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Method for preparing telbivudine

A technology of telbivudine and thymidine, applied in sugar derivatives, organic chemistry, etc., can solve the problems of unfavorable environmental protection and safe production, low economic and social public benefits, and low comprehensive benefits, and achieve effective It is beneficial to environmental protection and safe production, reduces synthesis time and production cost, and improves comprehensive benefits

Inactive Publication Date: 2009-02-11
SHAXING CHEM TAIZHOU CITY
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

At the same time, there are many types of solvents used, and the amount of solvents used is large, which is not conducive to environmental protection and safe production, and the economic and social benefits are low.
Route ② uses 2-deoxy-L-ribose as a raw material. Although the process route is reduced, the raw material 2-deoxy-L-ribose is not easy to obtain. Even if 2-deoxy-L-ribose is produced, the synthetic route will be extended. Comprehensive less efficient
Routes ③ and ④ also have the disadvantages of long synthetic route, complex process, high cost, great safety hazards, and low overall benefit

Method used

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  • Method for preparing telbivudine
  • Method for preparing telbivudine
  • Method for preparing telbivudine

Examples

Experimental program
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Effect test

Embodiment 1

[0024] The preparation of telbivudine uses 2'-deoxy-β-D-thymidine as the starting material, uses anhydrous pyridine as the solvent, and reacts with p-toluenesulfonyl chloride at a temperature of -5-0°C After 8-15 hours, 3,5-di-O-p-toluenesulfonyl-β-D-thymidine was generated, then added pyridine aqueous solution, centrifuged to remove the mother liquor, and dried to obtain a white crystal powder with a yield of 85 -93%; Add DMF to the above powder as a solution, that is, dimethylformamide solution, mix well, and at a temperature of 70-100°C, 3,5-di-O-tosyl-β-D-thymus Pyrimidine nucleoside reacts with potassium benzoate for 3-9 hours, undergoes transformation, removes p-toluenesulfonyl group, generates 3,5-di-O-benzoyl-β-L-thymidine, evaporates and concentrates, completely DMF was removed, and the yield was 78-86%; ammonia methanol was added to the above solution to hydrolyze 3,5-di-O-benzoyl-β-L-thymidine to obtain the target 2′-deoxy- β-L-thymidine, then evaporated and concen...

Embodiment 2

[0026] In the preparation method of telbivudine, 2′-deoxy-β-D-thymidine reacts with toluenesulfonyl chloride, the temperature is controlled at -4-0°C, and the time is 9-14 hours; 3,5- The reaction temperature of di-O-p-toluenesulfonyl-β-D-thymidine and potassium benzoate is controlled at 80-95° C. and the time is 4-8 hours. Other process steps and conditions are the same as in Example 1.

Embodiment 3

[0028] In the preparation method of telbivudine, 2'-deoxy-β-D-thymidine reacts with toluenesulfonyl chloride, the temperature is controlled at -4-1°C, and the time is 10-13 hours; 3,5 - Di-O-p-toluenesulfonyl-β-D-thymidine reacts with potassium benzoate at a controlled temperature of 85-90°C for 5-7 hours; 3,5-di-O-benzoyl- Methanol was used for recrystallization in the hydrolysis reaction of β-L-thymidine and ammonia methanol, and other process steps and conditions were the same as those in Example 1.

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Abstract

The invention relates to a preparation method for telbivudine, which pertains to the technical field of organic chemical engineering and comprises the following technical steps: (1) 2'-deoxidized-beta-D-thymine nucleoside is taken as a raw material and anhydrous pyridine is taken as a solvent; the raw material and the solvent react with p-toluenesulfonyl chloride at the temperature of minus 5 DEG C to 0 DEG C; then centrifugalization and drying are carried out, and 3, 5-di-O-P- toluenesulfonyl chloride-beta-D-thymine nucleoside is obtained; (2) DMF is taken as a solvent, and the 3, 5-di-O-P- toluenesulfonyl chloride-beta-D-thymine nucleoside reacts with potassium benzoate at the temperature of minus 70 DEG C to 100 DEG C; configuration inversion and evaporation concentration are carried out, thus obtaining 3, 5-di-O- benzoyl-beta-L-thymine nucleoside; (3) hydrolysis is carried out on the 3, 5-di-O- benzoyl-beta-L-thymine nucleoside by using amino methanol, and 2'-deoxidized-beta-L-thymine nucleoside is obtained, thus obtaining the target object telbivudine. The preparation method has simple technique and short synthesizing route greatly reduces synthesizing time and production cost; in addition, the varieties of the solvents used are few, and the dosage of the solvents is greatly reduced, thereby being beneficial to environmental protection and safety in production and remarkably increasing comprehensive benefit compared with the prior art.

Description

technical field [0001] The invention belongs to the technical field of organic chemical industry, in particular to a preparation method of telbivudine. Background technique [0002] Telbivudine, chemical name 2′-deoxy-β-L-thymidine; 1-(2-deoxy-β-L-ribofuranosyl)-5-methyluracil; 1-((2S, 4R,5S)-4-Hydroxy-5-hydroxymethyltetrahydrofuran-2-yl)-5-methyl-1H-pyrimidine-2,4-dione. The English name is Telbivudine, the trade name is Sobivudine; the molecular formula is C 10 h 14 N 2 o 5 , molecular weight 242.23. Its structural formula is: [0003] [0004] Telbivudine currently has the following process routes: ①Using L-arabinose as the starting material, reacting with HBr acetic anhydride solution, and reducing it with zinc powder to obtain 3,4-di-O-acetyl arabinose; React with methanol solution of HCl to get 3,4-di-O-acetyl-2-deoxy-L-arabinose; react with perchloric acid in acetic acid solution to get 2-deoxy-L-arabinose; in methanol solution React with p-toluoyl chloride...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07H19/073
Inventor 郭希杰何志勇李晓华
Owner SHAXING CHEM TAIZHOU CITY
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