<br/>The key retrosynthetic disconnections in the route development of two clinical candidates, BMS-986142 and BMS-919373, are catalytic transformations. BMS-986142 is a molecularly complex active pharmaceutical ingredient (API) due to the atypical presence of two atropisomeric bonds and an asymmetric tertiary alcohol, resulting in eight possible diastereomers. The strategy for the synthesis of this molecule with complete diastereomeric and enantiomeric control required mechanistic understanding of the key catalytic steps. Retrosynthetic analysis of BMS-919373 identifies the C5 aryl-aryl bond as an obvious point of disconnection.   While traditional methodology would employ a transition metal catalyzed cross coupling, such as a Suzuki reaction, the strategy for synthesis of this molecular recognized that the aminomethyl pyridine group could serve as a directing group for C-H activation to enable a more efficient synthesis that avoids the challenging preparation of the corresponding aryl halide.<br/>

Robust catalytic transformations: Value of mechanistic studies in process chemistry

2019 Fall National Meeting

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