【药物名称】KB-130015
化学结构式(Chemical Structure):
参考文献No.53173
标题:Receptor ligands
作者:Norinder, U.; Bajorath, J.; Stearns, J.F. (Karo Bio AB)
来源:WO 9220331
合成路线图解说明:

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No.649686
标题:Synthesis and preliminary characterization of a novel antiarrhythmic compound (KB130015) with an improved toxicity profile compared with amiodarone
作者:Carlsson, B.; Singh, B.N.; Temciuc, M.; Nilsson, S.; Li, Y.-L.; Mellin, C.; Malm, J.
来源:J Med Chem 2002,45(3),623
合成路线图解说明:

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.

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