Jie Xu, Ngiap-Kie Lim, Jacob C. Timmerman, Jeff Shen, Kyle Clagg, Ugo Orcel, Raphael Bigler, Etienne Trachsel, Roland Meier, Nicholas A. White, Johannes A. Burkhard, Lauren E. Sirois, Qingping Tian, Remy Angelaud, Stephan Bachmann*, Haiming Zhang* and Francis Gosselin,
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引用次数: 6
Abstract
A chromatography-free asymmetric synthesis of GDC-6036 (1) was achieved via a highly atroposelective Negishi coupling of aminopyridine 5 and quinazoline 6b catalyzed by 0.5 mol % [Pd(cin)Cl]2 and 1 mol % (R,R)-Chiraphite to afford the key intermediate (Ra)-3. An alkoxylation of (Ra)-3 with (S)-N-methylprolinol (4) and a global deprotection generates the penultimate heterobiaryl intermediate 2. A controlled acrylamide installation by stepwise acylation/sulfone elimination and final adipate salt formation and crystallization delivered high-purity GDC-6036 (1).
期刊介绍：
Organic Letters invites original reports of fundamental research in all branches of the theory and practice of organic, physical organic, organometallic,medicinal, and bioorganic chemistry. Organic Letters provides rapid disclosure of the key elements of significant studies that are of interest to a large portion of the organic community. In selecting manuscripts for publication, the Editors place emphasis on the originality, quality and wide interest of the work. Authors should provide enough background information to place the new disclosure in context and to justify the rapid publication format. Back-to-back Letters will be considered. Full details should be reserved for an Article, which should appear in due course.
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