134877-42-2

Usage

Uses

Used in Pharmaceutical Industry:
2-Deoxy-2,2-difluoro-D-ribofuranose-3,5-dibenzoate-1-methanesulfonate is used as an impurity in the development and production of Gemcitabine (G305028), a potential anticancer agent. Its presence in the synthesis process of Gemcitabine is crucial for the compound's effectiveness as an anticancer drug. The compound plays a role in modulating the activity and potency of Gemcitabine, making it a valuable component in the pharmaceutical industry's pursuit of novel cancer treatments.
Used in Research and Development:
In addition to its application in the pharmaceutical industry, 2-Deoxy-2,2-difluoro-D-ribofuranose-3,5-dibenzoate-1-methanesulfonate is also utilized in research and development efforts aimed at understanding the mechanisms of action and potential side effects of Gemcitabine. By studying the properties and interactions of 2-Deoxy-2,2-difluoro-D-ribofuranose-3,5-dibenzoate-1-methanesulfonate, researchers can gain insights into the broader class of nucleoside analogs and their potential applications in cancer therapy.
Used in Quality Control and Regulatory Compliance:
The presence of 2-Deoxy-2,2-difluoro-D-ribofuranose-3,5-dibenzoate-1-methanesulfonate as an impurity in Gemcitabine production necessitates its monitoring and control to ensure the safety and efficacy of the final drug product. As such, 2-Deoxy-2,2-difluoro-D-ribofuranose-3,5-dibenzoate-1-methanesulfonate is used in quality control processes to verify that the levels of impurities are within acceptable limits, adhering to regulatory guidelines and ensuring the overall quality of the anticancer agent.

InChI:InChI=1/C22H24O8S/c1-22(2)18(29-20(24)16-12-8-5-9-13-16)17(28-21(22)30-31(3,25)26)14-27-19(23)15-10-6-4-7-11-15/h4-13,17-18,21H,14H2,1-3H3/t17-,18-,21-/m1/s1

Upstream product

• 153012-08-9 C₁₉H₁₆F₂O₆ 
• 124-63-0 methanesulfonyl chloride 
• 1173824-58-2 (2R,3R)-2-((benzoyloxy)methyl)-4,4-difluoro-5-hydroxyoxolan-3-yl benzoate 
• 134877-42-2 3,5-di-O-benzoyl-2-deoxy-2,2-difluoro-1-O-methanesulfonyl-D-erythro-pentofuranose 
• 143157-25-9 3,5-di-O-benzoyl-2-deoxy-2,2-difluoro-D-α-ribofuranose 
• 95058-77-8 2-deoxy-2,2-difluoro-1-carbonylribose 
• 928797-50-6 ethyl (3R,S)-2,2-difluoro-3-hydroxy-(2,2-dimethyldioxolpent-4-yl)propionate 
• 122111-01-7 2-deoxy-2,2-difluoro-D-erythro-pentonic acid γ-lactone 3,5-dibenzoate 

Downstream Products

• 143157-23-7 1-(2'-deoxy-2',2'-difluoro-3',5'-di-O-benzoyl-D-ribofuranosyl)-4-acetamidopyrimidin-2-one 
• 134790-40-2 C₂₃H₁₉F₂N₃O₆ 
• 134790-39-9 (2'-deoxy-2',2'-difluorocytidine)-3',5'-dibenzoate 
• 103882-84-4 2’-deoxy-2’,2’-difluoro-cytidine 
• 155568-06-2 3',5'-di-O-benzoyl-2'deoxy-2',2',5-trifluorocytidine 
• 122111-05-1 2'-deoxy-2',2'-difluorocytidine hydrochloride 
• 122111-03-9 gemcitabine hydrochloride 
• 1203469-67-3 C₂₇H₂₃F₂N₃O₇ 
• 183202-53-1 3-(3,5-di-O-benzoyl-2-deoxy-2,2-difluoro-β-D-ribofuranosyl)-7-acetyl-3,5,6,7-tetrahydro-2H-pyrrolo[2,3-d]pyrimidin-2-one 
• 1006598-32-8 1-(3',5'-di-O-benzoyl-2',2'-difluoro-α-D-pentofuranos-1'-yl)-5-(E)-bromovinyluracil 
• 1006598-31-7 1-(3',5'-di-O-benzoyl-2',2'-difluoro-β-D-pentofuranos-1'-yl)-5-(E)-bromovinyluracil 
• 1251462-76-6 1-(3,3-difluoro-4-benzoyloxy-5-benzoyloxymethyl-tetrahydro-furan-2-yl)-1,3,4,7-tetrahydro-[1,3]diazepin-2-one 
• 1251462-79-9 1-(3,3-difluoro-4-benzoyloxy-5-benzoyloxymethyl-tetrahydro-furan-2-yl)-1,3,4,7-tetrahydro-[1,3]diazepin-2-one 
• 1155863-81-2 C₂₃H₁₉F₂N₃O₆ 

