Reaction SMILES: ClN1C(=O)CCC1=O.C(O)(C(F)(F)F)=O.COC(N[C@@H](C(C)C)C(N1[C@H](C2NC=C(C3C=CC(C4C=C5C(=CC=4)N=C(C4N=C([C@@H]6C[C@@H]7[C@@H](C7)N6C([C@@H](NC(=O)OC)C(C)C)=O)NC=4)C=C5)=CC=3)N=2)C[C@@H]2[C@H]1C2)=O)=O.Cl[C:77]1[N:78]=[C:79]([C@@H:121]2[CH2:126][C@@H:125]3[C@@H:123]([CH2:124]3)[N:122]2[C:127]([C@@H:129]([NH:133][C:134](=[O:137])[O:135][CH3:136])[CH:130]([CH3:132])[CH3:131])=[O:128])[NH:80][C:81]=1[C:82]1[CH:91]=[CH:90][C:89]2[C:84](=[CH:85][CH:86]=[C:87]([C:92]3[CH:97]=[CH:96][C:95]([C:98]4[NH:102][C:101]([C@@H:103]5[CH2:108][C@@H:107]6[C@@H:105]([CH2:106]6)[N:104]5[C:109](=[O:119])[C@@H:110]([NH:114][C:115]([O:117][CH3:118])=[O:116])[CH:111]([CH3:113])[CH3:112])=[N:100][C:99]=4[Cl:120])=[CH:94][CH:93]=3)[CH:88]=2)[N:83]=1>CN(C=O)C.CO>[Cl:120][C:99]1[N:100]=[C:101]([C@@H:103]2[CH2:108][C@@H:107]3[C@@H:105]([CH2:106]3)[N:104]2[C:109](=[O:119])[C@@H:110]([NH:114][C:115]([O:117][CH3:118])=[O:116])[CH:111]([CH3:112])[CH3:113])[NH:102][C:98]=1[C:95]1[CH:96]=[CH:97][C:92]([C:87]2[CH:88]=[C:89]3[C:84](=[CH:85][CH:86]=2)[N:83]=[C:82]([C:81]2[N:80]=[C:79]([C@@H:121]4[CH2:126][C@@H:125]5[C@@H:123]([CH2:124]5)[N:122]4[C:127]([C@@H:129]([NH:133][C:134](=[O:137])[O:135][CH3:136])[CH:130]([CH3:131])[CH3:132])=[O:128])[NH:78][CH:77]=2)[CH:91]=[CH:90]3)=[CH:93][CH:94]=1
Reactant: COC(=O)N[C@H](C(=O)N1[C@@H]2C[C@@H]2C[C@H]1c1nc(Cl)c(-c2ccc(-c3ccc4nc(-c5[nH]c([C@@H]6C[C@H]7C[C@H]7N6C(=O)[C@@H](NC(=O)OC)C(C)C)nc5Cl)ccc4c3)cc2)[nH]1)C(C)C
Agent: COC(=O)N[C@H](C(=O)N1[C@@H]2C[C@@H]2C[C@H]1c1nc(-c2ccc(-c3ccc4nc(-c5c[nH]c([C@@H]6C[C@H]7C[C@H]7N6C(=O)[C@@H](NC(=O)OC)C(C)C)n5)ccc4c3)cc2)c[nH]1)C(C)C
Agent: O=C1CCC(=O)N1Cl
Solvent: CO
Solvent: O=C(O)C(F)(F)F
Solvent: CN(C)C=O
Product: COC(=O)N[C@H](C(=O)N1[C@@H]2C[C@@H]2C[C@H]1c1nc(-c2ccc3cc(-c4ccc(-c5[nH]c([C@@H]6C[C@H]7C[C@H]7N6C(=O)[C@@H](NC(=O)OC)C(C)C)nc5Cl)cc4)ccc3n2)c[nH]1)C(C)C
Temperature: 50 °C
Reaction time: 16 h

Procedure:
N-Chlorosuccinimide (6.01 mg, 0.045 mmol) was added to a stirred solution of a TFA salt of methyl ((1S)-1-(((1R,3S,5R)-3-(4-(6-(4-(2-((1R,3S,5R)-2-((2S)-2-((methoxycarbonyl)amino)-3-methylbutanoyl)-2-azabicyclo[3.1.0]hex-3-yl)-1H-imidazol-4-yl)phenyl)-2-quinolinyl)-1H-imidazol-2-yl)-2-azabicyclo[3.1.0]hex-2-yl)carbonyl)-2-methylpropyl)carbamate (Example 80) (26 mg, 0.022 mmol) in DMF (0.5 mL) and the reaction mixture was stirred at 50° C. for 16 h. The reaction was diluted with MeOH, filtered and purified by preparative HPLC (H2O-MeOH with 0.1% TFA buffer) to yield two products: 1) A TFA salt of methyl ((1S)-1-(((1R,3S,5R)-3-(4-chloro-5-(6-(4-(4-chloro-2-((1R,3S,5R)-2-((2S)-2-((methoxycarbonyl)amino)-3-methylbutanoyl)-2-azabicyclo[3.1.0]hex-3-yl)-1H-imidazol-5-yl)phenyl)-2-quinolinyl)-1H-imidazol-2-yl)-2-azabicyclo[3.1.0]hex-2-yl)carbonyl)-2-methylpropyl)carbamate (12.4 mg) as yellow solid. LC-MS retention time 3.871 min; m/z 882.55 (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 8.53 (d, J=8.8 Hz, 1H), 8.26 (d, J=8.8 Hz, 1H), 8.23 (s, 1H), 8.17 (s, 2H), 7.82-7.93 (m, 4H), 5.16 (dd, J=8.8, 5.3 Hz, 1H), 5.06 (t, J=7.2 Hz, 1H), 4.53-4.63 (m, 2H), 3.68-3.76 (m, 2H), 3.67 (s, 6H), 2.44-2.60 (m, 4H), 2.11-2.24 (m, 2H), 1.97-2.09 (m, 2H), 1.09-1.18 (m, 2H), 1.03 (dd, J=6.8, 3.3 Hz, 6H), 0.95 (dd, J=6.8, 2.4 Hz, 6H), 0.75-0.87 (m, 2H). 2) A TFA salt of methyl ((1S)-1-(((1R,3S,5R)-3-(4-(6-(4-(4-chloro-2-((1R,3S,5R)-2-((2S)-2-((methoxycarbonyl)amino)-3-methylbutanoyl)-2-azabicyclo[3.1.0]hex-3-yl)-1H-imidazol-5-yl)phenyl)-2-quinolinyl)-1H-imidazol-2-yl)-2-azabicyclo[3.1.0]hex-2-yl)carbonyl)-2-methylpropyl)carbamate (4.8 mg) as yellow solid. LC-MS retention time 2.98 min; m/z 848.60 (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 8.64 (d, J=8.8 Hz, 1H), 8.34 (s, 1H), 8.32 (s, 1H), 8.25-8.29 (m, 2H), 8.09 (d, J=8.8 Hz, 1H), 7.86-7.96 (m, 4H), 5.18-5.25 (m, 1H), 5.03-5.09 (m, 1H), 4.53-4.62 (m, 2H), 3.64-3.83 (m, 2H), 3.64-3.69 (m, 6H), 2.42-2.70 (m, 4H), 1.97-2.24 (m, 4H), 1.08-1.17 (m, 2H), 1.02 (dd, J=6.8, 2.4 Hz, 6H), 0.94 (t, J=6.8 Hz, 6H), 0.76-0.91 (m, 2H).