Reaction SMILES: Cl.[C:2]([OH:8])([C:4]([F:7])([F:6])[F:5])=[O:3].[CH3:9][O:10][C:11]([NH:13][C@@H:14]([CH:58]([CH3:60])[CH3:59])[C:15]([N:17]1[C@H:22]([C:23]2[NH:24][C:25]([C:28]#[C:29][C:30]3[CH:31]=[C:32]4[C:37](=[CH:38][CH:39]=3)[CH:36]=[C:35]([C:40]3[NH:44][C:43]([C@@H:45]5[CH2:50][C@@H:49]6[C@@H:47]([CH2:48]6)[N:46]5C(OC(C)(C)C)=O)=[N:42][CH:41]=3)[CH:34]=[CH:33]4)=[CH:26][N:27]=2)[CH2:21][C@@H:20]2[C@H:18]1[CH2:19]2)=[O:16])=[O:12].[CH3:61][O:62][C:63]([NH:65][C@@H:66]([CH:70]1[CH2:75][CH2:74]OCC1)[C:67]([OH:69])=O)=[O:64].CCN(C(C)C)C(C)C.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>O1CCOCC1.CN(C=O)C>[C:2]([OH:8])([C:4]([F:7])([F:6])[F:5])=[O:3].[CH3:9][O:10][C:11]([NH:13][C@@H:14]([CH:58]([CH3:60])[CH3:59])[C:15]([N:17]1[C@H:22]([C:23]2[NH:27][CH:26]=[C:25]([C:28]#[C:29][C:30]3[CH:31]=[C:32]4[C:37](=[CH:38][CH:39]=3)[CH:36]=[C:35]([C:40]3[N:44]=[C:43]([C@@H:45]5[CH2:50][C@@H:49]6[C@@H:47]([CH2:48]6)[N:46]5[C:67](=[O:69])[C@@H:66]([NH:65][C:63](=[O:64])[O:62][CH3:61])[CH:70]5[CH2:4][CH2:2][O:8][CH2:74][CH2:75]5)[NH:42][CH:41]=3)[CH:34]=[CH:33]4)[N:24]=2)[CH2:21][C@@H:20]2[C@H:18]1[CH2:19]2)=[O:16])=[O:12]
Reactant: COC(=O)N[C@H](C(=O)O)C1CCOCC1
Reactant: COC(=O)N[C@H](C(=O)N1[C@@H]2C[C@@H]2C[C@H]1c1ncc(C#Cc2ccc3cc(-c4cnc([C@@H]5C[C@H]6C[C@H]6N5C(=O)OC(C)(C)C)[nH]4)ccc3c2)[nH]1)C(C)C
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: O=C(O)C(F)(F)F
Solvent: C1COCCO1
Product: COC(=O)N[C@H](C(=O)N1[C@@H]2C[C@@H]2C[C@H]1c1nc(C#Cc2ccc3cc(-c4c[nH]c([C@@H]5C[C@H]6C[C@H]6N5C(=O)[C@@H](NC(=O)OC)C5CCOCC5)n4)ccc3c2)c[nH]1)C(C)C
Reaction time: 4 h

Procedure:
4M HCl (0.32 mL, 1.3 mmol) in dioxane was added to mixture of a TFA salt of (1R,3S,5R)-tert-butyl 3-(5-(6-((2-((1R,3S,5R)-2-((S)-2-(methoxycarbonylamino)-3-methylbutanoyl)-2-azabicyclo[3.1.0]hexan-3-yl)-1H-imidazol-5-yl)ethynyl)naphthalen-2-yl)-1H-imidazol-2-yl)-2-azabicyclo[3.1.0]hexane-2-carboxylate (Intermediate 158) (60 mg, 0.064 mmol) in dioxane (0.5 mL) and the reaction was stirred vigorously for 4 h. The reaction was concentrated to dryness. Then (S)-2-(methoxycarbonylamino)-2-(tetrahydro-2H-pyran-4-yl)acetic acid (18.2 mg, 0.084 mmol), DMF (0.5 mL), DIPEA (0.067 mL, 0.39 mmol) and finally HATU (31.8 mg) were added to the crude material and the reaction was stirred at rt for 1 h. The reaction was partially concentrated with a stream on nitrogen, diluted with MeOH, filtered and purified preparative HPLC (MeOH/water with a TFA buffer) and then repurified preparative HPLC (MeOH/water with an ammonium acetate buffer). The material was purified a third time by preparative HPLC (MeOH/water with a TFA buffer) to yield a TFA salt of methyl ((1S)-2-((1R,3S,5R)-3-(4-(6-((2-((1R,3S,5R)-2-((2S)-2-((methoxycarbonyl)amino)-3-methylbutanoyl)-2-azabicyclo[3.1.0]hex-3-yl)-1H-imidazol-4-yl)ethynyl)-2-naphthyl)-1H-imidazol-2-yl)-2-azabicyclo[3.1.0]hex-2-yl)-2-oxo-1-(tetrahydro-2H-pyran-4-yl)ethyl)carbamate (27.7 mg) as a white solid. LC-MS retention time 3.291 min; m/z 803.67 (MH+). LC data was recorded on a Shimadzu LC-10AS liquid chromatograph equipped with a PHENOMENEX® Luna 3u C18 2.0×50 mm column using a SPD-10AV UV-Vis detector at a detector wave length of 220 nM. The elution conditions employed a flow rate of 0.8 mL/min, a gradient of 100% Solvent A/0% Solvent B to 0% Solvent A/100% Solvent B, a gradient time of 4 min, a hold time of 1 min, and an analysis time of 5 min where Solvent A was 10% MeOH/90% H2O/0.1% trifluoroacetic acid and Solvent B was 10% H2O/90% MeOH/0.1% trifluoroacetic acid. MS data was determined using a MICROMASS® Platform for LC in electrospray mode. 1H NMR (400 MHz, MeOD) δ ppm 8.27 (s, 1H), 8.19 (s, 1H), 8.06 (d, J=8.8 Hz, 1H), 7.99-8.03 (m, 2H), 7.88 (dd, J=8.5, 1.8 Hz, 1H), 7.78 (s, 1H), 7.68 (dd, J=8.5, 1.5 Hz, 1H), 5.15 (dd, J=9.0, 7.0 Hz, 1H), 5.09 (dd, J=9.3, 6.5 Hz, 1H), 4.80 (d, 2H), 4.54 (d, J=6.5 Hz, 1H), 3.87-3.93 (m, 1H), 3.70-3.79 (m, 3H), 3.68 (s, 3H), 3.67 (s, 3H), 3.54-3.63 (m, 1H), 3.34-3.40 (m, 1H), 2.59-2.74 (m, 2H), 2.40-2.55 (m, 2H), 2.00-2.22 (m, 4H), 1.71-1.81 (m, 2H), 1.51-1.63 (m, 2H), 1.05-1.14 (m, 2H), 1.01 (d, J=6.8 Hz, 3H), 0.93 (d, J=6.8 Hz, 3H), 0.88 (br. s., 2H).