A Process Chemistry Benchmark for sp2-sp3 Cross Couplings.
J Org Chem
; 86(15): 10380-10396, 2021 08 06.
Article
em En
| MEDLINE
| ID: mdl-34255510
ABSTRACT
As sp2-sp3 disconnections gain acceptance in the medicinal chemist's toolbox, an increasing number of potential drug candidates containing this motif are moving into the pharmaceutical development pipeline. This raises a new set of questions and challenges around the novel, direct methodologies available for forging these bonds. These questions gain further importance in the context of process chemistry, where the focus is the development of scalable processes that enable the large-scale delivery of clinical supplies. In this paper, we describe our efforts to apply a wide variety of standard, photo-, and electrochemical sp2-sp3 cross-coupling methods to a pharmaceutically relevant intermediate and optimize each through a combination of high throughput and mechanistically guided experimentation. With data regarding the performance, benefits, and limitations of these novel methods, we evaluate them against a more traditional two-step palladium-catalyzed process. This work reveals trends and similarities between these sp2-sp3 bond-forming methods and suggests a path forward for further refinements.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Preparações Farmacêuticas
/
Benchmarking
Idioma:
En
Revista:
J Org Chem
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
Estados Unidos