(4-Fluorophenyl)(1-methyl-1H-imidazol-5-yl)methanone → (3-(4-(1H-Pyrazol-1-yl)benzyl)-4-chloro-2-methoxyquinolin-6-yl)(4-fluorophenyl)(1-methyl-1H-imidazol-5-yl)methanol

Participants

Reaction Steps

A solution of n-BuLi (2.5 M in hexanes, 0.07 mL, 0.175 mmol) was added dropwise by syringe to a solution of 3-(4-(1H-pyrazol-1-yl)benzyl)-6-bromo-4-chloro-2-methoxyquinoline (75.8 mg, 0.177 mmol, Intermediate 16) in dry THF (3 mL) in a dry ice-acetone bath. After 1 minute, a solution of (4-fluorophenyl)(1-methyl-1H-imidazol-5-yl)methanone (37.8 mg, 0.185 mmol, Intermediate 29: step b) in dry THF (0.6 mL) was added dropwise. The reaction mixture was stirred for 5 minutes in a dry ice-acetone bath, then 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 flash column chromatography (silica gel, 0-50% EtOAc-Hexanes) to provide the title compound as a clear foam. 1H NMR (400 MHz, CDCl3) δ ppm 8.12 (d, J=2.1 Hz, 1H), 7.84 (d, J=2.4 Hz, 1H), 7.77 (d, J=8.7 Hz, 1H), 7.66 (d, J=1.6 Hz, 1H), 7.57-7.50 (m, 3H), 7.35 (d, J=8.6 Hz, 2H), 7.34-7.29 (m, 2H), 7.25 (s, 1H), 7.04-6.96 (m, 2H), 6.45-6.40 (m, 1H), 6.30 (s, 1H), 4.30 (s, 2H), 4.08 (s, 3H), 3.34 (s, 3H); MS m/e 554.1 [M+H]+.

Provenance & Evidence