Looking for breakthrough ideas for innovation challenges? Try Patsnap Eureka!

A kind of preparation method of decitabine intermediate

An intermediate, citabine technology, applied in the direction of preparation of sugar derivatives, chemical instruments and methods, esterified saccharides, etc., can solve the problems of harsh reaction conditions, low market supply, high cost, etc., to achieve easy operation and control, reduce Handling hazards, effects of avoiding use of toxic solvents

Active Publication Date: 2016-02-03
SHANDONG NEWTIME PHARMA
View PDF3 Cites 3 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0015] The starting material used in this route is azacitidine, and special reagents TiPSh, phenyl thiochloroformate, and TTMSS are used. The market supply is small, the cost is high, and the reaction conditions are harsh.

Method used

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

Image

Smart Image Click on the blue labels to locate them in the text.
Viewing Examples
Smart Image
  • A kind of preparation method of decitabine intermediate
  • A kind of preparation method of decitabine intermediate
  • A kind of preparation method of decitabine intermediate

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0067] Synthesis of Intermediate I

[0068] Add 1200g of 2-deoxy-D-ribose and 12L of anhydrous methanol into the reaction kettle, and stir at room temperature until the solid is completely dissolved, and the system is a light yellow transparent solution. 2.4 L of HCl-methanol solution with a mass fraction of HCl of 1% was added dropwise through a constant pressure funnel. After the dropwise addition was complete, it was stirred for 40 minutes. 600 ml of pyridine was added and stirring was continued for 30 minutes. After suction filtration, the filter cake was washed with anhydrous methanol, and the filtrate was evaporated to dryness under reduced pressure at 0.01Mpa to obtain 2.1Kg of intermediate I as an oil.

[0069] Synthesis of Intermediate II

[0070] Add 1.185Kg of intermediate I and 8L of anhydrous pyridine into the reaction kettle, control the reaction temperature at -20°C, add 4.552KgFmoc-Cl in three batches, each with an interval of 1 hour, after the addition is c...

Embodiment 2

[0074] Synthesis of Intermediate I

[0075] Add 1200g of 2-deoxy-D-ribose and 12L of anhydrous methanol into the reaction kettle, stir at room temperature until the solids are completely dissolved, and the system is a light yellow transparent solution. 2.4 L of HCl-methanol solution with a mass fraction of HCl of 0.5% was added dropwise through a constant pressure funnel. After the dropwise addition was complete, it was stirred for 40 minutes. 600 ml of pyridine was added and stirring was continued for 30 minutes. After suction filtration, the filter cake was washed with anhydrous methanol, and the filtrate was evaporated to dryness under reduced pressure at 0.01Mpa to obtain Intermediate I as an oil.

[0076] Synthesis of Intermediate II

[0077] Add 1.185Kg of intermediate I, 8L of anhydrous pyridine to the reaction kettle, control the reaction temperature between 0°C, add 4.552KgFmoc-Cl in two equal batches, and the interval between the two batches is half an hour. After...

Embodiment 3

[0081] Synthesis of Intermediate I

[0082] Add 1200g of 2-deoxy-D-ribose and 12L of anhydrous methanol into the reaction kettle, and stir at room temperature until the solid is completely dissolved, and the system is a light yellow transparent solution. 2.4 L of HCl-methanol solution with a mass fraction of HCl of 1.2% was added dropwise through a constant pressure funnel. After the dropwise addition was complete, it was stirred for 40 minutes. 600 ml of pyridine was added and stirring was continued for 30 minutes. After suction filtration, the filter cake was washed with anhydrous methanol, and the filtrate was evaporated to dryness under reduced pressure at 0.01Mpa to obtain 2.1Kg of intermediate I as an oil.

[0083] Synthesis of Intermediate II

[0084] Add 1.185Kg of intermediate I, 8L of anhydrous pyridine to the reaction kettle, control the reaction temperature between 10°C, add 4.552KgFmoc-Cl in two equal batches, and the interval between the two batches is half an...

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

PUM

No PUM Login to View More

Abstract

The invention discloses a preparation method of a decitabine intermediate compound 1-acetoxyl-2-deoxidized-3,5-bi-O-fluorene methyl cyslohexyl-D-ribofuranose. The structural formula of the compound is shown in img file='DDA0000455164900000011.TIF' wi='648' he='304' / , and the preparation method comprises the following steps: o-methylation of 2'-deoxidized-D-ribose 1-bit hydroxyl; b) protection of 3,5-bit hydroxyl; and c) acylation of 1-bit-O-methyl. The invention also discloses a method for preparing decitabine employing the intermediate as a raw material.

Description

technical field [0001] The invention relates to a preparation method of a decitabine intermediate compound 1-acetyloxy-2-deoxy-3,5-di-O-fluorenylmethoxycarbonyl-D-ribofuranose, which belongs to the field of medicine and chemical industry. Background technique [0002] Decitabine (also known as Dezocitadine), chemical name: 4-amino-1-(2-deoxy-β-D-erythrofuranose)-1,3,5-triazine-2(1H)- Ketone is an analogue of 2′-deoxycytidine, the structural formula is (I): [0003] [0004] Decitabine is a specific DNA methyltransferase inhibitor that can be phosphorylated by deoxycytidine kinase and incorporated into DNA in the form of phosphate. High concentration of decitabine incorporation can inhibit DNA synthesis to induce cell death and exert its cytotoxic effect; low concentration of decitabine incorporation can replace cytosine in tumor cells and covalently bind to DNA methyltransferase , inactivates DNA methyltransferases without causing cell death. [0005] Decitabine was de...

Claims

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

Application Information

Patent Timeline
no application Login to View More
Patent Type & Authority Patents(China)
IPC IPC(8): C07H13/12C07H1/00C07H19/12
Inventor 白文钦曹守敬赵桂芳
Owner SHANDONG NEWTIME PHARMA
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Patsnap Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Patsnap Eureka Blog
Learn More
PatSnap group products

Browse by: Latest US Patents, China's latest patents, Technical Efficacy Thesaurus, Application Domain, Technology Topic, Popular Technical Reports.

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap|About US| Contact US: help@patsnap.com