Reaction SMILES: [CH3:1][O:2][C:3]([NH:5][C@H:6]([C:10]([N:12]1[C@@H:16]([CH3:17])[CH2:15][CH2:14][C@H:13]1[C:18]1[NH:22][C:21]2[C:23]3[C:28]([CH:29]=[CH:30][C:20]=2[N:19]=1)=[CH:27][C:26]1[C:31]2[C:36]([CH2:37][O:38][C:25]=1[CH:24]=3)=[CH:35][C:34]([C:39]1[NH:43][C:42]([C@@H:44]3[CH2:48][C@H:47]([CH2:49][O:50][CH3:51])[CH2:46][N:45]3C(OC(C)(C)C)=O)=[N:41][CH:40]=1)=[CH:33][CH:32]=2)=[O:11])[CH:7]([CH3:9])[CH3:8])=[O:4].Cl.[CH3:60][O:61][C:62]([NH:64][C@@H:65]([C@@H:69]([CH3:72])[CH2:70][CH3:71])[C:66]([OH:68])=O)=[O:63].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C>C(Cl)Cl.CN(C=O)C>[CH3:1][O:2][C:3]([NH:5][C@@H:6]([CH:7]([CH3:9])[CH3:8])[C:10]([N:12]1[C@@H:16]([CH3:17])[CH2:15][CH2:14][C@H:13]1[C:18]1[NH:22][C:21]2[C:23]3[C:28]([CH:29]=[CH:30][C:20]=2[N:19]=1)=[CH:27][C:26]1[C:31]2[C:36]([CH2:37][O:38][C:25]=1[CH:24]=3)=[CH:35][C:34]([C:39]1[NH:43][C:42]([C@@H:44]3[CH2:48][C@H:47]([CH2:49][O:50][CH3:51])[CH2:46][N:45]3[C:66](=[O:68])[C@@H:65]([NH:64][C:62](=[O:63])[O:61][CH3:60])[C@@H:69]([CH3:72])[CH2:70][CH3:71])=[N:41][CH:40]=1)=[CH:33][CH:32]=2)=[O:11])=[O:4]
Reactant: COC[C@H]1C[C@@H](c2ncc(-c3ccc4c(c3)COc3cc5c(ccc6nc([C@@H]7CC[C@H](C)N7C(=O)[C@@H](NC(=O)OC)C(C)C)[nH]c65)cc3-4)[nH]2)N(C(=O)OC(C)(C)C)C1
Reactant: CC[C@H](C)[C@H](NC(=O)OC)C(=O)O
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: CN(C)C=O
Product: CC[C@H](C)[C@H](NC(=O)OC)C(=O)N1C[C@@H](COC)C[C@H]1c1ncc(-c2ccc3c(c2)COc2cc4c(ccc5nc([C@@H]6CC[C@H](C)N6C(=O)[C@@H](NC(=O)OC)C(C)C)[nH]c54)cc2-3)[nH]1
Temperature: 25 °C
Reaction time: 1 h
Yield: 59.5 %

Procedure:
tert-Butyl (2S,4S)-2-[5-(2-{(2S,5S)-1-[N-(methoxycarbonyl)-L-valyl]-5-methylpyrrolidin-2-yl}-1,11-dihydroisochromeno[4′,3′:6,7]naphtho[1,2-d]imidazol-9-yl)-1H-imidazol-2-yl]-4-(methoxymethyl)pyrrolidine-1-carboxylate (179 mg, 0.226 mmol) was dissolved in DCM (4 mL) and HCl (4.0 M in dioxane, 1 mL) was added. The reaction mixture was stirred for 1 h at RT then concentrated under reduced pressure. The resulting residue was treated with (2S,3S)-2-(methoxycarbonylamino)-3-methylpentanoic acid (51 mg, 0.27 mmol), HATU (95 mg, 0.25 mmol), DMF (2 mL) and DIPEA (0.39 mL, 2.3 mmol). After stirring for 6 min, the reaction was quenched with H2O, filtered and purified by reverse phase HPLC to afford methyl {(2S,3S)-1-[(2S,4S)-2-(5-{2-[(2S,5S)-1-{(2S)-2-[(methoxycarbonyl)amino]-3-methylbutanoyl}-5-methylpyrrolidin-2-yl]-1,11-dihydroisochromeno[4′,3′:6,7]naphtho[1,2-d]imidazol-9-yl}-1H-imidazol-2-yl)-4-(methoxymethyl)pyrrolidin-1-yl]-3-methyl-1-oxopentan-2-yl}carbamate (116 mg, 59%). MS (ESI) m/z 864 [M+H]+. 1H NMR (400 MHz, cd3od) δ 8.57 (d, J=14.7 Hz, 1H), 8.45 (s, 1H), 8.20 (d, J=14.4 Hz, 1H), 8.15-7.98 (m, 2H), 7.91 (dd, J=21.8, 14.1 Hz, 2H), 7.85-7.69 (m, 2H), 7.69-7.48 (m, 2H), 5.42-5.12 (m, 5H), 4.34 (dd, J=22.3, 13.7 Hz, 1H), 4.30-4.10 (m, 2H), 3.87-3.73 (m, 1H), 3.73-3.63 (m, 7H), 3.62-3.48 (m, 2H), 3.48-3.38 (m, 4H), 3.35 (s, 3H), 2.95-2.70 (m, 1H), 2.70-2.55 (m, 2H), 2.55-2.20 (m, 2H), 2.20-1.91 (m, 3H), 1.77 (d, J=42.0 Hz, 1H), 1.65 (d, J=6.6 Hz, 3H), 1.43 (t, J=24.6 Hz, 1H), 1.28 (d, J=6.2 Hz, 1H), 1.23-1.01 (m, 3H), 0.98 (d, J=6.6 Hz, 3H), 0.90 (dd, J=13.1, 5.9 Hz, 10H).