A case study on the synthesis of novel CRF-1 antagonists containing the 2,3-dihydro-1H-pyrrolo[2,3-b]pyridine moiety is presented. The development of ever more efficient synthetic routes allowed the progression of three candidates at the same time. A manufacturing route was identified and successfully demonstrated on a pilot-plant scale to prepare 100 kg of the CRF-1 antagonist GW876008.

The use of commercially available resins to prepare novel and stable polymer supported thioimidates was investigated. Polymer supported thioimidates were found to enable acetamidine formation in a convenient manner, with a significantly easier workup than solution-phase reactions.