Novel synthesis method for key intermediate of anti-hepatitis B drug Entecavir

A technology of entecavir and synthesis method, which is applied in the field of synthesis of pharmaceutical intermediates, can solve the problems of harsh operating conditions, high price of entecavir, long synthesis route and the like, and achieves the effects of less side reactions, unique and novel design, and fast speed.

Pending Publication Date: 2019-02-15
DONGGUAN UNIV OF TECH
View PDF1 Cites 2 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0004] At present, the price of entecavir on the market is expensive, an important fac

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
  • Novel synthesis method for key intermediate of anti-hepatitis B drug Entecavir

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0034] 1) Synthesis of formula 2 compound:

[0035] At 0°C and under the protection of nitrogen, titanium tetrachloride (1.2 mL) was slowly added dropwise to a solution of the compound of formula 1 (2.5 g, 9.97 mmol) in dichloromethane (60 mL), the solution turned yellow and stirred for 5 minutes, At this temperature, diisopropylethylamine (1.9mL) was continued to be added dropwise, and after the dropwise addition, the flask was transferred to -78°C for reaction, and the solution quickly turned dark red; the compound of formula 9 (0.51g, 9.06 mmol) of dichloromethane (7mL) solution was slowly injected into the above solution, and after reacting for 2 hours, a saturated ammonium chloride solution (10mL) was added to the mixed system, extracted with dichloromethane (3×80mL), and the resulting mixture was combined The organic phase was washed with saturated brine and dried over anhydrous sodium sulfate, concentrated under reduced pressure to remove the organic solvent, and the ob...

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 discloses a novel synthesis method for a key intermediate of the anti-hepatitis B drug Entecavir. The method is characterized in that a known compound as shown by Formula 1 is adopted asa starting material, and synthesis of target molecules is achieved through a series of reaction steps such as Evans aldol reaction, hydroxyl protection through tert-butyldimethylsilyl chloride, reductive removal of a chiral auxiliary group through diisobutyl aluminum hydride (DIBAL-H) to obtain an aldehyde, addition of a Grignard reagent into the aldehyde, protection of a newly generated hydroxylthrough tert-butyldimethylsilyl, double-bond epoxidation reaction, free-radical ring closing reaction, hydroxyl protection through p-methoxybenzyl, etc. The method disclosed by the invention has theadvantages of unique and novel designing of the whole route, mild reaction conditions for the reaction steps, high rate, relatively fewer side effects, and high simplicity and convenience in operation; and common chemical reagents are adopted in the route, and raw materials are cheap and can be easily obtained, so that the synthesis cost can be greatly reduced.

Description

technical field [0001] The invention relates to a method for synthesizing a drug intermediate, in particular to a method for synthesizing a key intermediate of entecavir, a medicine for treating hepatitis B. Background technique [0002] Chronic hepatitis B seriously affects human health, especially in my country, where the number of infected people and the number of deaths due to liver diseases are extremely high, which has caused great harm and impact on our society and life. In terms of drug treatment, the anti-hepatitis B antiviral drugs currently recognized by experts are divided into two categories, namely interferon drugs (including common interferon, peginterferon) and nucleoside drugs (such as entecavir, Adelaide, etc.) Fovey, Lamivudine, etc.). Entecavir, a new generation of first-line anti-hepatitis B virus drug, can effectively and selectively inhibit hepatitis B virus, and its drug resistance is the lowest compared with some other antiviral western medicines, s...

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): C07F7/18
CPCC07F7/1892
Inventor 王晓季黄双平刘丽霞李琳张雪松杨陈阳李旺王建新
Owner DONGGUAN UNIV OF TECH
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