A kind of preparation method of cbz valganciclovir

Abstract

The invention discloses a preparation method of CBZ-valganciclovir, and belongs to the field of preparation of valganciclovir. The preparation method of the CBZ-valganciclovir comprises the following steps: adding wet ganciclovir, DMF, trimethyl orthoacetate and p-toluenesulfonic acid in a reactor, stirring and reacting at room temperature, then adding water for hydrolysis, distilling water and carrying out low boiling, adding the trimethyl orthoacetate, reacting at the temperature of 25 DEG C, then adding water for hydrolysis, adjusting PH to be neutral, distilling water and carrying out low boiling, enabling residual liquor to be subjected to next reaction directly, adding DCC, DMAP and CBZ-L-valine in the residual liquor, stirring and reacting at room temperature, adding hydrochloric acid and stirring, and carrying out suction filtering to obtain filtrate, taking the filtrate to regulate pH of reaction liquid to be 7-8, then separating out white solid after adding water, cooling with ice water and then continuing stirring and reacting, carrying out suction filtering, washing filter cakes with water, and air-drying to obtain white solid which is CBZ-valganciclovir monoester. By the preparation method of the CBZ-valganciclovir, a preparation technology of the monoester is simplified, cost is saved, emission of pollutants is reduced, and quality of synthesized monoester is guaranteed.

Description

technical field [0001] The invention belongs to the field of preparation of valganciclovir, more specifically, relates to a preparation method of CBZ-valganciclovir. Background technique [0002] Valganciclovir is the L-valyl ester (prodrug) of ganciclovir, which is rapidly converted into ganciclovir by acylases in the small intestine and liver after oral administration, and is used for acquired immunodeficiency syndrome (AIDS). ) patients with cytomegalovirus (CMV) retinitis, and cytomegalovirus (CMV) infection after organ transplantation, it is the first choice for the prevention of CMV infection in the world. Cytomegalovirus (CMV) belongs to the herpesviridae family. The virus is in a dormant state in individuals with normal immune function, but when the immune function is impaired, such as AIDS patients, patients receiving immunosuppressants after organ transplantation, etc., The virus can cause illness. The most common condition of CMV in HIV / AIDS patients is CMV reti...

AI Technical Summary

Problems solved by technology

[0005] Therefore, in summary, the ubiquitous shortcoming in the existing stage is to generate a large amount of diesters and a large amount of residual ganciclovir, if the residue of ganciclovir is less, more diesters will be formed, and the content of monoesters will further increase. Reduce, if the content of diester is reduced, the content of ganciclovir remains largely, and the content of monoester is not guaranteed and is very low. The general patent literature is to achieve a ratio of 40-50% of monoester, ganciclovir The ratio of clovir and diester is 50-60%, and then separated by cumbersome separation methods, the separation of monoester and diester is difficult to achieve, and the separated diester is useless, only hydrolyzed ganciclovir can be recovered

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