FR-194738
Chemical Name: (E)-N-(6,6-Dimethylhept-2-en-4-ynyl)-N-ethyl-N-[3-[2-methyl-2-(thien-3-ylmethoxy)propoxy]benzyl]amine hydrochloride
CAS No. 204067-52-7, 204067-45-8 (free base), 204067-51-6 (oxalate)
项目整合开发状态: Preclinical
项目研究机构: Fujisawa (Originator)
合成路线:Ethyl 2-(3-formylphenoxy)acetate (III) was prepared by alkylation of 3-hydroxybenzaldehyde (I) with ethyl bromoacetate (II) in the presence of K2CO3 and KI.Reduction of aldehyde (III) with NaBH4 provided the benzyl alcohol (IV),which was further protected as the silyl ether (V) by treatment with tert-butyldimethylsilyl chloride and imidazole.Addition of methylmagnesium bromide to the ester function of (V) yielded the tertiary alcohol (VI).Condensation of the sodium alkoxide of (VI) with 3-(bromomethyl)thiophene (VII) furnished ether (VIII).After desilylation of (VIII) employing tetrabutylammonium fluoride,the resultant benzyl alcohol (IX) was treated with methanesulfonyl chloride and triethylamine to afford mesylate (X).Alkylation of amine (XI) with mesylate (X) furnished the target tertiary amine,which was finally treated with HCl in EtOAc to afford the corresponding hydrochloride salt.
📌 参考资料/链接：
参考文献标题:Substd.amine derivs.
文献作者:Okumura,H.; Washizuka,K.; Fujii,N.; Takasugi,H.(Fujisawa Pharmaceutical Co.,Ltd.)
参考来源:JP 2000517314; WO 9808838
📄 详细内容
合成路线:Ethyl 2-(3-formylphenoxy)acetate (III) was prepared by alkylation of 3-hydroxybenzaldehyde (I) with ethyl bromoacetate (II) in the presence of K2CO3 and KI.Reduction of aldehyde (III) with NaBH4 provided the benzyl alcohol (IV),which was further protected as the silyl ether (V) by treatment with tert-butyldimethylsilyl chloride and imidazole.Addition of methylmagnesium bromide to the ester function of (V) yielded the tertiary alcohol (VI).Condensation of the sodium alkoxide of (VI) with 3-(bromomethyl)thiophene (VII) furnished ether (VIII).After desilylation of (VIII) employing tetrabutylammonium fluoride,the resultant benzyl alcohol (IX) was treated with methanesulfonyl chloride and triethylamine to afford mesylate (X).Alkylation of amine (XI) with mesylate (X) furnished the target tertiary amine,which was finally treated with HCl in EtOAc to afford the corresponding hydrochloride salt.
参考文献标题:Synthesis and biological activity of a novel squalene epoxidase inhibitor,FR194738
文献作者:Sawada,M.; Okumura,H.; Washizuka,K.-I.
参考来源:Bioorg Med Chem Lett 2004,14(3),633
产品链接: CAS No. 204067-52-7›› 产品链接: CAS No.204067-45-8››