Intermediate for synthesizing azidothimidine, preparation thereof and use in azidothimidine synthesis

A kind of technology of zidovudine and intermediate, which is applied to the intermediate of synthesizing zidovudine and the preparation thereof and the application field of the intermediate in synthesizing zidovudine, can solve the problems of repetition, lengthy steps and the like, Achieve the effect of short route, low cost and mild reaction conditions

Active Publication Date: 2009-03-04
JIANGSU PUXIN PHARMA CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0009] However, if the β-thymidine synthesized by this route continues to synthesize zidovudine, the steps will be lengthy. In fact, some steps such as protection and deprotection will be repeated.

Method used

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  • Intermediate for synthesizing azidothimidine, preparation thereof and use in azidothimidine synthesis
  • Intermediate for synthesizing azidothimidine, preparation thereof and use in azidothimidine synthesis
  • Intermediate for synthesizing azidothimidine, preparation thereof and use in azidothimidine synthesis

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0045] Methyl 2-deoxy-D-ribofuranoside

[0046] At room temperature, 2-deoxy-D-ribose (26.8 g, 0.20 mol) was dissolved in anhydrous methanol (300 ml), and stirred to dissolve. Add 1% hydrogen chloride-methanol solution in one portion. The stirring reaction was continued at room temperature for 3 hours, and the end point of the reaction was detected by TLC (dichloromethane:methanol=10:1). After the reaction was completed, sodium carbonate (24.5 g, 0.23 mol) was added to the reaction solution, and stirring was continued for 1 hour at room temperature. Methanol was distilled off under reduced pressure, dichloromethane (300ml) was added to the residue to dissolve, filtered, and insoluble matter was filtered off. The filtrate was concentrated to dryness to obtain 30.6 g of a light yellow oil.

Embodiment 2

[0048] Methyl 5-O-p-chlorobenzoyl-2-deoxy-D-ribofuranoside

[0049] At room temperature, the compound of Example 1 (23.4 g, 0.16 mol) was dissolved in dichloromethane (500 ml), and stirred evenly. The temperature was cooled to 0°C in an ice bath, and triethylamine (30.8ml, 0.22mol) was added. A solution of p-chlorobenzoyl chloride (24.4ml, 0.19mol) in dichloromethane (80ml) was slowly added dropwise under a controlled temperature of 0-5°C. The dropwise addition was completed in 4 hours, and the end point of the reaction was detected by TLC (ethyl acetate:petroleum ether=1:2). After the reaction was completed, the reaction solution was continuously stirred at 0-5° C. for 1 hour, and was directly used for the next reaction without any treatment. It can also be treated as follows: ice water (200ml) is added to the reaction solution and stirring is continued for 1 hour. Separate the organic phase, and wash the organic phase with saturated sodium bicarbonate solution (300ml×3) a...

Embodiment 3

[0051] Methyl 3-O-methylsulfonyl-5-O-p-chlorobenzoyl-2-deoxy-D-ribofuranoside

[0052] At 0-5°C, triethylamine (30.8ml) was added to the reaction solution in Example 2, and stirred for 5 minutes. Methanesulfonyl chloride (21.7 g, 0.19 mol) in dichloromethane (50 ml) was added dropwise at a controlled temperature of 0-5°C. The dripping was completed in about 30 minutes, and the stirring was continued for 1 hour after the dripping, and the end point of the reaction was detected by TLC (ethyl acetate:petroleum ether=1:1). After the reaction was completed, ice water (200 ml) was added to the reaction solution, and stirring was continued for 1 hour. The organic phase was separated, and the organic phase was washed successively with 5% hydrochloric acid (200ml×3), saturated sodium bicarbonate solution (300ml×3), and saturated brine (300ml). Dry over anhydrous sodium sulfate. Filter and concentrate the filtrate to dryness under reduced pressure. Column chromatography gave 49.0 g ...

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Abstract

The invention discloses an intermediate with a following structural formula (I) for synthesizing zidovudine, wherein R1 is a hydroxyl protective group, R2 is C1-C12 alkyl or C6-C30 aryl, and X is halogen. The invention also discloses a preparation method of the intermediate and application thereof on synthesizing zidovudine. The method for synthesizing zidovudine from the intermediate has the advantages of mild reaction conditions, short lines, high yield, good intermediate stereoselectivity, low cost, and no need of Beta-thymidine intermediate, and is suitable for the industrial production.

Description

technical field [0001] The present invention relates to a compound, its preparation method and application of the compound, in particular to an intermediate for synthesizing zidovudine and the preparation method of the intermediate. The present invention also relates to the application of the intermediate in the synthesis of zidovudine. Background technique [0002] Zidovudine is the world's first anti-AIDS drug approved by the US FDA. Because of its definite curative effect, it has become the most basic component of the "cocktail" therapy. At present, zidovudine has actually become a standard drug, and it will be used as a reference for the development of any new product of the same kind to be recognized by the academic and clinical circles. [0003] At present, the method for synthesizing zidovudine with β-thymidine as a raw material is an effective method, and its synthetic route mainly contains the following two: 1. The route reported in US5124442 is shown in the follow...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07H5/02C07H13/00C07H19/06
CPCY02P20/55
Inventor 李金亮闫丽
Owner JIANGSU PUXIN PHARMA CO LTD
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