A Scaleable Synthesis of Fiduxosin

A Scaleable Synthesis of Fiduxosin

Fiduxosin (1) has been under development at Abbott Laboratories for the treatment of benign prostatic hyperplasia. A convergent strategy required methodologies for preparation of an enantiomerically pure 3,4-cis-disubstituted pyrrolidine and a 2,3,5-trisubstituted thienopyrazine in a regiospecific m...

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Bibliographic Details
Published in:Organic process research & development Vol. 8; no. 6; pp. 897 - 902
Main Authors: Haight, Anthony R, Bailey, Anne E, Baker, William S, Cain, Michael H, Copp, Richard R, DeMattei, John A, Ford, Kelley L, Henry, Rodger F, Hsu, Margaret C, Keyes, Robert F, King, Steven A, McLaughlin, Maureen A, Melcher, Laura M, Nadler, William R, Oliver, Patricia A, Parekh, Shyamal I, Patel, Hemant H, Seif, Louis S, Staeger, Mike A, Wayne, Gregory S, Wittenberger, Steven J, Zhang, Weijiang
Format: Journal Article
Language:English
Published: American Chemical Society 01-11-2004
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Summary:Fiduxosin (1) has been under development at Abbott Laboratories for the treatment of benign prostatic hyperplasia. A convergent strategy required methodologies for preparation of an enantiomerically pure 3,4-cis-disubstituted pyrrolidine and a 2,3,5-trisubstituted thienopyrazine in a regiospecific manner. A [3+2] cycloaddition of an enantiopure azomethine ylide followed by a diastereoselective crystallization was employed to prepare the benzopyranopyrrolidine in high diastereomeric and enantiomeric purity. Conditions for reduction of an O-aryl lactone susceptible to epimerization were developed, and cyclization of the alcohol/phenol to the ether was accomplished in high yield. The thienopyrazine was prepared by condensation of methyl thioglycolate and a regiospecifically prepared 2-bromo-3-cyano-5-phenylpyrazine. Conditions for effective halogen substitutive deamination to prepare regiospecific trisubstituted pyrazines will be described.
ISSN:1083-6160
1520-586X
DOI:10.1021/op049889k