|
|||||
|
|
A Buchwald–Hartwig Protocol to Enable Rapid Linker Exploration of Cereblon E3-Ligase PROTACs** |
|
| Authors: | Dr Thomas G Hayhow Rachel E A Borrows Dr Coura R Diène Gary Fairley Dr Charlene Fallan Dr Shaun M Fillery Dr James S Scott Dr David W Watson |
| Institution: | 1. Medicinal Chemistry, Oncology R&D, Research and Early Development, AstraZeneca, Cambridge Science Park, Unit 310 Darwin Building, Cambridge, CB4 0WG UK;2. Medicinal Chemistry, Oncology R&D, Research and Early Development, AstraZeneca, Macclesfield Campus, Etherow Building, Silk Road Industrial Estate, Macclesfield, SK10 2NA UK |
| Abstract: | 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. |
| Keywords: | amination cereblon drug discovery PEPPSI PROTAC |