Citation: Yuan Shuo, Wang Sixi, Zhao Min, Zhang Danqing, Chen Jinjie, Li Jian-Xin, Zhang Jingya, Song Yihui, Wang Jinyi, Yu Bin, Liu Hongmin. Brønsted acid-promoted 'on-water' C(sp³)-H functionalization for the synthesis of isoindolinone/[1, 2, 4]triazolo[1, 5-a] pyrimidine derivatives targeting the SKP2-CKS1 interaction[J]. Chinese Chemical Letters, ;2020, 31(2): 349-352. doi: 10.1016/j.cclet.2019.07.019 shu

Brønsted acid-promoted 'on-water' C(sp³)-H functionalization for the synthesis of isoindolinone/[1, 2, 4]triazolo[1, 5-a] pyrimidine derivatives targeting the SKP2-CKS1 interaction

School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou 450001, China

yubin@zzu.edu.cn

liuhm@zzu.edu.cn

Received Date: 19 May 2019
Revised Date: 1 July 2019
Accepted Date: 8 July 2019
Available Online: 10 July 2019

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The isoindolinone and biaryl scaffolds are prevalent in natural products and drug molecules, which have showed broad and interesting biological activities. The efficient construction of such hybridized molecules and biological evaluation are of great interest to medicinal chemistry community. In this communication, we report an efficient Brønsted acid-promoted C(sp³)-H functionalization approach that enables the rapid construction of biologically important isoindolinone/[1,2,4]triazolo[1, 5-a]pyrimidine hybrids from 5-methyl-7-(2, 4, 6-trimethoxyphenyl)-[1,2,4]triazolo[1, 5-a]pyrimidine, 2-formylbenzoic acid and various anilines. The title compounds were generated in high to excellent yields (up to 96%) regardless of the electronic nature and steric effects of the substituents. In this reaction, an isoindolinone scaffold, one C-C single bond, and two C-N bonds were formed simultaneously with high atom economy. In this work, we have envisioned that the methyl group linked to the electron-deficient Nheterocycles could be used as a new synthetic handle for late-state diversification and may have broad applications in the field of organic and medicinal chemistry. Besides, the title compounds have exhibited promising activity against the SKP2-CKS1 interaction.
- Isoindolinone,
- [1, 2, 4]Triazolo[1, 5-a]pyrimidine,
- Biaryl scaffold,
- C(sp³)-H activation,
- Molecular hybridization,
- SKP2-CKS1 interaction
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通讯作者: 陈斌, bchen63@163.com

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沈阳化工大学材料科学与工程学院沈阳 110142

Brønsted acid-promoted 'on-water' C(sp3)-H functionalization for the synthesis of isoindolinone/[1, 2, 4]triazolo[1, 5-a] pyrimidine derivatives targeting the SKP2-CKS1 interaction

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通讯作者: 陈斌, bchen63@163.com

Brønsted acid-promoted 'on-water' C(sp³)-H functionalization for the synthesis of isoindolinone/[1, 2, 4]triazolo[1, 5-a] pyrimidine derivatives targeting the SKP2-CKS1 interaction