Efficient Synthesis of ESI-09, A Novel Non-cyclic Nucleotide EPAC Antagonist.

A concise and efficient synthetic approach to producing a novel non-cyclic nucleotide EPAC antagonist ESI-09 and its new analogs is reported. Key features of the synthesis include a mild and reliable one-pot procedure for an isoxazole synthon, as well as a modified one-pot protocol for the cyanomethyl ketone key intermediate. The synthesis requires inexpensive starting materials and only three linear steps for the completion in a total yield of 53%.