A New Method for Synthesis of Nolatrexed Dihydrochloride

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• 作者：Xueqing Zhao ; Fei Li ; Weiping Zhuang ; Xiaowen Xue ; Yuanyang Lian ; Jianhui Fan ; Dongsheng Fang
• 刊名：Organic Process Research & Development
• 出版年：2010
• 出版时间：March 19, 2010
• 年：2010
• 卷：14
• 期：2
• 页码：346-350
• 全文大小：162K
• 年卷期：v.14,no.2(March 19, 2010)
• ISSN：1520-586X

文摘

A new synthetic method for nolatrexed dihydrochloride (thymitaq) has been developed. The synthesis was accomplished in three steps featuring the direct conversion of the starting 4-bromo-5-methylisatin into the methyl anthranilate by potassium peroxydisulfate/sodium methoxide. In the final Ullmann reaction potassium carbonate was employed in place of sodium hydride, and the amount of copper catalysts was significantly reduced. Moreover, sodium sulfide solution was utilized to efficiently remove copper under approximately neutral conditions instead of hydrogen sulfide/methanol under strongly acidic conditions. By means of these modifications, nolatrexed dihydrochloride was ensured to be prepared in good yield and high purity.