posted on 2023-06-09, 02:14authored byAdam J Close, Rhiannon N Jones, Cory A Ocasio, Paul Kemmitt, S Mark Roe, John SpencerJohn Spencer
Nitration of three regioisomers of bromo-fluorobenzaldehyde proceeds regioselectively, notably with H2SO4/HNO3 at 0 °C. The thereby synthesized tetrasubstituted aromatics, endowed with orthogonal substituents, can be elaborated via Pd-catalysed coupling, reduction and reductive amination reactions. As a test-case, these compounds were converted into EGFR inhibitors related to Gefitinib, whose activity was rationalised by docking studies.
Funding
Astra Zeneca regioselective transition metal mediated routes; G0878; AZ