One-Pot, Three-Component Sulfonimidamide Synthesis Exploiting the Sulfinylamine Reagent N-Sulfinyltritylamine, TrNSO
One-Pot, Three-Component Sulfonimidamide Synthesis Exploiting the Sulfinylamine Reagent N-Sulfinyltritylamine, TrNSO
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DOI：
10.1002/anie.201708590
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发表时间：
2017-11-20
影响因子：
16.6
通讯作者：
Willis, Michael C.
中科院分区：
文献类型：
--
作者：
Davies, Thomas Q.;Hall, Adrian;Willis, Michael C.
磺酰亚胺酰胺在药物化学和农业化学中是越来越重要的分子，但它们的制备需要冗长的合成序列，这可能限制了它们的应用。我们描述了一种从广泛使用的有机金属试剂和胺一锅从头合成磺酰亚胺酰胺。这种方便有效的工艺使用稳定的亚磺酰胺试剂N-亚磺酰三苯甲基胺（TrNSO）作为关键，该试剂可在10克规模上一步完成。与从硫醇或其衍生物开始的经典方法相反，我们基于TrNSO的方法有助于将三种反应组分快速组装成各种不同取代的磺酰亚胺，其中包含医学相关部分，包括吡啶和吲哚。制备并评价了含磺酰胺的考克斯-2抑制剂塞来昔布的类似物。
Sulfonimidamides are increasingly important molecules in medicinal chemistry and agrochemistry, but their preparation requires lengthy synthetic sequences, which has likely limited their use. We describe a one-pot denovo synthesis of sulfonimidamides from widely available organometallic reagents and amines. This convenient and efficient process uses a stable sulfinylamine reagent, N-sulfinyltritylamine (TrNSO), available in one step on 10gram scale, as a linchpin. In contrast to classical approaches starting from thiols or their derivatives, our TrNSO-based approach facilitates the rapid assembly of the three reaction components into a variety of differentially substituted sulfonimidamides containing medicinally relevant moieties, including pyridines and indoles. Analogues of the sulfonamide-containing COX-2 inhibitor Celecoxib were prepared and evaluated.