-药物合成数据库

【药物名称】

化学结构式(Chemical Structure):

参考文献No.	483114
标题:	A novel (benzodifuranyl)aminoalkane with extremely potent activity at the 5-HT2A receptor
作者:	Parker, M.A.; Marona-Lewicka, D.; Lucaites, V.L.; Nelson, D.L.; Nichols, D.E.
来源:	J Med Chem 1998,41(26),5148

合成路线图解说明: Alkylation of hydroquinone (I) with 1-bromo-2-chloroethane and K2CO3 in acetone gave the bis(2-chloroethyl)ether (II), which was then brominated in the presence of Fe in CCl4 to provide dibromocompound (III). Lithiation, followed by intramolecular cyclization, upon treatment with two equivalents of n-BuLi in THF at 0 C furnished the tetrahydrobenzodifuran (IV). Subsequent formylation with dichloromethyl methyl ether in the presence of SnCl4 yielded aldehyde (V). This was condensed with nitroethane in the presence of ammonium acetate, and the resulting nitropropene compound (VI) was reduced with LiAlH4 to afford the aminopropane (VII). Protection of (VII) with trifluoroacetic anhydride and Et3N gave trifluoroacetamide (VIII), and then bromination in AcOH afforded bromide (IX). The aromatic benzodifuran (X) was obtained by dihydrogenation with dichlorodicyanobenzoquinone (DDQ) in toluene, and finally, the amide was deprotected by hydrolysis with NaOH to afford the target amine, which was isolated as the hydrochloride salt.

参考文献No.	579437
标题:	Dihydrobenzofuran analogues of hallucinogens. 3. Models of 4-substituted (2,5-dimethoxyphenyl)alkylamine derivatives with rigidified methoxy groups
作者:	Monte, A. P.; Marona-Lewicka, D.; Parker, M.A.; Wainscott, D.B.; Nelson, D.L.; Nichols, D.E.
来源:	J Med Chem 1996,39(15),2953-2961

合成路线图解说明: Alkylation of hydroquinone (I) with 1-bromo-2-chloroethane and K2CO3 in acetone gave the bis(2-chloroethyl)ether (II), which was then brominated in the presence of Fe in CCl4 to provide dibromocompound (III). Lithiation, followed by intramolecular cyclization, upon treatment with two equivalents of n-BuLi in THF at 0 C furnished the tetrahydrobenzodifuran (IV). Subsequent formylation with dichloromethyl methyl ether in the presence of SnCl4 yielded aldehyde (V). This was condensed with nitroethane in the presence of ammonium acetate, and the resulting nitropropene compound (VI) was reduced with LiAlH4 to afford the aminopropane (VII). Protection of (VII) with trifluoroacetic anhydride and Et3N gave trifluoroacetamide (VIII), and then bromination in AcOH afforded bromide (IX). The aromatic benzodifuran (X) was obtained by dihydrogenation with dichlorodicyanobenzoquinone (DDQ) in toluene, and finally, the amide was deprotected by hydrolysis with NaOH to afford the target amine, which was isolated as the hydrochloride salt.