Dimethylformamide → 4-(3-{(5-Fluoro-8-methoxychroman-6-yl)-[4-(5-trifluoromethyl-[1,2,4]oxadiazol-3-yl)phenylamino]methyl}-5-oxo-4,5-dihydro-[1,2,4]triazol-1-yl)thiazole-5-carboxylic acid ethyl ester

Participants

Reaction Conditions

Reaction Steps

To 4 ml of a DMF solution containing 111 mg of [2-(5-fluoro-8-methoxychroman-6-yl)-2-[4-(5-trifluoromethyl-[1,2,4]oxadiazol-3-yl)phenylimino]-1-methylsulfanylethylidene]carbamic acid methyl ester (Example (189a)), 37 mg of 4-hydrazinothiazole-5-carboxylic acid ethyl ester (Example (185c)) and 0.031 ml of triethylamine were added. The resulting mixture was stirred at 85° C. for 20 hours under a nitrogen atmosphere. The reaction mixture was concentrated. The residue was dissolved in 4 ml of methanol and 0.032 ml of acetic acid, and then 83 mg of sodium cyanotrihydroborate was added thereto. The mixture was stirred at room temperature for 15 hours, and then 100 ml of ethyl acetate and 50 ml of water were added thereto. The organic layer was washed with 50 ml of water and then with 50 ml of saturated brine and was dried over anhydrous magnesium sulfate. The desiccating agent was removed by filtration, and the filtrate was concentrated under reduced pressure. The residue was purified by NAM silica gel column chromatography (methanol-ethyl acetate) to give the title compound (74 mg).

Provenance & Evidence