Triethylamine → 3-(3-{(3,4-Dimethoxyphenyl)-[4-(5-methyl-[1,2,4]oxadiazol-3-yl)phenylamino]methyl}-5-oxo-4,5-dihydro-[1,2,4]triazol-1-yl)thiophene-2-carboxylic acid

Participants

Reaction Conditions

Reaction Steps

After adding 30 mg of 3-hydrazinothiophene-2-carboxylic acid methyl ester and 25 μl of triethylamine to a solution of 80 mg of {2-(3,4-dimethoxyphenyl)-2-[4-(5-methyl-[1,2,4]oxadiazol-3-yl)phenylimino]-1-methylsulfanylethylidene}carbamic acid methyl ester (Example (36d)) in 3 ml of DMF, the mixture was stirred at 85° C. for 18 hours under a nitrogen atmosphere. The reaction mixture was concentrated, and the residue was dissolved in 2 ml of methanol and 2 ml of THF. After adding 35 μl of acetic acid and 56 mg of sodium cyanotrihydroborate to the solution, the mixture was stirred at room temperature for 15 hours. Next, 2 ml of an aqueous 1N sodium hydroxide solution was added to the reaction mixture, and stirring was continued at room temperature for 2 hours. After adding 2 ml of 1N hydrochloric acid to the reaction mixture, extraction was performed with ethyl acetate. The organic layer was washed with saturated brine and dried over anhydrous magnesium sulfate. The desiccating agent was filtered off and the filtrate was concentrated under reduced pressure. The residue was purified by NAM silica gel column chromatography (methanol-ethyl acetate) to give 70 mg of 3-(3-{(3,4-dimethoxyphenyl)-[4-(5-methyl-[1,2,4]oxadiazol-3-yl)phenylamino]methyl}-5-oxo-4,5-dihydro-[1,2,4]triazol-1-yl)thiophene-2-carboxylic acid.

Provenance & Evidence