Synthesis process of the industrial production of gemcitabine hydrochloride

Abstract

The invention relates to a synthesis process of industrial production of gemcitabine hydrochloride and pertains to the field of chemical product synthesis process. The invention takes 2, 3-oxygen-isopentylidene-D-glyceraldehyde as the raw materials and respectively uses TBDPSCl and benzoyl chloride to protect hydroxyl to produce an intermediate after addition, ring opening and cyclization. The intermediate is condensed with cytosine after reduction and methyl sulfonylation and then acquires gemcitabine hydrochloride after de-protection and salification. The invention has the advantage that TBDPSCl is adopted to protect one of hydroxyls, thus increasing the stability of the intermediate double benzoyl and facilitating the separation and purification of the product. The invention solves the problem in the prior gemcitabine hydrochloride production process that the intermediate double benzoyl protector is unstable and easily de-protected in alkalescence, thus affecting the product quality and yield. The total yield of the synthesis process is 17.9 percent and the purity is above 99.8 percent, thus being particularly applicable to the industrial production of gemcitabine hydrochloride.

Description

Technical field: [0001] The present invention relates to a synthesis process of known compounds, in particular to a synthesis process for industrial production of gemcitabine hydrochloride. Background technique: [0002] Gemcitabine hydrochloride is a known compound. Its chemical name is 2′-deoxy-2′, 2′-difluorocytidine hydrochloride, and its English name is gemcitabine hydrochloride. Gemcitabine hydrochloride is a cell cycle-specific anti-metabolite drug that mainly acts on tumor cells in the DNA synthesis phase, that is, cells in the S phase. Under certain conditions, it can prevent the progression from the G1 phase to the S phase; it can be used alone in clinical applications. It can also be used in combination with other drug treatments. The main process of producing gemcitabine hydrochloride at present is: [0003] [0004] However, in the above-mentioned known process, because the intermediate bisbenzoyl protected compound is unstable, it is very easy to deprotec...

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Problems solved by technology

[0004] But in the above-mentioned known technology, because its intermediate bisbenzoyl protection is unstable, it is very easy to deprotect under alkaline conditions, which affects product quality and yield, which is an important defect of the above-mentioned technology.

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