新产品编号:131815
Chemical Name: 4-[3-[3-[3-[4-(2-Ethoxyphenyl)piperazin-1-yl]propoxy]-4-(4-methylbenzyloxy)benzoyl]indol-1-yl]butyric acid potassium salt
CAS No. 173364-91-5
项目整合开发状态: Preclinical
项目研究机构: Zeria (Originator)
合成路线:Title compound was prepared by two synthetic ways.Friedel-Crafts acylation of N-(phenylsulfonyl)indole (II) with acid chloride (I) with concomitant O-debenzylation in the presence of AlCl3 yielded ketone (III).Then,hydroxyl group alkylation of (III) with alpha-bromo-p-xylene (IV) provided p-methylbenzyl ether (V).Subsequent displacement of the chloro group in (IV) by 1-(2-ethoxyphenyl)piperazine (VI) furnished (VII).After hydrolysis of sulfonyl group of (VII) with KOH,the resulting deprotected indole (VIII) was alkylated with ethyl 4-bromobutyrate to give (IX).Finally,hydrolysis of the ethyl ester of (IX) by means of ethanolic KOH provided the title carboxylic acid potassium salt.
合成路线:In a related procedure,dihydroxybenzoyl indole (X) was selectively alkylated at 4-hydroxyl group with alpha-bromo-p-xylene (IV) to provide ether (XI).Further alkylation of (XI) with 1-bromo-3-chloropropane gave (XII).Then,halogen displacement in (XII) by piperazine (VI) furnished the precursor ethyl ester (IX),which was finally hydrolyzed to the target carboxylic acid as above.
📌 参考资料/链接：
参考文献标题:Indole deriv.and medicine containing the same
文献作者:Yoshida,K.; Kurimoto,T.; Takei,M.; Sato,H.(Zeria Pharmaceutical Co.,Ltd.)
参考来源:EP 0753511; US 5760040; WO 9526955
📄 详细内容
合成路线:Title compound was prepared by two synthetic ways.Friedel-Crafts acylation of N-(phenylsulfonyl)indole (II) with acid chloride (I) with concomitant O-debenzylation in the presence of AlCl3 yielded ketone (III).Then,hydroxyl group alkylation of (III) with alpha-bromo-p-xylene (IV) provided p-methylbenzyl ether (V).Subsequent displacement of the chloro group in (IV) by 1-(2-ethoxyphenyl)piperazine (VI) furnished (VII).After hydrolysis of sulfonyl group of (VII) with KOH,the resulting deprotected indole (VIII) was alkylated with ethyl 4-bromobutyrate to give (IX).Finally,hydrolysis of the ethyl ester of (IX) by means of ethanolic KOH provided the title carboxylic acid potassium salt.
合成路线:In a related procedure,dihydroxybenzoyl indole (X) was selectively alkylated at 4-hydroxyl group with alpha-bromo-p-xylene (IV) to provide ether (XI).Further alkylation of (XI) with 1-bromo-3-chloropropane gave (XII).Then,halogen displacement in (XII) by piperazine (VI) furnished the precursor ethyl ester (IX),which was finally hydrolyzed to the target carboxylic acid as above.
参考文献标题:Dual-acting agents with alpha1-adrenoceptor antagonistic and steroid 5 alpha-reductase inhibitory activities.Synthesis and evaluation of arylpiperazine derivatives
文献作者:Sato,H.; Kitagawa,O.; Aida,Y.; Chikazawa,J.; Kurimoto,T.; Takei,M.; Fukuta,Y.; Yoshida,K.
参考来源:Bioorg Med Chem Lett 1999,9(11),1553