Hoechst Marion Roussel

Merrell Pharmaceuticals, Inc.

Robert Duquid

James R McCarthy

Donald Paul Matthews

Jeffrey S Sabol

James R McConnell

Richard E Donaldson

The present invention is directed toward a novel process of preparing 2'-exocyclic vinylfluoride derivatives of cytidine analogues for use as ribonucleotide reductase inhibitors. The novel process of the present invention utilizes a cytidine derivative as the required starting material and provides the ribonucleotide reductase inhibitor in a more efficient than the reaction sequence. The process is more efficient than the process disclosed by McCarthy et al. in European Patent Application Publication No. 0 372 268 published Jun. 13, 1990, in that it requires fewer chromatographies and results in an overall yield of greater than 25% for the five steps. The present invention further provides the ribonucleotide reductase inhibitor in a four step reaction sequence and results in an overall yield of greater than 35%.

Process for the preparation of ribonucleotide reductase inhibitors

The present invention is directed toward a novel process of preparing 2'-exocyclic vinylfluoride derivatives of cytidine analogues for use as ribonucleotide reductase inhibitors. The novel process of the present invention utilizes a cytidine derivative as the required starting material and provides the ribonucleotide reductase inhibitor in a more efficient five step reaction sequence. The present invention further provides the ribonucleotide reductase inhibitor in a four step reaction sequence and results in an overall yield of greater than 35%.

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Richmond, VA, United States of America

Robert Duquid