Phosphorus oxychloride → 4-Chloro-1,5-naphthyridine-3-carbonitrile

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Reaction Steps

A mixture of 4-hydroxy-1,5-naphthyridine-3-carbonitrile (C-4) (2.0 g, 11.7 mmol, 1.0 eq) in phosphoroxychloride (40 mL, 424 mol, 36.2 eq) is stirred at reflux for 3 h. The mixture is cooled to RT and concentrated in vacuo. The residue is poured into ice-water (50 mL) and neutralized with saturated aqueous NaHCO1 solution to adjust the pH to 8 while keeping the temperature below 5° C. The mixture is extracted with DCM (3×50 mL). The combined organic layer is washed with brine, dried over Na2SO4 and filtered. The filtrate is concentrated in vacuo and the residue is purified by flash column chromatography on silica gel (1.25% MeOH-DCM) to afford the product, 4-chloro-1,5-naphthyridine-3-carbonitrile (C-5).

Provenance & Evidence