Efficient N-arylation of 4-chloroquinazolines en route to novel 4-anilinoquinazolines as potential anticancer agents

Rodolfo H V Nishimura; Thiago Dos Santos; Valter E Murie; Luciana C Furtado; Leticia V Costa-Lotufo; Giuliano C Clososki

doi:10.3762/bjoc.17.206

Efficient N-arylation of 4-chloroquinazolines en route to novel 4-anilinoquinazolines as potential anticancer agents

Beilstein J Org Chem. 2021 Dec 22:17:2968-2975. doi: 10.3762/bjoc.17.206. eCollection 2021.

Authors

Rodolfo H V Nishimura^{1

2}, Thiago Dos Santos¹, Valter E Murie¹, Luciana C Furtado³, Leticia V Costa-Lotufo³, Giuliano C Clososki^{1

2}

Affiliations

¹ Núcleo de Pesquisas em Produtos Naturais e Sintéticos, Departamento de Ciências BioMoleculares, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Av. do Café s/n, Ribeirão Preto-SP 14040-903, Brazil.
² Departamento de Química, Faculdade de Filosofia, Ciências e Letras de Ribeirão Preto-SP, Universidade de São Paulo, Av. dos Bandeirantes 3900, Ribeirão Preto-SP 14090-901, Brazil.
³ Instituto de Ciências Biomédicas, Universidade de São Paulo, Av. Lineu Prestes 1524, 05508-900 São Paulo-SP, Brazil.

Abstract

Microwave-mediated N-arylation of 4-chloroquinazolines in THF/H₂O rapidly and efficiently afforded a library of novel 6-halo-2-phenyl-substituted 4-anilinoquinazolines. The methodology was compatible with numerous ortho-, meta-, and para-substituted N-methylanilines as well as substituted anilines and furnished the corresponding 4-anilinoquinazolines in good yields. Preliminary screening of the synthesized compounds against tumor cells (HCT-116 and T98G) showed promising antiproliferative properties.

Keywords: 4-anilinoquinazoline; 4-chloroquinazoline; N-arylation; anticancer agents; microwave irradiation.

Grants and funding

The authors gratefully thank financial support for this work by the Brazilian foundations: Fundação de Amparo à Pesquisa do Estado de São Paulo – FAPESP (Grant numbers: 2015/01466-9, 2015/21364-6, 2015/17177-6, 2017/18235-5, 2020/08987-2 and 2018/14150-8); Conselho Nacional de Desenvolvimento Científico e Tecnológico - CNPq (Grant number: 140137/2018-1 and 140146/2020-2); and Coordenação de Aperfeiçoamento Pessoal de Nível Superior - CAPES.