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