Benzylic C-H isocyanation/amine coupling sequence enabling high-throughput synthesis of pharmaceutically relevant ureas.
Chem Sci
; 12(30): 10380-10387, 2021 Aug 04.
Article
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| MEDLINE
| ID: mdl-34377424
ABSTRACT
C(sp3)-H functionalization methods provide an ideal synthetic platform for medicinal chemistry; however, such methods are often constrained by practical limitations. The present study outlines a C(sp3)-H isocyanation protocol that enables the synthesis of diverse, pharmaceutically relevant benzylic ureas in high-throughput format. The operationally simple C-H isocyanation method shows high site selectivity and good functional group tolerance, and uses commercially available catalyst components and reagents [CuOAc, 2,2'-bis(oxazoline) ligand, (trimethylsilyl)isocyanate, and N-fluorobenzenesulfonimide]. The isocyanate products may be used without isolation or purification in a subsequent coupling step with primary and secondary amines to afford hundreds of diverse ureas. These results provide a template for implementation of C-H functionalization/cross-coupling in drug discovery.
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01-internacional
Base de datos:
MEDLINE
Tipo de estudio:
Guideline
Idioma:
En
Revista:
Chem Sci
Año:
2021
Tipo del documento:
Article