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

A kind of preparation method of (r)-9-[(2-phenoxy phosphoric acid methoxy) propyl group] adenine

A technology of diphenyl phosphite and methyl tert-butyl ether, which is applied in the field of technological synthesis of -9-[propyl] adenine, can solve the problems of complicated operation procedures, difficult ester group control and the like

Active Publication Date: 2022-07-08
QILU PHARMA CO LTD
View PDF5 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0024] The method needs to first prepare tenofovir diphenyl ester and then transesterify to prepare mixed phosphate ester, and finally tenofovir diphenyl ester or mixed phosphate ester (compound of formula III) is hydrolyzed to prepare formula I compound. Selective hydrolysis of an ester group is more difficult to control

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 (r)-9-[(2-phenoxy phosphoric acid methoxy) propyl group] adenine
  • A kind of preparation method of (r)-9-[(2-phenoxy phosphoric acid methoxy) propyl group] adenine
  • A kind of preparation method of (r)-9-[(2-phenoxy phosphoric acid methoxy) propyl group] adenine

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0091] At room temperature, put 16 mL of pyridine into the reaction flask, add 2.0 g of tenofovir, 6.5 g of diphenyl phosphite, and heat the system to 110-120 ° C, react at this temperature for 4 hours, and TLC detects the raw material tenofovir. Wei basically disappeared, the reaction system was lowered to room temperature, filtered, and the filter cake was washed with 20 mL of methyl tert-butyl ether slurry and dried to obtain 2.31 g of the compound of formula I with a yield of 91.7% and a purity of 99.1%.

Embodiment 2

[0098] At room temperature, put 16 mL of pyridine into the reaction flask, add 2.0 g of tenofovir, 16.3 g of diphenyl phosphite, heat the system to 100-110 ° C, react at this temperature for 6 hours, and TLC detects the raw material tenofovir. Wei basically disappeared, the reaction system was lowered to room temperature, filtered, and the filter cake was washed with 20 mL of ethyl acetate slurry and dried to obtain 2.30 g of the compound of formula I with a yield of 90.9% and a purity of 98.0%.

Embodiment 3

[0100] At room temperature, put 16 mL of pyridine into the reaction flask, add 2.0 g of tenofovir and 6.5 g of diphenyl phosphite, and heat the system to 100-110 ° C, react at this temperature for 6 hours, and TLC detects the raw material tenofovir. Wei basically disappeared, the reaction system was lowered to room temperature, filtered, and the filter cake was washed with 20 mL of isopropyl ether slurry and dried to obtain 2.29 g of the compound of formula I with a yield of 90.6% and a purity of 99.0%.

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 process method for synthesizing tenofovir alafenamide intermediate (R)-9-[(2-phenoxyphosphate methoxy)propyl]adenine, using (R)-9 -(2-phosphoryl methoxypropyl)adenine is a starting material, in the presence of a suitable solvent M, it is prepared by reacting with diphenyl phosphite / or with diphenyl phosphite and phenol. The solvent M is selected from pyridine, 2,6-lutidine, triethylamine, diisopropylethylamine; preferably pyridine. The beneficial effect of the method is that: in the preparation process of the compound of formula I, diphenyl phosphite is used to carry out the esterification reaction, and the yield and the purity are greatly improved. % or more, the production cost is greatly reduced; and the method is simple in operation, short in reaction time, high in production efficiency, and easy to scale up; in addition, the method has simple post-treatment process and little environmental pollution, and is suitable for industrial production.

Description

technical field [0001] The invention relates to a method for synthesizing an important intermediate of tenofovir alafenamide fumarate, in particular to a kind of (R)-9-[(2-phenoxyphosphate methoxy)propyl]adenosine The invention relates to a technological synthesis method of glutin, belonging to the technical field of medicine and its intermediates. Background technique [0002] [0003] Tenofovir alafenamide fumarate (compound of formula II, trade name: VEMLIDY) is a hepatitis B virus (HBV) nucleoside analog reverse transcriptase inhibitor, suitable for adults with compensated liver disease Treatment of chronic hepatitis B virus infection. The drug has a very high antiviral effect when it is lower than one-tenth the dose of Viread (tenofovir disoproxil fumarate tablets, Viread, TDF), a listed drug of Gilead, and can improve renal function and renal function. Skeletal aspect parameters. In addition, two-in-one and three-in-one compounds containing tenofovir alafenamide ...

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): C07D235/00
CPCC07F9/65616
Inventor 范传文齐宪亮李玉浩周豪杰王群
Owner QILU PHARMA 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