title: Photoredox catalysis in a complex pharmaceutical setting: toward the preparation of JAK2 inhibitor LY2784544.
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.
authors.affiliation: Department of Chemistry, University of Michigan , Ann Arbor, Michigan 48109, United States.
authors.forename: James J
authors.initials: JJ
authors.lastname: Douglas
authors.forename: Kevin P
authors.initials: KP
authors.lastname: Cole
authors.forename: Corey R J
authors.initials: CR
authors.lastname: Stephenson
mesh_terms: D002384:Catalysis; D007093:Imidazoles / Q000138:chemical synthesis* / Q000737:chemistry; D053614:Janus Kinase 2 / Q000037:antagonists & inhibitors* / Q000737:chemistry*; D008027:Light; D015394:Molecular Structure; D010084:Oxidation-Reduction; D055668:Photochemical Processes; D011720:Pyrazoles / Q000138:chemical synthesis* / Q000737:chemistry; D011724:Pyridazines / Q000138:chemical synthesis* / Q000737:chemistry
chemical_list: D007093:Imidazoles; C581039:LY2784544; D011720:Pyrazoles; D011724:Pyridazines; C507924:JAK2 protein, human; D053614:Janus Kinase 2