A Concise Enantioselective Synthesis of Fluorinated Pyrazolo-Piperidine GSK3901383A Enabled by an Organocatalytic Aza-Michael Addition.

Barron, Benedict; Edge, Colin; Fenner, Sabine; Shrives, Harry; Sollis, Steven; Whiting, Matthew; Valette, Damien

Barron, Benedict; Edge, Colin; Fenner, Sabine; Shrives, Harry; Sollis, Steven; Whiting, Matthew; Valette, Damien.

Afiliación

Barron B; Drug Substance Development, GSK, Gunnels Wood Road, Stevenage, Hertfordshire SG1 2NY, U.K.
Edge C; Computational Chemistry, GSK, Gunnels Wood Road, Stevenage, Hertfordshire SG1 2NY, U.K.
Fenner S; Drug Substance Development, GSK, Gunnels Wood Road, Stevenage, Hertfordshire SG1 2NY, U.K.
Shrives H; Medicinal Chemistry, GSK, Gunnels Wood Road, Stevenage, Hertfordshire SG1 2NY, U.K.
Sollis S; Medicinal Chemistry, GSK, Gunnels Wood Road, Stevenage, Hertfordshire SG1 2NY, U.K.
Whiting M; Drug Substance Development, GSK, Gunnels Wood Road, Stevenage, Hertfordshire SG1 2NY, U.K.
Valette D; Drug Substance Development, GSK, Gunnels Wood Road, Stevenage, Hertfordshire SG1 2NY, U.K.

Org Lett ; 26(8): 1533-1538, 2024 Mar 01.

Article en En | MEDLINE | ID: mdl-38363757

ABSTRACT

ABSTRACT

A highly enantioselective organocatalytic aza-Michael addition of 4-nitro-pyrazole to ethyl (E)-2,2-difluoro-5-oxopent-3-enoate has been developed. This reaction enabled a concise, four-step, stereoselective synthesis of highly functionalized 3,3-difluoro-4-pyrazolo-piperidine GSK3901383A, a key intermediate for the synthesis of a leucine-rich repeat kinase 2 inhibitor API. Computational analysis provided insight into the steric requirements of the catalytic system, enabling rational selection of a highly selective catalyst.

Texto completo

Añadir a Mi BVS

Imprimir

XML

PubMed Links

Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Org Lett Asunto de la revista: BIOQUIMICA Año: 2024 Tipo del documento: Article País de afiliación: Reino Unido Pais de publicación: Estados Unidos

Texto completo

Añadir a Mi BVS

Imprimir

XML

PubMed Links

Buscar en Google