 7.01-7.06 (1 H, m), 6.91-6.99 (2 H, m), 5.60 (0.6 H, s), 5.41-5.51 (1 H, m), 5.10 (0.4 H, s), 5.02 (0.6 H, d, J=12.5 Hz), 4.89 (1 H, d, JAB=12.4 Hz.), 4.79 (0.6 H, d, J=10.7 Hz), 4.69-4.75 (2 H, m), 4.60 (0.4 H, d, J=10.4 Hz), 4.37-4.49 (2.8 H, m), 4.12 (0.6 H, dd, J=18.8, 6.0 Hz), 3.70 (0.6 H, t, J=13.7 Hz), 3.63 (0.4 H, t, J=13.7 Hz), 2.47-2.60 (1 H, m), 2.13-2.21 (1 H, m.), 1.97-2.05 (1 H, m). LCMS (M+H) calcd for C26H26FN4O6: 509.18; found: 509.14.
