(1-Methyl-1H-imidazol-5-yl)(6-(trifluoromethyl)pyridin-3-yl)methanone → (3-(4-(1H-Pyrazol-1-yl)benzyl)-4-chloro-2-methoxy-8-methylquinolin-6-yl)(1-methyl-1H-imidazol-5-yl)(6-(trifluoromethyl)pyridin-3-yl)methanol

Participants

Reaction Conditions

Reaction Steps

n-Butyllithium (1.6 M in hexane; 1.84 mL, 2.936 mmol) was added dropwise to a suspension of the 3-(4-(1H-pyrazol-1-yl)benzyl)-6-bromo-4-chloro-2-methoxy-8-methylquinoline (1 g, 2.26 mmol, Intermediate 19: step b) and (1-methyl-1H-imidazol-5-yl)(6-(trifluoromethyl)pyridin-3-yl)methanone (0.63 g, 2.49 mmol, Intermediate 36: step c) in dry THF (23 mL) at −78° C. over a 2 minute period. After complete addition stirring was continued at −78° C. for 10 minutes then warmed in an ice bath to 0° C. The mixture was stirred for 1 hour then quenched with saturated aqueous NH4Cl and warmed to room temperature. After stirring for 10 minutes layers were separated and the aqueous layer extracted with EtOAc. The combined organic extracts were dried over Na2SO4, filtered, evaporated in vacuo and chromatographed (0-5% MeOH in acetonitrile) to provide the title compound as an amorphous solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 9.15 (s, 1H), 8.84 (d, J=2.0 Hz, 1H), 8.41 (d, J=2.5 Hz, 1H), 8.00-8.07 (m, 1H), 7.92-7.99 (m, 2H), 7.87 (s, 1H), 7.72 (d, J=8.6 Hz, 3H), 7.57 (s, 1H), 7.33 (d, J=9.1 Hz, 2H), 7.16 (s, 1H), 6.40-6.59 (m, 1H), 4.29 (s, 2H), 4.07 (s, 3H), 3.53 (s, 3H) 2.65 (s, 3H); MS (ESI) 619.

Provenance & Evidence