新产品编号:87519
Chemical Name: 2-[3-[4-(3-Chlorophenyl)-2(S)-methylpiperazinyl]propyl]-1,2,4-triazolo[4,3-a]pyridin-3(2H)-one L-(+)-tartrate
CAS No. 161968-03-2, 161905-64-2 (free base), 161968-06-5 (maleate salt (1:1)), 161968-05-4 (sulfate(1:1))
项目整合开发状态: Preclinical
项目研究机构: Angelini (Originator)
合成路线:The reaction of 3-chloroaniline (I) with ethanolamine (II) by means of 47% HBr by heating at 170 C gives N-(3-chlorophenyl)ethylenediamine (III),which is condensed with ethyl 2-bromopropionate (IV) by means of triethylamine in refluxing toluene yielding the alanine derivative (V).The cyclization of (V) with refluxing 2N HCl affords the piperazinone (VI),which is reduced with LiAlH4 in ethyl ether providing 1-(3-chlorophenyl)-3-methylpiperazine (VII).The alkylation of (VII) with 1-bromo-3-chloropropane (VIII) by means of NaOH in acetone/water gives 4-(3-chlorophenyl)-1-(3-chloropropyl)-2-methylpiperazine (IX),which is condensed with the sodium salt of 1,2,4-triazolo[4,3-a]pyridin-3(2H)-one (X) in refluxing xylene/isobutanol yielding the target compound as a racemic mixture (XI).Finally,this compound is submitted to optical resolution with L-(+)-tartaric acid (XII).
📌 参考资料/链接：
参考文献标题:Pharmacologically active enantiomers
文献作者:Baiocchi,L.; Cioli,V.(Angelini Group)
参考来源:EP 0707587; JP 1996512036; WO 9501354
📄 详细内容
合成路线:The reaction of 3-chloroaniline (I) with ethanolamine (II) by means of 47% HBr by heating at 170 C gives N-(3-chlorophenyl)ethylenediamine (III),which is condensed with ethyl 2-bromopropionate (IV) by means of triethylamine in refluxing toluene yielding the alanine derivative (V).The cyclization of (V) with refluxing 2N HCl affords the piperazinone (VI),which is reduced with LiAlH4 in ethyl ether providing 1-(3-chlorophenyl)-3-methylpiperazine (VII).The alkylation of (VII) with 1-bromo-3-chloropropane (VIII) by means of NaOH in acetone/water gives 4-(3-chlorophenyl)-1-(3-chloropropyl)-2-methylpiperazine (IX),which is condensed with the sodium salt of 1,2,4-triazolo[4,3-a]pyridin-3(2H)-one (X) in refluxing xylene/isobutanol yielding the target compound as a racemic mixture (XI).Finally,this compound is submitted to optical resolution with L-(+)-tartaric acid (XII).
参考文献标题:Effect of modifications of the alkylpiperazine moiety of trazodone on 5HT2A and alpha1 receptor binding affinity
文献作者:Giannangeli,M.; Gazzolla,N.; Luparini,M.R.; Magnani,M.; Mabilia,M.; Picconi,G.; Tomaselli,M.; Baiocchi,L.
参考来源:J Med Chem 1999,42(3),336
产品链接: CAS No.161905-64-2››