S-19812

Chemical Name: 4-[4,5-Bis(4-methoxyphenyl)thien-2-yl]-N-hydroxy-N-methylbutyramide
CAS No. 181308-68-9
项目整合开发状态: Preclinical
项目研究机构: Servier (Originator)
合成路线:Condensation of (4-methoxyphenyl)acetic acid (I) with anisole (II) in hot PPA produced ketone (III).Subsequent treatment of (III) with the Vilsmeier reagent afforded chloroaldehyde (IV).The required thiophene (VI) was then obtained by cyclization with ethyl mercaptoacetate (V) in the presence of NaOEt.After basic hydrolysis of the ester group of (VI),the resulting acid (VII) was decarboxylated by means of copper in quinoline at 180 C,yielding thiophene (VIII).Stannic chloride-promoted Friedel-Crafts acylation of (VIII) with 3-(methoxycarbonyl)propionyl chloride (IX) gave ketoester (X).The keto group of (X) was further reduced employing triethylsilane in trifluoroacetic acid to afford (XI).Hydrolysis of the methyl ester of (XI),followed by treatment with oxalyl chloride furnished acid chloride (XII).The title hydroxamic acid was then obtained by coupling of (XII) with O-(tert-butyldimethylsilyl)-N-methylhydroxylamine and subsequent acid-catalyzed desilylation.