KW-7158

Chemical Name: 3,3,3-Trifluoro-2-hydroxy-2-methyl-N-(10-oxo-4,10-dihydrothieno[3,2-c][1]benzothiepin-9-yl)propanamide 5,5-dioxide
CAS No. 214763-95-8
项目整合开发状态: Phase II
项目研究机构: Kyowa Hakko (Originator)
合成路线:Alkylation of 3-aminothiophenol (II) with methyl 3-(bromomethyl)thiophene-2-carboxylate (I) provides thioether (III).After protection of the amino group of (III) as the corresponding acetamide (IV),its methyl ester group is hydrolyzed under alkaline conditions,to provide the carboxylic acid (V).Activation of acid (V) with trifluoroacetic anhydride,followed by cyclization in the presence of boron trifluoride etherate gives rise to a mixture of regioisomeric thienobenzothiepinones (VI) and (VII),which are separated by column chromatography.Acidic hydrolysis of the desired isomer (VII) provides amine (VIII).Acid chloride (X),prepared by chlorination of 3,3,3-trifluoro-2-hydroxy-2-methylpropanoic acid (IX),is then condensed with amine (VIII) to furnish amide (XI).Finally,oxidation of the sulfide group of (XI) to the title sulfone is accomplished by treatment with m-chloroperbenzoic acid