Reaction SMILES: C([O:5][C:6]([N:8]1[CH2:12][CH2:11][CH2:10][CH:9]1[C:13]1[NH:14][C:15]([C:18]2[CH:27]=[CH:26][C:25]3[C:20](=[CH:21][CH:22]=[C:23]([C:28]4[CH:33]=[CH:32][C:31]([C:34]5[NH:35][C:36]([CH:39]6[CH:44]7[CH2:45][CH:41]([CH2:42][CH2:43]7)[N:40]6[C:46](=[O:59])[CH:47]([NH:54][C:55]([O:57][CH3:58])=[O:56])[CH:48]6[CH2:53][CH2:52][O:51][CH2:50][CH2:49]6)=[N:37][CH:38]=5)=[CH:30][CH:29]=4)[CH:24]=3)[CH:19]=2)=[CH:16][N:17]=1)=O)(C)(C)C.Cl.[CH3:61][O:62][C:63]([NH:65][CH:66]([C:70]1[CH:75]=[CH:74][CH:73]=[CH:72][CH:71]=1)C(O)=O)=[O:64].CCN(C(C)C)C(C)C.CCOC(C(C#N)=NOC(N1CCOCC1)=[N+](C)C)=O.F[P-](F)(F)(F)(F)F>C(Cl)Cl.CO>[CH3:58][O:57][C:55](=[O:56])[NH:54][CH:47]([CH:48]1[CH2:53][CH2:52][O:51][CH2:50][CH2:49]1)[C:46]([N:40]1[CH:39]([C:36]2[NH:35][C:34]([C:31]3[CH:30]=[CH:29][C:28]([C:23]4[CH:22]=[CH:21][C:20]5[C:25](=[CH:26][CH:27]=[C:18]([C:15]6[NH:14][C:13]([CH:9]7[CH2:10][CH2:11][CH2:12][N:8]7[C:6](=[O:5])[CH:66]([NH:65][C:63]([O:62][CH3:61])=[O:64])[C:70]7[CH:75]=[CH:74][CH:73]=[CH:72][CH:71]=7)=[N:17][CH:16]=6)[CH:19]=5)[CH:24]=4)=[CH:33][CH:32]=3)=[CH:38][N:37]=2)[CH:44]2[CH2:43][CH:42]1[CH2:41][CH2:45]2)=[O:59]
Reactant: COC(=O)NC(C(=O)N1C2CCC(C2)C1c1ncc(-c2ccc(-c3ccc4cc(-c5cnc(C6CCCN6C(=O)OC(C)(C)C)[nH]5)ccc4c3)cc2)[nH]1)C1CCOCC1
Reactant: COC(=O)NC(C(=O)O)c1ccccc1
Agent: CCOC(=O)C(C#N)=NOC(N1CCOCC1)=[N+](C)C
Agent: Cl
Agent: F[P-](F)(F)(F)(F)F
Solvent: ClCCl
Solvent: CCN(C(C)C)C(C)C
Solvent: CO
Product: COC(=O)NC(C(=O)N1CCCC1c1ncc(-c2ccc3cc(-c4ccc(-c5cnc(C6C7CCC(C7)N6C(=O)C(NC(=O)OC)C6CCOCC6)[nH]5)cc4)ccc3c2)[nH]1)c1ccccc1
Temperature: 25 °C
Reaction time: 2 h
Yield: 73.7 %

Procedure:
To a solution of 2-(5-{6-[4-(2-{2-[2-Methoxycarbonylamino-2-(tetrahydro-pyran-4-yl)-acetyl]-2-azabicyclo[2.2.1]hept-3-yl}-3H-imidazol-4-yl)-phenyl]-naphthalen-2-yl}-1H-imidazol-2-yl)-pyrrolidine-1-carboxylic acid tert-butyl ester (0.26 g, 0.32 mmol) in CH2Cl2 (3.5 mL) and MeOH (0.2 mL) was added HCl (in dioxanes, 4 M, 1.6 mL, 6.4 mmol). The resulting solution was stirred at room temperature for 2 h and concentrated. The resulting solid was slurried in CH2Cl2 (3.5 mL) and DMF (0.5 mL). Methoxycarbonylamino-phenyl-acetic acid (0.08 g, 0.39 mmol) and DIPEA (0.250 mL, 1.43 mmol) were added and the solution was cooled to 0° C. (external, ice bath). COMU (0.16 g, 0.36 mmol) was added and the reaction was stirred at 0° C. for 3 h. The solution was diluted with CH2Cl2 and washed with saturated sodium bicarbonate and brine. The aqueous layers were back extracted with CH2Cl2. The combined organic layers were dried over Na2SO4 and concentrated. The crude oil was purified by preparative HPLC (Gemini, 15→60% MeCN in H2O (0.1% TFA)). The combined fractions were concentrated until the aqueous layer remained. A small amount of MeOH was added to make the solution homogenous before it was basified with saturated sodium bicarbonate. The resulting precipitate was filtered, washed with H2O, and dried in vacuo to provide [2-(3-{5-[4-(6-{2-[1-(2-Methoxycarbonylamino-2-phenyl-acetyl)-pyrrolidin-2-yl]-3H-imidazol-4-yl}-naphthalen-2-yl)-phenyl]-1H-imidazol-2-yl}-2-aza-bicyclo[2.2.1]hept-2-yl)-2-oxo-1-(tetrahydro-pyran-4-yl)-ethyl]-carbamic acid methyl ester (0.21 g, 72%). LCMS-ESI+: calc'd for C51H54N8O7: 890.41 (M+); Found: 891.95 (M+H+).