Reaction SMILES: C([Mg]Cl)(C)C.Br[C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][N:8]=1.C(OC)(=O)C1C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C[O:43][C:44]([C:46]1([NH:50][C:51]([C:53]2[CH:61]=[C:60]3[C:56]([C:57]([CH:64]4[CH2:68][CH2:67][CH2:66][CH2:65]4)=[C:58](Br)[N:59]3[CH3:62])=[CH:55][CH:54]=2)=[O:52])[CH2:49][CH2:48][CH2:47]1)=[O:45].[Cl-].[NH4+].C(OC(C)C)(=O)C.Cl.[OH-].[Na+].C(O)(=O)C>[Zn+2].[Br-].[Br-].C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C(O)CC.C1COCC1.CN1CCCC1=O>[CH:64]1([C:57]2[C:56]3[C:60](=[CH:61][C:53]([C:51]([NH:50][C:46]4([C:44]([OH:45])=[O:43])[CH2:47][CH2:48][CH2:49]4)=[O:52])=[CH:54][CH:55]=3)[N:59]([CH3:62])[C:58]=2[C:7]2[CH:12]=[CH:11][CH:10]=[CH:9][N:8]=2)[CH2:68][CH2:67][CH2:66][CH2:65]1
Reactant: Brc1ccccn1
Reactant: COC(=O)C1(NC(=O)c2ccc3c(C4CCCC4)c(Br)n(C)c3c2)CCC1
Agent: [Pd+2]
Agent: CC(=O)[O-]
Agent: CC(C)[Mg]Cl
Solvent: CC(=O)OC(C)C
Solvent: CC(=O)O
Solvent: COC(=O)c1ccccc1
Product: Cn1c(-c2ccccn2)c(C2CCCC2)c2ccc(C(=O)NC3(C(=O)O)CCC3)cc21
Temperature: 35 °C
Reaction time: 0.5 h

Procedure:
To a solution of i-PrMgCl in THF (10 mL, 20 mmol) was added 2-bromopyridine (1.93 g, 20.2 mmol) at room temperature in one portion. The mixture was stirred at 35° C. for 0.5 h. To the deep-red solution was added ZnBr2 (4.50 g, 20 mmol) under argon and the resulting mixture was stirred at 70° C. for 0.5 h to obtain a thick off-white slurry. 1-Methyl-2-pyrrolidinone (20 mL) was added and followed by methyl benzoate (1.1 mL, 8.7 mmol). The mixture was stirred at 70° C. for 0.5 h and then cooled to room temperature. Palladium acetate (39.1 mg, 0.17 mmol), triphenylphosphine (182.6 mg, 0.70 mmol) and 1-[(2-bromo-3-cyclopentyl-1-methyl-1H-indole-6-carbonyl)-amino]-cyclobutanecarboxylic acid methyl ester (3.768 g, 8.70 mmol) were added. The mixture was stirred at 90° C. until no starting material was left (˜3 h) as monitored by HPLC. Saturated ammonium chloride (20 mL), isopropyl acetate (20 mL) and THF (10 mL) were added. The pH of the mixture was adjusted to 4-5 using 4 HCl (˜3 mL) and the mixture was stirred at 60° C. for 5 minutes and then transferred to a separatory funnel. The aqueous layer was separated and extracted with isopropyl acetate (20 mL) at 60° C. The combined organic phases were washed with a mixture of saturated ammonium chloride (10 mL) and water (10 mL) at 60° C. The organic layer was extracted with 4 N HCl (15 and 10 mL). To the combined extracts cooled in an ice-water bath was slowly added 50% NaOH (9.40 g, 117.5 mmol). The mixture was heated to reflux until the batch inside temperature reached 89-90° C. n-Propanol (10 mL) was added and the mixture was stirred at 90° C. for 1 h. After the mixture was cooled to 60° C., acetic acid (1.57 g, 26.1 mmol) was slowly added to adjust the pH to 5-6. The resulting white suspension was stirred at 60° C. for 1 h and allowed to cool to room temperature in 2 h. The white precipitate was collected by filtration and the wet cake was rinsed with 2:1 water/n-propanol (15 mL) and water (50 mL). The solid was dried under vacuum until a constant weight (2.67 g, 74%). 1H NMR (400 MHz, DMSO-d6) δ 12.25 (s, 1H), 8.92 (s, 1H), 8.80 (d, J=4.0 Hz, 1H), 8.13 (s, 1H), 7.98 (dt, J=1.5, 7.5 Hz, 1H), 7.70 (d, J=8.5, 1H), 7.68-7.56 (m, 2H), 7.52-7.45 (m, 1H), 3.71 (s, 3H), 3.21-3.08 (m, 1H), 2.68-2.55 2H), 2.42-2.28 (m, 2H), 2.05-1.80 (m, 8H), 1.70-1.55 (m, 2H).