Reaction Steps
A solution of ethyl (7S,10R)-11-(((benzyloxy)carbonyl)amino)-3-hydroxy-10,12,12-trimethyl-4-oxo-6,7,8,9,10,11-hexahydro-4H-7,10-methanopyrimido[1,2-a]azocine-2-carboxylate (1.4595 g, 3.11 mmol), (4-fluorophenyl)methanamine (1.143 mL, 10.00 mmol) and Et3N (1.394 mL, 10 mmol) in EtOH (25 mL) was heated at reflux for 14 h. the reaction mixture was then cooled, diluted with Et2O (100 mL), washed with 1N aq. HCl (1×25 mL), water (2×25 mL) followed by brine (25 mL), then dried (Na2SO4), filtered and concentrated to give a brown paste. The product was purified by preparative HPLC using a C18-column and 40-90% methanol/water (0.1 trifluoroacetic acid) to afford the title compound (0.367 g, 0.669 mmol, 22% yield) as a light brown solid. 1H NMR (500 MHz, CDCl3) δ: 12.21 (0.3 H, brs), 12.08 (0.7 H, s), 8.24 (0.3 H, brs), 7.71 (0.7 H, t, J=6.1 Hz), 7.18-7.38 (8 H, m), 6.92-7.05 (2 H, m), 4.98-5.21 (4 H, m), 4.52-4.58 (1H, m), 4.41-4.47 (1 H, m), 3.67 (0.7 H, d, J=15.6 Hz), 3.56 (0.3 H, d, J=15.6 Hz), 2.08 (0.7 H, t, J=8.1 Hz), 2.01-2.06 (0.3 H, m), 1.73-1.87 (2 H, m), 1.40-1.49 (1H, m), 1.37 (2 H, s), 1.28-1.35 (1 H, m), 1.25 (1 H, s), 1.00 (2 H, s), 0.99 (2 H, s), 0.95 (1 H, s), 0.92 (1 H, s). LCMS (M+H) calcd for C30H34FN4O5: 549.25; found: 549.28. Purity: >96%.
