FR-59960, FK-960

Chemical Name: N-(4-Acetyl-1-piperazinyl)-4-fluorobenzamide monohydrate
CAS No. 133920-70-4 (anhydrous)
项目整合开发状态: Phase II
项目研究机构: Fujisawa (Originator)
合成路线:This compound can be obtained by two different ways:1) The acetylation of 1-nitrosopiperazine (I) with acetyl chloride and pyridine in dioxane gives 1-acetyl-4-nitrosopiperazine (II),which is reduced with Zn and acetic acid/water to 1-acetyl-4-aminopiperazine (III).Finally,this compound is acylated with 4-fluorobenzoyl chloride (IV) by means of triethylamine in dichloromethane.2) The nitrosation of piperazine (V) with NaNO2/HCl in water,followed by condensation with benzyloxycarbonyl chloride (VI) by means of NaOH yields 1-(benzyloxycarbonyl)-4-nitrosopiperazine (VII),which is reduced with Zn and acetic acid/water as before to the corresponding amino derivative (VIII).The acylation of (VIII) with 4-fluorobenzoyl chloride and triethylamine in dichloromethane affords N-[4-(benzyloxycarbonyl)piperazin-1-yl]-4-fluorobenzamide (IX),which is deprotected with HBr in acetic acid to yield N-(1-piperazinyl)-4-fluorobenzamide (X).Finally,this compound is acetylated with acetic anhydride/NaOH in water.
📌 参考资料/链接:
参考文献标题:New aminopiperazine derivs
文献作者:Oku,T.; Todo,E.; Yokota,Y.; Kayakiri,H.; Hashimoto,M.(Fujisawa Pharmaceutical Co.,Ltd.)
参考来源:EP 0436734; JP 1991510050; US 5250528; WO 9101979

📄 详细内容


合成路线:This compound can be obtained by two different ways:1) The acetylation of 1-nitrosopiperazine (I) with acetyl chloride and pyridine in dioxane gives 1-acetyl-4-nitrosopiperazine (II),which is reduced with Zn and acetic acid/water to 1-acetyl-4-aminopiperazine (III).Finally,this compound is acylated with 4-fluorobenzoyl chloride (IV) by means of triethylamine in dichloromethane.2) The nitrosation of piperazine (V) with NaNO2/HCl in water,followed by condensation with benzyloxycarbonyl chloride (VI) by means of NaOH yields 1-(benzyloxycarbonyl)-4-nitrosopiperazine (VII),which is reduced with Zn and acetic acid/water as before to the corresponding amino derivative (VIII).The acylation of (VIII) with 4-fluorobenzoyl chloride and triethylamine in dichloromethane affords N-[4-(benzyloxycarbonyl)piperazin-1-yl]-4-fluorobenzamide (IX),which is deprotected with HBr in acetic acid to yield N-(1-piperazinyl)-4-fluorobenzamide (X).Finally,this compound is acetylated with acetic anhydride/NaOH in water.

参考文献标题:Novel intermediate for synthetic use and process for producing aminopiperazine derivs
文献作者:Oku,T.; Kayakiri,H.; Tanaka,H.(Fujisawa Pharmaceutical Co.,Ltd.)
参考来源:WO 9500502


合成路线:This compound can be obtained by two different ways:1) The acetylation of 1-nitrosopiperazine (I) with acetyl chloride and pyridine in dioxane gives 1-acetyl-4-nitrosopiperazine (II),which is reduced with Zn and acetic acid/water to 1-acetyl-4-aminopiperazine (III).Finally,this compound is acylated with 4-fluorobenzoyl chloride (IV) by means of triethylamine in dichloromethane.2) The nitrosation of piperazine (V) with NaNO2/HCl in water,followed by condensation with benzyloxycarbonyl chloride (VI) by means of NaOH yields 1-(benzyloxycarbonyl)-4-nitrosopiperazine (VII),which is reduced with Zn and acetic acid/water as before to the corresponding amino derivative (VIII).The acylation of (VIII) with 4-fluorobenzoyl chloride and triethylamine in dichloromethane affords N-[4-(benzyloxycarbonyl)piperazin-1-yl]-4-fluorobenzamide (IX),which is deprotected with HBr in acetic acid to yield N-(1-piperazinyl)-4-fluorobenzamide (X).Finally,this compound is acetylated with acetic anhydride/NaOH in water.

参考文献标题:FK-960
文献作者:Graul,A.; Tracy,M.; Castar,J.
参考来源:Drugs Fut 1997,22(8),830


合成路线:The reaction of 4-nitrobenzoic acid ethyl ester (I) with 18FK in DMSO at 150 C gives 4-18Fluorobenzoic acid ethyl ester (II),which is hydrolyzed with NaOH to yield the corresponding free acid (III) Finally,this compound is condensed with 4-acetylpiperazine-1-amine (IV) by means of WSC and HOBT in DMF to afford the target labeled compound.Alternatively,4-18Fluorobenzoic acid ethyl ester (II) can also be obtained by reaction ethyl 4-aminobenzoate triflate salt (V) with 18FK in DMSO at 120 C.
参考文献标题:Synthesis of 18F labelled FK960,a candidate anti-dementia drug,and PET studies in conscious monkeys
文献作者:Murakami,Y.; et al.
参考来源:J Label Compd Radiopharm 2002,45(14),1219


产品链接: CAS No. 133920-70-4››