(1-Methyl-1H-imidazol-5-yl)(6-(trifluoromethyl)pyridin-3-yl)methanone → (2,4-Dichloro-3-(3-fluorophenyl)-8-methylquinolin-6-yl)(1-methyl-1H-imidazol-5-yl)(6-(trifluoromethyl)pyridin-3-yl)methanol

Beteiligte Stoffe

Reaktionsbedingungen

Reaktionsschritte

n-BuLi (1.6 M in hexane, 1.91 mL, 3.05 mmol) was added over approximately 1 minute to a solution of 6-bromo-2,4-dichloro-3-(3-fluorophenyl)-8-methylquinoline (1.23 g, 3.20 mmol, Intermediate 50, step c) in THF (10 mL) under argon at −78° C. After 1 minute, a solution of (1-methyl-1H-imidazol-5-yl)(6-(trifluoromethyl)pyridin-3-yl)methanone (817 mg, 3.20 mmol, Intermediate 15, step c) in 10 mL THF under argon was added via cannula. The resulting mixture was stirred at −78° C. for 10 minutes, then transferred to an ice water bath and stirred 1 hour. The reaction was quenched by addition of saturated aqueous NH4Cl, diluted with water and extracted with EtOAc (3×). The organic phase was dried (Na2SO4), filtered, and concentrated. The residue was purified by flash column chromatography (silica gel, 45-60% CH3CN in [2% conc. aqueous NH4OH in DCM, aqueous phase removed]) to afford the title compound as a cream colored solid. 1H NMR (400 MHz, CHLOROFORM-d) δ 8.83 (s, 1H), 8.14 (dd, J=1.83, 7.46 Hz, 1H), 7.92 (d, J=8.31 Hz, 1H), 7.65 (d, J=8.31 Hz, 1H), 7.57-7.62 (m, 1H), 7.44-7.53 (m, 1H), 7.20 (td, J=2.20, 8.31 Hz, 1H), 7.09 (t, J=6.60 Hz, 1H), 7.01-7.07 (m, 1H), 6.29 (d, J=0.98 Hz, 1H), 6.02 (br. s., 1H), 3.37 (s, 3H), 2.74 (s, 3H). MS m/e 561.2 [M+H]+.

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