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

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

A technology of methoxy phosphate and adenine, which is applied in the field of preparation of (R)-9-[2-(methoxy phosphate) propyl] adenine, which can solve the dangers, high requirements for reaction conditions, and inconvenient operation and other problems, to achieve the effect of less environmental pollution, high product yield and simple operation

Inactive Publication Date: 2016-01-20
天津药物研究院药业有限责任公司
View PDF7 Cites 2 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0013] Compound (I) can be obtained by the above two methods. Both methods need to use nitrogen protection in the reaction, the reaction conditions are relatively high, and the operation is inconvenient. The first method will generate hydrogen, and the actual operation is more dangerous. The cost of using magnesium tert-butoxide in the second method is relatively high, and the reaction reagent sodium amide used in the third method is relatively active, and the reaction is not easy to control, which limits further large-scale production

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

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0030] At room temperature, dissolve 100.0g of compound (II) in 400mL DMF in a three-necked flask, then cool to 5-10°C, maintain the temperature, add 23.5g of lithium amide and stir for 0.5h, then heat to 25-30°C, maintain the temperature and stir After 2h, 49.2g of magnesium chloride was added and stirred for another 1h. Raise the temperature to 50-55°C, maintain the temperature and stir the reaction for 4h. Then the temperature was raised to 75-80°C, and then 250.0g of compound (Ⅲ) was added, and the temperature was maintained and the reaction was stirred for 4h. After the reaction is complete, cool down to room temperature, add 60.0 g of glacial acetic acid to the mixture, and distill off the solvent under reduced pressure below 70°C. Add 500mL of dichloromethane and 100mL of water to the residual species, stir for 1h, filter, rinse the filter cake with 20mL of dichloromethane, combine the filtrate, stir for 0.5h and then stand for layering, take the dichloromethane layer,...

Embodiment 2

[0032] At room temperature, dissolve 100.0g of compound (II) in 400mL DMF in a three-necked flask, then cool to 5-10°C, maintain the temperature, add 23.5g of lithium amide and stir for 0.5h, then heat to 25-30°C, maintain the temperature and stir After 2h, 49.2g of magnesium chloride was added and stirred for another 1h. Raise the temperature to 50-55°C, maintain the temperature and stir the reaction for 4h. Then the temperature was raised to 75-80°C, and then 250.0g of compound (Ⅲ) was added, and the temperature was maintained and the reaction was stirred for 4h. After the reaction is complete, cool down to room temperature, add 60.0 g of glacial acetic acid to the mixture, and distill off the solvent under reduced pressure below 70°C. Add 500mL of dichloromethane and 100mL of water to the residual species, stir for 1h, filter, rinse the filter cake with 20mL of dichloromethane, combine the filtrate, stir for 0.5h and then stand for layering, take the dichloromethane layer,...

Embodiment 3

[0034]At room temperature, dissolve 50.0g of compound (II) in 200mL DMF in a three-necked flask, then cool to 5-10°C, maintain the temperature, add 11.8g of lithium amide and stir for 0.5h, then heat to 25-30°C, maintain the temperature and stir After 2h, 24.6g of magnesium chloride was added and stirred for another 1h. Raise the temperature to 50-55°C, maintain the temperature and stir the reaction for 4h. Then the temperature was raised to 75-80°C, and then 125.0 g of compound (Ⅲ) was added, and the temperature was maintained and stirred for 4 hours. After the reaction is complete, cool down to room temperature, add 30.0 g of glacial acetic acid to the mixture, and distill off the solvent under reduced pressure below 70°C. Add 250mL of dichloromethane and 50mL of water to the residual species, stir for 1h, filter, rinse the filter cake with 10mL of dichloromethane, combine the filtrates, stir for 0.5h and then stand for layering, take the dichloromethane layer, and remove i...

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 relates to a preparation method of (R)-9-[2-(phosphonomethoxy) propyl] adenine. The preparation method comprises the steps of taking (R)-9-(2-hydroxypropyl) adenine as an initial compound and dissolving the (R)-9-(2-hydroxypropyl) adenine into DMF (dimethyl formamide), using lithium amide to participate in a reaction, slowly dropwise adding diethyl p-toluenesulfonyloxymethyl phosphonate, then, performing a heating reaction, and after treatment, using hydrobromic acid to remove ethyl, so as to obtain the (R)-9-[2-(Phosphonomethoxy) propyl] adenine. The initial material used by the preparation method is easy to obtain, safe and stable, the synthetic method is simple to operate, the product yield is high, the purity is high, the pollution to environment is relatively small, and a simple and feasible method is provided for the mass production of the compound, namely the (R)-9-[2-(Phosphonomethoxy) propyl] adenine.

Description

technical field [0001] The invention belongs to the field of preparation of nucleoside anti-hepatitis B virus (HBV) and anti-AIDS virus (HIV) drug tenofovir disoproxil fumarate intermediate, more specifically relates to a preparation compound (R) - A novel approach to 9-[2-(phosphomethoxy)propyl]adenine. Background technique [0002] Tenofovir disoproxil fumarate is a nucleoside reverse transcriptase inhibitor for the treatment of HIV and HBV infection, (R)-9-[2-(phosphomethoxy)propyl]adenine is An important intermediate for the synthesis of tenofovir disoproxil fumarate, and an active ingredient for its pharmacological effects after entering the body. The molecular formula of (R)-9-[2-(phosphomethoxy)propyl]adenine is: C 9 h 14 N 5 o 4 P, molecular weight: 287.21, its [0003] The chemical structural formula is as follows: [0004] [0005] I [0006] The preparation method has been reported: foreign literature: WO2008007392A2; method of preparation. The basic ...

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
Inventor 任晓峰张智强李果赵钊宋金津李慧龙赵欣吴海明李静雅王凯
Owner 天津药物研究院药业有限责任公司
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