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Synthesis process for Adefovir ester of anti hepatitis type B virus medicine

A technology of adefovir dipivoxil and a synthesis method, which is applied in the field of synthesis technology for preparing anti-hepatitis B virus drug adefovir dipivoxil, can solve problems such as being unsuitable for industrialized production, and achieve the advantages of improving yield, reducing cost and reducing pollution. Effect

Inactive Publication Date: 2005-01-05
嘉兴锐奇服饰有限公司
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  • Abstract
  • Description
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  • Application Information

AI Technical Summary

Problems solved by technology

[0018] 1. While the condensation of the side chain and adenine generates a 9-position substituent, it is easy to form a 7-isomer. The properties of the two are similar, and they must be separated and purified by silica gel column chromatography, which is not suitable for industrial production;
[0019] 2. Preparation of key intermediate PMEA by hydrolysis of 9-(dialkoxyphosphorylmethoxyethyl)-adenine requires the use of hydrolysis reagent trimethylbromosilane, and the reaction is carried out in acetonitrile, both of which are toxic Dangerous goods, likely to cause serious environmental problems

Method used

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  • Synthesis process for Adefovir ester of anti hepatitis type B virus medicine
  • Synthesis process for Adefovir ester of anti hepatitis type B virus medicine
  • Synthesis process for Adefovir ester of anti hepatitis type B virus medicine

Examples

Experimental program
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Effect test

Embodiment

[0037] (1) Preparation of Chloroethyl Chloromethyl Ether (III)

[0038] In a 1500ml three-necked flask, add 846g (705ml, 10.5mol) of 2-chloroethanol and 316g (10.9mol) of pulverized paraformaldehyde, and pass in dry hydrogen chloride gas under stirring for 24 hours. After the stirring was stopped, the reaction solution was divided into two layers; the lower layer was separated and dried with calcium chloride. After filtration, the filtrate was fractionated under reduced pressure, and the fraction with a boiling range of 80-84° C. / 28-30 mmHg was collected to obtain 743 g of chloroethyl chloromethyl ether (III), with a yield of 54.9%.

[0039] (2) Preparation of three-(2,2,2-trifluoroethyl) phosphite (IV)

[0040] In 46 grams of trifluoroethanol, 21 grams of phosphorus trichloride was added, and the mixture was stirred and reacted at 80-90° C. for 4 hours. Fractional distillation yielded 41 grams of tris-(2,2,2-trifluoroethyl)phosphite (IV), 130-131°C / 74-78mmHg.

[0041] (3) ...

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Abstract

The invention provides a synthetic method of anti-hepatitis B virus medicine Adefovir dipivoxil, including the steps: (1) preparing chloroethyl chloromethylether; (2) preparing chloroethyl methylether; (3) preparing 2-[bis(trifluoroethyl)-phosphoryl methoxyl] ethyl chloride; (4) preparing 9-[bis(trifluoroethoxyl)-phosphoryl methoxyl ethyl]-adenine; (5) preparing PMEA; (6) preparing 9-[bis[(isopentanoyl)methoxyl]phosphinyl]-methoxyl]adenine; it has the characters of process easy to apply, environmental protection and higher yield.

Description

technical field [0001] The invention relates to a synthesis process for preparing anti-hepatitis B virus drug adefovir dipivoxil. technical background [0002] 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 as many as 30 million people with clinical symptoms. Currently, clinically effective anti-HBV drugs are mainly interferon and namivudine. However, the effective rate of interferon treatment is only 30-50%, and it is often accompanied by toxic and side effects such as flu-like symptoms and leukopenia; Namifuridine treatment is prone to drug resistance, and after 2 years of continuous medication, the incidence of drug resistance is as high as 40-50%. This can lead to serious consequences such as the acute attack of hepatitis. [0003] Adefovir dipivoxil [chemical name 9-[bis[(isovaleryloxy) methoxy] phosphinyl]-methoxy] ...

Claims

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Application Information

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IPC IPC(8): A61P1/16A61P31/12C07F9/6561
Inventor 胡小侠陈铁钎
Owner 嘉兴锐奇服饰有限公司
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