Ni-Catalyzed C-H Functionalization in the Formation of a Complex Heterocycle: Synthesis of the Potent JAK2 Inhibitor
Monica A Fitzgerald1, Omid Soltani1, Carolyn Wei1
1Chemical Development, Bristol-Myers Squibb, One Squibb Drive, New Brunswick, New Jersey 08903, United States.
Abstract:
BMS-911543 is a complex pyrrolopyridine investigated as a potential treatment for myeloproliferative disorders. The development of a short and efficient synthesis of this molecule is described. During the course of our studies, a Ni-mediated C-N bond formation was invented, which enabled the rapid construction of the highly substituted 2-aminopyridine core. The synthesis of this complex, nitrogen-rich heterocycle was accomplished in only eight steps starting from readily available materials.
Related Concept Videos
[4+2] Cycloaddition of Conjugated Dienes: Diels–Alder Reaction
Benzene to 1,4-Cyclohexadiene: Birch Reduction Mechanism
Reduction of Benzene to Cyclohexane: Catalytic Hydrogenation
Reduction of Alkenes: Asymmetric Catalytic Hydrogenation
The metal catalyst used can be either heterogeneous or homogeneous. When hydrogenation of an alkene generates a chiral center, a pair of enantiomeric products is expected to form. However, an enantiomeric excess of one of the products can be facilitated using an enantioselective reaction or an...
Cyclohexenones via Michael Addition and Aldol Condensation: The Robinson Annulation
Reduction of Alkynes to cis-Alkenes: Catalytic Hydrogenation
Like alkenes, alkynes can be reduced to alkanes in the presence of transition metal catalysts such as Pt, Pd, or Ni. The reaction involves two sequential syn additions of hydrogen via a cis-alkene intermediate.


