Supercharge Your Innovation With Domain-Expert AI Agents!

Preparation method of tenofovir alafenamide (TAF) synthesized through three-step method

A technology of tenofovir alafenamide and ethylphosphonamide, which is applied in the field of preparation of tenofovir alafenamide by three-step method, can solve the problems of difficult industrial production, large environmental pollution and high preparation cost , to achieve the effect of simple method, environmental friendliness and low cost

Pending Publication Date: 2019-12-10
JIANGXI AGRICULTURAL UNIVERSITY
View PDF1 Cites 2 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0003] The object of the present invention is to provide a kind of preparation method of tenofovir alafenamide that is green, pollution-free, environment-friendly, raw material is easy to get, source is wide, cost is low, method is simple, is suitable for industrialized production, the preparation method It solves the problems of high preparation cost, large environmental pollution and difficulty in industrial production in the prior art

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 tenofovir alafenamide (TAF) synthesized through three-step method

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0020]The preparation method of tenofovir alafenamide: phenoxy N-(1-isopropoxyformyl) ethyl phosphoramidite (271.25 g, 1.00 mol), paraformaldehyde (36.80 g, 1.20 mol ) and toluene (0.80 L) were placed in a three-necked flask, and triethylamine (50.50 g, 0.50 mol) was slowly added dropwise at 25 °C. After the addition was completed, the temperature was raised to 90 °C and stirred for 2 h. Reflux for 3 h. Cooling, washing with water, and drying to obtain product 3: 2-(2,3,4,5-tetrafluorophenyl)formyl-3-(1-hydroxy-1-phenylmethyl)aminoethyl acrylate Toluene solution. Cool the toluene solution of product 3 to 5 °C, slowly add triethylamine (50.50 g, 0.50 mol) dropwise, and continue to drop p-toluenesulfonyl chloride (190.65 g, 1.00 mol) at this temperature after the dropwise addition, and wait After the dropwise addition, the temperature was slowly raised to room temperature and stirred for 2 h. Wash with water and dry to obtain product 4: toluene solution of p-toluenesulfonylox...

Embodiment 2

[0022] The preparation method of tenofovir alafenamide: phenoxy N-(1-isopropoxyformyl) ethyl phosphoramidite (271.25 g, 1.00 mol), paraformaldehyde (36.80 g, 1.20 mol ) and anisole (0.80 L) were placed in a three-necked flask, and pyridine (39.55 g, 0.50 mol) was slowly added dropwise at 25 °C. After the addition was completed, the temperature was raised to 90 °C and stirred for 2 h. Reflux for 3 h. Cooling, washing with water, and drying to obtain product 3: 2-(2,3,4,5-tetrafluorophenyl)formyl-3-(1-hydroxy-1-phenylmethyl)aminoethyl acrylate Anisole solution. Cool the anisole solution of product 3 to 5°C, slowly add pyridine (39.55 g, 0.50 mol) dropwise, and continue to add benzenesulfonyl chloride (176.65 g, 1.00 mol) dropwise at this temperature slowly after the dropwise addition, and wait until the dropwise After the addition was completed, the temperature was slowly raised to room temperature and stirred for 2 h. Washed with water and dried to obtain product 4: an aniso...

Embodiment 3

[0024] The preparation method of tenofovir alafenamide: phenoxy N-(1-isopropoxyformyl) ethyl phosphoramidite (271.25 g, 1.00 mol), formaldehyde (36.80 g, 1.20 mol) and 1,2-Dichloroethane (0.80 L) was placed in a three-necked flask, and N-methylimidazole (41.05 g, 0.50 mol) was slowly added dropwise at 25 °C. After the addition was completed, the temperature was raised to 90 °C and stirred for 2 h. The reaction The liquid was clear, and the temperature was slowly raised to reflux for 3 h. Cooling, washing with water, and drying to obtain product 3: 2-(2,3,4,5-tetrafluorophenyl)formyl-3-(1-hydroxy-1-phenylmethyl)aminoethyl acrylate 1,2-dichloroethane solution. Cool the 1,2-dichloroethane solution of product 3 to 5 °C, slowly add N-methylimidazole (41.05 g, 0.50 mol) dropwise, and continue to drop methanesulfonyl chloride ( 114.55 g, 1.00 mol), after the dropwise addition was completed, the temperature was slowly raised to room temperature, and stirred for 2 h. Wash with water...

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 tenofovir alafenamide (TAF). The preparation method comprises the steps that phenoxy N-(1-isopropoxyformyl)ethyl phosphoramidite (2) is taken as a raw material, and after the raw material is subjected to a nucleophilic addition reaction, a sulfonylation reaction and a nucleophilic substitution reaction, splitting is conducted to obtain the TAF. The preparation method has the advantages that environmental protection is realized, pollution is avoided, environmental friendliness is realized, the raw material is easy to obtain, wide in source and lowin cost, and the method is simple and suitable for industrial production, and the problems of high preparation cost and difficult industrial production in the prior art are solved through the preparation method.

Description

technical field [0001] The invention relates to the field of organic medicinal chemistry, in particular to a preparation method for synthesizing tenofovir alafenamide by a three-step method. Background technique [0002] Tenofovir Alafenamide (TAF), is a new type of nucleotide reverse transcriptase inhibitor, developed by Gilead, USA, for the treatment of chronic hepatitis B virus infection and compensatory liver disease. Tenofovir alafenamide is an oral prodrug of Tenofovir disoproxil Viread (TFV), which is an improved version of the marketed drug Tenofovir disoproxil fumarate (TDF). Compared with TDF, The clinical dosage of TAF is smaller, and it is easier to enter the cells to exert its drug effect, the antiviral effect is stronger, and the adverse reactions are reduced. Tenofovir alafenamide compound patent CN200410097845, expires in July 2021. Therefore, it is of great theoretical and practical significance to study the synthesis and production of tenofovir alafenami...

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
IPC IPC(8): C07F9/6561
CPCC07F9/65616
Inventor 黄建平黄国平方文超黄川邹柳红余荣静
Owner JIANGXI AGRICULTURAL UNIVERSITY
Features
  • R&D
  • Intellectual Property
  • Life Sciences
  • Materials
  • Tech Scout
Why Patsnap Eureka
  • Unparalleled Data Quality
  • Higher Quality Content
  • 60% Fewer Hallucinations
Social media
Patsnap Eureka Blog
Learn More

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

© 2025 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap|About US| Contact US: help@patsnap.com