- Titanium-promoted highly stereoselective synthesis of α,α-difluoro-β,γ-dihydroxyester. Simple route to 2-deoxy-2,2-difluororibose
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The highly stereoselective synthesis of α,α-difluoro-β,γ-dihydroxyesters is described.Reformatsky reaction of bromo- or iododifluoroacetate with D-glyceraldehyde provide (3R,4R)-2,2-difluoro-4,5-O-cyclohexylidene-3-triethylsiloxypentanoic acid ethyl ester in high yield, with more than 95percent diastereoselectivity, by asymmetric induction promoted by Cp2TiCl2.The reaction affords a simple and practical route to 2-deoxy-2,2-difluororibose.
- Matsumura, Yasushi,Fujii, Hajime,Nakayama, Toshiaki,Morizawa, Yoshitomi,Yasuda, Arata
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- High-selectivity synthesis method for gemcitabine intermediate
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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.
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Paragraph 0055-0056
(2021/01/29)
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- Method for synthesizing 2- deoxy -2,2- difluoropentanoic acid -1- ketone -3,5- dibenzoin (by machine translation)
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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)
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Paragraph 0054-0057
(2020/03/09)
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- Method for preparing Gemcitabine intermediate from chiral catalyst
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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.
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Paragraph 0031; 0036; 0037; 0042; 0043; 0048
(2019/05/28)
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- Gemcitabine intermediate preparation method
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The present invention provides a gemcitabine intermediate preparation method, wherein a compound 1 is adopted as a raw material, and six reactions such as esterification, fluorization, hydrolysis, oxidation, Mitsunobu, and reduction are performed to prepare a compound 7. According to the present invention, the method has characteristics of simple operation and high yield, and is suitable for industrial production. The compounds 1-7 are defined in the specification.
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Paragraph 0018; 0039; 0040; 0041
(2016/12/07)
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- STEREOSELECTIVE SYNTHESIS OF BETA-NUCLEOSIDES
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A process of stereoselectively synthesizing β-nucleoside of formula (I), e.g., 2'-deoxy-2,2'-difluorocytidine, is described. The process includes reacting a tetrahydrofuran compound of the following formula: in which wherein R1, R2, R3, R4, and L as defined in the specification, with a nucleobase derivative in the presence of an oxidizing agent.
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- Novel and Highly Stereoselective Process for Preparing Gemcitabine and Intermediates Thereof
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The present invention provides a novel and highly stereoselective process for preparing gemcitabine, which is suitable for industrial production, wherein, it includes the following reactions. Additionally, the invention discloses the key intermediates. The definition for the groups of G1, G2, G3, G4, and G5 are described in the specification.
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Page/Page column 7
(2010/08/03)
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- NOVEL SYNTHESIS OF BETA-NUCLEOSIDES
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This invention relates to a process of stereoselectively synthesizing β-nucleoside, e.g., 2′-deoxy-2,2′-difluorocytidine.
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Page/Page column 4; 7
(2009/05/28)
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- A NOVEL AND HIGHLY STEREOSELECTIVE PROCESS FOR PREPARING GEMCITABINE AND INTERMEDIATES THEREOF
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The present invention provides a novel and highly stereoselective process for preparing gemcitabine, which is suitable for industrial production, wherein, it includes the following reactions. Additionally, the invention discloses the key intermediates. The definition for the groups of G1, G2, G3, G4, and G5 are described in the specification.
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Page/Page column 19
(2009/01/20)
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- Process for Preparing Gemcitabine and Associated Intermediates
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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.
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Page/Page column 7; 11-12
(2008/06/13)
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- PREPARATION OF GEMCITABINE
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A process for preparation of gemcitabine hydrochloride and purification thereof.
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Page/Page column 18
(2008/06/13)
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- SYNTHESIS OF 2-DEOXY-2, 2-DI FLUORO-D-RIBO FURANOSE-3, 5 DI(4-METHY/4-NITRO-CHLORO)BENZOATE AND ITS CONVERSION TO GEMCITABINE HYDROCHLORIDE THEREOF
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The invention describes the synthesis of hereto unreported 2-deoxy-2,2-difluoro-D-ribofuranose-3,5-di-(aroyl) derivative of formula-Vb, where in R=;CH3,CI,NO2 and its conversion to Gemcitabine HCl of formula-I, an anti cancer product.
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Page/Page column 9; 15
(2008/06/13)
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- STEREOSELECTIVE SYNTHESIS OF β-NUCLEOSIDES
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This invention relates to a process for stereoselectively preparing a nucleoside of the following formula: wherein R3, R4, and B are defined herein. The process includes reacting a furanose compound with a nucleobase in the presence
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Page/Page column 10
(2008/06/13)
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- AN IMPROVED PROCESS FOR THE MANUFACTURE OF HIGH PURE GEMCITABINE HYDROCHLORIDE
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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.
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Page/Page column 7; 12
(2010/02/14)
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- Dosing regimen for gemcitabine HCV therapy
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A dosage regiment for the treatment of a Flaviviridae infection, including a hepatitis C viral infection, that includes administering gemcitabine (or its salt, prodrug or derivative, as described herein) in a dosage range of approximately 50 mg/m2 /
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- Deoxyribonolactone lesion in DNA: Synthesis of fluorinated analogues
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Mono- and difluorinated derivatives of 2-deoxyribonolactone were synthesized using diastereoselective Reformatski reaction as a key step.
- Crey, Caroline,Dumy, Pascal,Lhomme, Jean,Kotera, Mitsuharu
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p. 1093 - 1095
(2007/10/03)
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