Practical Asymmetric Synthesis of RO5114436, a CCR5 Receptor Antagonist

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• 作者：Xiaojun Huang ; Erin O’ ; Brien ; Felicia Thai ; Gary Cooper
• 刊名：Organic Process Research & Development
• 出版年：2010
• 出版时间：May 21, 2010
• 年：2010
• 卷：14
• 期：3
• 页码：592-599
• 全文大小：221K
• 年卷期：v.14,no.3(May 21, 2010)
• ISSN：1520-586X

文摘

A practical asymmetric synthesis of a 3,7-diazabicyclo[3.3.0]octane derivative (1), a representative of a new class of potent CCR5 receptor antagonists, is described. The benzylamine stereogenic center of 1 was introduced by a ruthenium-catalyzed asymmetric reductive amination using (R)-MeOBIPHEP as ligand. Aldehyde 4, prepared by Parikh−Doering oxidation, was used without workup in the reductive amination reaction, which not only simplified the process but also overcame the instability of 4. The 3,7-diazabicyclo[3.3.0]octane core was obtained by a [3 + 2] cycloaddition.