5-Bromo-2-(trifluoromethyl)pyridine → (4-Chloro-2-methoxy-3-(4-(methylsulfonyl)benzyl)quinolin-6-yl)(1-methyl-1H-imidazol-5-yl)(6-(trifluoromethyl)pyridin-3-yl)methanol

Participants

Reaction Conditions

Reaction Steps

Isopropyl magnesium chloride LiCl complex (1.3 M in THF, 0.7 mL, 0.904 mmol) was added dropwise to a solution of 5-bromo-2-(trifluoromethyl)pyridine (0.2 g, 0.904 mmol) in dry THF 5 mL) at 0° C. The mixture was stirred at 0° C. for five minutes then at room temperature for 30 minutes. A suspension of (4-chloro-2-methoxy-3-(4-(methylsulfonyl)benzyl)quinolin-6-yl)(1-methyl-1H-imidazol-5-yl)methanone (0.085 g, 0.181 mmol, Intermediate 38: step b) in THF (5 mL) was added rapidly at 0° C. and the reaction mixture was stirred and allowed to warm to room temperature. The homogeneous amber solution was stirred at room temperature for 4 hours, then heated at 45° C. for 12 hours. Once cooled the reaction mixture was quenched with saturated aqueous NH4Cl, diluted with H2O and extracted with EtOAc (2×). The EtOAc extracts were washed with brine, dried (Na2SO4), filtered, evaporated in vacuo and chromatographed (DCM/MeOH) to provide the title compound. 1H NMR (400 MHz, CDCl3) δ ppm 8.80 (s, 1H), 8.15 (d, J=2.0 Hz, 1H), 7.87-8.00 (m, 1H), 7.78-7.87 (m, 3H), 7.65 (d, J=8.1 Hz, 1H), 7.57 (d, J=2.0 Hz, 1H), 7.46 (d, J=8.6 Hz, 2H), 7.32 (s, 1H), 6.33 (s, 1H), 5.30 (s, 1H), 4.37 (s, 2H), 4.08 (s, 3H), 3.36 (s, 3H), 3.01 (s, 3H); MS (ESI) 617.9.

Provenance & Evidence