Park Cheol-Min
Cancer Research, Global Pharmaceutical R&D, Abbott Laboratories, 100 Abbott Park Rd., Abbott Park, Illinois 60064, USA.
J Org Chem. 2006 Jan 6;71(1):413-5. doi: 10.1021/jo051982z.
[reaction: see text] The basicity of an amine has a great impact on physicochemical properties and pharmacokinetics. To attenuate the basicity of morpholine, a bicyclic amine was designed and synthesized with the introduction of an additional beta-oxygen. A transannular cyclization and reduction of a bridgehead alpha-chloro amine functionality produces the topographically unusual amine (pKa = 6.7) in good yield.
[反应:见正文] 胺的碱性对物理化学性质和药代动力学有很大影响。为了减弱吗啉的碱性,设计并合成了一种双环胺,引入了一个额外的β-氧原子。桥头α-氯胺官能团的跨环环化和还原以良好的产率生成了拓扑结构不寻常的胺(pKa = 6.7)。