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.

As part of a drug discovery program, 4-pyrazin-2-yl-1H-pyrrole-2-carboxamides were accessed along with a number of bicyclic analogues. Routes to these compounds were largely absent from the scientific literature. The synthesis of a 4-(pyrazin-2-yl)-1H-pyrrole-2-carboxamide and several fused bicyclic analogues all using standard procedures (SNAr, borylation, C–C cross couplings, hydrolysis, amide bond formation, cyclisation, halogenation, and alkylation) from readily available starting materials is reported. The synthetic sequences range from 4–12 steps per final compound, with yields of isolated intermediates ranging from 20 to ∼100%.