Development and Scale-Up of a Copper-Catalyzed Sulfamidation Coupling Reaction

IF 4.3 3区 材料科学 Q1 ENGINEERING, ELECTRICAL & ELECTRONIC
Neil K. Adlington*, Paul S. Siedlecki, Ian Derrick, Simon D. Yates, Andrew D. Campbell, Paula Tomlin and Thomas Langer, 
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引用次数: 1

Abstract

The plant-scale manufacture of AZD5069 involved the assembly of a pyrimidine sulfonamide (AZD5069 MAPI) via Pd-catalyzed coupling of a chloropyrimidine derivative with an azetidinesulfonamide. This step revealed a number of operational and commercial challenges, in particular the difficulty of removing palladium residues to an acceptably low level and the increasingly prohibitive costs of the metal, ligand, and scavenger used. An alternative, copper-catalyzed Ullmann–Goldberg coupling reaction was investigated, developed, and ultimately successfully operated in four pilot plant batches of >50 kg scale.

Abstract Image

铜催化磺化偶联反应的发展与规模化
AZD5069的工厂规模生产涉及通过pd催化氯嘧啶衍生物与氮杂基磺酰胺的偶联组装嘧啶磺酰胺(AZD5069 MAPI)。这一步骤暴露了许多操作和商业上的挑战,特别是难以将钯残留物去除到可接受的低水平,以及金属、配体和所用清除剂的成本越来越高。研究开发了另一种铜催化的Ullmann-Goldberg偶联反应,并最终在四个50公斤规模的中试工厂中成功运行。
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来源期刊
CiteScore
7.20
自引率
4.30%
发文量
567
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