Method for preparing and purifying Valganciclovir hydrochloride

A technology of valganciclovir hydrochloride and weight, applied in the field of valganciclovir hydrochloride, can solve the problems of troublesome post-processing, increased cost, and large potential safety hazard, and achieves easy and convenient post-processing operation, reduced reaction steps, and potential safety hazard. big effect

Active Publication Date: 2015-01-07
SICHUAN KELUN PHARMA RES INST CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

But the second kind of method still generally has some shortcomings and deficiencies, such as when esterification, adopts dicyclohexylcarbodiimide (DCC) mostly as dehydrating agent, because the dicyclohexylurea (DCU) that generates after its reaction is relatively Difficult to clean, bring a lot of trouble to post-processing
In addition, precious metals are mostly used as catalysts in the hydrogenation reaction to remove protecting groups. This reaction not only has a great safety hazard, but also may have excessive heavy metal residues after the reaction, which not only increases the difficulty of product purification, but also improves cost

Method used

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  • Method for preparing and purifying Valganciclovir hydrochloride
  • Method for preparing and purifying Valganciclovir hydrochloride
  • Method for preparing and purifying Valganciclovir hydrochloride

Examples

Experimental program
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Effect test

Embodiment 1

[0026] Embodiment 1: the preparation of valganciclovir hydrochloride

[0027] Step 1: Preparation of N,O-trityl ganciclovir

[0028] Add 82g of ganciclovir, 770g of DMF, 173g of TEA and 0.8g of DMAP in the reaction flask, stir evenly to form a white suspension, heat up to about 50°C, and add dropwise 238g of trityl chloride and 770g DMF solution, after adding, keep warm at 45-50°C and stir for 15 hours; after the reaction is completed, cool down to 10°C and stir for 30 minutes, filter, rinse the solid with 150g DMF, combine the filtrate, slowly add 1750g water, finish adding, and leave at room temperature After stirring for 2 hours, it was filtered, and the obtained solid was stirred and washed with 350 g of water and 350 g of ethyl acetate in turn, and dried to obtain 146.8 g of off-white solid, yield: 61.7%.

[0029] Step 2: Preparation of N, O-trityl-O-(N-Boc-L-valine) ganciclovir

[0030] Add 28.21g of N-Boc-L-valine, 100g of DMF, and 14g of TEA into the reaction flask, ...

Embodiment 2

[0036] Embodiment 2: the preparation of valganciclovir hydrochloride

[0037] Step 1: Preparation of N,O-trityl ganciclovir

[0038] Add 200g of ganciclovir, 1600g of DMF, 500g of TEA and 1.0g of DMAP in the reaction flask, stir evenly to form a white suspension, heat up to about 55°C, and add dropwise 540g of trityl chloride and 1600g of DMF solution, after adding, keep warm at 48-55°C and stir for 12 hours; after the reaction, cool down to 10°C and stir for 30 minutes, filter, rinse the solid with 400g DMF, combine the filtrate, slowly add 4500g of water, finish adding, in After stirring at room temperature for 2 hours, it was filtered, and the obtained solid was washed with 800 g of water and 800 g of ethyl acetate in turn, and dried to obtain 368.9 g of off-white solid, yield: 63.6%.

[0039] Step 2: Preparation of N, O-trityl-O-(N-Boc-L-valine) ganciclovir

[0040] Add 108g of N-Boc-L-valine, 432g of DMF, and 72g of TEA into the reaction flask, stir evenly, cool down to...

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PUM

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Abstract

The invention provides a method for preparing and purifying Valganciclovir hydrochloride, characterized by using ganciclovir as a raw material and carrying out N,O triphenylmethyl protection, esterification, deprotection, salt transformation and recrystallization to obtain Valganciclovir hydrochloride. According to the invention, by using mixed anhydride method and avoiding using DCC, the posttreatment is simple; by using BOC protection to replace the CBZ protection used in the prior art, the reaction procedures are simplified, and the need for using noble metal Pd is avoided. The invention is suitable for industrial production.

Description

technical field [0001] The invention relates to a novel method for preparing and purifying valganciclovir hydrochloride. Background technique [0002] Cytomegalovirus (CMV) is a herpes-like virus that is in a dormant state in individuals with normal immune function, but when the immune function is compromised (such as AIDS patients, patients receiving immunosuppressants after organ transplantation, etc.), the virus It will cause a series of clinical manifestations such as retinitis. In people with ADIS, the most common condition caused by CMV is CMV retinitis, an eye infection that can lead to blindness. Ganciclovir (CAS: 82410-32-0) is currently one of the most effective drugs against CMV infection clinically, but because of its poor oral bioavailability, only 6% to 9%, it can only be used for Administration by injection. The infection caused by cytomegalovirus often requires long-term maintenance treatment after induction treatment. If the maintenance treatment is maint...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07D473/18
Inventor 崔德修李重阳李文忠
Owner SICHUAN KELUN PHARMA RES INST CO LTD
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