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

Synthetic method of ridecevir D-ribonolactone

A synthesis method and ribonucleic acid technology are applied in the field of synthesis of Remdesivir D-ribonolactone, which can solve the problems of high environmental protection pressure, easy generation of impurities, numerous processes, etc., and achieve environmental protection pressure improvement, production cost reduction, The effect of simplifying the synthesis process

Pending Publication Date: 2022-03-08
NANTONG CHANGYOO PHARMATECH CO LTD
View PDF5 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0015] The purpose of the present invention is to provide a synthetic method of remdesivir D-ribonolactone, to solve the present stage of the synthetic method of remdesivir D-ribonolactone proposed in the above background technology, there are many procedures and cost High, easy to produce impurities, low yield, high pressure on environmental protection

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
  • Synthetic method of ridecevir D-ribonolactone
  • Synthetic method of ridecevir D-ribonolactone
  • Synthetic method of ridecevir D-ribonolactone

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0031] S1, preparation of compound RD-1

[0032] Weigh 100g, 0.67mol of D-ribose, 25.5g, 0.165mol, 0.25eq of diazabicyclo, 500ml of tetrahydrofuran, 158g, 0.73mol, 1.1eq of pyridinium chlorochromate;

[0033] First, fully stir and dissolve D-ribose, diazabicyclo and tetrahydrofuran according to the above-mentioned weighing amount, and then cool down to 0-5°C under the protection of nitrogen, and then slowly add pyridinium chlorochromate in batches. Reactions were carried out for 2 to 3 hours under monitoring (e.g. figure 1 shown), after the reaction is completed, add 6.5g, 62.5mmol of sodium bisulfite to quench at 0-5°C, stir for 30 minutes, then concentrate at 45-50°C under vacuum to form a reaction solution. Then hot filtration was carried out with absolute ethanol, and concentrated to obtain 85 g of compound RD-1 as a white solid, with a yield of 86%.

[0034] S2, preparation of compound RD-2

[0035] Weigh 70g, 0.5mol of compound RD-1, 350g of dichloromethane, 0.6g, 0.0...

Embodiment 2

[0041] S1, preparation of compound RD-1

[0042]Weigh 100g, 0.67mol of D-ribose, 20.5g, 0.135mol, 0.20eq of diazabicyclo, 500ml of tetrahydrofuran, 288g, 1.34mol, 2.0eq of pyridinium chlorochromate;

[0043] First, stir D-ribose with diazabicyclo and tetrahydrofuran according to the above weighing amount, and then cool down to 0-5°C under the protection of nitrogen, then slowly add pyridinium chlorochromate in batches, and carry out under TLC monitoring. 2 to 3 hours of reaction (such as figure 1 shown), after the reaction is completed, add 6.5g, 62.5mmol of sodium bisulfite to quench at 0-5°C, stir for 30 minutes, concentrate under vacuum at 45-50°C to form a reaction solution, and then Filtrated with absolute ethanol and concentrated to obtain 66 g of compound RD-1 as a white solid, with a yield of 65%.

[0044] S2, preparation of compound RD-2

[0045] Weigh 60g, 0.40mol of compound RD-1, 330g of dichloromethane, 0.5g, 0.004mol, 0.01eq of 4-dimethylaminopyridine, 41.4g, ...

Embodiment 3

[0051] S1, preparation of compound RD-1

[0052] Weigh 100g, 0.67mol of D-ribose, 25.5g, 0.165mol, 0.25eq of diazabicyclo, 500ml of 50% tetrahydrofuran aqueous solution, 100g, 0.5mol, 0.6eq of pyridinium chlorochromate;

[0053] First, fully stir and dissolve D-ribose, diazabicyclo and 50% tetrahydrofuran aqueous solution according to the above weighing amount, and then cool down to 0-5°C under the protection of nitrogen, and then slowly add pyridinium chlorochromate in batches , and reacted for 2 to 3 hours under TLC monitoring (such as figure 1 shown), after the reaction is completed, add 6.5g, 62.5mmol of sodium bisulfite to quench at 0-5°C, stir for 30 minutes, concentrate at 45-50°C under vacuum to form a reaction solution, and then After hot filtration with absolute ethanol, 60 g of white solid compound RD-1 was obtained by concentration, and the yield was 59%.

[0054] S2, preparation of compound RD-2

[0055] Weigh 60g, 0.40mol of compound RD-1, 300g of dichlorometh...

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 synthesis method of ridecevir D-ribonolactone, which is characterized by comprising the following three synthesis steps: S1, preparation of a compound RD-1; s2, preparing a compound RD-2; and S3, preparing a target product compound RD-3. According to the method for synthesizing the ridecevir D-ribonolactone by using the cheap and easily available D-ribose as the starting material, the pyridinium chlorochromate oxidation reaction, the acetyl protection reaction, the acetonylidene protection hydroxyl reaction and other reactions are utilized, so that the synthesis process route is short, the operation difficulty is effectively simplified, the high-temperature reaction is avoided, and the method is suitable for industrial production. The synthesis process is safer and more reliable, the energy is effectively saved, the yield is improved, the synthesis process can be completed without using highly toxic substances, the generation of toxic and harmful wastewater is effectively avoided, and the environment is improved, so that the industrial production can be well realized.

Description

technical field [0001] The invention belongs to the technical field of chemical medicines, and in particular relates to a method for synthesizing remdesivir D-ribonolactone. Background technique [0002] Remdesivir is a nucleoside analogue, CAS registration number: 1809249-37-3, shown in structural formula II, developed by Gilead Sciences of the United States, the US FDA gave the green light to Remdesivir , approving the drug for hospitalized COVID-19 patients. Remdesivir is also an orphan drug for the treatment of Ebola virus infection, and it has also become the first drug approved in the United States for patients with new crowns. For the emergency treatment of 2019-nCoV infected patients. It has antiviral activity. In HAE cells, the EC50 value for SARS-CoV and MERS-CoV is 74 nM. In delayed brain tumor cells, the EC50 value for murine hepatitis virus is 30 nM. It shows a good curative effect on coronavirus and is a potential drug for the treatment of new coronaviruses....

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): C07D493/04
CPCC07D493/04
Inventor 李科颖李泽标陈丹顾文超胡顺卫邹林
Owner NANTONG CHANGYOO PHARMATECH CO LTD
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