122111-01-7Relevant articles and documents
High-selectivity synthesis method for gemcitabine intermediate
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, (2021/01/29)
The invention discloses a high-selectivity synthesis method for a gemcitabine intermediate. The high-selectivity synthesis method specifically comprises the following process: Step 1, synthesis of T1;Step2, synthesis of T2, to be specific, 550kg of hydrogen peroxide is dropwise added into the T1, and a reaction is controlled to produce the T2; Step3, synthesis of T3, to be specific, sodium acetate trihydrate or sodium carbonate is added into a reaction kettle, the PH value is adjusted with glacial acetic acid, a 10%-15% sodium hypochlorite aqueous solution is dropwise added, and a reaction iscontrolled to produce the T3; Step 4, synthesis of T4; Step 5, synthesis of T5; Step 6, synthesis of T6; Step 7, synthesis of T7; Step 8, synthesis of T8; and Step9, T8 configuration transformation.The high-selectivity synthetic method for the gemcitabine intermediate can reduce the production cost, and meanwhile, can also increase the yield of the gemcitabine intermediate.
Method for synthesizing 2- deoxy -2,2- difluoropentanoic acid -1- ketone -3,5- dibenzoin (by machine translation)
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, (2020/03/09)
The invention takes 2,2 - dimethyl - 4444444H-1, 3-dioxane - 4 4-one and difluorobromoacetic acid as the reaction raw material, without having a specific chiral configuration, to selectively synthesize a specific configuration cyclization product, under the action of a monovalent copper salt and a chiral ligand . reaction is simpler, and Reformatsky environment-friendly, is avoided under slightly acidic condition by hydrolysis, of, the cyclization product of the cyclization product. The preparation ;NaBH, reduces side reactions. 4 - I2 The reduction system can selectively reduce the carboxylic acid without reducing the reduction effect, of the lactone by . and has the 2 -deoxy - 2222,dibenzofuran sugar - 1 1-ketone - 3333,5-dibenzoin synthesis route, is simple, environment-friendly, total yield . for industrial production, can be effectively reduced. (by machine translation)
Method for preparing Gemcitabine intermediate from chiral catalyst
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Paragraph 0031; 0036; 0037; 0042; 0043; 0048, (2019/05/28)
The invention relates to a method for preparing a Gemcitabine intermediate from a chiral catalyst, and belongs to the technical field of synthesis of medical intermediates. In order to solve the problem that the existing reaction is poor in stereoselectivity, the invention provides the method for preparing the Gemcitabine intermediate from the chiral catalyst; the method comprises the following steps: performing a condensation reaction on R-glyceraldehyde acetonide and difluoro halogenated ethyl acetate in an inert organic solvent under the combined catalytic action of active zinc powder and delta-amino alcohol ligands to obtain a corresponding intermediate; performing deprotection and lactonization treatment on the intermediate and performing a reaction on the intermediate and benzoyl chloride in the presence of an acid-binding agent to obtain the corresponding Gemcitabine intermediate. A product obtained with the method provided by the invention has an ee value being as high as 98% or above, the content of an erythro form product is high, and the obtained product does not need to be refined and can be directly used for next reaction.
Thiophene-expanded guanosine analogues of Gemcitabine
Chen, Zhe,Ku, Therese C.,Seley-Radtke, Katherine L.
, p. 4274 - 4276 (2020/12/14)
The chemotherapeutic drug Gemcitabine, 2′,2′-difluoro-2′-deoxycytidine, has long been the standard of care for a number of cancers. Gemcitabine's chemotherapeutic properties stem from its 2′,2′-difluoro-2′-deoxyribose sugar, which mimics the natural nucleoside, but also disrupts nucleic acid synthesis, leading to cell death. As a result, numerous analogues have been prepared to further explore the biological implications for this structural modification. In that regard, a thieno-expanded guanosine analogue was of interest due to biological activity previously observed for the tricyclic heterobase scaffold. Several analogues were prepared, including the McGuigan ProTide, however the parent nucleoside exhibited the best chemotherapeutic activity, specifically against breast cancer cell lines (89.53% growth inhibition).
PREPARATION OF GEMCITABINE AND INTERMEDIATES THEREOF
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Page/Page column 13, (2010/05/14)
The present patent application relates to a process for the preparation gemcitabine or a salt thereof. More particularly it relates to preparation of 3,5- dihydroxy protected -2-deoxy-2,2-difluoro -1-oxoribose, an intermediate used in the preparation of gemcitabine and its salts by using cyclohexylidene or cyclopentylidene protecting group, with high yield and purity.
Process for Preparing Gemcitabine and Associated Intermediates
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Page/Page column 13, (2008/06/13)
The present invention provides processes for preparing novel chemical substances that are useful as intermediates in the preparation of gemcitabine and processes for preparing gemcitabine therewith. Exemplary intermediates include mixtures of D-erythro and D-threo (3R- and 3S-) isomers of 3-(hydroxy)-2,2-difluoro-3-(2,2-dimethyldioxolan-4-yl)propionic acid salts. Also provided is a novel process for selectively isolating the D-erythro and D-threo isomers of the said salts in purities of at least about 95%, and processes of using them for preparing nucleoside analogs such as, e.g., gemcitabine and intermediates and analogs thereof.
AN IMPROVED ONE POT PROCESS FOR MAKING KEY INTERMEDIATE FOR GEMCITABINE HCL
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Page/Page column 13; 15-16, (2010/11/27)
An improved one pot process for preparing 2-deoxy-D-erythro-2,2-difluoro-pentafuranose-1-ulose-3,5-dibenzoate of Formula (I) comprising hydrolysis of (erythro:threo) alkyl-3-dioxalan-4-yl-2,2-difluoro-3-hydroxy propionate of Formula (III) where alkyl group is having C1-C4 number of carbon atoms using a mild acid and selectively isolating 2-deoxy-D-erythro-2,2-difluoro-pentafuranose-1-ulose-3,5-dibenzoate from the mixture of erythro and threo enantiomers using ethyl acetate, ethylene dichloride and diisopropyl ether as solvents with improved yield and purity.
AN IMPROVED PROCESS FOR THE MANUFACTURE OF HIGH PURE GEMCITABINE HYDROCHLORIDE
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Page/Page column 7; 13; 15, (2010/02/14)
A process for the preparation of Gemcitabine hydrochloride of formula (I) of extra high purity by the reaction of (R) -2,3-0-isopropylidene glyceraldehyde of formula (II) with ethyl bromo difluoroacetate of formula (III) followed by hydrolytic cyclization of the product of formula (IV) converting the product into a dibenzoyl derivative of formula (V) of high purity reducing the product of formula (V) and converting the resultant lactol into a mesylate of formula (VI) followed by coupling the mesylate of formula (VI) with bis-silyl acetyl cytosine of formula (X) and subsequently deblocking and purifying.
