Hydrochloric Acid → (2,4-dimethoxy-benzyl)[1,2,4]thiadiazol-5-yl-amine N-(2,4-dimethoxybenzyl)-1,2,4-thiadiazol-5-amine

Participants

Reaction Steps

A mixture of 5-amino-1,2,4-thiadiazole (1.00 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 concentrated in vacuo, and the resulting 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 overnight at ambient temperature. An 2M aqueous solution of hydrogen chloride (1 mL) was added followed by a 2M aqueous solution of sodium hydroxide (10 mL). The mixture was concentrated in vacuo, water (20 mL) added and the mixture extracted with ethyl acetate (2×30 mL). The combined organics were washed with brine (20 mL), dried, and concentrated in vacuo. The residue was purified by silica gel column chromatography (ISCO™ column, 25% to 60% ethyl acetate in heptane gradient elution) to furnish a semi-solid residue. 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