Development of a Diversity-Oriented Approach to Oxazole-5-amide Libraries

A highly versatile route to oxazole-5-amides is presented. Conversion of readily accessible oxazole-5-trifluoroacetamides into their Boc-protected 5-aminooxazole derivatives provides intermediates amenable to parallel amide synthesis utilizing a reliable, one-pot, acylation−deprotection procedure. During preparation of the N-Boc compounds from trifluoroacetamides, a competing intramolecular rearrangement giving rise to novel N-(oxazol-5-yl)-2,2,2-trifluoroacetimidates was identified, the extent of which is primarily determined by the choice of reaction conditions.

本研究报道了一条通用性极强的恶唑-5-酰胺（oxazole-5-amides）合成路线。将易得的恶唑-5-三氟乙酰胺（oxazole-5-trifluoroacetamides）转化为叔丁氧羰基（Boc）保护的5-氨基恶唑衍生物，所得中间体可通过可靠的一锅法酰化-脱保护程序用于平行酰胺合成。在由三氟乙酰胺制备N-Boc保护化合物的过程中，我们发现存在竞争性分子内重排反应，该反应会生成新型N-(恶唑-5-基)-2,2,2-三氟乙酰亚胺酸酯（N-(oxazol-5-yl)-2,2,2-trifluoroacetimidates），其反应程度主要由反应条件的选择决定。