L-Carvone chloride 5 was prepared according to the literature [8 (link),25 (link)]. To a mixture of 5-amino-1,3,4-thiadiazole-2-thiol (2.00 g, 15.0 mmol) and potassium hydroxide (0.89 g, 15.9 mmol) in ethanol (20 mL) and water (5 mL), a solution of L-carvone chloride 5 (2.59 g, 14.0 mmol) in ethanol (10 mL) was added dropwise, and then the reaction mixture was stirred at room temperature for 12 h. After the reaction was completed, the mixture was extracted with ethyl acetate (30 mL × 3), and the combined organic layer was washed with a saturated sodium chloride solution (30 mL). The organic layer was separated out and concentrated under reduced pressure to obtain L-carvone-based 1,3,4-thiadiazole-amine as a crude product.
The obtained crude product of L-carvone-based 1,3,4-thiadiazole-amine was re-dissolved in DCM (25 mL), and chloroacetyl chloride (1.12 g, 9.92 mmol) was injected into the solution. The reaction mixture was kept for stirring at room temperature and monitored by TLC until the reaction was completed. Subsequently, the reaction mixture was concentrated in vacuum, and the residue was further purified by column chromatography (PE:EA = 5:1, v/v) to obtain L-carvone-based 1,3,4-thiadiazole-amide intermediate 6 as a white powder with a yield of 71.6%.
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