One-Flask Synthesis of Pyrazolo[3,4-d]pyrimidines from 5-Aminopyrazoles and Mechanistic Study.

ABSTRACT: A novel one-flask synthetic method was developed in which 5-aminopyrazoles were reacted with N,N-substituted amides in the presence of PBr?. Hexamethyldisilazane was then added to perform heterocyclization to produce the corresponding pyrazolo[3,4-d]pyrimidines in suitable yields. These one-flask reactions thus involved Vilsmeier amidination, imination reactions, and the sequential intermolecular heterocyclization. To study the reaction mechanism, a series of 4-formyl-1,3-diphenyl-1H-pyrazol-5-yl-N,N-disubstituted formamidines, which were conceived as the chemical equivalent of 4-(iminomethyl)-1,3-diphenyl-1H-pyrazol-5-yl-formamidine, were prepared and successfully converted into pyrazolo[3,4-d]pyrimidines. The experiments demonstrated that the reaction intermediates were the chemical equivalents of 4-(iminomethyl)-1,3-diphenyl-1H-pyrazol-5-yl)formamidines. The rate of the reaction could be described as being proportional to the reactivity of amine reactants during intermolecular heterocyclization, especially when hexamethyldisilazane was used.

SUBMITTER: Yen WP 

PROVIDER: S-EPMC6154590 | biostudies-literature | 2017 May

REPOSITORIES: biostudies-literature