122111-11-9

Basic information

• Product Name: 2-Deoxy-2,2-difluoro-D-erythro-pentofuranose-3,5-dibenzoate-1-methanesulfonate
• Synonyms: D-ERYTHRO-PENTOFURANOSE, 2-DEOXY-2,2-DIFLUORO-, 3,5-DIBENZOATE 1-METHANESULFONATE;2-deoxy-2,2-difluoro-d-erythro-pentofuranose-3,5-dibenzoate-1-methanesulfonate;2-DEXY-2,2-DIFLUORO-3,5-O-DIBENZOYLRIBOSE MESYLATE;2-Deoxy-2,2-difluoro-D-erythro-ribofuranose-3,5-dibenzoate 1-Methanesulfonate;3,5-Di-O-benzoyl-2-deoxy-2,2-difluoro-1-O-methanesulfonyl-D-ribofuranoside;GeMcitabine InterMediate 8;T8, 2-Deoxy-2,2-difluoro-D-erythro-pentofuranose-3,5-dibenzoate-1-Methanesulfonate;((2R,3R)-3-(Benzoyloxy)-4,4-difluoro-5-((Methylsulfonyl)oxy)tetrahydrofuran-2-yl)Methyl benzoate
• CAS NO: 122111-11-9
• Molecular Formula: C₂₀H₁₈F₂O₈S
• Molecular Weight: 456.41
• EINECS: 1592732-453-0
• Product Categories: Aromatics Compounds;Aromatics;Carbohydrates & Derivatives;Intermediates
• Mol File: 122111-11-9.mol

Chemical Properties

• Boiling Point: 588.439 °C at 760 mmHg
• Flash Point: 309.677 °C
• Appearance: Brown liquid
• Density: 1.464 g/cm³
• Vapor Pressure: 2.41E-11mmHg at 25°C
• Refractive Index: 1.652
• Storage Temp.: 2-8°C
• Solubility: Chloroform, Methanol
• CAS DataBase Reference: 2-Deoxy-2,2-difluoro-D-erythro-pentofuranose-3,5-dibenzoate-1-methanesulfonate(CAS DataBase Reference)
• NIST Chemistry Reference: 2-Deoxy-2,2-difluoro-D-erythro-pentofuranose-3,5-dibenzoate-1-methanesulfonate(122111-11-9)
• EPA Substance Registry System: 2-Deoxy-2,2-difluoro-D-erythro-pentofuranose-3,5-dibenzoate-1-methanesulfonate(122111-11-9)

Safety Data

• Hazardous Substances Data: 122111-11-9(Hazardous Substances Data)

Usage

Chemical Properties

Brown Liquid

Uses

Different sources of media describe the Uses of 122111-11-9 differently. You can refer to the following data:
1. Gemcitabine intermediate
2. Gemcitabine intermediate.

InChI:InChI=1/C9H11F2N3O4/c10-9(11)6(16)4(3-15)18-7(9)14-2-1-5(12)13-8(14)17/h1-2,4,6-7,15-16H,3H2,(H2,12,13,17)/t4-,6-,7-/m0/s1

Upstream product

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

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 
• 143157-24-8 uridine 
• 143157-27-1 ((2R,3R,5R)-3-(benzoyloxy)-5-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-4,4-difluorotetrahydrofuran-2-yl)methyl benzoate 
• 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 
• 1321580-98-6 C₂₅H₂₅F₂IN₃O₉P 

Relevant articles and documents

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.

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.

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.

PROCESS FOR THE PREPARATION OF GEMCITABINE HYDROCHLORIDE

Disclosed is the preparation of 2-deoxy-D-erythro-2,2-difluoro-ribofuranose-3,5-dibenzoate: a known intermediate for the preparation of Gemcitabine, by means of a reduction process; further disclosed is the purification of Gemcitabine by chromatography and the purification of Gemcitabine hydrochloride by crystallization techniques from ternary solvent mixtures. The main advantage of the invention is providing Gemcitabine hydrochloride with purity in conformity with the Pharmacopoeia requirements, as well as a process particularly convenient from the industrial point of view.

Process for the preparation of gemcitabine chlorohydrate

Disclosed is the preparation of 2-deoxy-D-erythro-2,2-difluororibofuranose-3,5-dibenzoate: a known intermediate for the preparation of Gemcitabine, by means of a reduction process; further disclosed is the purification of Gemcitabine by chromatography and the purification of Gemcitabine hydrochloride by crystallization techniques from ternary solvent mixtures. The main advantage of the invention is providing Gemcitabine hydrochloride with purity in conformity with the Pharmacopoeia requirements, as well as a process particularly convenient from the industrial point of view.

NOVEL MODULATORS OF CELL CYCLE CHECKPOINTS AND THEIR USE IN COMBINATION WITH CHECKPOINT KINASE INHIBITORS

In its many embodiments, the present invention provides a novel class of pyrimidine analogs of formula (V) as targeted mechanism-based modulators of cell cycle checkpoints. Cancers and/or malignancies can be treated by administration of a cell cycle checkpoint modulator of the invention. Also discussed are suitable combinations of the cell cycle checkpoint modulator with a checkpoint kinase inhibitor to produce synergistic apoptosis in cancer cells. The invention includes methods of treating cancers by administering the combination of the cell cycle checkpoint modulator and the checkpoint kinase inhibitor, pharmaceutical compositions comprising the activator as well as the combination and pharmaceutical kits

AN IMPROVED PROCESS FOR THE MANUFACTURE OF HIGH PURE GEMCITABINE HYDROCHLORIDE

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.