Reaction SMILES: C([O:3][C:4]([CH:6]1[CH:11]([N:12]([CH2:33][C:34]2[CH:39]=[CH:38][C:37]([F:40])=[CH:36][CH:35]=2)[C:13](=[O:32])[CH2:14][C:15]2[NH:20][C:19]3[CH:21]=[CH:22][C:23]([NH:25][S:26]([CH3:29])(=[O:28])=[O:27])=[CH:24][C:18]=3[S:17](=[O:31])(=[O:30])[N:16]=2)[CH2:10][CH:9]=[CH:8][CH2:7]1)=O)C.[O-]CC.[Na+].Cl>C(O)C>[F:40][C:37]1[CH:38]=[CH:39][C:34]([CH2:33][N:12]2[C@@H:11]3[C@@H:6]([CH2:7][CH:8]=[CH:9][CH2:10]3)[C:4]([OH:3])=[C:14]([C:15]3[NH:20][C:19]4[CH:21]=[CH:22][C:23]([NH:25][S:26]([CH3:29])(=[O:28])=[O:27])=[CH:24][C:18]=4[S:17](=[O:31])(=[O:30])[N:16]=3)[C:13]2=[O:32])=[CH:35][CH:36]=1.[F:40][C:37]1[CH:38]=[CH:39][C:34]([CH2:33][N:12]2[CH:11]3[CH:6]([CH2:7][CH:8]=[CH:9][CH2:10]3)[C:4]([OH:3])=[C:14]([C:15]3[NH:20][C:19]4[CH:21]=[CH:22][C:23]([NH:25][S:26]([CH3:29])(=[O:28])=[O:27])=[CH:24][C:18]=4[S:17](=[O:31])(=[O:30])[N:16]=3)[C:13]2=[O:32])=[CH:35][CH:36]=1
Reactant: CCOC(=O)C1CC=CCC1N(Cc1ccc(F)cc1)C(=O)CC1=NS(=O)(=O)c2cc(NS(C)(=O)=O)ccc2N1
Agent: CC[O-]
Agent: Cl
Agent: [Na+]
Solvent: CCO
Product: CS(=O)(=O)Nc1ccc2c(c1)S(=O)(=O)N=C(C1=C(O)C3CC=CCC3N(Cc3ccc(F)cc3)C1=O)N2
Product: CS(=O)(=O)Nc1ccc2c(c1)S(=O)(=O)N=C(C1=C(O)[C@@H]3CC=CC[C@@H]3N(Cc3ccc(F)cc3)C1=O)N2
Temperature: 60 °C
Reaction time: 1.5 h
Yield: 110.3 %

Procedure:
The crude 6-{(4-fluoro-benzyl)-[2-(7-methanesulfonylamino-1,1-dioxo-1,4-dihydro-1λ6-benzo[1,2,4]thiadiazin-3-yl)-acetyl]-amino}-cyclohex-3-enecarboxylic acid ethyl ester (0.41 mmol) was dissolved in ethanol (2 mL) and a 21% w/w solution of sodium ethoxide in ethanol (0.64 mL, 1.73 mmol) was added at 25° C. The reaction mixture was stirred at 60° C. under a nitrogen atmosphere for 1.5 h. A 1.0 M aqueous hydrochloric acid solution (5 mL) was added at 0° C. (pH=1) and the mixture was stirred at 0° C. for 20 min. The precipitated solid was collected, washed with water (3×5 mL) and recrystallized from ethyl acetate and hexanes to give a first batch of the desired product, N-{3-[1-(4-fluoro-benzyl)-4-hydroxy-2-oxo-1,2,4a,5,8,8a-hexahydro-quinolin-3-yl]-1,1-dioxo-1,4-dihydro-1λ6-benzo[1,2,4]thiadiazin-7-yl}-methanesulfonamide (123.6 mg). The filtrate was then extracted with ethyl acetate and the combined organic layers were concentrated in vacuo to give a second batch of the crude desired product, N-{3-[1-(4-fluoro-benzyl)-4-hydroxy-2-oxo-1,2,4a,5,8,8a-hexahydro-quinolin-3-yl]-1,1-dioxo-1,4-dihydro-1λ6-benzo[1,2,4]thiadiazin-7-yl}-methanesulfonamide (96.9 mg). The combined batches of the crude product were further purified by prep-HPLC (30-100% acetonitrile in water with 0.05% trifluoroacetic acid as gradient) to afford two isomers of the desired product. cis-N-{3-[1-(4-fluoro-benzyl)-4-hydroxy-2-oxo-1,2,4a,5,8,8a-hexahydro-quinolin-3-yl]-1,1-dioxo-1,4-dihydro-1λ6-benzo[1,2,4]thiadiazin-7-yl}-methanesulfonamide (66 mg, 0.121 mmol, 29.5% over two steps). 1H NMR (DMSO-d6, 400 MHz): δ 2.05-2.30 (m, 4H), 2.69-2.83 (m, 1H), 3.05 (s, 3H), 3.88 (bs, 1H), 4.42-4.62 (m, 1H), 4.91 (d, 1H, J=15.2 Hz), 5.47-5.56 (m, 1H), 5.59-5.66 (m, 1H), 7.17 (t, 2H, J=8.8 Hz), 7.43-7.51 (m, 3H), 7.56-7.58 (m, 2H), 10.14 (s, 1H), 13.67 (bs, 1H). LC-MS (ESI) calcd for C24H23FN4O6S2 546.1, found 547.2 [M+H+]. Anal. calcd for C24H23FN4O6S2 0.5H2O: C, 51.88; H, 4.35; N, 10.08; found: C, 52.23; H, 4.40; N, 10.19. trans-N-{3-[1-(4-fluoro-benzyl)-4-hydroxy-2-oxo-1,2,4a,5,8,8a-hexahydro-quinolin-3-yl]-1,1-dioxo-1,4-dihydro-1λ6-benzo[1,2,4]thiadiazin-7-yl}-methanesulfonamide (14.8 mg, 0.027 mmol, 6.6% over two steps). 1H NMR (DMSO-d6, 400 MHz): δ 1.78-2.02 (m, 2H), 2.09-2.27 (m, 2H), 2.50-2.62 (m, 1H), 3.07 (s, 3H), 3.60-3.72 (m, 1H), 4.58 (d, 1H, J=15.2 Hz), 5.04 (d, 1H, J=15.6 Hz), 5.54-5.62 (m, 1H), 5.66-5.74 (m, 1H), 7.14 (t, 2H, J=8.6 Hz), 7.29-7.37 (m, 2H), 7.52 (d, 1H, J=8.4 Hz), 7.57-7.65 (m, 2H), 10.18 (bs, 1H), 11.65 (bs, 1H), 13.97 (bs, 1H). LC-MS (ESI) calcd for C24H23FN4O6S2 546.1, found 547.2 [M+H+].