【药物名称】Zanapezil fumarate, TAK-147
化学结构式(Chemical Structure):
参考文献No.17841
标题:Condensed heterocyclic cpds., their production and use
作者:Goto, G.; Ishihara, Y.; Miyamoto, M. (Takeda Chemical Industries, Ltd.)
来源:EP 0487071; US 5273974
合成路线图解说明:

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No.273710
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
作者:Ishihara, Y.; Hirai, K.; Miyamoto, M.; Goto, G.
来源:J Med Chem 1994,37(15),2292-9
合成路线图解说明:

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No.290296
标题:TAK-147
作者:Mealy, N.; Rabasseda, X.; Casta馿r, J.
来源:Drugs Fut 1995,20(3),248
合成路线图解说明:

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.

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