摘要
以1-Boc-3-氮杂环丁酮和甲基三苯基溴化磷为起始原料,经Wittig反应、加成环化、脱卤、羰基还原、成醚、哌嗪取代、苯甲酸甲酯衍生物取代、水解、磺胺缩合、脱Boc和四氢吡喃取代反应,合成了一个新型的含四元螺环胺四氢吡喃结构的磺胺类Venetoclax衍生物,总产率22%,其结构经~1H NMR和HR-MS(ESI)表征。
A novel sulfanilamide Venetoclax derivative containing a four-membered spirocycle amine tetrahydropyran moiety, with total yield of 22%, was synthesized by an eleven-step route of wittig reaction, addition cyclization, dehalogenation, carbonyl reduction, etherification, piperazine substitution, methyl benzoate derivative substitution, hydrolysis reaction, sulfanilamide condensation, deprotection of Boc group and tetrahydropyran substitution using 1-N-Boc-3-azetidinone and methyltriphenylphosphonium bromide as starting materials. The structure was characterized by ~1H NMR and HR-MS(ESI).
引文
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