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

Chemical synthesis of triacetylganciclovir

A technology of chemical synthesis and ganciclovir, applied in the field of chemical synthesis of triacetyl ganciclovir, can solve the problems of many other impurities, inability to carry out refining and purification, and need to be refined for about 8 times to be barely qualified, and achieve selectivity. Good results

Inactive Publication Date: 2009-07-08
张小顺 +1
View PDF1 Cites 4 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

The purity of triacetylganciclovir obtained by the preparation method of Chinese patent CN99127165 is very low, generally only 67%. Sometimes there will be an unknown impurity of about 15%, which is very difficult to remove after being hydrolyzed into ganciclovir, and the triacetyl ganciclovir prepared by it is in the form of syrup, so it cannot be refined and purified, and it is directly hydrolyzed into ganciclovir in production. After ganciclovir is refined, because there are too many impurities, and the purification of ganciclovir to remove impurities is much more difficult than that of triacetyl ganciclovir, the ganciclovir obtained by hydrolysis needs to be refined about 8 times to be barely Passed, process reproducibility is poor
[0003] And owing to adopting 2,9 diacetylguanine is difficult to completely react as starting material, the triacetylganciclovir that obtains by CN99127165, the aftertreatment method of 1999 contains relatively high unreacted purine derivatives, and the prepared more The guanine impurity of ciclovir is very high, and other impurities are also very high, it needs more than 8 times of water purification, and the yield is very low

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
  • Chemical synthesis of triacetylganciclovir
  • Chemical synthesis of triacetylganciclovir

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0033] Feeding molar ratio monoacetylguanine: 1,3-dichloro-2-(acetoxymethoxy) propane: catalyst is 1:1.5:0.03, catalyst is p-toluenesulfonic acid, organic solvent is toluene, and its consumption is 5 times the weight of monoacetylguanine.

[0034] In a 250ml four-necked flask equipped with a thermometer, a reflux condenser, a constant pressure dropping funnel, and a mechanical stirrer, add 19.3g (100mmol) of monoacetylguanine, 1,3-dichloro-2-(acetoxymethoxy base) propane 30.2g (150mmol), toluene 96.5g and catalyst 0.58g. After the addition, heat up to 100°C, and react at 100°C for 48 hours, followed by TLC monitoring (developing solvent: chloroform-methanol-ammonia (8:2:0.2)), after the reaction is complete, stop heating, cool naturally, and cool with ice-salt water. Temperature 0°C, filter with suction, wash the filter cake with 20ml of acetone, put the solid into a three-neck flask, soak and stir with 80ml of acetone for 10 minutes, filter with suction, and dry the filter c...

Embodiment 2

[0049] Feeding molar ratio monoacetylguanine: 1,3-dichloro-2-(acetoxymethoxy)propane: catalyst is 1:1.1:0.015, catalyst is concentrated sulfuric acid, organic solvent is xylene, and its consumption is mono 5 times the weight of acetylguanine.

[0050] In a 250ml four-necked flask equipped with a thermometer, a reflux condenser, a constant pressure dropping funnel, and a mechanical stirrer, add 19.3g (100mmol) of monoacetylguanine, 1,3-dichloro-2-(acetoxymethoxy base) propane 22.1 g (110 mmol), xylene 96.5 g and catalyst 0.15 g. After the addition, heat up to 120°C, and react at 120°C for 24 hours, followed by TLC monitoring (developing solvent: chloroform-methanol-ammonia (8:2:0.2)), after the reaction is complete, stop heating, cool naturally, and cool with ice-salt water. The temperature is 0°C, suction filtration, the filter cake is washed with 20ml of acetone, the solid is put into a three-neck flask, soaked with 80ml of acetone and stirred for 10 minutes, suction filtrat...

Embodiment 3

[0065] Feeding molar ratio monoacetylguanine: 1,3-dichloro-2-(acetoxymethoxy) propane: catalyst is 1:1.5:0.03, catalyst is p-toluenesulfonic acid, organic solvent is DMF, and its consumption is 5 times the weight of monoacetylguanine.

[0066] In a 250ml four-necked flask equipped with a thermometer, a reflux condenser, a constant pressure dropping funnel, and a mechanical stirrer, add 19.3g (100mmol) of monoacetylguanine, 1,3-dichloro-2-(acetoxymethoxy base) propane 30.2g (150mmol), DMF96.5g and catalyst 0.58g. After the addition, heat up to 150°C, and react at 150°C for 48 hours, followed by TLC monitoring (developing solvent: chloroform-methanol-ammonia (8:2:0.2)), after the reaction is complete, stop heating, cool naturally, and cool with ice-salt water. The temperature is 0°C, suction filtration, the filter cake is washed with 20ml of acetone, the solid is put into a three-neck flask, washed with 80ml of acetone and stirred for 10 minutes, suction filtered, the filter ca...

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

PropertyMeasurementUnit
boiling pointaaaaaaaaaa
Login to View More

Abstract

The invention discloses a chemical synthesis method for triacetylganciclovir of a structural formula (I). The synthesis method comprises that: monoacetylguanine of a structural formula (II) and 1,3-dihalo-2-(acetoxylmethoxy) propane of a structural formula (III) are used raw materials to be reacted in a solvent A at 100 to 150 DEG C in the presence of a catalyst to form dihalo-2- acetyl- ganciclovir; the dihalo-2- acetyl- ganciclovir and an acetate are completely reacted in an organic solvent B at 70 to 150 DEG C; and the triacetylganciclovir is obtained after post treatment. The invention is reasonable in process, high in reaction yield, high in product purity and low in production cost and has good process application value.

Description

(1) Technical field [0001] The present invention relates to a kind of triacetylganciclovir {9-[2-acetoxy-1-(acetoxymethyl)ethoxy]methyl-2-acetamido-6-oxo-purine} chemical synthesis method. (2) Background technology [0002] Regarding the synthesis of ganciclovir, there are many methods reported in the literature, but the basic principle is the same. Since 1982, many companies have applied for patents, but basically using guanine and its derivatives as the main raw material and various Condensation reaction of acetoxymethyl ether or halomethyl ether. Hubei Medical Research Institute (Chinese Patent CN99127165, 1999) adopts diacetylguanine and 1,3-dihalo-2-propoxymethanol alkyl carboxylate to carry out condensation, dehalogenation and hydrolysis to obtain ganciclovir, which The bar technique relates to the synthesis of an important intermediate, namely triacetyl ganciclovir mentioned in the present invention, triacetyl ganciclovir obtains ganciclovir through hydrolysis, and ...

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): C07D473/18
Inventor 张小顺
Owner 张小顺
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