KB-130015
{2,6-二碘-4-[(2-甲基-1-苯并呋喃-3-基)甲基]苯氧基}乙酸Chemical Name: 2-[2,6-Diiodo-4-(2-methyl-1-benzofuran-3-ylmethyl)phenoxy]acetic acid
CAS No. 147030-48-6
项目整合开发状态: Preclinical
项目研究机构: Karo Bio (Originator)
合成路线:Friedel-Crafts acylation of 2-methylbenzofuran (I) with p-anisoyl chloride (II) in the presence of SnCl4 afforded the benzoyl benzofuran derivative (III).Ketone (III) reduction to the corresponding benzyl benzofuran (IV) was accomplished employing either LiAlH4 or NaBH4 and ZnI2.The methyl ether group of (IV) was then cleaved with melted pyridine hydrochloride to give phenol (V).Aromatic iodination of (V) with either I2/KI or with ICl in morpholine led to the diiodo phenol (VI).This was then alkylated with ethyl bromoacetate (VII) to furnish ester (VIII),which was finally hydrolyzed with NaOH to the target carboxylic acid.
📌 参考资料/链接：
参考文献标题:Receptor ligands
文献作者:Norinder,U.; Bajorath,J.; Stearns,J.F.(Karo Bio AB)
参考来源:WO 9220331
📄 详细内容
合成路线:Friedel-Crafts acylation of 2-methylbenzofuran (I) with p-anisoyl chloride (II) in the presence of SnCl4 afforded the benzoyl benzofuran derivative (III).Ketone (III) reduction to the corresponding benzyl benzofuran (IV) was accomplished employing either LiAlH4 or NaBH4 and ZnI2.The methyl ether group of (IV) was then cleaved with melted pyridine hydrochloride to give phenol (V).Aromatic iodination of (V) with either I2/KI or with ICl in morpholine led to the diiodo phenol (VI).This was then alkylated with ethyl bromoacetate (VII) to furnish ester (VIII),which was finally hydrolyzed with NaOH to the target carboxylic acid.
参考文献标题:Synthesis and preliminary characterization of a novel antiarrhythmic compound (KB130015) with an improved toxicity profile compared with amiodarone
文献作者:Carlsson,B.; Singh,B.N.; Temciuc,M.; Nilsson,S.; Li,Y.-L.; Mellin,C.; Malm,J.
参考来源:J Med Chem 2002,45(3),623
产品链接: CAS No. 147030-48-6››