3',4'-Dimethoxycinnamic acid → 3-Cyclohexyl-5-[2-(3,4-dimethoxy-phenyl)-vinyl]-[1,2,4]oxadiazole

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Reaction Steps

To a solution of 1.43 g (6.9 mmol) of 3-(3,4-dimethoxy-phenyl)-acrylic acid (compound of Example 2; Step 1) in 22 mL of toluene, 1.21 g (7.5 mmol) of 1,1-carbonyldiimidazole was added in portions at 25° C. to 30° C. under inert atmosphere. To the thickened mixture, 22 mL of toluene was added and the resulting mixture was stirred at 25° C. to 30° C. for 60 to 90 min. A solution of N-hydroxycyclohexanecarboximidamide (compound of Example 59; 2 g, 14 mmol) in 5 mL of toluene was added to the above reaction mixture at 25° C. to 30° C. The reaction mixture was stirred at 25° C. to 30° C. under nitrogen for 12-14 h, followed by stirring at 100° C. to 105° C. for 6-8 h. After completion of the reaction, the reaction mixture was cooled to 25° C. to 30° C. and quenched with 10 mL of chilled water under stirring at 25° C. to 30° C. The organic layer was separated, and the aqueous layer was washed with 5 mL of toluene. The organic layers were combined and washed with 10 mL of 1N HCl solution, 10 mL of 5% sodium bicarbonate solution and 10 mL of 10% sodium chloride solution. The organic layer was distilled completely to obtain a crude residue, which was purified by column chromatography (silica gel, chloroform-methanol) to yield the title compound.

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