Azobisisobutyronitrile → 7-bromo-5-(2-chloro-4-fluorophenyl)-1-(2,6-dichlorophenyl)-1,6-naphthyridin-2(1H)-one

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Reaction Steps

To 7-bromo-5-(2-chloro-4-fluorophenyl)-1-(2,6-dichlorophenyl)-3,4-dihydro-1,6-naphthyridin-2(1H)-one (2.33 g, 4.65 mmol) in 75 mL of CCl4 was added recrystallized N-bromosuccinimide (993 mg, 5.58 mmol) and 2,2′azobis(2-methylpropionitrile) (76.4 mg, 0.465 mmol). The resulting reaction mixture was evacuated and flushed with argon 3 times, then heated and maintained at reflux for 2.5 h. 1,8-diazabicyclo[5.4.0]undec-7-ene (695 μL, 4.65 mmol) was added and the reaction mixture was cooled to rt, washed with 140 mL of half-saturated aqueous NaHCO3, and the aqueous layer was back-extracted with 2×70 mL of ethyl acetate. The combined organic layers were washed with brine, dried over Na2SO4, and concentrated under reduced pressure. The product was purified by flash chromatography on Biotage 40M column, eluting with a gradient system of 90:10 hexanes-ethyl acetate to 80:20 hexanes-ethyl acetate to yield 7-bromo-5-(2-chloro-4-fluorophenyl)-1-(2,6-dichlorophenyl)-1,6-naphthyridin-2(1H)-one as an off white solid. Mass spectrum (ESI) 497 (M+1). 1H NMR (500 MHz, CDCl3): δ 6.64 (s, 1H); 6.79 (d, J=10.1 Hz, 1H); 7.21 (m, 1H), 7.31 (m, 1H); 7.54 (m, 3H); 7.65 (m, 2H),

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