Photoredox catalysis in a complex pharmaceutical setting: toward the preparation of JAK2 inhibitor LY2784544.
J Org Chem
; 79(23): 11631-43, 2014 Dec 05.
Article
em En
| MEDLINE
| ID: mdl-25356724
ABSTRACT
We report a detailed investigation into the application of visible light-mediated photocatalysis to a challenging bond construction in a complex pharmaceutical target. The optimized reaction allowed the direct coupling of N-methylmorpholine with an unfunctionalized pyridazine in good yield and selectivity, and with high purity of the product isolated via crystallization. The reaction also facilitated the expedient synthesis of a range of analogues via the use of other commercially available N-methyl substituted tertiary amines, and therefore it represents an attractive tool for medicinal chemistry. Furthermore, a number of other interesting photoredox reactions were discovered during the course of this investigation, such as a formal methylation reaction via C-N bond cleavage, functionalization of C-H bonds alpha to amides, and a visible light-mediated iminium ion reduction.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Pirazóis
/
Piridazinas
/
Janus Quinase 2
/
Imidazóis
Idioma:
En
Ano de publicação:
2014
Tipo de documento:
Article