Sodium Carbonate → 9-Fluoro-7-(5-fluoro-pyridin-3-yl)-1-methyl-4,5-dihydro-[1,2,4]triazolo[4,3-a]quinoline

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Reaction Steps

7-Bromo-9-fluoro-4,5-dihydro-1-methyl-[1,2,4]triazolo[4,3-a]quinoline (157-5, 0.25 g, 0.89 mmol) was dissolved in toluene (6.3 mL), and an aqueous 2.0 M sodium carbonate solution (2.8 mL), an ethanolic solution (2.8 mL) of 5-fluoropyridin-3-yl-3-boronic acid (0.19 g, 1.33 mmol) and tetrabutylammonium bromide (0.29 g, 0.89 mmol) were added. The mixture was deoxygenated under reduced pressure and flushed with nitrogen. After having repeated this cycle several times catalyst Pd(OAc)2 (0.01 g, 5 mol %) was added and the resulting suspension was heated under reflux for 18 h. After cooling, ethyl acetate (10 mL) and water (10 mL) were added and the organic layer was separated. The water phase was extracted with ethyl acetate (2×10 mL). The combined organic phases were washed with brine, dried over Na2SO4, filtered over a short plug of CELITE and evaporated under reduced pressure. The crude compound was purified by flash chromatography on silica gel to obtain title compound (white solid); 1H NMR (CDCl3, 500 MHz) δ 8.67 (t, J=1.5 Hz, 1H), 8.52 (d, J=2.7 Hz, 1H), 7.59 (ddd, J=2.0, 2.6 Hz, JHF=9.2 Hz, 1H), 7.39 (dd, J=1.9 Hz, JHF=14.6 Hz, 1H), 7.41 (d, J=1.7 Hz, 1H), 3.13 (t, J=7.5 Hz, 2H), 3.04 (t, J=7.5 Hz, 2H), 2.65 (d, JHF=8.3 Hz, 3H); MS (ESI): m/z=299 [M+H]+.

Provenance & Evidence