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A Buchwald–Hartwig Protocol to Enable Rapid Linker Exploration of Cereblon E3‐Ligase PROTACs **
Author(s) -
Hayhow Thomas G.,
Borrows Rachel E. A.,
Diène Coura R.,
Fairley Gary,
Fallan Charlene,
Fillery Shaun M.,
Scott James S.,
Watson David W.
Publication year - 2020
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.202003137
Subject(s) - cereblon , amination , linker , chemistry , bifunctional , combinatorial chemistry , aryl , alkyl , ubiquitin ligase , organic chemistry , computer science , biochemistry , ubiquitin , catalysis , programming language , gene
A palladium‐catalysed Buchwald–Hartwig amination for lenalidomide‐derived aryl bromides was optimised using high throughput experimentation (HTE). The substrate scope of the optimised conditions was evaluated for a range of alkyl‐ and aryl‐ amines and functionalised aryl bromides. The methodology allows access to new cereblon‐based bifunctional proteolysis targeting chimeras with a reduced step count and improved yields.