Dexrazoxane preparation method

A technology of dextropropylimine and amides, which is applied in the field of preparation of dextropropylimine, can solve the problems of complex synthesis route and harsh reaction conditions of dextropropylimine, achieve high application value and development prospect, easy industrialization, and simplify The effect of process operations

Active Publication Date: 2020-02-18
YANGTZE RIVER PHARM GRP CO LTD
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  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0011] The present invention provides a simple and effective preparation method of dextropropylimine, aiming at the complicated synthetic route, harsh reaction conditions and low yield of dextrop

Method used

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  • Dexrazoxane preparation method

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Effect test

Embodiment 1

[0032] Preparation of dextropropanimine

[0033] Add (S)-1,2-diaminopropane-tetraacetic acid (10g) into a reaction flask equipped with a water separator, add N,N-dimethylformamide (50ml), ammonium formate (20.6g), Heat to 150°C, separate the reflux from the water separator, stir for 10 hours, concentrate, add 20 ml of purified water and stir for 0.5 hours, filter, and dry to obtain 7.1 g of crude dextropropylimine (yield 81%), HPLC purity 99.2 %.

[0034] Add the crude product of dextropropylimine to the reaction flask, add N,N-dimethylformamide (14ml) and heat to 80°C, stir and dissolve, add absolute ethanol (64ml), cool down to 20°C-30°C for crystallization Stir for 1 hour, filter and dry to obtain 6.2 g (yield 87%), HPLC purity 99.83%.

Embodiment 2

[0036] Preparation of dextropropanimine

[0037] Add (S)-1,2-diaminopropane-tetraacetic acid (120g) into a reaction flask equipped with a water separator, add N,N-dimethylformamide (480ml), ammonium formate (240g), and heat To 150°C, the water separator separated the reflux, stirred for 10 hours, concentrated, added 360ml of purified water and stirred for 0.5 hours, filtered, and dried to obtain 83g of crude dextranimine (yield 81%), HPLC purity 98.9%.

[0038] Add the crude product of dextropropylimine to the reaction flask, add N,N-dimethylformamide (208ml) and heat to 80°C, stir and dissolve, add absolute ethanol (624ml), cool down to 20°C-30°C for crystallization Stir for 1 hour, filter and dry to obtain 70 g (yield 84%), HPLC purity 99.72%.

Embodiment 3

[0040] Preparation of dextropropanimine

[0041] Add (S)-1,2-diaminopropane-tetraacetic acid (15g) into a reaction flask equipped with a water separator, add N,N-dimethylacetamide (60ml), ammonium formate (25g), and heat To 155°C, the water separator separated the reflux, stirred for 18 hours, concentrated under reduced pressure, added 45ml of purified water and stirred for 0.5 hours, filtered and dried to obtain 10.3g of the target product (yield 79%), HPLC purity 99.3%.

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Abstract

The invention discloses a dexrazoxane preparation method. According to the preparation method, (S)-1,2-diaminopropane-tetraacetate and alkali metal salt thereof are used as raw materials, and ammoniumsalt is used as an ammonium source to prepare dexrazoxane. By the adoption of the preparation method, tedious technological operation is avoided, the technological operation is easier and more convenient, and therefore the preparation method is more adaptive to industrial amplifying production.

Description

technical field [0001] The invention relates to medicine synthesis technology, in particular to a preparation method of dextropropimine. Background technique [0002] Dexrazoxane is the dextroisomer of razoxane, also known as dexrazoxane or derazoxane, and its structural formula is as formula 1: [0003] [0004] Dextropropimine is a lipophilic cyclic derivative of the chelating agent ethylenediaminetetraacetic acid, which is clinically used as a chemoprotectant, mainly for the prevention of anthracycline-induced cardiotoxicity. Dextropropylimine was developed by Chiron Corporation of the United States, first launched in Italy in 1992, and approved by FDA in July 1995. [0005] At present, there are mainly three kinds of synthetic methods of dextropropylimine: the first one is to obtain dextropropimine by cyclization of 1,2-propylenediaminetetraacetic acid; Amide cyclization to obtain dextropropimine, the third is 1,2-propanediamine tetraacetate cyclization to obtain de...

Claims

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Application Information

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IPC IPC(8): C07D241/08
CPCC07D241/08C07B2200/07
Inventor 周崴海徐浩宇蔡伟高小刚陈子章黄淑萍郝秀斌李浩冬夏雨
Owner YANGTZE RIVER PHARM GRP CO LTD
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