(4-Chloro-2-methoxy-3-(4-(trifluoromethyl)benzyl)quinolin-6-yl)(2,6-dimethylpyridin-3-yl)methanol → (4-Chloro-2-methoxy-3-(4-(trifluoromethyl)benzyl)quinolin-6-yl)(2,4-dimethylthiazol-5-yl)(1-methyl-1H-1,2,3-triazol-5-yl)methanol

Participants

Reaction Conditions

Reaction Steps

To a flask containing 6-bromo-4-chloro-2-methoxy-3-(4-(trifluoromethyl)benzyl)quinoline (500 mg, 116 mmol, Intermediate 12: step d) was added THF (15 mL) at room temperature which resulted in a colorless homogeneous mixture. The solution was cooled to −70° C. (the solution remained homogeneous) and then n-butyllithium (2.5 M in hexanes, 0.45 mL, 1.13 mmol) was added dropwise. The color of the solution became a dark brown. After 1 minute, (2,4-dimethylthiazol-5-yl)(1-methyl-1H-1,2,3-triazol-5-yl)methanone (275 mg, 1.24 mmol in 2 mL THF, Intermediate 23: step b) was introduced and the color of the mixture went from dark brown to greenish to light orange color all within 1 minute. The mixture was allowed to warm to 0° C. over 45 minutes at which time the reaction was quenched with aqueous NH4Cl solution. The mixture was diluted further with water and extracted with EtOAc (3×45 mL). The combined organics were washed with brine, dried over MgSO4, filtered and concentrated to afford a light orange foam. The crude was chromatographed on silica gel (initially using 10% CH3CN-toluene then changing to 80% CH3CN-DCM) to provide the title compound as an off white solid.

Provenance & Evidence