Dimethylformamide → 4-Chloropyrido(3,2-d)pyrimidine

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Reaction Steps

To a stirred solution of pyrido[3,2-d]pyrimidin-4-ol (A-2) (16 g, 109 mmol, 1.0 eq) and DMF (0.4 mL) in DCM (200 mL) at RT, oxalyl chloride (23.2 mL, 272 mmol, 2.5 eq) is added dropwise (over 5 min) and the resulting mixture is stirred at reflux overnight. The mixture is allowed to cool to RT and concentrated in vacuo. The residue is diluted with water (200 mL), neutralized with saturated aqueous NaHCO3 solution below 10° C. to adjust the pH to 8-9 and then extracted with ethyl acetate (4×100 mL). The combined organic layers are washed with brine, dried over Na2SO4 and filtered. The filtrate is concentrated in vacuo. The residue is purified by flash column chromatography on silica gel (16-50% ethyl acetate-petro ether) to afford the product, 4-chloropyrido[3,2-d]pyrimidine (A-3).

Provenance & Evidence