Reaction SMILES: [CH3:1][O:2][C:3]([NH:5][C@H:6]([C:11]([N:13]1[C@@H:17]([CH3:18])[CH2:16][CH2:15][C@H:14]1[C:19]1[NH:20][C:21]([C:24]2[CH:29]=[C:28]3[CH2:30][O:31][C:32]4[CH:57]=[C:56]5[C:35]([CH:36]=[CH:37][C:38]6[N:42]=[C:41]([C@@H:43]7[CH2:47][CH2:46][C@H:45]([CH3:48])[N:44]7[C:49]([O:51]C(C)(C)C)=O)[NH:40][C:39]=65)=[CH:34][C:33]=4[C:27]3=[CH:26][CH:25]=2)=[CH:22][N:23]=1)=[O:12])[C@H:7]([CH2:9][CH3:10])[CH3:8])=[O:4].Cl.[CH3:59][C@@H:60]1[CH2:65][CH:64]([C@H:66]([NH:70][C:71]([O:73][CH3:74])=[O:72])C(O)=O)[CH2:63][C@@H:62]([CH3:75])[O:61]1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.C(N(C(C)C)CC)(C)C>ClCCl.CO.Cl>[CH3:59][C@@H:60]1[CH2:65][CH:64]([C@H:66]([NH:70][C:71]([O:73][CH3:74])=[O:72])[C:49]([N:44]2[C@@H:45]([CH3:48])[CH2:46][CH2:47][C@H:43]2[C:41]2[NH:40][C:39]3[C:56]4[C:35]([CH:36]=[CH:37][C:38]=3[N:42]=2)=[CH:34][C:33]2[C:27]3[C:28]([CH2:30][O:31][C:32]=2[CH:57]=4)=[CH:29][C:24]([C:21]2[NH:20][C:19]([C@@H:14]4[CH2:15][CH2:16][C@H:17]([CH3:18])[N:13]4[C:11](=[O:12])[C@@H:6]([NH:5][C:3](=[O:4])[O:2][CH3:1])[C@@H:7]([CH3:8])[CH2:9][CH3:10])=[N:23][CH:22]=2)=[CH:25][CH:26]=3)=[O:51])[CH2:63][C@@H:62]([CH3:75])[O:61]1
Reactant: COC(=O)N[C@H](C(=O)O)C1C[C@@H](C)O[C@H](C)C1
Reactant: CC[C@H](C)[C@H](NC(=O)OC)C(=O)N1[C@@H](C)CC[C@H]1c1ncc(-c2ccc3c(c2)COc2cc4c(ccc5nc([C@@H]6CC[C@H](C)N6C(=O)OC(C)(C)C)[nH]c54)cc2-3)[nH]1
Agent: CN(C)C(On1nnc2cccnc21)=[N+](C)C
Agent: Cl
Agent: F[P-](F)(F)(F)(F)F
Solvent: CCN(C(C)C)C(C)C
Solvent: ClCCl
Solvent: CO
Product: CC[C@H](C)[C@H](NC(=O)OC)C(=O)N1[C@@H](C)CC[C@H]1c1ncc(-c2ccc3c(c2)COc2cc4c(ccc5nc([C@@H]6CC[C@H](C)N6C(=O)[C@@H](NC(=O)OC)C6C[C@@H](C)O[C@H](C)C6)[nH]c54)cc2-3)[nH]1
Temperature: 40 °C
Reaction time: 3 h
Yield: 23.3 %

Procedure:
To a solution of tert-butyl (2S,5S)-2-[9-(2-{(2S,5S)-1-[N-(methoxycarbonyl)-L-isoleucyl]-5-methylpyrrolidin-2-yl}-1H-imidazol-5-yl)-1,11-dihydroisochromeno[4′,3′:6,7]naphtho[1,2-d]imidazol-2-yl]-5-methylpyrrolidine-1-carboxylate (0.30 g, 0.39 mmol) in a mixture of dichloromethane (4 mL) and methanol (0.5 mL) was added HCl (4M in dioxanes, 1.45 mL, 5.80 mmol). The solution was heated to 40° C. for 1 h and cooled to room temperature. The solution was then concentrated in vacuo. The resulting solid was dissolved in DMF (3 mL), followed by the addition of (S)-2-((2R,6R)-2,6-dimethyltetrahydro-2H-pyran-4-yl)-2-(methoxycarbonylamino)acetic acid (0.11 g, 0.46 mmol), HATU (0.18 g, 0.48 mmol), and diisopropylethylamine (0.3 mL, 1.72 mmol). The resulting solution was stirred at room temperature for 3 h. Aqueous HCl (6M, 4 drops) was added and the solution was purified by reverse phase HPLC (Gemini column, 10-53% MeCN/H2O/0.1% TFA). The desired fractions were combined, and the organics were concentrated in vacuo. The resulting aqueous solution was basified with saturated NaHCO3 to provide a white precipitate. The solid was filtered and dried to provide methyl {(2S,3S)-1-[(2S,5S)-2-(5-{2-[(2S,5S)-1-{(2S)-2-[(2R,6R)-2,6-dimethyltetrahydro-2H-pyran-4-yl]-2-[(methoxycarbonyl)amino]acetyl}-5-methylpyrrolidin-2-yl]-1,11-dihydroisochromeno[4′,3′:6,7]naphtho[1,2-d]imidazol-9-yl}-1H-imidazol-2-yl)-5-methylpyrrolidin-1-yl]-3-methyl-1-oxopentan-2-yl}carbamate (0.082 g, 23%) as a white powder. LCMS-ESI+: calc'd for C50H62N8O9: 903.08 (M+). Found: 903.84 (M+H+). 1H NMR (400 MHz, Methanol-d4) δ 8.36-8.22 (m, 1H), 7.98-7.82 (m, 1H), 7.69-7.20 (m, 8H), 5.22-5.07 (m, 3H), 5.02 (d, 1H), 4.73-4.64 (m, 1H), 4.49 (s, 3H), 4.26-3.97 (m, 4H), 3.79 (d, 1H), 3.72 (s, 1H), 3.63-3.52 (m, 4H), 3.47-3.32 (m, 1H), 2.61-2.43 (m, 1H), 2.32-1.98 (m, 4H), 1.95-1.78 (m, 1H), 1.79-1.65 (m, 1H), 1.54 (s, 4H), 1.41 (d, 2H), 1.28-1.09 (m, 3H), 1.04 (dd, 6H), 0.90 (d, 1H), 0.88-0.59 (m, 10H).