1,3-Diaryl-1H-pyrazoles, serving as privileged heterocyclic scaffolds, demonstrate significant application potential in pharmaceutical development, functional materials, and agrochemical industries.…

New synthetic methodologies that access complex saturated building blocks enable the synthesis of drug molecules with unique properties. Here, we report collaborative efforts between Pfizer’s Medicinal Chemistry, Medicinal Chemistry Synthesis Development, and Pharmaceutical Sciences Small Molecule (PSSM) groups for the development of kilogram-scale-enabled synthesis of a type II brain penetrant cMET inhibitor, PF-07907063. The chemistry presented herein demonstrates the importance of implementing a green chemistry approach for developing and applying new transformations throughout the drug development pipeline. Specifically, synthetic planning rooted in the 12 Principles of Green Chemistry led to advancements in deoxygenative photoredox-nickel dual catalysis and cross-electrophile nickel catalysis. The final route significantly lowered the process mass intensity (PMI), increased the yield of the final API, and allowed for the purification of key intermediates through crystallization versus purging impurities via column chromatography, among other improvements.

Analysis of the crystal structure of [di­hydro­bis­(pyrazol-1-yl)borato]tris­(tetra­hydro­furan)magnesium(II) tetra­benzyl­borate reveals a pronounced boat-shaped central Mg(N–N)2B moiety with a weak pseudo-axial B—H⋯Mg inter­action. A novel counter-ion, [B(C7H7)4)]−, has been obtained by the reaction between KBH4 and (PhCH2)MgCl to produce a polymeric potassium tetra­benzyl­borate with predominant (η6-C6H5)⋯K and (η3-C6H5)⋯K inter­actions.

Proceedings of the National Academy of Sciences (PNAS), a peer reviewed journal of the National Academy of Sciences (NAS) - an authoritative source of high-impact, original research that broadly spans...