Dimethylformamide → 4-Chloro-6-fluoro-1,7-naphthyridine-3-carbonitrile

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Reaction Steps

To 10 g of 6-fluoro-4-hydroxy-[1,7]naphthyridine-3-carbonitrile under an inert atmosphere in 150 mL of methylene chloride was added 24 mL of oxalyl chloride followed by 0.4 mL of N,N-dimethyl formamide. After two hours at reflux, an additional 5 mL of oxalyl chloride and 0.3 mL of N,N-dimethyl formamide was added. After an additional hour at reflux, the reaction was poured into ice-water and solid potassium carbonate was added carefully to a pH of about 8. The chloroform layer was washed with brine, dried with sodium sulfate, and stripped to give a crude product. This material was further purified by passing it through a plug of silica gel with chloroform and recrystallizing from a mixture of chloroform and hexanes to give 10 g (92%) of 4-chloro-6-fluoro-[1,7]naphthyridine-3-carbonitrile as a yellowish solid: melting point 150-155° C.; mass spectrum (m/e): M+H2O—Cl 190.0.

Provenance & Evidence