Sulfuric Acid → Ethyl 6-amino-5-chloro-2-cyclopropylpyrimidine-4-carboxylate

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Reaction Steps

Sulfuric acid (1.97 g, 20 mmol) was added dropwise to 5-chloro-2-cyclopropyl-6-(diethoxymethyl)-4-pyrimidinamine (i.e. the product of Example 6) (2.71 g, 10 mmol) in acetonitrile (27.5 mL) at room temperature. The temperature rose to 35° C. When the mixture had cooled to 29° C. ammonium persulfate (0.5 g, 2.21 mmol) was added in one portion. After stirring for 20 h at room temperature the mixture was poured into saturated aqueous sodium bicarbonate solution (100 mL). The mixture was extracted with ethyl acetate (2×70 mL). The combined extracts were dried and evaporated to leave the product as an off-white solid (1.32 g, 55% yield). Product purified by chromatography on silica gel (eluted with 40:60 ethyl acetate-hexanes) followed by washing with hydrochloric acid (1 N) melted at 93-95° C.

Provenance & Evidence