Method for synthesizing adefovir dipivoxil ester

A technology of adefovir dipivoxil and synthetic method, which is applied in the field of drug synthesis, can solve the problems of low yield, complex process, and long reaction steps, and achieve high total yield, high yield, and short synthetic route steps Effect

Active Publication Date: 2008-03-05
FUJIAN COSUNTER PHARMA
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  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0032] Above method reaction step is long, a

Method used

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  • Method for synthesizing adefovir dipivoxil ester
  • Method for synthesizing adefovir dipivoxil ester
  • Method for synthesizing adefovir dipivoxil ester

Examples

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Embodiment 1

[0056] 1. Synthesis of 1-chloro-2-chloromethoxyethane (3)

[0057] Feeding amount:

[0058]

[0059] Steps:

[0060] Suspend 30.0 g of paraformaldehyde (2) in 80.5 g of 2-chloroethanol (1), stir at room temperature, pass through anhydrous hydrogen chloride gas for 22 hours, the solid is dissolved, and the water layer is separated. The organic layer was dried by adding 20.0 g of anhydrous calcium chloride, passed through nitrogen for 4 h, filtered and distilled under reduced pressure, and 90.6 g of bp62-66°C / 29Mg light yellow transparent liquid (3) was collected with a yield of 70.2%. Quality control method: bp62-66℃ / 29mmHg.

[0061] Attachment: Preparation of anhydrous hydrogen chloride gas: Mix concentrated hydrochloric acid and sodium chloride evenly, slowly add concentrated sulfuric acid dropwise, and the generated hydrogen chloride gas is dried by concentrated sulfuric acid.

[0062] 2. Diethyl 2-chloroethoxymethylate (4)

[0063] Feeding ratio

[0064]

[0065]...

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Abstract

The present invention relates to medicine synthesis technology, and is especially Adefovir dipivoxil synthesizing process, which includes the following steps: 1. methylation reaction of 2-chlorethanol, paraformaldehyde and anhydrous hydrogen chloride to produce 1-chloro-2-chloromethoxyl ethane; 2. reaction of 1-chloro-2-chloromethoxyl ethane and trimorpholinyl phosphate to obtain 2-dimorpholinyl chloroethoxyl methyl phosphonate; 3. condensation of 2-dimorpholinyl chloroethoxyl methyl phosphonate and adenine in DMF in the presence of anhydrous K2CO3 catalyst to obtain 9-(2-dimorpholinylphsphonomethoxylethyl) adenine; 4. hydrochloric acid hydrolysis of 9-(2-dimorpholinylphsphonomethoxylethyl) adenine in DMF aqua to obtain 9-(2-phsphonomethoxylethyl) adenine; and 5. reaction of 9-(2-phsphonomethoxylethyl) adenine and chloromethyl pivalate in DMF under the catalysis of triethylamine to obtain Adefovir dipivoxil.

Description

Technical field: [0001] The invention relates to a drug synthesis method, in particular to a synthesis method of anti-hepatitis B drug adefovir dipivoxil. Background technique: [0002] Adefovir dipivoxil is a new type of oral broad-spectrum antiviral drug, which inhibits viral transcription and replication by inhibiting viral DNA polymerase and cryotron transcriptase, and has a strong inhibitory effect on hepatitis B virus and HIV. It also has a strong inhibitory effect on lamivudine and famciclovir-resistant hepatitis B virus. It is a ring-opening nucleoside reverse transcriptase inhibitor and a prodrug of adefovir (PMEA). The degree of adefovir dipivoxil is larger than that of adefovir dipivoxil. Adefovir dipivoxil was developed by Gilead Sciences of the United States. It was approved by the U.S. FDA on September 20, 2002 for the first time. Its English name is Adefovir Dipivoxil, its trade name is Hepsera, and its chemical name is 9-{2 -[bis(pivaloyloxymethoxy)phosphono...

Claims

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Application Information

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IPC IPC(8): C07F9/6561
Inventor 陈国华康惠燕
Owner FUJIAN COSUNTER PHARMA
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