Hydrochloric Acid → N-(2,4-dimethoxybenzyl)-1,2,4-thiadiazol-5-amine

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Reaction Steps

A mixture of 5-amino-1,2,4-thiadiazole (1 g, 9.89 mmol) and 2,4-dimethoxybenzaldehyde (1.81 g, 10.9 mmol) in toluene (30 mL) was refluxed under Dean-Stark conditions for 2 hours. The reaction mixture was evaporated and the residue taken up in methanol (25 mL), sodium borohydride (600 mg, 15.9 mmol) was added carefully in small portions (vigorous effervescence after each addition), and the reaction was left to stir for 18 hours at ambient temperature. A 2M aqueous solution of hydrogen chloride (1 mL) was added followed by a 2M aqueous solution of sodium hydroxide (10 mL). The bulk of the methanol was evaporated, water (20 mL) was added and the mixture extracted with ethyl acetate (2×30 mL). The combined organic phase was washed with brine (20 mL), dried, and concentrated in vacuo. The residue was purified by silica gel column chromatography (ISCO™ column 120 g; 25-60% ethyl acetate in heptane gradient elution) to furnish a semi-solid residue that was re-evaporated from heptane. tert-Butylmethyl ether (2-3 mL) was added, followed by heptane (2-3 mL). The resulting solid was collected by filtration, washed with heptane and dried to afford the title compound (1.22 g).

Provenance & Evidence