Unlock instant, AI-driven research and patent intelligence for your innovation.

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

A CBZ-L-, high-purity technology, applied in organic chemistry and other directions, can solve the problems of inability to eliminate DCU, Pd-C reduction of Pd-C, and the number of times of application of Pd-C is not suitable for industrial production, and achieves a high utilization rate of palladium carbon. Effect

Active Publication Date: 2014-07-23
SHANDONG JINCHENG PHARMACEUTICAL GROUP CO LTD
View PDF7 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0004] 3、关于CBZ-万乃洛韦制备方法的文献资料包括US6107302、EP0308065、US4957924CN1903854、CN10202064、CN1903854、CN101787027US4957924、EP0976750等,其中US6107302、CN1903854、CN101787027、EP0308065、US4957924、EP0976750、US495792中介绍的方法使用DCC Condensation can not eliminate DCU, which will affect the next step of Pd-C reduction and affect the number of applications of Pd-C, which is not suitable for industrial production;

Method used

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

Image

Smart Image Click on the blue labels to locate them in the text.
Viewing Examples
Smart Image
  • Preparation method of high-purity carbamazepine (CBZ)-valaciclovir

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0023] Dissolve 25.1g of CBZ-L-valine in 100ml of N,N-dimethylformamide, add 11.2g of sodium carbonate, control the temperature at 0°C, slowly add 11.8g of ethyl chloroformate dropwise, and control the dropping time for about 1h , the dropwise addition is completed, keep warm for 2h, filter, then add 0.2g DMAP to the filtrate, heat up to 20°C, add 20g of acyclovir, keep warm for 6h, stop the reaction, concentrate the reaction solution, add 200ml of methanol, heat and recrystallize, cool down to 0 °C, filtered to obtain 31.6g white CBZ-valaciclovir solid, the product yield was 79%, and the liquid phase purity was greater than 99%.

Embodiment 2

[0025] Dissolve 25.1g of CBZ-L-valine in 100ml of N,N-dimethylformamide, add 8.0g of pyridine, control the temperature at 30°C, slowly add 11.8g of ethyl chloroformate dropwise, and control the dropping time for about 1h. After the dropwise addition, keep warm for 2 hours, filter, then add 0.2g DMAP and 20g acyclovir to the filtrate, heat up to 20°C, keep warm for 6h, stop the reaction, concentrate the reaction solution, add 200ml of methanol, heat and recrystallize, cool down to 0°C, After filtration, 34.1 g of white CBZ-valaciclovir solid was obtained, the product yield was 85%, and the liquid phase purity was greater than 99%.

Embodiment 3

[0027] Dissolve 25.1g of CBZ-L-valine in 100ml of N,N-dimethylformamide, add 8.0g of pyridine, control the temperature at -10°C, slowly add 11.8g of ethyl chloroformate dropwise, and control the dropping time for about 1h0 , the dropwise addition is completed, keep warm for 2h, filter, then add 0.2g DMAP to the filtrate, heat up to 20°C, 20g acyclovir, keep warm for 6h, stop the reaction, concentrate the reaction solution, add 200ml ethanol, heat recrystallization, cool down to 0°C , filtered to obtain 36.2g of white CBZ-valaciclovir solid, the product yield was 90%, and the liquid phase purity was greater than 99%.

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

PUM

PropertyMeasurementUnit
purityaaaaaaaaaa
chromatographic purityaaaaaaaaaa
Login to View More

Abstract

The invention relates to a preparation method of high-purity carbamazepine (CBZ)-valaciclovir, belonging to the technical field of medicament synthesis. The preparation method is characterized by comprising the following steps of: dissolving CBZ-L-valine in a solvent, and adding the CBZ-L-valine solution into ethyl chloroformate under the action of an acid applying agent to obtain mixed anhydride; adding the obtained mixed anhydride into 4-dimethylamino pyridine, controlling the temperature to 20-50DEG C, and adding and suspending initial raw material acyclovir into the solvent; after the reaction, filtering out obtained solid in a reaction system, and concentrating to obtain white solid at reduced pressure; heating and dissolving by the solvent, concentrating to obtain the white solid at reduced pressure, cooling and crystallizing after clearly dissolving, and filtering to obtain a crystallized product; and drying to obtain the high-purity CBZ-valaciclovir. The condensation is carried out by utilizing the mixed anhydride, the DCC (dicyclohexylcarbodiimide) can not be used in the process of reaction, the residual of the DCU is unavailable in the product, and the preparation method is good for the use rate of palladium carbon, so that the preparation method is an effective method for preparing the high-purity CBZ-valaciclovir.

Description

technical field [0001] The invention relates to a preparation method of high-purity CBZ-valaciclovir, which belongs to the technical field of drug synthesis. Background technique [0002] 1. CBZ-valaciclovir is a synthetic valaciclovir hydrochloride, which is the precursor of acyclovir, which is hydrolyzed into acyclovir in the body to inhibit the virus. It has strong inhibitory effect on herpes simplex virus Ⅰ (HSV-Ⅰ) and herpes simplex virus Ⅱ (HSV-Ⅱ), and weak inhibitory effect on varicella herpes virus, Epstein-Barr virus and cytomegalovirus. Its mechanism of action is to limit the synthesis of viral DNA and inhibit its replication. [0003] 2. After oral administration, valaciclovir hydrochloride is rapidly absorbed and converted into acyclovir, and the peak time of maternal acyclovir in blood is 0.88-1.75hr. The oral bioavailability is 67±13%, 3-5 times that of acyclovir. After oral absorption, valaciclovir hydrochloride is widely distributed and can be distributed ...

Claims

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

Application Information

Patent Timeline
no application Login to View More
Patent Type & Authority Patents(China)
IPC IPC(8): C07D473/18
Inventor 郑庚修赵攀峰马崇雷
Owner SHANDONG JINCHENG PHARMACEUTICAL GROUP CO LTD