3 research outputs found
PAT Application in the Expedited Development of a Three-Step, One-Stage Synthesis of the Dipeptide Intermediate of HCV Protease Inhibitor Faldaprevir
A concise
scalable synthesis of a chiral dipeptide acid, key substructure
of the HCV protease inhibitor faldaprevir, has been developed. A green
process with an E-factor of 9.2 was achieved utilizing process analytical
technology (PAT) to allow effective processing of multiple-steps in
a one-stage operation. Mixed anhydride/oxazolone formation, peptide
coupling, saponification, and then crystallization of the desired
dipeptide acid were completed within 10 h. MultiMaxIR was used to
detect the formation and consumption rates of key intermediates and
to provide initial safety data which was subsequently confirmed by
more comprehensive process safety testing. Further kinetic analysis
was performed to determine the range of operability space to ensure
conditions for a robust process