RESUMO
Late-stage functionalization (LSF) is a powerful method to quickly generate new analogues of a lead structure without resorting to de novo synthesis. We have leveraged Baran Diversinates to carry out late-stage functionalizations on lead structures from internal drug discovery projects and accurately predicted regioselectivities using computational methods. Our functionalization successfully afforded specific regioisomers which were in line with our predictions. To enhance reactivity, decrease reaction time, and increase reaction yields, we have developed new functionalization conditions involving iron(III) catalysis. Finally, we demonstrate how our LSF reactions using Baran Diversinates can lead to new analogues with improved in vitro DMPK parameters.