Process for the preparation of gemcitabine hydrochloride
AssigneePrime European Therapeucials S.p.A.
InventorsAlberto Varalli, Paolo Anesa, Maria Argese, Giuseppe Guazzi
Life of this patent
Estimating the term…
Abstract
Disclosed is the preparation of 2-deoxy-D-erythro-2,2-difluoro-ribofuranose-3,5-dibenzoate, a known intermediate for the preparation of Gemcitabine, by means of a reduction process; further disclosed is the purification of Gemcitabine by chromatography and the purification of Gemcitabine hydrochloride by crystallization techniques from ternary solvent mixtures. The main advantage of the invention is providing Gemcitabine hydrochloride with purity in conformity with the Pharmacopoeia requirements, as well as a process particularly convenient from the industrial point of view.
Claims4
Process for the preparation of Gemcitabine hydrochloride
- which comprises the purification of crude Gemcitabine by ion exchange chromatography, the dissolution of the obtained Gemcitabine in methanol and the precipitation of Gemcitabine hydrochloride from concentrated hydrochloric acid and ethyl acetate.
Process for the preparation of Gemcitabine hydrochloride comprising the following steps:
- a) the reduction of 2-deoxy-D-erythro-2,2-difluoro-ribofuranos-1-ulose-3,5-dibenzoate
- with calcium or sodium borohydride to afford 2-deoxy-D-erythro-2,2-difluoro-ribofuranose-3,5-dibenzoate:
- b) the transformation of the hydroxyl group at the 1- position into a leaving group and the reaction with acetylcytosine to give Gemcitabine base;
- c) the purification of Gemcitabine base by ion exchange chromatography;
- d) the dissolution of Gemcitabine base obtained at step c) in methanol and the subsequent addition of an aqueous solution of concentrated hydrochloric acid and ethyl acetate to give a precipitate consisting of Gemcitabine hydrochloride;
- e) the recovery of Gemcitabine hydrochloride obtained at step d) and the recrystallization from water, methanol and ethyl acetate.
Dependencies are inferred from the claim text.