Synthetic method of valganciclovir hydrochloride

Abstract

The invention discloses a method for synthesizing valganciclovir hydrochloride, which comprises the following steps: with 1,3-dichloro-2-acetoxymethoxypropane as an initial raw material, preparing monochlorinated ganciclovir, and carrying out esterification, hydrolysis and deprotection salification to finally obtain the valganciclovir hydrochloride. The invention provides a synthesis method of siganciclovir hydrochloride, which avoids the problem of separation and conversion of N-7 and N-9 isomers in the diacetyl guanine condensation process. The method directly synthesizes monochlorinated ganciclovir without using ganciclovir, instead of the synthesis of monoacetyl ganciclovir in the prior art, so that the method avoids the problem of diester compound separation caused by ganciclovir residues, has the advantages of short process steps, simple operation, convenient purification and low cost, is beneficial to industrial production, and is suitable for synthesis of valganciclovir hydrochloride.

Description

technical field [0001] The invention belongs to the technical field of organic synthesis, and in particular relates to a synthetic method of valganciclovir hydrochloride. Background technique [0002] Valganciclovir hydrochloride is a cytomegalovirus (CMV) nucleoside analog DNA polymerase inhibitor, it is a prodrug of the antiviral drug ganciclovir, and its bioavailability is higher than that of the traditional drug ganciclovir 10 times, while the toxicity is greatly reduced. It is clinically used to treat acute retinitis caused by CMV infection in patients with acquired immunodeficiency syndrome (AIDS), and to prevent and treat secondary CMV infection in organ transplant recipients. Valganciclovir has become the best new drug for the treatment of CMV infection due to its safer, more convenient administration method and higher bioavailability. Its structural formula is: [0003] For the synthesis of valganciclovir hydrochloride, most of the current production techniques...

AI Technical Summary

Problems solved by technology

[0005] In the synthetic process of intermediate triacetyl ganciclovir, there are separation and conversion problems of N-7 and N-9 isomers in this process route, and the separation process is loaded down with trivial details, which seriously affects the process yield; in the preparation of ganciclovir In the valganciclovir hydrochloride process, a large number of residues of ganciclovir in the orthoester protection process will lead to the generation of diesters in the subsequent process, which is also difficult to separate, and often requires additional purification steps to obtain a product with higher purity. The steps are cumbersome and seriously affect the process yield

At present, the existing production technology of valganciclovir hydrochloride has problems such as long process route, complicated industry, low yield, and unfavorable industrialized production.

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