Reaction Steps
A solution of n-BuLi (2.5 M in hexanes, 1.85 mL, 4.62 mmol) was added dropwise by syringe to a solution of 6-bromo-4-chloro-2-methoxy-3-(4-(trifluoromethyl)benzyl)quinoline (2.00 g, 4.65 mmol, Intermediate 47: step d) in dry THF (30 mL) in a dry ice-acetone bath. After 1.5 minutes, a solution of (1-methyl-1H-imidazol-5-yl)(6-(trifluoromethyl)pyridin-3-yl)methanone (1.26 g, 4.92 mmol, Intermediate 36: step c) in dry THF (5 mL) was added dropwise. The reaction mixture was stirred for 2 minutes in a dry ice-acetone bath, then the reaction flask was placed into an ice-water bath. After 10 minutes, the mixture was warmed to room temperature and the reaction was quenched with saturated ammonium chloride. The mixture was partitioned between water and DCM. The separated aqueous phase was further extracted with DCM. The organic phase was dried (Na2SO4), filtered, and concentrated to provide the title compound as crude white solid. MS m/e 607.2 [M+H]+ Example 62A was purified by chiral HPLC (ChiralPak AD, 50:50 methanol/ethanol) to provide two enantiomers, Example 62B and Example 62C. The first eluting enantiomer was Example 62B: 1H NMR (500 MHz, CDCl3) δ ppm 8.80 (d, J=1.8 Hz, 1H), 8.19 (d, J=2.0 Hz, 1H), 7.94 (s, 1H), 7.85 (dd, J=8.2, 1.9 Hz, 1H), 7.79 (d, J=8.5 Hz, 1H), 7.61 (d, J=8.5 Hz, 1H), 7.52 (dd, J=8.8, 2.1 Hz, 1H), 7.47 (d, J=8.2 Hz, 2H), 7.36 (d, J=8.1 Hz, 2H), 7.05 (s, 1H), 6.15 (s, 1H), 4.30 (s, 2H), 4.07 (s, 3H), 3.29 (s, 3H); MS m/e 607.2 [M+H]+ and the second eluting enantiomer was Example 62C: 1H NMR (500 MHz, CDCl3) δ ppm 8.80 (d, J=1.7 Hz, 1H), 8.19 (d, J=2.0 Hz, 1H), 7.99 (s, 1H), 7.86 (dd, J=8.2, 1.8 Hz, 1H), 7.79 (d, J=8.8 Hz, 1H), 7.61 (d, J=8.3 Hz, 1H), 7.53 (dd, J=8.8, 2.1 Hz, 1H), 7.47 (d, J=8.2 Hz, 2H), 7.37 (d, J=8.1 Hz, 2H), 7.06 (s, 1H), 6.16 (s, 1H), 4.30 (s, 2H), 4.07 (s, 3H), 3.30 (s, 3H); MS m/e 607.2 [M+H]+.