Relevant academic research and scientific papers

Method for recovering mother liquor of gemcitabine intermediate

The invention provides a method for recovering mother liquor of a gemcitabine intermediate, and relates to the technical field of purification. The method for recovering the mother liquor of the gemcitabine intermediate provided by the invention comprises the following steps of: performing acidolysis of crystallization mother liquor containing a compound 5 and a compound 10 so as to obtain a mixture of a compound 3 and a compound 9; mixing the mixture of the compound 3 and the compound 9 with aniline, and performing dehydration reaction to obtain a mixture of Schiff base 12 and the compound 9; performing separation of the mixture of the Schiff base 12 and the compound 9 to obtain high-purity Schiff base 12; performing hydrolysis of the high-purity Schiff base 12 to obtain the compound 3; and mixing the compound 3 with methylsulfonyl chloride, and performing acylation reaction so as to obtain the high-purity compound 5. The method provided by the invention can remove the compound 10 in the crystallization mother liquor to obtain the high-purity compound 5, so that the yield and the purity of hydrochloride, namely gemcitabine hydrochloride, are improved.

High-selectivity synthesis method for gemcitabine intermediate

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.

Purification method of gemcitabine intermediate

The invention provides a purification method of a gemcitabine intermediate, and belongs to the technical field of drug intermediate synthesis. According to the invention, a compound 2 in an existing method (shown in a formula 1 and a formula 2 in a background art) is reduced to obtain a mixture containing a compound 3 and a byproduct compound 9; the mixture reacts with aniline; dehydration condensation reaction of the compound 3 and aniline is achieved; Schiff base is generated; the Schiff base and the byproduct compound 9 are easy to separate; a high-purity compound 3 can be obtained by performing simple acidic hydrolysis and separation on the separated Schiff base; the high-purity compound 3 is subjected to sulfonylation reaction to synthesize a gemcitabine hydrochloride key intermediate compound 5, so that the yield and the purity of the compound 5 can be improved, and the preparation yield and the product quality of the raw material medicine gemcitabine hydrochloride are ensured.

Preparation method of gemcitabine intermediate methylsulfonyl ester

The invention relates to a preparation method of a gemcitabine intermediate methylsulfonyl ester, and belongs to the technical field of drug intermediate synthesis. In order to solve the problems of low conversion rate and large amount of waste liquid in the prior art, the preparation method of the gemcitabine intermediate methylsulfonyl ester is provided. The method comprises the step that in a mixed solvent of a water-insoluble organic solvent and catalytic amount isopropyl alcohol, a compound 2-deoxy-2,2-difluoro-D-erythro-1-furazolidone-3,5-dibenzoyl ester in formula I is subjected to a reduction reaction to be converted into a compound in formula II in the coexistence of aluminum isopropoxide and sodium tert-butoxide; cooling is carried out to control the temperature of a reaction liquid to be lower than 5 DEG C, methylsufonyl chloride is added to perform an esterification reaction, and the corresponding compound gemcitabine intermediate methylsulfonyl ester in formula III is obtained. The preparation method of the gemcitabine intermediate methylsulfonyl ester can effectively increase the reaction speed and conversion rate, reduces the generation of impurities, has higher yield and purity requirements, can achieve a one-pot reaction, and simplifies the production operation.

Industrial preparation process for key intermediate sulfonated saccharide of Gemcitabine

The invention relates to a preparation method for a compound represented by a formula (I) shown in the description, i.e., a key intermediate sulfonated saccharide of Gemcitabine. The final product is prepared through subjecting a compound represented by a formula (II) shown in the description to sodium borohydride reduction, hydroxyl protection and resolution. The method is simple in process, high in yield and high in product purity and has no need of harsh reaction conditions, thereby being very suitable for industrial production.

