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

Preparation method of (R)-9-[(2-phenoxyphosphonomethoxy)propyl]adenine

A technology of diphenyl phosphite and methyl tert-butyl ether, which is applied in the field of process synthesis of -9-[propyl]adenosine, can solve the problems of difficult ester group control and complicated operation procedures. The processing operation is simple and easy, the reaction efficiency is improved, and the process and time are saved.

Active Publication Date: 2019-09-24
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
  • Preparation method of (R)-9-[(2-phenoxyphosphonomethoxy)propyl]adenine
  • Preparation method of (R)-9-[(2-phenoxyphosphonomethoxy)propyl]adenine
  • Preparation method of (R)-9-[(2-phenoxyphosphonomethoxy)propyl]adenine

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0091] At room temperature, put 16mL of pyridine into the reaction bottle, add 2.0g of tenofovir, 6.5g of diphenyl phosphite, raise the temperature of the system to 110-120°C, react at this temperature for 4 hours, TLC detects that the raw material tenofovir Wei basically disappeared, the reaction system was lowered to room temperature, filtered, the filter cake was washed with 20 mL of methyl tert-butyl ether, 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 16mL of pyridine into the reaction bottle, add 2.0g of tenofovir, 16.3g of diphenyl phosphite, raise the temperature of the system to 100-110°C, react at this temperature for 6 hours, TLC detects that the raw material tenofovir Wei basically disappeared, the reaction system was cooled to room temperature, filtered, 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 16mL of pyridine into the reaction bottle, add 2.0g of tenofovir, 6.5g of diphenyl phosphite, raise the temperature of the system to 100-110°C, react at this temperature for 6 hours, TLC detects that the raw material tenofovir Wei basically disappeared, the reaction system was cooled to room temperature, filtered, the filter cake was washed with 20 mL of isopropyl ether, 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 for synthesizing tenofovir alafenamide intermediate (R)-9-[(2-phenoxyphosphonomethoxy)propyl]adenine. (R)-9-(2-phosphonomethoxypropyl)adenine is taken as a starting material to carry out a reaction with diphenyl phosphite or with diphenyl phosphite and phenol for preparation in the presence of a proper solvent M, wherein the solvent M is selected from a group consisting of pyridine, 2,6-lutidine, triethylamine and diisopropylethylamine, and preferably pyridine. The beneficial effects of the method are as follows: in a preparation process of a compound represented by a formula I, an esterification reaction is carried out by using diphenyl phosphite, and the yield and purity are greatly improved, wherein the yield in a specific experiment reaches 90% or above, the purity reaches 98% or above, and thus production cost is greatly reduced; the method is simple in operation, short in reaction time and high in production efficiency and is easy for amplification; and in addition, the method is simple in post-treatment process, has small environmental pollution, and is suitable for industrial production.

Description

technical field [0001] The present invention relates to a synthetic method of an important intermediate of tenofovir alafenamide fumarate, in particular to a (R)-9-[(2-phenoxyphosphorylmethoxy)propyl] gland The technical synthesis method of fatin belongs to the technical field of medicine and intermediates thereof. 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 the dose is lower than one-tenth of Gilead's marketed drug Viread (tenofovir disoproxil fumarate tablets, Viread, TDF), and can improve renal function and Skeletal parameters. In addition, the two-in-one and three-in-one compound containing tenofovir alafenamide fumarate, which is used to treat HIV virus infection, has a...

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): C07F9/6561
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