Reaction SMILES: [C:1]([O:5][C:6]([NH:8][C@@H:9]1[C:27](=[O:28])[N:26]2[C@@H:22]([CH2:23][C@@H:24]([O:29][C:30]3[C:39]4[C:34](=[CH:35][C:36]([O:40][CH3:41])=[CH:37][CH:38]=4)[N:33]=[C:32]([C:42]4[CH:47]=[CH:46][CH:45]=[CH:44][CH:43]=4)[CH:31]=3)[CH2:25]2)[C:21](=[O:48])[NH:20][C@@:19]2([C:49]([OH:51])=[O:50])[C@@H:17]([CH2:18]2)[CH:16]=[CH:15][CH2:14][CH2:13][CH2:12][CH2:11][CH2:10]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[N+](C([O-])=O)(C([O-])=O)=[N-].[K+].[K+].CC(O)=O>CO>[C:1]([O:5][C:6]([NH:8][C@@H:9]1[C:27](=[O:28])[N:26]2[C@@H:22]([CH2:23][C@@H:24]([O:29][C:30]3[C:39]4[C:34](=[CH:35][C:36]([O:40][CH3:41])=[CH:37][CH:38]=4)[N:33]=[C:32]([C:42]4[CH:43]=[CH:44][CH:45]=[CH:46][CH:47]=4)[CH:31]=3)[CH2:25]2)[C:21](=[O:48])[NH:20][C@@:19]2([C:49]([OH:51])=[O:50])[C@@H:17]([CH2:18]2)[CH2:16][CH2:15][CH2:14][CH2:13][CH2:12][CH2:11][CH2:10]1)=[O:7])([CH3:4])([CH3:2])[CH3:3]
Reactant: COc1ccc2c(O[C@@H]3C[C@H]4C(=O)N[C@]5(C(=O)O)C[C@H]5C=CCCCCC[C@H](NC(=O)OC(C)(C)C)C(=O)N4C3)cc(-c3ccccc3)nc2c1
Agent: COc1ccc2c(O[C@@H]3C[C@H]4C(=O)N[C@]5(C(=O)O)C[C@H]5/C=C\CCCCC[C@H](NC(=O)OC(C)(C)C)C(=O)N4C3)cc(-c3ccccc3)nc2c1
Agent: [K+]
Agent: [N-]=[N+](C(=O)[O-])C(=O)[O-]
Solvent: CO
Solvent: CC(=O)O
Product: COc1ccc2c(O[C@@H]3C[C@H]4C(=O)N[C@]5(C(=O)O)C[C@H]5CCCCCCC[C@H](NC(=O)OC(C)(C)C)C(=O)N4C3)cc(-c3ccccc3)nc2c1
Reaction time: 12 h
Yield: 59.2 %

Procedure:
Step i of Method B) To a solution of 470 mg (0.67 mmol) of (1S,4R,65,14S,18R)-8-cis-14-tert-butoxycarbonylamino-18-(7-methoxy-2-phenylquinolin-4-yloxy)-2,15-dioxo-3,16-diazatricyclo[14.3.0.04,6]nona-dec-7-ene-4-carboxylic acid and 1.90 g (11.7 mmol) of potassium diazodicarboxylate (prepared as in Org. React. 1991, 40, p.91) in 20 mL of MeOH, was added a solution of 1.34 mL (22.4 mmol) of glacial AcOH in 20 mL of MeOH slowly dropwise via syringe pump over 6.5 h. This procedure was repeated twice, but using a 12 h time interval instead of 6.5 h during which the reaction was stopped at approximately 90% completion. The mixture was concentrated in vacuo and then chromatographed over 20 g of SiO2 (eluted with 5% MeOH/CH2Cl2). The resulting residue was dissolved in 18 mL of MeOH and injected nine times (9×2 mL injections) onto a preparative HPLC column: Xterra C18 30×100 mm S5, 30% to 75% Solvent B/A for 30 min gradient, hold time 5 min; where Solvent A is 10% MeOH/90% H2O with 0.1% TFA, Solvent B is 90% MeOH/10% H2O with 