Method for preparing intermediate in process of preparing bendamustine hydrochloride

Abstract

The invention provides a method for preparing an intermediate in the process of preparing bendamustine hydrochloride. The prepared intermediate is [1-methyl-2-(4'-ethyl butyrate)-5-N,N-bis(2'-chloroethyl)]-1H-benzimidazole or [1-methyl-2-(4'-methyl butyrate)-5-N,N-bis(2'-chloroethyl)]-1H-benzimidazole. The method comprises the following steps of: (1) putting a compound shown as a formula I into a reactor, adding an organic solvent for dissolving, adding a reducing agent into the reactor, reacting at the temperature of lower than 25 DEG C, regulating the pH value until a solution is neutral, and filtering, washing and drying a solid precipitate to obtain a crude product; and (2) dissolving the crude product in a mixture of methanol and water, stirring in ice water to precipitate a solid, and filtering, washing and drying the solid precipitate to obtain a target product. The yield is over 74 percent, the prepared key intermediate has the purity of over 99.5 percent, the content of a single impurity is less than 0.1 percent, and the method has the advantages of high yield and high product stability and is easy to operate and suitable for industrial production.

Description

technical field

[0001] The invention relates to a preparation method of an intermediate in the preparation process of bendamustine hydrochloride. Background technique

[0002] Bendamustine hydrochloride (bendamustine hydrochloride) is an alkylation antineoplastic drug developed by Merckle Company, which was launched in Germany in October 2003 under the trade name Ribomustine. It is clinically used for single or combined treatment of breast cancer, chronic lymphocytic leukemia, non-Hodgkin's lymphoma (stage II-IV), Hodgkin's disease, and plasmacytoma. Clinical application shows that its single treatment or combined treatment of breast cancer has definite curative effect, can significantly reduce the recurrence rate and mortality, and has small adverse reactions and good safety.

[0003] There are many synthetic routes of bendamustine hydrochloride. "Chinese Journal of New Drugs" (volume 16, issue 23, 2007, pages 1960-1961, referred to as reference document 1 in the present ...

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