Reaction SMILES: [NH:1]1[CH2:5][CH2:4][CH2:3][CH2:2]1.N(CC(O)=O)C.P([O-])([O-])([O-])=O.[K+].[K+].[K+].[OH:20][C:21]1[C@H:30]2[C@H:25]([C@H:26]3[CH2:31][C@@H:29]2[CH2:28][CH2:27]3)[N:24]([CH2:32][CH2:33][CH:34]([CH3:36])[CH3:35])[C:23](=[O:37])[C:22]=1[C:38]1[NH:43][C:42]2[CH:44]=[CH:45][C:46](I)=[CH:47][C:41]=2[S:40](=[O:50])(=[O:49])[N:39]=1>CN(C)C=O.[Cu]I>[O:50]=[S:40]1(=[O:49])[C:41]2[CH:47]=[C:46]([N:1]3[CH2:5][CH2:4][CH2:3][CH2:2]3)[CH:45]=[CH:44][C:42]=2[NH:43][C:38]([C:22]2[C:23](=[O:37])[N:24]([CH2:32][CH2:33][CH:34]([CH3:35])[CH3:36])[C@@H:25]3[C@H:30]([C:21]=2[OH:20])[C@@H:29]2[CH2:31][C@H:26]3[CH2:27][CH2:28]2)=[N:39]1
Reactant: C1CCNC1
Reactant: CC(C)CCN1C(=O)C(C2=NS(=O)(=O)c3cc(I)ccc3N2)=C(O)[C@@H]2[C@H]3CC[C@H](C3)[C@@H]21
Agent: [Cu]I
Agent: CNCC(=O)O
Agent: O=P([O-])([O-])[O-]
Solvent: CN(C)C=O
Product: CC(C)CCN1C(=O)C(C2=NS(=O)(=O)c3cc(N4CCCC4)ccc3N2)=C(O)[C@@H]2[C@H]3CC[C@H](C3)[C@@H]21
Temperature: 80 °C
Reaction time: 26 h
Yield: 82.2 %

Procedure:
Pyrrolidine (15 μL, 0.180 mmol), sarcosine (N-methyl glycine) (3.2 mg, 0.018 mmol), copper (I) iodide (3.4 mg, 0.018 mmol), and potassium phosphate (57.3 mg, 0.270 mmol) were placed in a flask under a nitrogen atmosphere. (1R,2S,7R,8S)-6-Hydroxy-5-(7-iodo-1,1-dioxo-1,4-dihydro-1λ6-benzo[1,2,4]thiadiazin-3-yl)-3-(3-methyl-butyl)-3-aza-tricyclo[6.2.1.02,7]undec-5-en-4-one (prepared as described in Example 34, 50 mg, 0.090 mmol) was dissolved in N,N-dimethylformamide (1 mL) and added to the above mixture. The mixture was stirred at 80° C. for 26 h. Additional pyrrolidine (50 μL, 0.60 mmol), sarcosine (N-methyl glycine) (10 mg, 0.056 mmol), and copper (I) iodide (15 mg, 0.079 mmol) were added and the mixture was stirred at 80° C. for another 16 h until LC-MS analysis indicated completion of the reaction. The reaction was repeated at the same scale as described above and after stirring at 80° C. for 24 h, additional pyrrolidine (50 μL, 0.60 mmol), sarcosine (N-methyl glycine) (10 mg, 0.056 mmol), and copper (I) iodide (15 mg, 0.079 mmol) were added and the mixture was stirred at 80° C. for another 18 h until LC-MS analysis indicated completion of the reaction. Both batches were combined and filtered through a plug of Celite. The filter cake was washed with 10% methanol in dichloromethane (2×2 mL) and N,N-dimethylformamide (2 mL). The filtrate was concentrated in vacuo and the residue was purified by prep-HPLC [Column Luna 5μ C18 (2) 100 Å AXIA 150×21.2 mm, 5 micron, 30%-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, (1R,2S,7R,8S)-5-(1,1-dioxo-7-pyrrolidin-1-yl-1,4-dihydro-1λ6-benzo[1,2,4]thiadiazin-3-yl)-6-hydroxy-3-(3-methyl-butyl)-3-aza-tricyclo[6.2.1.02,7]undec-5-en-4-one (36.7 mg, 0.074 mmol, 40.9%), as a yellow solid. 1H NMR (400 MHz, DMSO-d6) δ: 0.92 (6H, d, J=5.5 Hz), 1.21-1.60 (9H, m), 1.96-1.99 (4H, m), 2.52-2.52 (1H, m), 2.62-2.65 (1H, m), 2.94-2.98 (1H, m), 3.03-3.10 (1H, m), 3.27-3.30 (4H, m), 3.60-3.71 (2H, m), 6.71 (1H, d, J=2.3 Hz), 6.90 (1H, dd, J1=9.2 Hz, J2=2.7 Hz), 7.41 (1H, d, J=9.5 Hz). LC-MS (ESI) calcd for C26H34N4O4S 498.23, found 499.4 [M+H+]. Anal. calcd for C26H34N4O4S.0.5 H2O: C, 61.51; H, 6.95; N, 11.04; found: C, 61.45, H, 6.74; N, 10.91.