Identification of a Manufacturing Route of Novel CRF-1 Antagonists Containing a 2,3-Dihydro-1H-pyrrolo[2,3-b]pyridine Moiety

A case study on the synthesis of novel CRF-1 antagonists containing the 2,3-dihydro-1H-pyrrolo[2,3-6]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.