A practical synthesis of multitargeted antifolate LY231514
A practical synthesis of multitargeted antifolate LY231514
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DOI：
10.1021/op9802172
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发表时间：
1999-05-01
影响因子：
3.4
通讯作者：
Kobierski, ME
中科院分区：
文献类型：
--
作者：
Barnett, CJ;Wilson, TM;Kobierski, ME
报道了一种新型吡咯并[2，3-d]嘧啶类抗肿瘤药物LY 231514（1）的合成方法。2-溴-4-芳基丁醛9与2，4-二氨基-6-羟基嘧啶（10）的反应以良好的产率区域选择性地提供了代表药物核心结构的吡咯并[2，3-d]嘧啶11。通过常规方法同化谷氨酸残基完成合成。优化合成路线的开发强调避免分离相对不稳定的醛和溴醛中间体。
A concise and scalable synthesis of LY231514 (1), a new pyrrolo[2,3-d]pyrimidine-based antitumor agent, is presented. Reaction of 2-bromo-4-arylbutanal 9 with 2,4-diamino-6-hydroxypyrimidine (10) regioselectively provided pyrrolo[2,3-d] pyrimidine 11, representing the core structure of the drug, in good yield. Assimilation of the glutamic acid residue by conventional means completed the synthesis. Development of the optimized synthetic route emphasized avoiding isolation of the relatively unstable aldehyde and bromoaldehyde intermediates.