Tetrahydrofuran → (1-Methyl-1H-imidazol-5-yl)(3-phenyl-2,4-bis(trifluoromethyl)quinolin-6-yl)(pyridin-2-yl)methanol

Participants

Reaction Steps

A solution of n-BuLi (2.5 M in hexanes, 0.10 mL, 0.25 mmol) was added dropwise by syringe to a solution of 6-iodo-3-phenyl-2,4-bis(trifluoromethyl)quinoline (122 mg, 0.261 mmol, Intermediate 8, step d) in dry THF (4.5 mL) in a dry ice-acetone bath. After 2 min, a solution of (1-methyl-1H-imidazol-5-yl)(pyridin-2-yl)methanone (0.0540 g, 0.288 mmol, Intermediate 11, step b) in dry THF (0.25 mL) was added dropwise. The reaction mixture was stirred for 5 min in a dry ice-acetone bath, then the reaction flask was placed into an ice-water bath. After 5 min, the mixture was warmed to room temperature and the reaction was quenched with methanol and water. The mixture was partitioned between water and ethyl acetate. The separated aqueous phase was further extracted with ethyl acetate. The organic phase was dried (Na2SO4), filtered, and concentrated. The crude product was purified by reverse-phase chromatography (acetonitrile w/0.05% TFA in water). Saturated sodium bicarbonate was used to form the free-base product, which was extracted with DCM and concentrated to provide the title compound as a white solid. 1H NMR (500 MHz, CDCl3) δ 8.66 (d, J=4.4 Hz, 1H), 8.32 (d, J=8.9 Hz, 1H), 8.26 (d, J=2.0 Hz, 1H), 8.05 (dd, J=8.9, 1.8 Hz, 1H), 7.75 (td, J=7.7, 1.7 Hz, 1H), 7.51 (s, 1H), 7.49-7.40 (m, 3H), 7.35 (dd, J=7.0, 5.3 Hz, 1H), 7.28 (s, 1H), 7.22 (d, J=7.9 Hz, 1H), 6.72 (s, 1H), 6.39 (s, 1H), 3.44 (s, 3H). MS m/e 529.2 [M+H]+.

Provenance & Evidence