Development of a Practical Synthesis of a Functionalized Pyrrolo[2,1-f][1,2,4]triazine Nucleus

详细信息    查看全文

• 作者：Bin Zheng ; David A. Conlon ; R. Michael Corbett ; Melissa Chau ; Dau-Ming Hsieh ; Agnes Yeboah ; Daniel Hsieh ; Jale M眉slehiddino臒lu ; William P. Gallagher ; Jeffrey N. Simon ; Justin Burt
• 刊名：Organic Process Research & Development
• 出版年：2012
• 出版时间：November 16, 2012
• 年：2012
• 卷：16
• 期：11
• 页码：1846-1853
• 全文大小：330K
• 年卷期：v.16,no.11(November 16, 2012)
• ISSN：1520-586X

文摘

Functionalized pyrrolotriazine 1b is a key heterocyclic building block in the synthesis of BMS-690514, a potent anticancer agent. Described herein are our development activities that led to the efficient preparation of 1b on a large scale. The key transformations include a selective C-alkylation of an oxalacetate salt with a hydrazonyl bromide to form a 2-hydrazonoethyl-3-oxosuccinate, followed by cyclodehydration to an aminopyrrole. Subsequent deprotection and condensation with formamidine afforded the pyrrolotriazine scaffold. Further elaboration of this core provided the desired pyrrolotriazinyl amine.