Preparation method of high-purity carbamazepine (CBZ)-valaciclovir

A technology of valacyclovir and CBZ-L-, which is applied in the field of preparation of high-purity CBZ-valacyclovir, can solve the problem of high product impurity content, and achieve the effects of improving product purity, reducing energy consumption and shortening reaction time.

Active Publication Date: 2010-07-28
LIVZON GROUP CHANGZHOU KONY PHARMA
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0006] In order to overcome the above-mentioned defects, the technical problem to be solved in the present invention is: for the problem that the product im...

Method used

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  • Preparation method of high-purity carbamazepine (CBZ)-valaciclovir

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Experimental program
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Embodiment 1

[0031] Put 800ml of N,N-dimethylformamide into the reaction flask, add 25g of acyclovir, 50g of N-benzyloxycarbonyl-L-valine and 0.5g of 4-dimethylaminopyridine under stirring, and cool to 10°C Next, add 40 g of dicyclohexylcarbodiimide, and keep the reaction at 5-10°C for 2 hours, then raise the temperature to 20-25°C within 55-65 minutes, and keep the reaction for 15 hours. The solid in the reaction system (reaction by-product dicyclohexyl urea) was filtered off with suction, the filtrate was concentrated under reduced pressure to obtain an oily substance, and 300ml of ethanol was added to heat to dissolve the concentrate. After the solution was clear, it was cooled to -5~0°C to crystallize for 10 hours. After suction filtration, the resulting solid was heated and dissolved with 250ml of ethanol, and after dissolving, cooled to -5-0°C to crystallize for 10 hours. Suction filtration, the obtained solid was heated and dissolved with 100ml of N,N-dimethylformamide, then the obt...

Embodiment 2

[0033] Put 800ml of N,N-dimethylformamide into the reaction flask, add 25g of acyclovir, 50g of N-benzyloxycarbonyl-L-valine and 0.5g of 4-dimethylaminopyridine under stirring, and cool to 10°C Next, 40 g of dicyclohexylcarbodiimide was added, and the temperature was kept at 5-10° C. for 1 hour, then the temperature was raised to 20-25° C. within 115-125 minutes, and kept for 15 hours. The solid in the reaction system (reaction by-product dicyclohexyl urea) was filtered off with suction, the filtrate was concentrated under reduced pressure to obtain an oily substance, 300ml of ethanol was added to dissolve the concentrate by heating, and after dissolving, cool to -5°C to crystallize for 10 hours. Suction filtration, the obtained solid was heated and dissolved with 100ml of N,N-dimethylformamide, then the obtained N,N-dimethylformamide solution was added to 600ml of hot water at a temperature between 55 and 65°C, and the Stir at 55°C for 30 minutes, filter with suction, and was...

Embodiment 3

[0035] Put 800ml of N,N-dimethylformamide into the reaction flask, add 25g of acyclovir, 50g of N-benzyloxycarbonyl-L-valine and 0.5g of 4-dimethylaminopyridine under stirring, and cool to 5°C Next, add 40 g of dicyclohexylcarbodiimide, and keep the reaction at 0-5°C for 2 hours, then raise the temperature to 20-25°C within 55-65 minutes, and keep the reaction for 15 hours. The solid in the reaction system (reaction by-product dicyclohexyl urea) was filtered off with suction, the filtrate was concentrated under reduced pressure to obtain an oily substance, 300ml of ethanol was added to dissolve the concentrate by heating, and after dissolving, cool to 0°C to crystallize for 10 hours. After suction filtration, the obtained solid was heated and dissolved with 250ml of ethanol, and after dissolving, cooled to 0°C for crystallization for 10 hours. Suction filtration, the obtained solid was heated and dissolved with 100ml of N,N-dimethylformamide, then the obtained N,N-dimethylform...

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Abstract

The invention relates to the technical field of pharmaceutical chemistry, in particular to a preparation method of high-purity carbamazepine (CBZ)-valaciclovir, which comprises the steps of: suspending acyclovir into N,N-dimethylformamide, adding CBZ-L-valine and 4-dimethylamino pyridine to obtain a turbid liquid, cooling the turbid liquid to 0-10 DEG C, adding dicyclohexylcarbodiimide, preserving the temperature for 1-5h, raising the temperature to 18-30 DEG C, controlling the temperature raising time to be 1-2h, filtering solid in a reaction system after carrying out heat preservation reaction for 10-20h at a temperature of 18-30 DEG C, decompressing and concentrating filtrate to obtain an oily matter, dissolving concentrate by heating through using alcohol, cooling crystal after being dissolved and filtering, recrystallizing and filtering the obtained solid by using alcohol, dissolving the obtained solid by heating through using the N,N-dimethylformamide with matched quantity to obtain a crude solution of the CBZ-valaciclovir, adding the solution into water with a temperature of 50-80 DEG C to make the solid to separate out, filtering, washing with water with a temperature of 50-80 DEG C to obtain a filter cake, and drying to obtain the high-purity CBZ-valaciclovir.

Description

technical field [0001] The invention relates to the technical field of medicinal chemistry, in particular to a preparation method of high-purity CBZ-valacyclovir. Background technique [0002] Valacyclovir hydrochloride is the prodrug of acyclovir, which is absorbed rapidly after oral administration and is quickly converted into acyclovir in the body. Its antiviral effect is played by acyclovir and is used for the treatment of type I and II herpes simplex and herpes zoster. This product has no effect on the central nervous system, respiratory and blood circulation system, autonomic nervous system, digestive system and smooth muscle. Valacyclovir hydrochloride has good water solubility and can be quickly absorbed by the human body when taken orally. Compared with acyclovir, it has a higher oral bioavailability, which is 3 to 4 times that of acyclovir. In terms of safety, valacyclovir is similar to acyclovir. According to the website of the British "New Scientist" magazine,...

Claims

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Application Information

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IPC IPC(8): C07D473/18
Inventor 陈敖李鸣海柏凤飞马立新
Owner LIVZON GROUP CHANGZHOU KONY PHARMA
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