10.1021/jo502288q.s001
James
J. Douglas
James
J.
Douglas
Kevin P. Cole
Kevin P.
Cole
Corey R. J. Stephenson
Corey
R. J. Stephenson
Photoredox Catalysis in a
Complex Pharmaceutical Setting:
Toward the Preparation of JAK2 Inhibitor LY2784544
American Chemical Society
2015
methylation reaction
JAK 2 Inhibitor LY 2784544We report
investigation
Photoredox Catalysis
photoredox reactions
Complex Pharmaceutical
bond construction
optimized reaction
unfunctionalized pyridazine
2015-12-17 06:09:06
Journal contribution
https://acs.figshare.com/articles/journal_contribution/Photoredox_Catalysis_in_a_Complex_Pharmaceutical_Setting_Toward_the_Preparation_of_JAK2_Inhibitor_LY2784544/2044806
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 <i>N</i>-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 <i>N</i>-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.