新产品编号:1378431
Chemical Name: 3-[4-(3-Cyclopentyloxy-4-methoxyphenyl)-2-oxopyrrolidin-1-yl]-5-(3-methoxybenzyloxy)-N2,N2-dimethylbenzohydrazide
项目整合开发状态: Preclinical
项目研究机构: Novartis (Originator)
合成路线:Methyl 5-hydroxy-3-iodobenzoate (I) was protected as the benzyl ether (II).Subsequent coupling of (II) with rolipram (III) in the presence of K2CO3 and copper catalyst afforded the N-aryl derivative (IV),which was debenzylated by hydrogenation over Pd/C.The resulting phenol (V) was alkylated with 3-methoxybenzyl chloride (VI) to provide ether (VII).Further basic hydrolysis of the methyl ester of (VII) yielded the corresponding carboxylic acid (VIII).This was finally coupled with N,N-dimethylhydrazine by means of EDC and HOBt to furnish the target hydrazide.
合成路线:Methyl 5-hydroxy-3-iodobenzoate (I) was protected as the benzyl ether (II).Subsequent coupling of (II) with rolipram (III) in the presence of K2CO3 and copper catalyst afforded the N-aryl derivative (IV),which was debenzylated by hydrogenation over Pd/C.The resulting phenol (V) was alkylated with 3-methoxybenzyl chloride (VI) to provide ether (VII).Finally,basic hydrolysis of the methyl ester of (VII) furnished the corresponding carboxylic acid.
📌 参考资料/链接：
参考文献标题:N-Arylrolipram derivatives as potent and selective PDE4 inhibitors
文献作者:Bacher,E.; Boer,C.; Bray-French,K.; Demnitz,F.W.; Keller,T.H.; Mazzoni,L.; M黮ler,T.; Walker,C.
参考来源:Bioorg Med Chem Lett 1998,8(22),3229
📄 详细内容
合成路线:Methyl 5-hydroxy-3-iodobenzoate (I) was protected as the benzyl ether (II).Subsequent coupling of (II) with rolipram (III) in the presence of K2CO3 and copper catalyst afforded the N-aryl derivative (IV),which was debenzylated by hydrogenation over Pd/C.The resulting phenol (V) was alkylated with 3-methoxybenzyl chloride (VI) to provide ether (VII).Further basic hydrolysis of the methyl ester of (VII) yielded the corresponding carboxylic acid (VIII).This was finally coupled with N,N-dimethylhydrazine by means of EDC and HOBt to furnish the target hydrazide.
参考文献标题:Synthesis and structure-activity relationship of N-arylrolipram derivatives as inhibitors of PDE4 isozymes
文献作者:Keller,T.H.; Bray-French,K.; Demnitz,F.W.; Muller,T.H.; Pombo-Villar,E.; Walker,C.
参考来源:Chem Pharm Bull 2001,49(8),1009