Adefovir dipivoxil monohydrate and preparation method thereof

A technology of adefovir dipivoxil and monohydrate, which is applied in the field of drug synthesis, can solve the problems of cumbersome operation, difficult preparation of adefovir dipivoxil hydrate, and unsuitability for large-scale production, and achieve simple and convenient operation and clinical convenience Effects of application, good stability and water solubility

Active Publication Date: 2015-03-04
SUZHOU ERYE PHARMA CO LTD
View PDF2 Cites 8 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

This method is relatively cumbersome to operate, needs to experience cooling and heating operations, and is limited by the crystallization bottle, and is not suitable for large-scale production
And, the product that it obtains contains the water of crystallization of different molecular numbers, is difficult to the desired adefovir dipivoxil hydrate of selective preparation

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
  • Adefovir dipivoxil monohydrate and preparation method thereof
  • Adefovir dipivoxil monohydrate and preparation method thereof
  • Adefovir dipivoxil monohydrate and preparation method thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0024] The preparation of embodiment 1 ethylene carbonate (intermediate I)

[0025]

[0026] Install a mechanical stirrer, thermometer and reflux condenser in a dry 10 L reaction flask. Add 3 kg (48.39 mol) of ethylene glycol, 6.24 kg (52.88 mol) of diethyl carbonate and 16.3 g of anhydrous potassium carbonate of about 40% of the calculated amount in sequence, stir, and heat to reflux, react for 30 minutes, and then The remaining 24.0 g of anhydrous potassium carbonate was added. Continue the reflux reaction for 5 hours, recover ethanol, cool and crystallize, filter, and wash the filter cake with cold absolute ethanol, then air-dry to obtain ethylene carbonate as a colorless crystalline solid 2.23g, Mp: 36~38°C , yield 52.4%, Mp: 39-40°C, yield 51%-59.5%.

Embodiment 2

[0027] Example 2 Preparation of 9-hydroxyethyladenine (intermediate II)

[0028]

[0029] Install a mechanical stirrer, a reflux condenser and a thermometer in a 10L reaction flask. 3kg (22.22mol) of adenine, 2.14kg (24.32mol) of ethylene carbonate, 20g (0.5mol) of sodium hydroxide and 7L of DMF were sequentially added thereto, stirred, and heated to reflux for 4 hours. After the reaction is completed, cool to room temperature, filter, wash the filter cake with DMF, and dry it in vacuum at 70° C. for 6 hours. The obtained 9-hydroxyethyladenine was 3.29kg of off-white solid powder, Mp: 225-227°C (decomposition), and the yield was 82.7%.

Embodiment 3

[0030] Example 3 Preparation of 9-[2-(diethoxyphosphorylmethoxy)ethyl]adenine (intermediate III)

[0031]

[0032] Install a mechanical stirrer, a dropping funnel and a thermometer in a 50 L dry reaction flask. Add 2kg (11.17mol) of intermediate II and 12L of DMF to it in sequence, stir, and cool to below 0°C, add 1.1kg (45.83mol) of 60% sodium hydride in batches to control the feeding speed, so that the reaction temperature is between 0 and 5°C between. After the addition is completed, continue to stir and react at 5°C for 1 hour, then add dropwise a solution containing 4.7kg (14.60mol) of diethyl toluenesulfonyloxymethyl phosphate and DMF8.5L, and control the rate of addition so that the reaction temperature is between Between 0 and 5°C, after the addition is complete, continue to stir and react at 5°C for 5 hours. After the reaction was completed, add glacial acetic acid to neutralize and adjust the pH value to 5-6, distill under reduced pressure and recover DMF, disso...

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 adefovir dipivoxil monohydrate and a preparation method thereof. According to the preparation method, water-containing acetone is taken as a solvent and is subjected to freeze drying so as to generate freeze-dried powder of adefovir dipivoxil monohydrate. The preparation method is easy and convenient to operate, monohydrate can be selectively prepared, the yield of adefovir dipivoxil monohydrate is high, and the purity of adefovir dipivoxil monohydrate is good; the preparation method is very applicable to large-scale production.

Description

[0001] technical field [0002] The invention relates to adefovir dipivoxil monohydrate and a preparation method thereof, belonging to the field of drug synthesis. Background technique [0003] Hepatitis B virus is a major disease that seriously threatens the health of our people. Carriers of hepatitis B virus in my country account for about one-tenth of the total population, and there are more than 30 million people with clinical symptoms. [0004] Adefovir Dipivoxil (Adefovir Dipivoxil) is Adefovir dipipivoxil, chemical name 9-[bis[(isovaleryloxy)]methoxy]phosphinyl]ethyl]adenine, is a nuclear Anti-hepatitis B virus drugs of glycosides were first developed by GILEAD SCIENCES INC, and were successively marketed in the United States, Europe and China from 2002 to 2005 for the treatment of hepatitis B. [0005] [0006] As a prodrug, adefovir dipivoxil can be dissociated into adefovir (PMEA) in vivo. Animal experiments and clinical pharmacokinetic tests have show...

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
Inventor 张健朱炜姚蝉艳陈学文
Owner SUZHOU ERYE PHARMA CO LTD
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Try Eureka
PatSnap group products

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

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap