Novel synthesis process for industrial production of gemcitabine
A technology of gemcitabine and synthesis process, which is applied in the field of synthetic technology for industrial production of gemcitabine, can solve the problems of high cost, complicated process, influence product quality and yield, etc., and achieves the effects of improving yield, saving cost and reducing steps
Inactive Publication Date: 2013-04-03
南京亚东启天药业有限公司
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Problems solved by technology
[0007] However, in the above-mentioned known process (1), since the benzoyl group is added to the intermediate in two steps, the process is complicated and the cost is high. In addition, the bisbenzoyl protecting group is not stable and is easily oxidized under alkaline conditions. Decomposition, affecting product quality and yield, is a serious defect of the above process
[0008] In the process (2), since the hydroxyl protecting group is added to the intermediate in two steps, the process is complicated, the cost is high, and the product quality and yield are affected, which is a serious defect of the above process
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Embodiment 1
[0034] (1) Preparation of 3,5-chloroacetyl-2-deoxy-2,2-difluoro-D-pentofuranose-1-one (2):
[0035] Under nitrogen protection and stirring, 2-deoxy-2.2-difluoro-D-pentofuranose-1-one (30.0g, 0.178mol), ethyl acetate (50mL), chloroacetyl chloride (22.2g, 0.196mol ), 4-dimethylaminopyridine (0.22g, 1.79mmol), and pyridine (28.3g, 0.357mol) were added to the flask, reacted at 50~55°C for 6h, then added petroleum ether (150mL), cooled to 0°C, After filtration, the filtrate was concentrated under reduced pressure to obtain yellow oil 2 (44.8 g, 78.4%).
[0036] (2) Preparation of 3,5-chloroacetyl-2-deoxy-2,2-difluoro-D-ribofuranose (3):
[0037] Under nitrogen protection and stirring, 3,5-chloroacetyl-2-deoxy-2,2-difluoro-D-pentofuranose-1-one (30.0g, 93.4mmol), methyl tert-butyl ether (120mL) was added to the flask, and red aluminum (40mL, 138.0mmol) was slowly added dropwise at -5°C, maintaining this temperature and continuing to stir for 15min, then adding trifluoroethanol (8m...
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The invention discloses a novel synthesis process for an industrial production of gemcitabine. The synthesis process for the industrial production of gemcitabine hydrochloride comprises the following steps: by using 2,3-oxo-isopentylidene-D-glyceraldehyde as a raw material, implementing an addition reaction, a ring-opening reaction and a cyclization reaction; and protecting a hydroxy group by acyl chloride to prepare an intermediate product. By protecting the base in one step, the step is reduced, the yield is improved and the cost is saved; and the synthesis process is specifically suitable for an overnight production.
Description
[0001] The invention provides a preparation method of gemcitabine and a novel synthesis process for industrial production of gemcitabine. Background technique [0002] Gemcitabine hydrochloride is a known marketed drug. Its chemical name is 2-deoxy-2,2-difluorodeoxycytidine hydrochloride (β-isomer), and its English name is gemcitabinehydrochloride. Its structure is similar to cytarabine. It is a difluoronucleoside anti-metabolite anti-cancer drug that destroys cell replication. It mainly acts on tumor cells in the DNA synthesis phase, that is, cells in the S phase. Under certain conditions, it can prevent the progress from the G1 phase to the S phase; it It has obvious cytotoxic activity on various cultured human and mouse tumors. It is a water-soluble analogue of deoxycytidine. It is an inhibitory enzyme substitute for ribonucleotide reductase. This enzyme The production of the required deoxynucleotides is critical during DNA synthesis and repair. At present, there are two...
Claims
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IPC IPC(8): C07H19/073C07H1/00
Inventor 蔡惠明
Owner 南京亚东启天药业有限公司