Pd Catalyzed C-N Bond Forming Reactions of 6-Bromo-2- cyclopropyl-3-(pyridyl-3-ylmethyl)-4-quinazolin-(3H)-one at Room Temperature

Author(s): Narender Pottabathini, Ramesh Garlapati, Venkateshwarlu Gurram, Suresh Poudapally, Pavan K. Machiraju, Somesh Sharma

Journal Name: Current Organocatalysis

Volume 3 , Issue 3 , 2016


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Abstract:

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.

Keywords: Cheminformatics, effect of dba, evaluation with various amines, modified quinazolinones, room temperature amination, screening studies.

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Article Details

VOLUME: 3
ISSUE: 3
Year: 2016
Published on: 25 July, 2016
Page: [291 - 300]
Pages: 10
DOI: 10.2174/2213337202666150915211710
Price: $25

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