ALX-0501
Chemical Name: 3-[2-(Dimethylamino)ethyl]-5-(5-methyl-2-thienyl)-1H-indole
CAS No. 199659-02-4
项目整合开发状态: Preclinical
项目研究机构: NPS Allelix (Originator)
合成路线:Condensation of 5-bromoindole (I) with oxalyl chloride produced (5-bromo-3-indolyl)glyoxyl chloride (II),which was subsequently treated with dimethylamine to give amide (III).Conversion of (III) to the tributylstannyl derivative (IV) was achieved by reaction with hexabutylditin in the presence of tetrakis(triphenylphosphine) palladium in refluxing dimethoxyethane.Palladium-catalyzed coupling of stannyl indole (IV) with 5-bromo-2-thiophenecarboxaldehyde (V) furnished the thienyl indole (VI).Finally,reduction of (VI) with LiAlH4 in boiling THF produced a mixture of the desired 5-methylthiophene derivative along with the 5-(hydroxymethyl) analogue (VII),that were separated by column chromatography.
📌 参考资料/链接：
参考文献标题:Thiophene- and furan-tryptamine derivs.
文献作者:Meng,Q.; Slassi,A.; Rakhit,S.(NPS Allelix Corp.)
参考来源:WO 9743281
📄 详细内容
合成路线:Condensation of 5-bromoindole (I) with oxalyl chloride produced (5-bromo-3-indolyl)glyoxyl chloride (II),which was subsequently treated with dimethylamine to give amide (III).Conversion of (III) to the tributylstannyl derivative (IV) was achieved by reaction with hexabutylditin in the presence of tetrakis(triphenylphosphine) palladium in refluxing dimethoxyethane.Palladium-catalyzed coupling of stannyl indole (IV) with 5-bromo-2-thiophenecarboxaldehyde (V) furnished the thienyl indole (VI).Finally,reduction of (VI) with LiAlH4 in boiling THF produced a mixture of the desired 5-methylthiophene derivative along with the 5-(hydroxymethyl) analogue (VII),that were separated by column chromatography.
参考文献标题:5-Thienyltryptamine derivatives as serotonin 5-HT1B/1D receptor agonists: Potential treatments for migraine
文献作者:Meng,C.Q.; Rakhit,S.; Lee,D.K.H.; Kamboj,R.; McCallum,K.L.; Mazzocco,L.; Dyne,K.; Slassi,A.
参考来源:Bioorg Med Chem Lett 2000,10(9),903