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Method for synthesizing valganciclovir hydrochloride by micro-channel reactor

A technology of valganciclovir hydrochloride and microchannel reactor, which is applied in the field of medicine to achieve the effects of suppressing hydrolysis by-products, improving clogging problems and reducing energy consumption

Pending Publication Date: 2022-01-04
仁合益康集团有限公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0011] The technical problem that the present invention needs to solve is to provide a kind of method that microchannel reactor synthesizes valganciclovir hydrochloride, can greatly improve the clogging problem of microchannel reactor in large-scale production; Palladium remains, improving product yield and purity

Method used

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  • Method for synthesizing valganciclovir hydrochloride by micro-channel reactor

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0033] S1. Weigh 50kg of the intermediate, add it into 350kg of methanol, add 11kg of hydrochloric acid under stirring, and form material A after fully stirring, and transport material A to module 1 of the microchannel reactor through a plunger pump, and enter the microchannel reactor after preheating and mixing. Reaction module sets of channel reactors;

[0034] S2. Weigh 8.55kg 10% palladium carbon, add in 128kg methanol, fully stir and mix to form material B, transport material B to module 1 of the microchannel reactor through the slurry pump, enter the microchannel reactor after preheating and mixing The reaction module group of;

[0035] S3. The reaction module group that transports hydrogen to the microchannel reactor reacts with the above-mentioned preheated material in the reaction module group, wherein: adjust the flow rate of the plunger pump so that the flow rate of material A is 60.0g / min, adjust the slurry The flow rate of the material pump is such that the flow ...

Embodiment 2

[0045] Embodiment 2 (ethanol)

[0046] S1. Weigh 50kg of the intermediate, add it to 350kg of ethanol, add 11kg of hydrochloric acid under stirring, and form material A after fully stirring, and transport material A to module 1 of the microchannel reactor through a plunger pump, and enter the microchannel reactor after preheating and mixing. Reaction module sets of channel reactors;

[0047] S2. Weigh 8.55kg 10% palladium carbon, add in 128kg ethanol, fully stir and mix to form material B, transport material B to module 1 of the microchannel reactor through the slurry pump, enter the microchannel reactor after preheating and mixing The reaction module group of;

[0048] S3. The reaction module group that transports hydrogen to the microchannel reactor reacts with the above-mentioned preheated material in the reaction module group, wherein: adjust the flow rate of the plunger pump so that the flow rate of material A is 60.0g / min, adjust the slurry The flow rate of the materia...

Embodiment 3

[0051] Embodiment 3 (different reaction temperature)

[0052] S1. Weigh 50kg of the intermediate, add it into 350kg of methanol, add 11kg of hydrochloric acid under stirring, and form material A after fully stirring, and transport material A to module 1 of the microchannel reactor through a plunger pump, and enter the microchannel reactor after preheating and mixing. Reaction module sets of channel reactors;

[0053] S2, take by weighing 8.55kg10% palladium charcoal, add in 128kg methanol, fully stir and mix to form material B, material B is transported in the module one of microchannel reactor through slurry pump, enters the module one of microchannel reactor after preheating and mixing React module group;

[0054] S3. The reaction module group that transports hydrogen to the microchannel reactor reacts with the above-mentioned preheated material in the reaction module group, wherein: adjust the flow rate of the plunger pump so that the flow rate of material A is 60.0g / min, ...

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Abstract

The invention discloses a method for synthesizing valganciclovir hydrochloride by a micro-channel reactor. A material A and a material B are respectively prepared and added into a micro-channel reactor, and then, hydrogen is introduced for hydrogenation reaction to obtain valganciclovir hydrochloride. The method can greatly improve the blockage problem of the micro-channel reactor in large-scale production. Meanwhile, palladium residues in large-scale production can be reduced, and the product yield and purity are improved.

Description

technical field [0001] The invention relates to a method for synthesizing valganciclovir hydrochloride in a microchannel reactor, belonging to the technical field of medicine. Background technique [0002] Valganciclovir hydrochloride is an oral anti-cell (CMV) infection drug developed by Roche, Switzerland, which was approved by the U.S. FDA in May 2001. It is clinically used to treat acute retinitis caused by CMV infection in patients with acquired immunodeficiency syndrome; prevent and treat secondary CMV infection in organ transplant recipients. This product is the prodrug of ganciclovir. After oral administration, it is rapidly hydrolyzed into ganciclovir by esterase in intestinal and liver cells, so as to exert its drug effect. Its oral absorption bioavailability is 10 times that of ganciclovir. , and the toxicity is greatly reduced, and has broad market prospects. In my country, valganciclovir hydrochloride is an urgently needed drug in clinical practice, but there ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D473/18
CPCC07D473/18Y02P20/584
Inventor 张玉辉张恺薛娜华圆田秀娟
Owner 仁合益康集团有限公司
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