Reaction Steps
The crude 2-[[2-(1,1-dioxo-1,4-dihydro-1λ6-benzo[1,2,4]thiadiazin-3-yl)-acetyl]-(4-fluoro-benzyl)-amino]-cyclopentanecarboxylic acid ethyl ester (0.503 mmol) was dissolved in ethanol (4 mL). A 21% w/w solution of sodium ethoxide in ethanol (1.8 mL) was added and the resulting reaction mixture was shaken for 16 h. A 1.0 M aqueous hydrochloric acid solution (9 mL) was added and the mixture was extracted with ethyl acetate (3×20 mL). The combined organic layers were dried over sodium sulfate, filtered, and concentrated in vacuo to afford the crude product, which was further purified by flash chromatography (Teledyne Isco RediSep Column; 0-100% ethyl acetate in hexanes) to afford the desired product, 3-(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 (114.2 mg, 0.259 mmol, 51.5% over two steps), as an off-white solid. LC-MS (ESI) calcd for C22H20FN3O4S 441.12, found 442.4 [M+H+]. The 1H NMR spectrum indicated a 4:1 mixture of cis- and trans-isomers. 1H NMR (CDCl3, 400 MHz): δ 1.54-1.77 (m, 3H), 1.87-2.13 (m, 2H), 2.26-2.34 (m, 1H, 80%), 2.36-2.49 (m, 1H, 20%), 2.88-2.93 (m, 1H, 20%), 3.11-3.16 (m. 1H, 80%), 3.69-3.77 (m, 1H), 4.30 (d, 1H, 80%, J=14.8 Hz), 4.43 (d, 1H, 20%, J=14.8 Hz), 5.00 (d, 1H, 20%, J=14.8 Hz), 5.09 (d, 1H, 80%, J=15.2 Hz), 7.03-7.10 (m, 2H), 7.17-7.35 (m, 3H), 7.36-7.42 (m, 1H), 7.55-7.60 (m, 1H), 7.91-7.95 (m, 1H). Anal. calcd for C22H20FN3O4S H2O: C, 57.50; H, 4.83; N, 9.15; found: C, 57.54; H, 4.53; N, 8.79.
