Reaction SMILES: [C:1]([O:5][C:6]([N:8]1[CH2:12][CH:11]([C:13]2[NH:14][CH:15]=[C:16]([C:18]3[CH:23]=[CH:22][C:21](Br)=[CH:20][CH:19]=3)[N:17]=2)[N:10]([C:25](=[O:35])[CH:26]([NH:30][C:31]([O:33][CH3:34])=[O:32])[CH:27]([CH3:29])[CH3:28])[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH3:36][O:37][C:38](=[O:64])[NH:39][CH:40]([C:44]([N:46]1[CH2:50][CH2:49][CH2:48][CH:47]1[C:51]1[NH:52][CH:53]=[C:54]([C:56]2[CH:61]=[CH:60][C:59]([C:62]#[CH:63])=[CH:58][CH:57]=2)[N:55]=1)=[O:45])[CH:41]([CH3:43])[CH3:42].C(N(CC)CC)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>[C:1]([O:5][C:6]([N:8]1[CH2:12][CH:11]([C:13]2[NH:14][CH:15]=[C:16]([C:18]3[CH:23]=[CH:22][C:21]([C:63]#[C:62][C:59]4[CH:60]=[CH:61][C:56]([C:54]5[N:55]=[C:51]([CH:47]6[CH2:48][CH2:49][CH2:50][N:46]6[C:44](=[O:45])[CH:40]([NH:39][C:38]([O:37][CH3:36])=[O:64])[CH:41]([CH3:43])[CH3:42])[NH:52][CH:53]=5)=[CH:57][CH:58]=4)=[CH:20][CH:19]=3)[N:17]=2)[N:10]([C:25](=[O:35])[CH:26]([NH:30][C:31]([O:33][CH3:34])=[O:32])[CH:27]([CH3:29])[CH3:28])[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]
Reactant: C#Cc1ccc(-c2c[nH]c(C3CCCN3C(=O)C(NC(=O)OC)C(C)C)n2)cc1
Reactant: COC(=O)NC(C(=O)N1CN(C(=O)OC(C)(C)C)CC1c1nc(-c2ccc(Br)cc2)c[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: CCN(CC)CC
Product: COC(=O)NC(C(=O)N1CCCC1c1nc(-c2ccc(C#Cc3ccc(-c4c[nH]c(C5CN(C(=O)OC(C)(C)C)CN5C(=O)C(NC(=O)OC)C(C)C)n4)cc3)cc2)c[nH]1)C(C)C
Temperature: 80 °C
Reaction time: 1 h
Yield: 34.5 %

Procedure:
A mixture of 4-(4-bromo-phenyl)-3′-(2-methoxycarbonylamino-3-methyl-butyryl)-2′,3′,4′,5′-tetrahydro-1H-[2,4′]biimidazolyl-1′-carboxylic acid tert-butyl ester (686 mg, 1.74 mmol), (1-{2-[4-(4-ethynyl-phenyl)-1H-imidazol-2-yl]-pyrrolidine-1-carbonyl}-2-methyl-propyl)-carbamic acid methyl ester (800 mg, 1.45 mmol), copper(I) iodide (28 mg, 0.14 mmol), tetrakis(triphenylphosphine)palladium(0) (167 mg, 0.14 mmol), triethylamine (2.0 mL, 14.5 mmol) and degassed dimethylformamide (10 mL) was stirred at 80° C. for 1 hour. (1-{2-[4-(4-Ethynyl-phenyl)-1H-imidazol-2-yl]-pyrrolidine-1-carbonyl}-2-methyl-propyl)-carbamic acid methyl ester (200 mg, 0.57 mmol) was added. After 1 hour the solvent was removed under reduced pressure. The residue was taken up in dichloromethane (50 mL) and washed with water (10 mL), saturated ammonium chloride (2×10 mL), dried over sodium sulfate and filtered. The solvent was removed under reduced pressure. The residue was subjected to flash chromatography with eluent of (10% methanol in ethyl acetate) and hexane. The product-containing fractions were combined and the solvent was removed under reduced pressure to yield 3′-(2-methoxycarbonylamino-3-methyl-butyryl)-4-[4-(4-{2-[1-(2-methoxycarbonylamino-3-methyl-butyryl)-pyrrolidin-2-yl]-1H-imidazol-4-yl}-phenylethynyl)-phenyl]-2′,3′,4′,5′-tetrahydro-1H-[2,4′]biimidazolyl-1′-carboxylic acid tert-butyl ester (439 mg, 0.50 mmol, 35%). C46H57N9O8 calculated 863.4 observed [M+1]+ 864.5; rt=1.91 min. 1H (DMSO-d6): δ=8.07 (m, 1H), 7.76 (m, 4H), 7.68 (m, H), 7.56 (d, J=7.6 Hz, 2H), 7.30 (d, J=8.8 Hz, 1H), 5.37 (m, 1H), 5.21 (m, 1H), 5.08 (m, 2H), 4.80 (m, 1H), 4.07 (t, J=7.2 Hz, 2H), 3.81 (m, 2H), 3.52 (s, 3H), 3.51 (s, 3H), 2.33 (m, 2H), 2.08 (m, 1H), 1.97 (m, 4H), 1.39 (s, 9H), 1.34 (m, 2H), 0.81 (m, 12H).