Method for preparing amifostine

Abstract

The invention relates to a method for preparing amifostine, comprising the following steps: a) reacting phthalimide with 1,3-dibromopropane in dipolar aprotic solvents to genenrate N-(3-bromopropyl) phthalimide; and b)reacting N-(3-bromopropyl) phthalimide with 2-oxazolidinone in dipolar aprotic solvents to generate 2,2-[3-(2-carbonyl-3-oxazole)propyl]-1H-isoindole-1,3(2H)-diketone; and using the one-pot process to prepare the amifostine directly from the intermediate 2,2-[3-(2-carbonyl-3-oxazole)propyl]-1H-isoindole-1,3(2H)-diketone, thus the production process can be simplified, and the production cost can be saved. In addition, primary amine is obtained by hydrazinolysis, thus the reaction conditions are mild, the side effect is low, and the post-treatment is simple. The method has the characteristics of easy obtainment of raw materials, low price, safe and convenient usage, little pollution, easy transportation, and the like.

Description

technical field [0001] The invention belongs to the technical field of pharmaceutical engineering, and in particular relates to a preparation method of amifostine, an adjuvant therapeutic agent for tumor radiotherapy or cytotoxic chemotherapy. Background technique [0002] Amifostine is the first broad-spectrum normal cell protective agent recognized by international authorities, and is mainly used for adjuvant therapy of various cancers. Applying this product before chemotherapy for lung cancer, ovarian cancer, breast cancer, nasopharyngeal cancer, bone tumor, digestive tract tumor, blood system tumor and other cancer patients can significantly reduce the damage caused by chemotherapy drugs to the kidney, bone marrow, heart, Ear and nervous system toxicity without reducing the efficacy of chemotherapy drugs. Applying this product before radiotherapy can significantly reduce the occurrence of xerostomia and mucositis. Amifostine was first developed by the U.S. Army Researc...

AI Technical Summary

Problems solved by technology

[0019] The inventor team compared the above different synthesis methods. The first method is the synthesis method of amifostine, which is currently more commonly used. The raw materials used are cheap, the reaction conditions are mild, and it is suitable for industrial production; but ethylene oxide is a toxic carcinogen It is flammable and explosive, not easy to transport over long distances, and is controlled by the public security department, so it has strong regional characteristics

Method 2 has the fewest reaction steps and provides the most direct method to obtain N-(2-hydroxyethyl)-1,3-propanediamine, an important intermediate of amifostine. It avoids the use of ethylene oxide and is not complicated. Harsh reaction conditions, but the azetidine used in it is a custom-made product in the laboratory, which is expensive and has not formed industrial production at present, which limits the feasibility of this method in actual production and application

The third method also avoids the use of ethylene oxide. However, acrylonitrile is also a highly toxic drug with a pungent and pungent smell. It is also controlled by the public security department. In addition, the reaction of converting nitrile groups to amino groups is either through hydrogenation or through lithium aluminum hydride. Reduction will bring obstacles to industrial production, and this change seems meaningless

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