文献类型： 外文期刊

第一作者： Hu Yuzhao

作者： Hu Yuzhao;Quan Haiyuan;Wang Liuyang;Wang Zhinan;Mei Xiangdong;Nin Jun;She Dongmei;Quan Haiyuan

作者机构：

关键词： 1,4-dihydropyridines; acetylacetic esters; isotope; synthesis

期刊名称：CHINESE JOURNAL OF ORGANIC CHEMISTRY （ 影响因子：1.344； 五年影响因子：0.956 ）

ISSN： 0253-2786

年卷期： 2021 年 41 卷 2 期

页码：

收录情况： SCI

摘要： 1,4-Dihydropyridines are important central motifs that are abundant in many biologically active molecules and drug molecules, as well as versatile building blocks for organic synthesis. Currently, there is no suitable method for the synthesis of C-13-labeled 1,4-dihydropyridine. A method was described for the synthesis of C-13(4)-1, 4-dihydropyridines in this article. Using C-13(2)-sodium acetate as the raw material for labeling, C-13(4)-acetoacetates were obtained by phosphoric acid acidification, C-13(2)-Acetic acid was acylated with N,N-carbonyldiimidazole to give C-13(2)-N-acetylimidazole. Then, the sodium salt of 1,2,3,4-C-13(4)-acetoacetylimidazole was synthesized from C-13(2)-N-acetylimidazole by Claisen condensation under the catalysis of sodium imidazolate. The sodium salt of 1,2,3,4-C-13(4)-acetoacetylimidazole was acidified with acetic acid to obtain 1,2,3,4-C-13(4)-acetoacetylimidazole, and then esterified with alcohol to obtain 1,2,3,4-C-13(4)-acetylacetic esters. 1,2,3,4-C-13(4)-acetylacetic esters were aminated by ammonium carbamate to give 1,2,3,4-C-13(4)-3-aminocrotonates. Subsequently, 5,6-position and its substituent carbon-labeled C-13(4)-nitrandipine, C-13(4)-amlodipine besylate and C-13(4)-amlodipine maleate were synthesized using Hantzsch modified method. The method has simple operation, mild reaction conditions, and high yield. This study provides a new idea for the introduction of 1,4-dihydropyridine which 5,6-position and its substituents are labeled with C-13 isotope. And it meets the independent synthesis requirements of stable isotope internal standards for the consistency evaluation of generic drugs in China.

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