KCS

Combinatorial solid-phase organic synthesis (SPOS) provides the main driving force for the preparation of small organic molecules libraries for application in lead discovery and high-throughput medicinal chemistry research within the pharmaceutical industry. Our research program has focused on the application of polymer-bound α-diazo-β-ketoesters as key building blocks for the diversity-oriented synthesis of a series of a nitrogen-containing heterocyclic compound libraries, including oxazoles, indoles, imidazolones, pyrazines and pyrazines, etc. Initially, ethyl 2-(2-azidophenylamino)-2-oxoacetate, which was previously obtained from the coupling reaction between ethyl 2-chloro-2-oxoacetate and azidoaniline was subjected to N-alkylation with various alkylating agents in presence of LiHMDS. Then, these alkylated products were cyclized by the treatment of TPP to yield corresponding 3-amino-1-quinoxalin-2 (1H)-ones via Staudinger reaction followed by aza-Wittig reaction, which can be finally derivatized by Lewis acid mediated smart cleavage.