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Increasing the Purity of Lafutidine Using a “Suicide Substrate”
Organic Process Research & Development ( IF 3.4 ) Pub Date : 2018-08-14 00:00:00 , DOI: 10.1021/acs.oprd.8b00070
Chengjun Wu 1 , Zhen Li 1 , Chunchao Wang 1 , Yanan Zhou 1 , Tiemin Sun 1
Affiliation  

When preparing lafutidine, we found that the main impurity was dihydrolafutidine. On the basis of the chemical structure of dihydrolafutidine and the mechanism of its production, we decided to use a “suicide substrate” in the drug preparation to increase the purity of lafutidine. By calculating the energy barrier of the reduction reaction with a quantum-chemical method and evaluating the appropriate physicochemical properties of the terminal olefins, we chose 1-hexene as the suicide substrate to effectively control the formation of dihydrolafutidine in the synthesis of lafutidine. The experimental results showed that the content of the impurity, dihydrolafutidine, decreased from 1.5% to less than 0.05%, proving that using a suicide substrate is an effective method to reduce the formation of the relevant byproduct in drug production. In addition, this method is operationally simple and is suitable for industrial applications.

中文翻译:

使用“自杀底物”提高拉夫替丁的纯度

当制备拉夫替丁时,我们发现主要杂质是二氢拉夫替丁。根据二氢拉夫替丁的化学结构及其生产机理,我们决定在药物制剂中使用“自杀底物”以提高拉夫替丁的纯度。通过使用量子化学方法计算还原反应的能垒并评估末端烯烃的适当理化性质,我们选择了1-己烯作为自杀底物,以有效地控制拉夫替丁合成中二氢拉夫替丁的形成。实验结果表明,杂质二氢拉夫替丁的含量从1.5%降至小于0.05%,证明使用自杀底物是减少药物生产中相关副产物形成的有效方法。此外,
更新日期:2018-08-14
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