Reaction Steps
(4aR,7aS)-3-[7-(1,1-Dioxo-4,5-dihydro-1H-1λ6-thiophen-2-yl)-1,1-dioxo-1,4-dihydro-1λ6-benzo[1,2,4]thiadiazin-3-yl]-1-(4-fluoro-benzyl)-4-hydroxy-1,4a,5,6,7,7a-hexahydro-[1]pyrindin-2-one (prepared as described in Example 44, 45 mg, 0.081 mmol) was dissolved in a 1:5 mixture of N,N-dimethylformamide and methanol (12 mL). 5% Palladium on charcoal (100 mg) was added. The flask was degassed and backfilled with hydrogen gas via balloon. The mixture was stirred at 25° C. for 16 h. The mixture was passed through a plug of Celite, washed with 10% methanol/dichloromethane, and the filtrate was concentrated in vacuo. The residue was purified by prep-HPLC [Column Luna 5μ C18 (2) 100 Å AXIA 50×21.2 mm, 5 micron, 40-95% in 7 min @ 30 mL/min flow rate, 0.05% trifluoroacetic acid in acetonitrile/0.05% trifluoroacetic acid in water] to afford the desired product as an inseparable mixture of two diastereomers, (4aR,7aS)-3-[7-(1,1-dioxo-tetrahydro-1λ6-thiophen-2-yl)-1,1-dioxo-1,4-dihydro-1λ6-benzo[1,2,4]thiadiazin-3-yl]-1-(4-fluoro-benzyl)-4-hydroxy-1,4a,5,6,7,7a-hexahydro-[1]pyrindin-2-one (20 mg, 0.036 mmol, 44%), as a white powder. 1H NMR (400 MHz, DMSO-d6) δ: 1.44-1.60 (3H, m), 1.95-2.40 (10H, m), 3.22-3.36 (3H, m), 3.86 (1H, bs), 4.47 (1H, d, J=14.4 Hz), 4.56 (1H, dd, J=12.4, 8.0 Hz), 4.91 (1H, d, J=15.2 Hz), 7.15 (2H, t, J=8.4 Hz), 7.39 (2H, m), 7.61 (1H, d, J=8.8 Hz), 7.71 (1H, dd, J=8.4, 2.4 Hz), 7.82 (1H, s). LC-MS (ESI) calcd for C26H26FN3O6S2 559.12, found 560.3 [M+H+].
