t-BuLi (3.25 mL of 1.5M solution in pentane) was added dropwise at −78° C. to Et2O (5 mL). To the resulting solution was added, via syringe, a solution of 2-bromo-5-(trifluoromethyl)pyridine (550 mg, 2.43 mmol) in Et2O (2.5 mL). Stirring at −78° C. was continued for 20 min after which the cold reaction mixture was transferred via cannula to a cooled (−78° C.) 1M solution of ZnCl2 in Et2O (5.25 mL, 5.35 mmol). The reaction was allowed to warm to room temperature and left to stir for 3 h. THF (10 mL) was then added and the resulting solution was transferred via cannula to a mixture of 5-bromo-3-chloro-1-(4-isopropoxyphenyl)-1H-indole-2-carboxylic acid ethyl ester (see Example 35, Method 1, step (b)) (531 mg, 1.22 mmol), Pd(dppf)Cl2 (118.4 mg, 0.145 mmol), CuI (56.2 mg, 0.295 mmol) and N-methylpyrrolidine-2-one (2.5 mL) under argon. The reaction was heated at 80° C. for 6 h, poured into NH4Cl (aq. sat., 50 mL) and extracted with t-BuOMe (3×25 mL). The combined organic extracts were washed with brine, dried (Na2SO4), then filtered through a Celite® pad and the filter cake was washed with t-BuOMe. The solvent was removed and the residue dissolved in dry Et2O and HCl (4M in dioxane; 360 μL, 1.4 mmol) was added. After stirring for 10 min, solvents were removed by evaporation and the residue was twice recrystallised from EtOH to yield the sub-title compound (462 mg, 75%).
