1 research outputs found
A Practical Synthesis of a PI3K Inhibitor under Noncryogenic Conditions via Functionalization of a Lithium Triarylmagnesiate Intermediate
We report a practical synthesis of PI3K inhibitor <b>GDC-0941</b>. The synthesis was achieved using a convergent approach
starting
from a thienopyrimidine intermediate through a sequence of formylation
and reductive amination followed by Suzuki-Miyaura cross-coupling.
Metalation of the thienopyrimidine intermediate involving the intermediacy
of triarylmagnesiates allowed formylation under noncryogenic conditions
to produce the corresponding aldehyde. We also investigated aminoalkylation
via a benzotriazolyl-piperazine substrate as an alternative to the
reductive amination route. We evaluated both palladium and nickel
catalyzed processes for the borylation and Suzuki-Miyaura cross-coupling.
Final deprotection and salt formation afforded the API