Hydrochloric Acid → (2,4-dimethoxy-benzyl)[1,2,4]thiadiazol-5-yl-amine 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), NaBH4 (600 mg, 15.9 mmol) was added carefully in small portions (vigorous effervescence after each addition), and the reaction was left stirring overnight at ambient temperature. Aqueous HCl (2M, 1 mL) was added followed by aqueous NaOH (2M, 10 mL). The bulk of the methanol was evaporated, water (20 mL) added and extracted with ethyl acetate (2×30 mL). The combined organic was washed brine (20 mL), dried, and evaporated. 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, 49%).

Provenance & Evidence