1,2-Dibromoethane → 9-(3-Chloro-4-fluoroanilino)-2,3-dihydro-1H-[1,4]oxazino[3,2-g]quinoline-8-carbonitrile

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Reaction Conditions

Reaction Steps

An amount of 6-amino-4-(3-chloro-4-fluoro-phenylamino)-7-hydroxy-quinoline-3-carbonitrile (4 g, 12.2 mmol) was stirred in 2-ethoxyethanol (480 mL), and to this were added 1,2-dibromoethane (22.9 g, 12.2 mmol), and potassium carbonate (10.1 g, 73 mmol), and the mixture was heated at 135° C. for 0.5 hours. After cooling to room temperature, the mixture was filtered over a thin silica pad and evaporated to an oil. To this was added ethyl acetate and saturated brine solution, and the layers were separated. The organic layer was dried on sodium sulfate and evaporated to a brown oil. Purification was carried out by flash chromatography (70% ethyl acetate in hexane) to yield a yellow solid (1.95 g, 45% yield), m.p. 244-245° C.; 1H NMR (DMSO-d6) δ 9.32 (s, 1H), 8.29 (s, 1H), 7.36 (m, 2H), 7.19 (s, 1H), 7.12 (m, 2H), 6.59 (s, 1H), 4.27 (m, 2H), 3.37 (m, 2H); HRMS (EI) m/z 355.07512 (M+1). Analysis for C18H12ClFN4.O0.1H2O.0.4CH3CO2C2H5: Found: C, 59.59; H, 3.66; N, 14.69. Calcd: C, 59.97; H, 3.93; N, 14.29.

Provenance & Evidence