FR-62732, FR-062732
Chemical Name: 3-(4-Aminopiperazin-1-ylcarbonylmethyl)-5-chlorobenzothiazolin-2-one hydrochloride
项目整合开发状态: Preclinical
项目研究机构: Fujisawa (Originator)
合成路线:This compound has been obtained by two related ways:1) The saponification of 2-(5-chloro-2-oxobenzothiazolin-3-yl)acetic acid methyl ester (I) with NaOH in methanol/water gives the corresponding free acid (II),which is condensed with piperazine (III) by means of TiCl4 in THF yielding the acyl piperazine (IV).The nitrosation of (IV) with isoamyl nitrite in dichloromethane affords the N-nitrosopiperazine (V),which is finally reduced with Zn and acetic acid to the target amino derivative.2) The nitrosation of piperazine (III) with NaNO2 and acetic acid gives 1-nitrosopiperazine (VI),which is reduced with Zn and acetic acid to 1-aminopiperazine (VII).The reaction of (VII) with benzaldehyde affords 1-(benzylideneamino)piperazine (VIII),which is condensed with of 2-(5-chloro-2-oxobenzothiazolin-3-yl)acetic acid (II) by means of SOCl2 and triethylamine in dichloromethane yielding the acyl piperazine (IX).Finally,this compound is debenzylated with hydroxylamine and HCl in acetonitrile/water.
📌 参考资料/链接：
参考文献标题:N-Containing fused heterocyclic cpds.,processes for the preparation thereof and pharmaceutical compsn.comprising the same
文献作者:Matsuo,M.; Nakaguchi,O.; Okumura,H.; Tsuji,K.; Ueda,I.(Fujisawa Pharmaceutical Co.,Ltd.)
参考来源:EP 0232740; JP 1987181253; US 4797399
📄 详细内容
合成路线:This compound has been obtained by two related ways:1) The saponification of 2-(5-chloro-2-oxobenzothiazolin-3-yl)acetic acid methyl ester (I) with NaOH in methanol/water gives the corresponding free acid (II),which is condensed with piperazine (III) by means of TiCl4 in THF yielding the acyl piperazine (IV).The nitrosation of (IV) with isoamyl nitrite in dichloromethane affords the N-nitrosopiperazine (V),which is finally reduced with Zn and acetic acid to the target amino derivative.2) The nitrosation of piperazine (III) with NaNO2 and acetic acid gives 1-nitrosopiperazine (VI),which is reduced with Zn and acetic acid to 1-aminopiperazine (VII).The reaction of (VII) with benzaldehyde affords 1-(benzylideneamino)piperazine (VIII),which is condensed with of 2-(5-chloro-2-oxobenzothiazolin-3-yl)acetic acid (II) by means of SOCl2 and triethylamine in dichloromethane yielding the acyl piperazine (IX).Finally,this compound is debenzylated with hydroxylamine and HCl in acetonitrile/water.
参考文献标题:Process development of a platelet aggregation inhibitor
文献作者:Zanka,A.; et al.
参考来源:Org Process Res Dev 1998,2(6),418