Schering Aktiengesellschaft

Berlex Biosciences Inc.

Randolph C Wirsching

John G Bauman

Helmut Vorbruggen

Konrad Krolikiewicz

This invention relates to a process for the production of 2-fluoropurine derivatives from 2-aminopurine derivatives, which are reacted in HF/pyridine or HF/pyridine/H.sub.2 O in the presence of a nitrite.

Process for the production of 2-fluoropurine derivatives

A process for the production of fludarabine or fludarabine phosphate is provided, wherein the nucleoside guanosine or a suitable derivative is employed as the starting material. The guanosine starting material is subjected to (a) conversion of the 6-keto group into a 6-amino group, (b) conversion of the 2-amino group to a 2-fluoro group, and (c) conversion of the ribofuranosyl moiety to an arabinofuranosyl moiety. Steps (a), (b), and (c) can be performed individually or concomitantly and in any sequence.

Process for the preparation of fludarabine or fludarabine phosphate from

This invention pertains to novel methods of synthesizing fludarabine, fludarabine phosphate and related nucleoside pharmacologic agents utilizing 6-azido-2-fluoropurine as a novel intermediate. In particular this invention pertains to a synthesis of fludarabine where the relatively low yield fluorination step is done before the costly coupling step.

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Livermore, CA, United States of America

Randolph C Wirsching