Elaboration of tetra-orthogonally-substituted aromatic scaffolds towards novel EGFR-kinase inhibitorsElectronic supplementary information (ESI) available. CCDC 1485121-1485123. For ESI and crystallographic data in CIF or other electronic format see DOI: 10.1039/c6ob01394e

Nitration of three regioisomers of bromo-fluorobenzaldehyde proceeds regioselectively, notably with H 2 SO 4 /HNO 3 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. Tetrasubstituted aromatic scaffolds have been elaborated and a number of EGFR inhibitors have been synthesised and their activity rationalised by docking studies.