Solid-phase synthesis of 5-amino-1-(substituted thiocarbamoyl)pyrazole and 1,2,4-triazole derivatives via dithiocarbazate linker
Solid-phase synthesis of 5-amino-1-(substituted thiocarbamoyl)pyrazole and 1,2,4-triazole derivatives via dithiocarbazate linker
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DOI：
10.1021/cc049931n
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发表时间：
2005-01-01
影响因子：
--
通讯作者：
Gong, YD
中科院分区：
文献类型：
--
作者：
Hwang, JY;Choi, HS;Gong, YD
报道了一种基于聚合物结合的二硫代肼基甲酸酯3与各种亲电试剂如3-乙氧基丙烯腈8和氰基碳酰亚胺9环化的平行固相合成5-氨基-1-（取代硫代氨基甲酰基）吡唑和1，2，4-三唑衍生物的通用方法。在梅里菲尔德树脂上与二硫化碳和Fmoc-肼发生亲核反应，生成聚合物结合的二硫代肼基甲酸酯3，作为随后杂环多样化的关键中间体。在热裂解条件下，用各种胺对这些聚合物结合的5-氨基-1-二硫代羧基吡唑4和1，2，4-三唑6进行进一步的亲核取代，产生所需的5-氨基-1-（取代的硫代氨基甲酰基）吡唑5和1，2，4-三唑7。反应的进程可以监测作为聚合物结合的中间体，通过ATR-FTIR光谱上的单珠。通过LC/MS、H-1 NMR和C-13 NMR光谱表征了从树脂裂解后以良好的四步总产率和高纯度获得的最终化合物。
A general method is reported for the parallel solid-phase synthesis of 5-amino-1-(substituted thiocarbamoyl)pyrazole and 1,2,4-triazole derivatives based on the cyclization of polymer-bound dithiocarbazate 3 with various electrophiles, such as 3-ethoxyacrylonitriles 8 and cyanocarboimidates 9. The polymer-bound dithiocarbazate 3, produced by nucleophilic reaction with carbon disulfide and Fmoc-hydrazine on the Merrifield resin, served as the key intermediate for subsequent heterocycle diversification. Further nucleophilic substitution on these polymer-bound 5-amino-1-dithiocarboxypyrazoles 4 and 1,2,4-triazoles 6 with various amines under thermal cleavage condition produced the desired 5-amino-1-(substituted thiocarbamoyl)pyrazoles 5 and 1,2,4-triazoles 7. The progress of reactions could be monitored as polymer-bound intermediates by ATR-FTIR spectroscopy on single bead. The final compounds, obtained in good four-step overall yields and high purities upon cleavage from the resins, were characterized by LC/MS, H-1 NMR, and C-13 NMR spectroscopy.