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Preparation method of valine acyclovir

A valacyclovir and valine technology, applied in the field of chemistry, can solve problems such as few synthetic and purification methods, and achieve the effects of low pressure, low temperature and high quality

Inactive Publication Date: 2014-09-17
STAR LAKE BIOSCI CO INC ZHAOQING GUANGDONG
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

There are few effective synthetic and purification methods for valacyclovir

Method used

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  • Preparation method of valine acyclovir
  • Preparation method of valine acyclovir
  • Preparation method of valine acyclovir

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0027] Add 30g of acyclovir, 300-450g of N,N-dimethylformamide, 30-100g of CBZ-L-valine, and 30g of N,N'-dicyclohexylcarboimide into a 1000mL three-necked bottle. -90g, 0.3-3g of 4-dimethylaminopyridine. Stir the reaction at 20-30°C for 10-15 hours.

[0028] Add 0.3-3 g of carbon powder to the reaction liquid, stir for 30 min at room temperature and suction filter to obtain X2 filtrate.

[0029] The obtained X2 filtrate was concentrated under reduced pressure, 300-600 g of methanol solution was added to the concentrate, refluxed to dissolve until it was dissolved, and then crystallized by gradient cooling, stirred at 50-55°C for 1 hour, and the stirring speed was 300-400r / min. Naturally lower the temperature to 30°C, cool down to 0°C in 1-2 hours, and stir at a speed of 50-100r / min. 30-60 g of methanol was washed by suction filtration at 0°C. The product X2 was dried at 80°C and weighed 57.2g. The product yield is 93.4%, and the purity of liquid chromatography is ≧99.5%

...

Embodiment 2

[0033] On the basis of Example 1, the organic solvent is a mixed solvent of methanol and ethanol, the volume ratio of methanol and ethanol is 8:2-9.5:0.5, the single yield is greater than 92.8%, and the purity is >99%.

Embodiment 3

[0035] 1. Add acyclovir 30g, N,N-dimethylformamide 300-450g, CBZ-L-valine 30-100g, N,N'-dicyclohexylcarbonyl Amine 30-90g, 4-dimethylaminopyridine 0.3-3g. Stir the reaction at 20-30°C for 10-15 hours.

[0036] 2. Add 0.3-3 g of carbon powder to the reaction solution, stir for 30 minutes at room temperature and suction filter to obtain X2 filtrate.

[0037] 3. Concentrate the obtained X2 filtrate under reduced pressure, add 300-600g of methanol solution to the concentrated solution, reflux to dissolve until clear, then crystallize by gradient cooling, stir at 50-55°C for 1 hour, and the stirring speed is 300-400r / min. Naturally lower the temperature to 30°C, cool down to 0°C in 1-2 hours, and stir at a speed of 50-100r / min. 30-60 g of methanol was washed by suction filtration at 0°C. The product X2 was dried at 80°C and weighed 56.7g. The product yield is 92.6%, and the liquid chromatography purity is ≧99.7%.

[0038] 4. Put 56.7g and 500-800g of methanol, 0.5-5g of 10% pa...

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Abstract

The invention relates to the field of chemistry, and particularly relates to a preparation method of valine acyclovir. The preparation method comprises the following steps: A, adding acyclovir and CBZ-L-valine to an N,N-dimethyl formamide solution, controlling the temperature between 20 DEG C and 30 DEG C, adding a reaction additive, and reacting for the time of 10-15 hours to obtain X2 and X3 reaction liquid; B, adding carbon powder to the reaction liquid, reducing the temperature to 0+ / -2 DEG C, filtering to remove an X3 substance, and concentrating, crystallizing and purifying filter liquor which contains X2 to obtain the X2; C, drying the X2 obtained from the step B, then dissolving the X2 into an organic solvent, adding a palladium carbon catalyst, introducing hydrogen, reacting at 20-25 DEG C for 5-10 hours, filtering after the reaction is finished, concentrating the filter liquor, and then crystallizing and purifying to obtain an X1 target product. The preparation method disclosed by the invention has the advantages of easiness for operation, cleanliness, environmental friendliness, high yield and small equipment investment.

Description

technical field [0001] The invention relates to the field of chemistry, in particular to a preparation method of valacyclovir. Background technique [0002] Val-acyclovir is a new generation of anti-herpes virus drug, which is the L-valyl ester hydrochloride of acyclovir and a prodrug of acyclovir. The bioavailability of acyclovir produced after metabolism is 3-5 times higher than that of direct oral acyclovir. It can also improve the compliance of patients, reduce the obvious advantages of pain associated with herpes zoster (ZAP), and has successfully replaced acyclovir as the first-line drug for the treatment of herpes zoster and genital herpes. It has been approved by the FDA for the treatment of herpes zoster and primary and recurrent genital herpes. There are few effective synthetic purification methods for valacyclovir. Contents of the invention [0003] For above-mentioned technical defect, the technical problem to be solved in the present invention is to provide...

Claims

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Application Information

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IPC IPC(8): C07D473/18
CPCC07D473/18
Inventor 杨艳庆龚美义崔锦栋朱耀匡朱文佳陈攀徐日俏周莹伍金兰
Owner STAR LAKE BIOSCI CO INC ZHAOQING GUANGDONG
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