Azido nucleosides and nucleotide analogs

Disclosed herein are 4′-azido-substituted nucleosides, nucleotides and analogs thereof, pharmaceutical compositions that include one or more of 4′-azido-substituted nucleosides, nucleotides and analogs thereof, and methods of synthesizing the same. Also disclosed herein are methods of ameliorating and/or treating a disease and/or a condition, including an infection from a paramyxovirus and/or an orthomyxovirus, with a 4′-azido-substituted nucleoside, a nucleotide and/or an analog thereof. Examples of viral infections include a respiratory syncytial viral (RSV) and influenza infection.

2′-Deoxy-2′,2′-difluorothymidine analogues for radiolabeling with fluorine-18 and other biomedical applications

Novel 2′-deoxy-2′,2′-difluorothymidine analogues with potential applications as antiviral, cytotoxic and cancer imaging agents have been synthesized. Introduction of the hydroxymethyl functionality at the 5-position of 2′-deoxy-2′,2′-difluoruridine provided a key intermediate with a suitable synthetic handle for the generation of these nucleoside derivatives.

SUBSTITUTED NUCLEOSIDES, NUCLEOTIDES AND ANALOGS THEREOF

Disclosed herein are nucleosides, nucleotides and analogs thereof, pharmaceutical compositions that include one or more of nucleosides, nucleotides and analogs thereof, and methods of synthesizing the same. Also disclosed herein are methods of ameliorating and/or treating a disease and/or a condition, including an infection from a paramyxovirus and/or an orthomyxovirus, with a nucleoside, a nucleotide and an analog thereof.

Design, synthesis and biological evaluation of 2′-deoxy-2′, 2′-difluoro-5-halouridine phosphoramidate ProTides

We report the synthesis of a series of novel 2′-deoxy-2′, 2′-difluoro-5-halouridines and their corresponding phosphoramidate ProTides. All compounds were evaluated for antiviral activity and for cellular toxicity. Interestingly, 2′-deoxy-2′,2′-difluoro-5-iodo- and -5-bromo-uridines showed selective activity against feline herpes virus replication in cell culture due to a specific recognition (activation) by the virus-encoded thymidine kinase.

Inactivation of lactobacillus leichmannii ribonucleotide reductase by 2',2'-difluoro2'-deoxycytidine s'-triphosphate: Covalent modification

Ribonucleotide reductase (RNR) from Lactobacillus leichmannii, a 76 kDa monomer using adenosylcobalamin (AdoCbl) as a cofactor, catalyzes the conversion of nucleoside triphosphates to deoxynucleotides and is rapidly ( 3H]- and [5-3H]F2CTP were synthesized and used independently to inactivate RNR. Sephadex G-50 chromatography of the inactivation mixture revealed that 0.47 equiv of a sugar was covalently bound to RNR and that 0.71 equiv of cytosine was released. Alternatively, analysis of the inactivated RNR by SDS-PAGE without boiling resulted in 33% of RNR migrating as a 110 kDa protein. Inactivation of RNR with a mixture of [1'-3H]F2CTP and [1'-2H]F 2CTP followed by reduction with NaBH4, alkylation with iodoacetamide, trypsin digestion, and HPLC separation of the resulting peptides allowed isolation and identification by MALDI-TOF mass spectrometry (MS) of a 3H/2H-labeled peptide containing C731 and C736 from the C-terminus of RNR accounting for 10% of the labeled protein. The MS analysis also revealed that the two cysteines were cross-linked to a furanone species derived from the sugar of F2CTP. Incubation of [1-3H]F2CTP with C119S-RNR resulted in 0.3 equiv of sugar being covalently bound to the protein, and incubation with NaBH4 subsequent to inactivation resulted in trapping of 2'-fluoro-2'-deoxycytidine. These studies and the ones in the preceding paper (DOI: 10.1021/bi9021318) allow proposal of a mechanism of inactivation of RNR by F2CTP involving multiple reaction pathways. The proposed mechanisms share many common features with F2CDP inactivation of the class I RNRs.