Multigram-scale synthesis of GSK 2,256,294, an inhibitor of soluble epoxide hydrolase in clinical evaluation

This paper described the development of an improved, practical and efficient protocol method for the multigram-scale synthesis of GSK 2,256,294, an orally bioavailable potent and selective inhibitor of sEH. The key to this optimization was the design and development of a novel synthetic strategy, which involved the preparation of 4-(aminomethyl)-3-(trifluoromethyl)benzonitrile (3) and 4-chloro-N,6-dimethyl-1,3,5-triazin-2-amine (6). The developed process provided an overall yield of 26.8%, which enabled us to rapidly synthesize large quantities of GSK 2,256,294 in 99% purity.Graphical abstract