Background: Quinazolinones are important subunits of many compounds that are of biological
and pharmaceutical interest including anticancer, antimicrobial, anti-inflammatory, antitubercular,
anti-HIV, and as an analgesic. Quinazolin[3H]-4-one systems were found to have distinctive
biological functions. On the other hand, 2,3-disubstituted quinazolin[3H]-4-one derivatives substitution
with various heterocyclic moieties displayed conspicuous anti-tubercular activity. Considering
the much broder range of pharmacological properties, several useful approaches to the construction of
modified quinazolinones have been developed with the help of Pd/L systems.
Methods: Various amines, Pd(OAc)2, Pd2(dba)3, Pd(dba)2, ligands, PtBu3, DavePhos, XantPhos, triphenylphosphine and
dppf, were utilised to assess the C-N reaction results. For analysis 1H NMR, LCMS and HRMS were used.
Results: After screening different conditions, Pd(dba)2, PtBu3, NaOtBu in THF was proved to be the best catalyst/ligand
system for Pd-catalyzed amination at room temperature. We evaluated the generality of the methodology with variety of
amines (aryl, heteroaryl and alkyl amines) participated in the Pd-catalyzed amination reactions. We reported the synthesis
of twenty four analogues utilizing these conditions. We have also investigated what cycle differences might exist in the
usage of two different Pd sources, Pd(dba)2 and Pd2(dba)3. It is known that dba (dibenzylideneacetone) can competitively
inhibit the catalytic cycles, also were interested to find out if in these cases it is inhibiting the catalytic cycle and assess
that dba is responsible for the difference in yields. In silico analysis is utilized to evaluate the diversity of the set of compounds
against shape space (PMI), polar surface area (PSA) calculations and relevant drug like properties (viz. HBA,
HBD, PSA, mol. wt., log P and Log D).
Conclusion: In summary, we have developed a room temperature C-N bond formation reaction with simple catalyst system.
We have thoroughly investigated the effect of dba in the amination reactions.