网站主页>>>项目整合精选>>>项目整合精选>>>Zanapezil fumarate, TAK-147

Zanapezil fumarate, TAK-147

扎那哌齐Chemical Name: 8-[3-(1-Benzylpiperidin-4-yl)propanoyl]-2,3,4,5-tetrahydro-1H-1-benzazepine fumarate; 3-(1-Benzylpiperidin-4-yl)-1-(2,3,4,5-tetrahydro-1H-1-benzazepin-8-yl)-1-propanone fumarate
CAS No. 142852-50-4 (free base), 142852-51-5 (fumarate salt (1:1))
项目整合开发状态: Discontinued
项目研究机构: Takeda (Originator)
合成路线:The Friedel-Crafts condensation of 1-acetyl-2,3,4,5-tetrahydro-1H-1-benzazepine (I) with 3-(1-acetylpiperidin-4-yl)propionyl chloride (II) by means of AlCl3 in 1,2-dichloroethane gives 3-(1-acetylpiperidin-4-yl)-1-(1-acetyl-2,3,4,5-tetrahydro-1H-1-benzazepin-8-yl)-1-propanone (III),which is deacetylated in refluxing concentrated aqueous HCl yielding 3-(piperidin-4-yl)-1-(2,3,4,5-tetrahydro-1H-1-benzazepin-8-yl)-1-propanone (IV).Finally,this compound is benzylated with benzyl bromide (V) and K2CO3 in ethanol affording the final product as free base,which is then treated with fumaric acid in MeOH/CH2Cl2.
📌 参考资料/链接:
参考文献标题:Condensed heterocyclic cpds.,their production and use
文献作者:Goto,G.; Ishihara,Y.; Miyamoto,M.(Takeda Chemical Industries,Ltd.)
参考来源:EP 0487071; US 5273974

📄 详细内容


合成路线:The Friedel-Crafts condensation of 1-acetyl-2,3,4,5-tetrahydro-1H-1-benzazepine (I) with 3-(1-acetylpiperidin-4-yl)propionyl chloride (II) by means of AlCl3 in 1,2-dichloroethane gives 3-(1-acetylpiperidin-4-yl)-1-(1-acetyl-2,3,4,5-tetrahydro-1H-1-benzazepin-8-yl)-1-propanone (III),which is deacetylated in refluxing concentrated aqueous HCl yielding 3-(piperidin-4-yl)-1-(2,3,4,5-tetrahydro-1H-1-benzazepin-8-yl)-1-propanone (IV).Finally,this compound is benzylated with benzyl bromide (V) and K2CO3 in ethanol affording the final product as free base,which is then treated with fumaric acid in MeOH/CH2Cl2.

参考文献标题:Central cholinergic agents.6.Synthesis and evaluation of 3-[1-(phenylmethyl)-4-piperidinyl]-1-(2,3,4,5-tetrahydro-1H-1-benzazepin-8-yl)-1-propanones and their analogs as central selective acetylcholinesterase inhibitors
文献作者:Ishihara,Y.; Hirai,K.; Miyamoto,M.; Goto,G.
参考来源:J Med Chem 1994,37(15),2292-9


合成路线:The Friedel-Crafts condensation of 1-acetyl-2,3,4,5-tetrahydro-1H-1-benzazepine (I) with 3-(1-acetylpiperidin-4-yl)propionyl chloride (II) by means of AlCl3 in 1,2-dichloroethane gives 3-(1-acetylpiperidin-4-yl)-1-(1-acetyl-2,3,4,5-tetrahydro-1H-1-benzazepin-8-yl)-1-propanone (III),which is deacetylated in refluxing concentrated aqueous HCl yielding 3-(piperidin-4-yl)-1-(2,3,4,5-tetrahydro-1H-1-benzazepin-8-yl)-1-propanone (IV).Finally,this compound is benzylated with benzyl bromide (V) and K2CO3 in ethanol affording the final product as free base,which is then treated with fumaric acid in MeOH/CH2Cl2.
参考文献标题:TAK-147
文献作者:Mealy,N.; Rabasseda,X.; Castar,J.
参考来源:Drugs Fut 1995,20(3),248


产品链接: CAS No. 142852-50-4››

产品链接: CAS No.142852-51-5››