A kind of refining method of hepatitis B treatment drug entecavir

Abstract

A method for refining the entecavir drug for treating hepatitis B, which is applied to the refining of the entecavir crude product with a composition of more than 98%, and is characterized in that it comprises the following steps: step 1, dissolving the entecavir crude product in water, and preparing a 5% entecavir solution, then add activated carbon to the solution for decolorization and impurity removal, then leave the solution at room temperature for crystallization to obtain crystalline entecavir; step 2. use methanol as a medium again to prepare the crystalline entecavir into a solid-liquid mixture, and reflux Beating and washing; step 3. filtering the slurry obtained in step 2 to obtain the filter residue recrystallized with water to obtain the refined entecavir essence. The invention has good refining effect, high yield, simple operation, low uncontrollability, small amount of solvent used, low cost, economical and practical advantages.

Description

technical field [0001] The invention belongs to the field of medicinal chemistry, and relates to a purification method of anti-hepatitis B virus drug entecavir, more precisely 2-amino-1,9-dihydro-9-[(1 S ,3 R ,4 S )-4-Hydroxy-3-hydroxymethyl-2-methylenecyclopentyl]-6 H - Purification method of purin-6-one monohydrate. Background technique [0002] Hundreds of millions of people around the world have been infected with hepatitis B virus, among which there are about 400 million chronic hepatitis B virus carriers. Among infected patients, about 15% to 40% will develop cirrhosis, liver failure or liver cancer. Globally, more than 500,000 people die from primary liver cancer every year, and as many as 80% of the primary liver cancers are caused by chronic hepatitis B. Hepatitis B has become the tenth leading cause of death worldwide. According to the latest data, the number of deaths due to liver disease in my country is close to 500,000 every year, causing economic losses ...

AI Technical Summary

Problems solved by technology

However, entecavir used as a medicine has high quality requirements and strict limits on impurities such as enantiomers. Among them, the single impurity requirement is less than 0.1%, and the total impurity requirement is less than 0.3%, so its preparation and refining process are very complicated. The technical requirements are relatively high, and there are related literature reports in the prior art. Regarding the process of purifying and refining Entecavir, the prior art discloses the technology of using resin method to elute and purify Entecavir, or the technology of using high-speed countercurrent chromatography to refine Entecavir, Though above-mentioned two methods can reach the quality requirement of purifying and refining, the production cost of two methods is all very high, and operation is complicated, more importantly, produces a large amount of elution solvents in its production process, causes certain environmental pollution, and elution solvent The price is high, it is difficult to reduce production costs, and the single methanol reflux purification process has the disadvantages of large reagent consumption, weak ability to remove impurities, and low yield

Therefore, the cost of entecavir refining method in the prior art is high, and the defect that quality is difficult to reach makes entecavir difficult to popularize and apply, and brings good news to patients