Reaction SMILES: [C:1]([C:3]1[NH:7][C:6]([C@@H:8]2[CH2:13][C@@H:12]3[C@@H:10]([CH2:11]3)[N:9]2[C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])=[N:5][CH:4]=1)#[CH:2].Br[C:22]1[CH:23]=[C:24]2[C:29](=[CH:30][CH:31]=1)[CH:28]=[C:27]([C:32]1[NH:36][C:35]([C@@H:37]3[CH2:42][C@@H:41]4[C@@H:39]([CH2:40]4)[N:38]3[C:43](=[O:53])[C@@H:44]([NH:48][C:49](=[O:52])[O:50][CH3:51])[CH:45]([CH3:47])[CH3:46])=[N:34][CH:33]=1)[CH:26]=[CH:25]2>CN(C=O)C.[Cu]I.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH3:51][O:50][C:49]([NH:48][C@@H:44]([CH:45]([CH3:47])[CH3:46])[C:43]([N:38]1[C@H:37]([C:35]2[NH:34][CH:33]=[C:32]([C:27]3[CH:28]=[C:29]4[C:24](=[CH:25][CH:26]=3)[CH:23]=[C:22]([C:2]#[C:1][C:3]3[N:7]=[C:6]([C@@H:8]5[CH2:13][C@@H:12]6[C@@H:10]([CH2:11]6)[N:9]5[C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[NH:5][CH:4]=3)[CH:31]=[CH:30]4)[N:36]=2)[CH2:42][C@@H:41]2[C@H:39]1[CH2:40]2)=[O:53])=[O:52]
Reactant: C#Cc1cnc([C@@H]2C[C@H]3C[C@H]3N2C(=O)OC(C)(C)C)[nH]1
Reactant: COC(=O)N[C@H](C(=O)N1[C@@H]2C[C@@H]2C[C@H]1c1ncc(-c2ccc3cc(Br)ccc3c2)[nH]1)C(C)C
Agent: [Cu]I
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Solvent: CN(C)C=O
Product: COC(=O)N[C@H](C(=O)N1[C@@H]2C[C@@H]2C[C@H]1c1nc(-c2ccc3cc(C#Cc4c[nH]c([C@@H]5C[C@H]6C[C@H]6N5C(=O)OC(C)(C)C)n4)ccc3c2)c[nH]1)C(C)C
Temperature: 60 °C
Reaction time: 24 h
Yield: 80.2 %

Procedure:
Nitrogen was bubbled through a mixture of (1R,3S,5R)-tert-butyl 3-(5-ethynyl-1H-imidazol-2-yl)-2-azabicyclo[3.1.0]hexane-2-carboxylate (Intermediate 122) (118 mg, 0.432 mmol), methyl (S)-1-((1R,3S,5R)-3-(5-(6-bromonaphthalen-2-yl)-1H-imidazol-2-yl)-2-azabicyclo[3.1.0]hexan-2-yl)-3-methyl-1-oxobutan-2-ylcarbamate (170 mg, 0.332 mmol) and CuI (3.17 mg, 0.017 mmol) in DMF (4 mL) and TEA (0.14 mL, 0.10 mmol) for 15 min. Then Pd(PPh3)4 (19.2 mg, 0.017 mmol) was added and the reaction vessel was sealed and heated at 60° C. overnight. The reaction was cooled and then additional CuI (5 mg) and TEA (100 μL) were added to the reaction and nitrogen was bubbled through the reaction for 15 min. Then additional Pd(PPh3)4 (12 mg) was added and the reaction was sealed and stirred at 70° C. for 24 h. The reaction was concentrated under high vacuum and the residue was partitioned between DCM (25 mL) and water (25 mL). The aqueous was extracted with DCM (2×10 mL) and the combined organics were washed with brine (˜20 mL), dried (MgSO4), filtered and concentrated to a viscous dark oil. The material was dissolved into MeOH, filtered and purified by preparative HPLC (MeOH/water, ammonium acetate buffer) to yield (1R,3S,5R)-tert-butyl 3-(4-((6-(2-((1R,3S,5R)-2-((S)-2-(methoxycarbonylamino)-3-methylbutanoyl)-2-azabicyclo[3.1.0]hexan-3-yl)-1H-imidazol-4-yl)naphthalen-2-yl)ethynyl)-1H-imidazol-2-yl)-2-azabicyclo[3.1.0]hexane-2-carboxylate (187.4 mg) as a yellow solid. The material was used without further purification. LC-MS retention time 1.720 min; m/z 704.59 (MH+). LC data was recorded on a Shimadzu LC-10AS liquid chromatograph equipped with a PHENOMENEX® Luna 3u C18 2.0×30 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 1.0 mL/min, a gradient of 100% Solvent A/0% Solvent B to 0% Solvent A/100% Solvent B, a gradient time of 2 min, a hold time of 1 min, and an analysis time of 3 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.