Bristol-myers Squibb Compnay

Gabriel M Galvin

Padam N Sharma

Susan D Boettger

Saibaba Racha

Edward J Gublo

Brian L Davis

Daniel A Benigni

Shu-Jen Chiang

Thomas P Tully

Gregory L Stein

Fahri T Comezoglu

Bruce Eagan

Dennis Gu

David Hou

Cary W McConlogue

Hsing Hou

Les Mintzmyer

Ivan Hargro

Robert Stankavage

Mark Mascari

A process is provided for preparing a dipeptidyl peptidase IV inhibitor of the structure is treated with TFAA in isopropyl acetate to protect the tertiary hydroxyl group as a trifluoroacetate group to form 4 (which is a novel intermediate) which is converted to acid chloride compound 5 (which is a novel compound) using Vilsmeier reagent or other chloro reaget and coupled with compound 6 in a heterogeneous mixture of ethyl acetate and aqueous bicabonate to give compound 7 The N,O-bis(trifluoroacetyl) groups of compound 7 are deprotected to give free base compound 10.

Process for preparing a dipeptidyl peptidase IV inhibitor and intermediates employed therein

A process is provided for preparing a dipeptidyl peptidase IV inhibitor of the structure wherein is treated with TFAA in isopropyl acetate to protect the tertiary hydroxyl group as a trifluoroacetate group to form 4 (which is a novel intermediate)which is converted to acid chloride compound 5 (which is a novel compound)using Vilsmeier reagent or other chloro reagent and coupled with compound 6 in a heterogeneous mixture of ethyl acetate and aqueous bicarbonate to give compound 7 The N,O-bis(trifluoroacetyl) groups of compound 7 are deprotected to give free base compound 10.

The present invention relates to improved methods for the production, isolation and purification of epothilone B. These methods include, for example, a fermentation process for the production of epothilone B, isolation via adsorption onto a resin, and subsequent purification.

Methods for the preparation, isolation and purification of epothilone B, and x-ray crystal structures of epothilone B

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Maple Valley, WA, United States of America

Gabriel M Galvin