Reaction Steps
A mixture of 3-benzyl-6-bromo-4-chloro-2-(trifluoromethyl)quinoline (632 mg, 1.58 mmol, Intermediate 72: step b), 1-(4-(1-methyl-1H-imidazole-5-carbonyl)piperidin-1-yl)ethanone (371 mg, 1.58 mmol, Intermediate 58: step c), and 15 mL of THF was sparged with N2 and cooled to −78° C. To the mixture was added n-BuLi (1.6 M in hexanes, 2.6 mL, 4.2 mmol) dropwise. The reaction mixture was stirred at −78° C. for 10 minutes, then the acetone-dry ice bath was replaced with a water-ice bath. Stirring was continued for 20 minutes at 4° C. Saturated NH4Cl (aq) was added and the organic layer was separated. The aqueous layer was extracted with dichloromethane. The combined organic phases were dried (Na2SO4), filtered, and concentrated to dryness. The crude material was purified by flash column chromatography (silica gel, 0-10% MeOH in DCM) followed by reverse phase HPLC (water/acetonitrile/0.1% TFA) to afford the title compound as a TFA salt. 1H NMR (400 MHz, MeOH-d4, ˜1:1 mixture of rotamers) δ 8.84 (s, 1H), 8.51 (d, J=9.09 Hz, 1H), 8.24 (d, J=9.09 Hz, 1H), 8.07 (s, 1H), 7.78 (d, J=9.09 Hz, 1H), 7.21-7.29 (m, 2H), 7.15-7.21 (m, 1H), 7.01 (d, J=7.07 Hz, 2H), 4.65 (d, J=13.14 Hz, 0.5H), 4.57 (s, 2H), 4.45 (d, J=13.14 Hz, 0.5H), 4.03 (d, J=13.64 Hz, 0.5H), 3.84 (d, J=14.15 Hz, 0.5H), 3.59 (s, 1.5H), 3.57 (s, 1.5H), 3.23-3.32 (m, overlapping with solvent), 3.03 (td, J=2.02, 13.14 Hz, 0.5H), 2.66-2.82 (m, 1H), 2.53 (td, J=2.53, 13.64 Hz, 0.5H), 2.09-2.24 (m, 1H), 2.07 (s, 1.5H), 2.02 (s, 1.5H), 1.41-1.60 (m, 1H), 1.26-1.39 (m, 1H), 1.11-1.26 (m, 1H), 1.05 (d, J=13.14 Hz, 0.5H); MS m/e 557.1 [M+H]+.
