Pyridine, hydrofluoride (1:1) → 5-Bromo-6-ethoxy-8-fluoro-1,7-naphthyridine

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Reaction Conditions

Reaction Steps

To a 100 mL round bottom flask was added 5-bromo-6-ethoxy-1,7-naphthyridin-8-amine (500 mg, 1.86 mmol), followed by pyridine hydrogen fluoride (10 mL). The mixture was cooled to 0° C. and sodium nitrite (0.154 mg, 2.24 mmol) was added in portions. The mixture was slowly warmed to room temperature over a period of 3 h. The reaction was neutralized with saturated NaHCO3 and extracted with ethyl acetate. The organic layer was washed with brine, dried over Na2SO4 and concentrated. The resultant residue was purified by silica gel to yield 5-bromo-6-ethoxy-8-fluoro-1,7-naphthyridine as a pale yellow solid (430 mg, 1.59 mmol, 85%). 1H NMR (400 MHz, CDCl3): δ ppm 8.87 (d, J=3.52 Hz, 1H), 8.42 (d, J=8.79 Hz, 1H), 7.65 (dd, J=8.13, 3.30 Hz, 1H), 4.55 (q, J=7.03 Hz, 2H), 1.49 (t, J=7.03 Hz, 3H). LC/MS m/z 273 [M+H].

Provenance & Evidence