Development of a scalable process for CI-1034, an endothelin antagonist

…, RJ McCabe, JG Mustakis, TN Nanninga…

Index: Jacks, Thomas E.; Belmont, Daniel T.; Briggs, Christopher A.; Horne, Nicole M.; Kanter, Gerald D.; Karrick, Greg L.; Krikke, James J.; McCabe, Richard J.; Mustakis, Jason G.; Nanninga, Thomas N.; Risedorph, Guy S.; Seamans, Ronald E.; Skeean, Richard; Winkle, Derick D.; Zennie, Thomas M. Organic Process Research and Development, 2004 , vol. 8, # 2 p. 201 - 212

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Citation Number: 40

Abstract

A concise, convergent multikilogram synthesis of CI-1034 (1), a potent endothelin receptor antagonist, is described. A 15-step preparation from commercially available o-vanillin and benzenesulfonyl chloride employs a remarkably robust Suzuki coupling between a boronic acid and an aromatic sulfonate ester as the key synthetic step. A scalable route capable of producing multikilogram quantities of CI-1034 with no chromatographic steps is described ...