0.1% TFA and flow rate is 40 ml/min). The pH of the combined fractions was adjusted to neutral using 6N aqueous NaOH solution and the MeOH removed in vacuo. The solution was adjusted to pH 4 using 3N aqueous HCl solution, and repeatedly extracted with EtOAC. The combined extracts were dried (MgSO4) and concentrated to afford 278 mg (59%) of (1S,4R,6R,14S,18R)-14-tert-Butoxycarbonylamino-18-(7-methoxy-2-phenyl-quinolin-4-yloxy)-2,15-dioxo-3,16-diazatricyclo[14.3.0.04,6]nonadecane-4-carboxylic acid: 1H NMR (500 MHz, methanol-d4) δ 1.23 (s, 9H), 1.12-1.49 (m, 11H), 1.50-1.67 (m, 4H), 1.71-1.86 (m, 2H), 2.54-2.60 (m, 1H), 2.65-2.72 (m, 1H), 3.94 (s, 3H), 4.05 (dd, J=11.29, 3.36 Hz, 1H), 4.28-4.33 (m, 1H), 4.65 (d, J=11.29 Hz, 1H), 4.70 (t, J=8.09 Hz, 1H), 5.55-5.61 (m, 1H), 7.07-7.15 (m, 1H), 7.28 (s, 1H), 7.38 (d, J=1.83 Hz, 1H), 7.50-7.59 (m, 3H), 8.04 (d, J=7.02 Hz, 2H), 8.15 (d, J=9.16 Hz, 1H). LC-MS m/e 701 (retention time: 3.01, method D, except gradient time increased from 2 to 4 min). Step ii/14j-Method B Preparation of Compound 15, Example 14, Preparation of (1S,4R,6R,14S,18R)-[4-Cyclopropanesulfonylaminocarbonyl-18-(7-methoxy-2-phenylquinolin-4-yloxy)-2,15-dioxo-3,16-diazatricyclo-[14.3.0.04,6]nonadec-14-yl]carbamic acid tert-butyl ester. Method B-Step ii/Step 14j) Following the analogous procedural and purification conditions of Steps lj and 12j, respectively, 100 mg (0.143 mmol) of (1S,4R,6R,14S,18R)-14-tert-Butoxycarbonylamino-18-(7-methoxy-2-phenyl-quinolin-4-yloxy)-2,15-dioxo-3,16-diazatricyclo[14.3.0.04,6]nonadecane-4-carboxylic acid was converted to 108 mg (93%) (1S,4R,6R,14S)-[4-Cyclopropanesulfonylaminocarbonyl-18-(7-methoxy-2-phenylquinolin-4-yloxy)-2,15-dioxo-3,16-diazatricyclo-[14.3.0.04,6]nonadec-14-yl]carbamic acid tert-butyl ester, Compound 15, Example 14: 1H NMR (500 MHz, methanol-d4) δ 1.20 (m, 9H) 0.83-1.83 (m, 21H), 2.48 (s, 1H), 2.73 (s, 1H), 2.95 (s, 1H), 3.94 (s, 3H), 4.04 (m, 1H), 4.24 (m, 1H), 4.67 (m, 2H), 5.60 (s, 1H), 7.12 (m, J=8.85 Hz, 1H), 7.30 (s, 1H), 7.38 (s, 1H), 7.57 (m, J=6.10 Hz, 3H), 8.03 (m, J=5.80 Hz, 2H), 8.16 (d, J=8.85 Hz, 1H). LC-MS m/e 804 (retention time: 1.73, method D. Method B-Stepiii/Step 15k: Preparation of Compound 16, Example 15, (1S,4R,6R,14S,18R)-Cyclopropanesulfonic acid [14-amino-18-(7-methoxy-2-phenylquinolin-4-yloxy)-2,15-dioxo-3,16-diazatricyclo[14.3.0.04,6]-nonadecane-4-carbonyl]amide dihydrochloride