title: Evaluation of electrophilic heteroaromatic substitution: synthesis of heteroaromatic-fused pyrimidine derivatives via sequential three-component heterocyclization.
abstract: A new sequential three-component heterocyclization was developed by reacting aromatic and heterocyclic substrates, including aminobenzenes, 1-aminonaphthalene, 2-aminopyrazines, 5-aminopyrazoles, 3-aminopyridine, 5-aminopyrimidine, 5-aminoquinoline, and 8-aminoquinoline, with formamide in the presence of PBr(3). The reaction gave the corresponding pyrazolo[3,4-d]pyrimidines in good yields (59-96%), except for aminobenzenes and 3-aminopyridine. A plausible reaction mechanism involving amidination, electrophilic substitution imination, and oxidative cyclization in three steps was proposed to account for the heterocyclization. The reactivity of the reaction was found proportional to the electrophilicity of the aromatic or heterocyclic substrate.
authors.affiliation: Graduate Institute of Pharmaceutical Chemistry, China Medical University, No. 91, Hsueh-Shih Road, Taichung, Taiwan 40402, Republic of China. wongfungfuh@yahoo.com.tw
authors.forename: Fung Fuh
authors.initials: FF
authors.lastname: Wong
authors.forename: Yu-Ying
authors.initials: YY
authors.lastname: Huang
authors.forename: Chun-Hsi
authors.initials: CH
authors.lastname: Chang
mesh_terms: D015057:1-Naphthylamine / Q000138:chemical synthesis* / Q000737:chemistry; D000631:Aminopyridines; D000634:Aminoquinolines / Q000138:chemical synthesis* / Q000737:chemistry; D003500:Cyclization; D006571:Heterocyclic Compounds / Q000138:chemical synthesis* / Q000737:chemistry*; D015394:Molecular Structure; D011720:Pyrazoles / Q000138:chemical synthesis* / Q000737:chemistry; D011743:Pyrimidines / Q000138:chemical synthesis
chemical_list: D000631:Aminopyridines; D000634:Aminoquinolines; D006571:Heterocyclic Compounds; D011720:Pyrazoles; D011743:Pyrimidines; C031283:3-aminopyridine; D015057:1-Naphthylamine