Hydrochloric Acid → 1-(4-Chloro-2-methoxy-3-(4-(methylsulfonyl)benzyl)quinolin-6-yl)-1-(1-methyl-1H-imidazol-5-yl)propan-1-ol

Participants

Reaction Steps

Ethyl magnesium bromide solution (3 M in Et2O, 0.1 mL, 0.334 mmol) was added slowly to a solution of 5-bromo-2-(trifluoromethyl)pyridine (0.075 g, 0.334 mmol) in dry THF (3 mL). The resulting cloudy solution was stirred at room temperature for 20 minutes, cooled to 0° C. and then (4-chloro-2-methoxy-3-(4-(methylsulfonyl)benzyl)quinolin-6-yl)(1-methyl-1H-imidazol-5-yl)methanone (0.056 g, 0.119 mmol, Intermediate 7: step e) in dry DCM (1 mL) was added. The resulting suspension was stirred at room temperature for 10 minutes then heated in a 60° C. oil bath, for 6 hours, then at 80° C. for an additional 12 hours. The mixture was cooled to room temperature, then H2O was added followed by 6 N aqueous HCl to bring the contents to a neutral pH. The solvents were removed under reduced pressure and the product extracted out with CH2Cl2 (2×). The combined organic extract was dried (Na2SO4), filtered, evaporated in vacuo and chromatographed (0-10% MeOH in DCM) to provide a yellow solid by-product. Further purification by RP-HPLC (water/acetonitrile/0.1% TFA) of this by-product provided the title compound as a white solid. 1H NMR (400 MHz, CD3OD) δ 8.80 (s, 1H), 8.32 (d, J=2.0 Hz, 1H), 7.84 (d, J=7.6 Hz, 4H), 7.51 (d, J=8.6 Hz, 3H), 4.44 (s, 2H), 4.07 (s, 3H), 3.53 (s, 3H), 3.07 (s, 3H), 2.26-2.48 (m, 2H), 0.83 (t, J=7.0 Hz, 3H); MS (ESI) 500 [M+H]+.

Provenance & Evidence