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

Process method for synthesizing Alzvudine

A process method and intermediate technology, applied in the synthesis of pyrimidine nucleosides and in the field of organic chemistry, can solve the problems of cumbersome reaction steps, cumbersome product refining, troublesome post-processing, etc., and achieve simple operation, environmental protection, and reduction of reaction steps Effect

Active Publication Date: 2022-03-08
TUOXIN GROUP +2
View PDF5 Cites 1 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0004] The second category: Chang Junbiao and others reported a multi-step reaction of fluorosugar to obtain 4'-azidouridine nucleoside, and then through chlorination, aminolysis, and removal of the protecting group at the same time. The reaction process is compared with The above method is relatively simple, but more waste is generated in the process of aminolysis, the refining of the final product is more cumbersome, and reagents with serious pollution such as phosphorus oxychloride are used
[0005] In the existing synthetic methods, the usual reaction step is to use hydroxyl groups to undergo chlorination followed by aminolysis, which requires the use of dangerous reagents such as phosphorus oxychloride, troublesome post-processing, and serious pollution. The reaction steps are relatively cumbersome for industrial production. High energy consumption required

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
  • Process method for synthesizing Alzvudine
  • Process method for synthesizing Alzvudine
  • Process method for synthesizing Alzvudine

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0028]

[0029] In the first step, add 2'-fluoro-4'-azido-uridine (20g, 0.038mol) into the reactor, then add 25% ammonia / methanol 100mL, heat up to 50-60°C for 5h, The liquid phase was tracked until the raw materials basically disappeared, the reaction solution was concentrated to a solid, and 60 mL of 75% ethanol was added to crystallize to obtain 9.8 g of the intermediate, with a yield of 89.5%.

[0030] In the second step, add intermediate 2 (9.8g, 0.034mol), hexamethyldisilazane (15g, 0.093mol) and acetamide (5.49g, 0.093mol) into the reactor, and heat up to 120°C for reaction After 24 hours, the reaction was tracked by liquid phase HPLC until the raw material 2 dropped below 1%. The reaction solution was lowered to room temperature, and 50 mL of methanol was slowly added, a large amount of white solids were precipitated, and 6.9 g of the crude product was obtained by suction filtration and drying, and 5.72 g (0.02 mol) of the finished product Azvudine was obtained by r...

Embodiment 2

[0032]

[0033] In the first step, add 2'-fluoro-4'-azido-uridine (20g, 0.038mol) into the reaction kettle, then add 25% ammonia / ethanol 100mL, heat up to 50-60°C for 5h, The liquid phase was tracked until the raw materials basically disappeared, the reaction solution was concentrated to a solid, and then 60 mL of 75% ethanol was added to crystallize to obtain 9.1 g of an intermediate with a yield of 84.2%.

[0034] In the second step, in the reactor, add intermediate 2 (9.1g, 0.032mol), hexamethyldisilazane (14.2g, 0.088mol) and acetamide (5.19g, 0.088mol), and raise the temperature to 120°C After 24 hours of reaction, liquid phase HPLC followed the reaction until the raw material 2 dropped below 1%. The reaction solution was lowered to room temperature, and 50 mL of methanol was slowly added, a large amount of white solids were precipitated, and 6.2 g of the crude product was obtained by suction filtration and drying, and 5.2 g (0.018 mol) of the finished product Azvudine...

Embodiment 3

[0036]

[0037] In the first step, add 2'-fluoro-4'-azido-uridine (20g, 0.038mol) and 100mL of methanol into the reactor, then add sodium methoxide (4.86g, 0.09mol), and heat up to 50 React at -60°C for 5 hours, track the liquid phase until the raw materials basically disappear, concentrate the reaction solution to a solid, and then add 60 mL of 75% ethanol to crystallize to obtain 8.2 g of the intermediate, with a yield of 75.2%.

[0038] In the second step, add intermediate 2 (8.2g, 0.028mol), hexamethyldisilazane (12.4g, 0.077mol) and acetamide (4.55g, 0.077mol) in the reaction kettle, and raise the temperature to 120°C After 24 hours of reaction, liquid phase HPLC followed the reaction until the raw material 2 dropped below 1%. The reaction solution was lowered to room temperature, and 50 mL of methanol was slowly added, a large amount of white solids were precipitated, and 5.8 g of the crude product was obtained by suction filtration and drying, and 4.8 g (0.016 mol) o...

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 process method for synthesizing Alzvudine, and belongs to the field of synthesis of a medical intermediate nucleoside. The method comprises the following steps: by taking a 2 '-fluoro-4'-azido-uridine intermediate as a raw material, carrying out alkaline hydrolysis to remove a protecting group, and then carrying out silyl ether aminolysis to obtain the alzovudine. The aminolysis product is obtained in one step, and reaction steps are reduced, so that the yield is improved; hexamethylsilazane and amide are adopted to directly convert 4-site hydroxyl of pyrimidine into amino, the operation is simple, less wastewater is generated in the reaction process, and environmental protection is facilitated. The whole process is simple to operate, the yield is stable in the amplification process, and the risk that the yield fluctuates and the product quality is influenced in the phosphorus oxychloride use process is avoided.

Description

technical field [0001] The invention belongs to the field of organic chemistry and relates to the synthesis of pyrimidine nucleosides, in particular to a process for synthesizing azvudine. Background technique [0002] Azvudine, chemical name: molecular formula is C 9 h 13 FN 6 o 4 , is a kind of HIV reverse transcriptase inhibitor, which can effectively inhibit the reverse transcription and replication of HIV in the body. The above-mentioned dual-target anti-HIV-1 drug. It can selectively enter CD4 cells or CD14 cells in peripheral blood mononuclear cells of HIV-1 target cells, and exert the function of inhibiting virus replication. The listing of this variety provides a new treatment option for HIV-1 infected persons. The methods currently reported in the literature are as follows: [0003] The first category: MarkSmith et al. reported that 4'-azido-uridine nucleoside was used as a raw material to first synthesize 2,2'-epoxyuridine through dehydration reaction, and ...

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 Applications(China)
IPC IPC(8): C07H19/06C07H1/00
CPCC07H19/06C07H1/00Y02P20/55
Inventor 杨邵华李涛刘沛马冠军王德地靳海燕刘亚利
Owner TUOXIN GROUP
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