利伐沙班中间体4-(4-氨基苯基)-3-吗啉酮的合成
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摘要
目的改进利伐沙班关键中间体4-(4-氨基苯基)-3-吗琳酮(Ⅰ)的合成方法。方法经与溴苯偶联、硝化、还原快速合成4-(4-氨基苯基)-3-吗啉酮。结果结合构建吗啉酮的环合反应,根据WO2006/63113等专利的相关报道,在溶剂二氧六环回流温度下对反应时间进行选择,选定最佳反应时间为2h,收率达到64.8%。结论该合成方法具有步骤少,绿色环保,具有良好工业前景等优点。
引文
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[4]Xing,Junhao;Yang,Lingyun,et al,Identification of anthranilamide derivatives as potential factor Xa inhibitors:Drug design,synthesis and biological evaluation[J].European Journal of Medicinal Chemistry,2015,95:388-399.
[5]Glickman S A,Easton,Schultz H S,et al.Preparation of N-substituted-3-morpho-lones[P].US:3092630,1963-06-04.
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