Hydrochloric Acid → N-[3-[(4aR,8aS)-1-[(4-fluorophenyl)methyl]-4-hydroxy-2-oxo-4a,5,6,7,8,8a-hexahydroquinolin-3-yl]-1,1-dioxo-4H-1$l^{6},2,4-benzothiadiazin-7-yl]methanesulfonamide

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Reaction Conditions

Reaction Steps

The crude (1R,2S)-2-{(4-fluoro-benzyl)-[2-(7-methanesulfonylamino-1,1-dioxo-1,4-dihydro-1λ6-benzo[1,2,4]thiadiazin-3-yl)-acetyl]-amino}-cyclohexanecarboxylic acid methyl ester (0.3 mmol) was dissolved in ethanol (4 mL). A 21% w/w solution of sodium ethoxide in ethanol (0.448 mL, 1.2 mmol) was added into the above solution. The mixture was stirred at 60° C. for 4 h. Upon cooling to 25° C., the mixture was poured into 1.0 M aqueous hydrochloric acid solution (50 mL). The aqueous layer was extracted with ethyl acetate (2×50 mL). The organic layer was dried over sodium sulfate, filtered and concentrated in vacuo to afford a light yellow solid. Purification by flash column chromatography (Teledyne Isco RediSep Flash Column; 5% methanol in dichloromethane) afforded the desired product, (4aR,8aS)-N-{3-[1-(4-fluoro-benzyl)-4-hydroxy-2-oxo-1,2,4a,5,6,7,8,8a-octahydro-quinolin-3-yl]-1,1-dioxo-1,4-dihydro-1λ6-benzo[1,2,4]thiadiazin-7-yl}-methanesulfonamide (49.7 mg, 0.09 mmol, 30% over two steps), as a light yellow solid. 1H NMR (400 MHz, DMSO-d6) δ: 1.13-2.34 (8H, m), 3.06 (3H, s), 3.46-3.69 (1H, m), 4.24-4.66 (2H, m), 4.98 (1H, d, J=16 Hz), 7.16 (2H, t, J=8 Hz), 7.39-7.59 (5H, m), 10.15 (1H, s). LC-MS (ESI) calcd for C24H25FN4O6S2 548.12, found 549.2 [M+H+].

Provenance & Evidence