吡唑并[1,5-a]嘧啶衍生物的合成在药理活性和生物制品方面具有重要作用。药物例如抗焦虑药Ocinaplon，安眠药Zaleplon和Inplon，杀菌剂吡唑磷，生物制品例如KDR激酶抑制剂，融合三环抑制剂前体，由罗氏公司最新开发的一种血清素5-HT₆受体，均含有吡唑并[1,5-a]嘧啶这种母核结构。有关吡唑并[1,5-a]嘧啶的构建报道较少，虽然取得了一些成果，但存在反应条件苛刻，合成方法繁琐，其卤化反应的毒性较大，原子利用率较低，不符合绿色化学的要求；在关于C-S偶联的相关报道当中，存在有产物的选择性不高，生成的底物较单一的问题。针对以上问题，本研究以吡唑并[1,5-a]嘧啶为骨架，通过一种反应高效，操作简便的方法合成一系列带有不同取代基的吡唑并[1,5-a]嘧啶环；使用NIS做碘源，对其进行选择性单/双碘化反应，反应条件绿色无污染；其次研究其C-S/Se的偶联反应，能够选择性的进行单硫/硒醚的取代，以水为溶剂且反应时间较短。本论文的工作内容具体如下：

第一部分：I₂催化β-酮腈与1H -吡唑-5-胺的环化反应。本章使用一种简单高效的方法，即单质碘做催化剂，1H-吡唑-5-胺和β-酮基腈为底物，合成吡唑并[1,5-a]嘧啶，在底物适用性研究中，以良好至优秀产率合成了一系列的吡唑并[1,5-a]嘧啶。该方法具有反应条件简单温和、底物范围广等优点，并可以进行克级规模放大反应。

第二部分：吡唑并[1,5-a]嘧啶与NXS的卤化反应研究。本章开发了一种用于吡唑并[1,5-a]嘧啶的卤化的方法，使用NXS (X=I, Br, Cl)作为卤源，反应过程绿色高效，首先通过改变吡唑并[1,5-a]嘧啶与NIS的比例和溶剂的种类，对吡唑并[1,5-a]嘧啶进行选择性的单碘化和二碘化取代，选择性较好，且能达到良好至优秀的产率；其次，在吡唑并[1,5-a]嘧啶与NBS和NCS的反应中，以中等至良好的产率，生成了一系列的二溴代产物和二氯代产物。该方法具有广泛的底物、良好的官能团耐受性和能够克级合成等特点。这项工作为构建结构多样的卤代吡唑并[1,5-a]嘧啶衍生物提供了一种有效的方法。

第三部分：吡唑并[1,5-a]嘧啶选择性C-S(Se)偶联反应研究。本章报告了一种简便的合成单芳基硫醚吡唑并[1,5-a]嘧啶的方法，使用单碘代吡唑并[1,5-a]嘧啶作为底物，磺酰肼作为硫源，使用水作为溶剂，在相转移催化剂PEG-400的催化下，以较短的时间，合成一系列单取代的芳基硫醚，具有产率良好，选择性高的特点。此外，该条件适用于C-Se的偶联反应，用于合成芳基硒取代的吡唑并[1,5-a]嘧啶。

本研究为吡唑并[1,5-a]嘧啶及其衍生物的构建提供了一种高效便捷的方法，其温和的反应条件，优良的产率，较高的选择性，大大拓宽了吡唑并[1,5-a]嘧啶类化合物的应用范围。

The synthesis of pyrazolo[1,5-a]pyrimidine derivatives plays an important role in pharmacological activities and biological products. Drugs such as anti-anxiety drugs Ocinaplon, sleeping drugs Zaleplon and Inplon, fungicides Pyrazophos, biological products such as KDR kinase inhibitors, precursors of fused tricyclic inhibitors, and a serotonin 5-HT₆ receptor newly developed by Roche, all contain the parent structure of pyrazolo[1,5-a]pyrimidine.

There are few reports on the construction of pyrazolo[1,5-a]pyrimidine. Although some achievements have been made, the reaction conditions and synthesis methods are harsh, the toxicity of the halogenation reaction is high, and the utilization rate of atoms is low, which does not meet the requirements of green chemistry. There are few reports on the C-S coupling of pyrazolo[1,5-a]pyrimidine. Among the existing synthesis methods, the product selectivity is not high and the substrate is relatively single. In order to solve the above problems, a series of pyrazolo[1,5-a]pyrimidine rings with different substituents were synthesized by using a highly efficient and easy to operate method with pyrazolo[1,5-a]pyrimidine as the backbone. NIS was used as iodine source to carry out selective single/double iodination reaction, and the reaction conditions were green and pollution-free. Secondly, the coupling reaction of C-S/Se is studied, which can selectively replace monosulfur/selenoether, water as solvent, and the reaction time is short. The work content of this thesis is as follows:

Part one: I₂-catalyzed cyclization of β-ketonitrile with 1H-pyrazol-5-amine. In this thesis, a simple and efficient method was used to synthesize pyrazolo[1,5-a]pyrimidine using I₂ as catalyst, 1H-pyrazo-5-amine and β-ketonitrile as substrates. In the substrate suitability study, a series of pyrazolo[1,5-a]pyrimidine were synthesized in good to excellent yields. This method has the advantages of simple and mild reaction conditions, a wide range of substrates, and the ability to amplify the reaction on a gram scale.

Part two: Halogenation of pyrazolo[1,5-a]Pyrimidines with NXS. This chapter developed a method for the halogenation of pyrazolo[1,5-a]pyrimidine, using NXS (X=I, Br, Cl) as the halogenating agent, the reaction process is green and efficient. Firstly, changing the ratio of pyrazolo[1,5-a]pyrimidines to NIS and the type of solvent, selective monoiodination and diiodination of pyrazolo[1,5-a]pyrimidine were performed with good selectivity and good to excellent yields. Secondly, in the reaction of pyrazolo[1,5-a]pyrimidine with NBS and NCS, a series of dibrominated and dichlorinated products were formed in moderate to good yields. This method is characterized by a wide range of substrates, good functional group tolerance, and the ability to synthesize at gram level. This work provides an efficient method for the construction of structurally diverse halo pyrazolo[1,5-a]pyrimidine derivatives.

Part three: Selective C-S(Se) coupling of pyrazolo[1,5-a]pyrimidine. This chapter reports a simple method for the synthesis of monoaryl thioether pyrazolo[1,5-a]pyrimidine, using monoiodo pyrazolo[1,5-a]pyrimidine as the substrate, sulfonyl hydrazide as the sulfur source, and water as the solvent. Under the catalysis of phase transfer catalyst PEG-400, a series of monosubstituted aryl thioethers are synthesized in a short time with good yield. Characteristic of high selectivity. Furthermore, the conditions are suitable for the coupling reaction of C-Se for the synthesis of arylse-substituted pyrazolo[1,5-a]pyrimidine.

This research provides an efficient and convenient method for the construction of pyrazolo[1,5-a]pyrimidine and its derivatives. Its mild reaction conditions, excellent yield and high selectivity greatly broaden the applied range of pyrazolo[1,5-a]pyrimidine compounds.

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