2-甲基吲哚衍生物的合成研究

摘要甲基基团是存在于药物小分子中最常见的碳片段之一,许多例子表明C-H转化成C-Me这个小小的改变却能极大地改变候选药物的生物活性，甚至能提高其IC50值100倍以上。在对候选药物的设计中甲基基团常常被引入来努力提高小分子的生物活性和物理性质，并且2-甲基吲哚的结构存在于众多药物活性分子中，在制药工业中甲基化反应被视为是一个非常有价值的合成反应。故此，研究了基于嘧啶单齿导向的金属钯催化吲哚C-2位的甲基化，以环境友好的甲基硼酸做甲基源，使用嘧啶基团作为容易安装且容易脱除的N-导向基团，一系列的吲哚类底物具有优异的官能团耐受性，最终能得到适度至良好的产率。42777

关键词碳氢活化甲基化钯催化导向基团吲哚

毕业设计说明书外文摘要

Title Synthesis of 2-Methyl indole derivatives

Abstract

The methyl group is one of the most commonly occurring carbon fragments in small-molecule drugs, a large number of examples have shown a simple change of C-H to C-Me can significantly improve the biological activity of a drug candidate, which even improves the IC50 value more than 100-fold. During the exercise of designing a drug candidate, methyl groups are commonly installed in an effort to improve a molecule,s biological activity and physical properties. 2-Methylindoles are present in many biologically active molecules, Synthetic reactions that install methyl groups are of value to the pharmaceutical industry. Therefore,the

Palladium-catalyzed C-2 methylation of indoles was accomplished with methylboronic acid as the methyl source through the use of 2-pyrimidyl group as an easily installed and readily removable N-directing group. A moderate to good yield can be achieved on a range of indole substrates with excellent functional group tolerance.

Keywords C-H activation methylation palladium-catalyzed directing group indoles

1 引言 1

1.1 课题背景 1

1.2 C-H键活化 1

1.3 甲基化 2

1.3.1 sp2C-H的甲基化 2

1.3.2 sp3 C-H键的甲基化 5

1.3.3 sp C-H键的甲基化 6

2 嘧啶导向金属钯催化的吲哚C-2位的甲基化反应研究 7

2.1 引言 7

2.2 本课题的研究目的和主要内容 8

2.2.1 研究目的 8

2.2.2 本课题的主要内容 8

2.3 实验所需试剂及仪器 9

2.3.1 主要实验仪器与试剂 9

2.3.2 测试仪器 10

2.4 底物合成 11

2.4.1 底物1a的合成及表征 11

2.4.2 底物1g的合成及表征 13

2.4.3 底物1h的合成及结构表征 14

2.4.4 底物1r的合成及产物表征 14

2.5 实验条件优化 15

2.5.1 催化剂的筛选 2-甲基吲哚衍生物的合成研究:http://www.751com.cn/huaxue/lunwen_43325.html