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

Tetrahedron Lett. 2013 Mar 20;54(12):1546-1549. doi: 10.1016/j.tetlet.2013.01.024.


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%.

Keywords: EPAC antagonist; ESI-09; cyanomethyl ketone; isoxazole; modified Kowalski's protocol.