丙烯酰胺
胺气处理
环戊二烯
电泳剂
加合物
化学
重氮甲烷
热稳定性
产量(工程)
组合化学
有机化学
单体
聚合物
材料科学
催化作用
冶金
作者
Annie R. Hooper,Alexander Burns
标识
DOI:10.1021/acsmedchemlett.2c00075
摘要
Acrylamides are privileged electrophiles used in targeted covalent therapies, often installed at the end of a synthetic sequence due to their reactive nature. Herein, we report several diene-acrylamide adducts with a range of thermal stabilities toward retro-Diels-Alder deprotection of the acrylamide, enabling this masked functionality to be introduced early in a synthetic route and deprotected in a specific temperature range. Through kinetic studies, we identify solvent and structural trends that impact the stability of trimethylsilyl cyclopentadiene (TMS-CP) acrylamide adducts. TMS-CP protected acrylamides were installed on several amine-containing drugs, whose acrylamides were thermally unveiled (T = 160 °C, time ≤ 1 h) in moderate to high yields. We also showcase the potential utility of this protection strategy by improving the yield of a base-promoted SNAr reaction when the acrylamide is masked.
科研通智能强力驱动
Strongly Powered by AbleSci AI