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

Preparation method of β-configuration decitabine precursor

A decitabine and configuration technology, applied in the field of preparation of decitabine precursors, can solve problems such as unfavorable enrichment of β-type products, and achieve the effects of simple post-processing, improved selectivity and good repeatability

Inactive Publication Date: 2018-04-24
ZHENGZHOU TECHN COLLEGE +1
View PDF13 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0006] In short, the prior art of directly using methoxy for direct coupling all teaches that it is not conducive to the enrichment of β-type products. Most of the literature is to convert the C1-position group, usually to a halogen or acyl group, and then perform coupling

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
  • Preparation method of β-configuration decitabine precursor

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0018] 60 mmol of 2,4-bis-(trimethylsilyl)-5-azacytosine with 50 mmol of 1-(2-butenyl)oxy-2-deoxy-3,5-di-O-acetyl -D-ribofuranose was dissolved in 500 mL of acetonitrile, the temperature was controlled to 0 °C, 10 mmol of trifluoromethanesulfonic acid was added, and 0 °C was continued, and the reaction was stirred for 2 hours, and the reaction was completed by HPLC monitoring. Quickly quench the reaction and wash the reaction mixture with 500 mL of saturated aqueous sodium bicarbonate solution, separate the organic layer, evaporate it to dryness under vacuum, and then recrystallize with toluene to obtain 14.75 g of solid, which is identified as 1-(2- Deoxy-3,5-di-O-acetyl-D-ribose)-4-amino-1,3,5-s-triazin-2-one, its purity detected by HPLC is 90%, and its β configuration is the same as α The content ratio of the configuration was 2.5.

[0019] 1 H-NMR(DMSO-d6)δ: 2.0(s, 6H), 2.2-3.0(m, 2H), 4.1(m, 1H), 4.3(m, 1H), 4.8(m, 1H), 5.2(m ,1H),6.1(m,1H),7.5(s,1H),7.6(s,1H),8.4(s,1H...

Embodiment 2-4

[0021] Use 1-allyloxy-2-deoxy-3,5-di-O-acetyl-D-ribofuranose to directly carry out the coupling reaction. For each condition, refer to the example cytosine raw material 1,2,4-di-( The amount of trimethylsilyl)-5-azacytosine is different, and the results are summarized as follows:

[0022]

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 provides a preparation method of a beta-configuration decitabine precursor. The preparation method comprises the following step: under the action of a Lewis acid catalyst, directly performing a coupling reaction on acylated sugar adopting the structure of 1-alkenylmethoxy-2-deoxy-3, 5-di-O-acetyl-D-ribofuranose and a silicon ether compound of 5-azacytosine to obtain beta-configuration 1-(2-deoxy-3,5-di-O-acetyl-D-ribose)-4-amino-1,3,5-s-triazine-2-one. The beta-configuration decitabine precursor is high in selectivity, good in repeatability and very high in molar yield and purity.

Description

technical field [0001] The present invention relates to a preparation method of decitabine precursor. Background technique [0002] The preparation process of decitabine is disclosed in many documents, and is roughly divided into three categories: isocyanate method, azacitidine deoxygenation method, and glycosidation method. The characteristic of glycosidation method is that the pyrimidine part is coupled with the ribose part, and the coupling reaction is obtained. The product of hydroxy-protected decitabine (referred to as decitabine precursor in this application) is finally deprotected (usually hydrolyzed) to obtain decitabine. As we all know, decitabine is a beta isomer, but it is usually obtained as a mixture of alpha and beta during preparation. Obviously, the content ratio of beta decitabine in the product and its purification complexity Both were directly affected by the proportion of beta form in the decitabine precursor before hydrolysis. [0003] Before coupling,...

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): C07H19/12C07H1/00
CPCC07H1/00C07H19/12
Inventor 闫生辉王云龙高玉红程春杰邓黎黎
Owner ZHENGZHOU TECHN COLLEGE
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