Synthesis Of Quinazolinone Derivatives

Quinazoline heterocyclic compound is an advantage skeleton structure in medicinal chemistry 。 It has a variety of bioactivity, such as antibacterial,anti-inflammatory, anti diabetes, tuberculosis, anti-tumor and anti-hiv. Therefore,these compounds have a broad application prospects in the pharmaceutical and pesticide. Nowadays, many methods have been developed to synthesize quinazoline derivatives, but there exist an amount of drawbacks such as high temperature, using transition metal catalysis and expensive reagents which have limitted the application of quinazoline heterocyclic compound. Moreover, Fluoro quinazoline heterocyclic compound were found having more potential bioactivity, chemical stability and lipotropy than quinazoline heterocyclic compound since the specific inductive and conjunctive effect of fluorine atoms, which may expand its application of quinazoline derivatives. And the synthesis of these compounds have been reported rarely, so it is still a challenge to find a effective method for synthesize quinazoline derivatives. This reserch has focuses on two issues of quinazoline derivatives.In part one, in the absence of catalyst, using cheap easy quinazolines as raw materials, N, N- dimethylformamide as nitrogen source, potassium tert-butoxide as base, a series of potential biological activity of 4-aminoquinazolines derivatives was rapidly efficient synthesized by direct-amination effect at room temperature.In part two, we have developed 2, 4-diarylquinazolines and N-Fluorobenzenesulfonimide(NFSI) fluorination reaction under palladium catalyst.L-proline was used as ligand, C-H key of aromatic ring was activated by palladium catalyst to form much fluoride quinazoline compounds through fluorination.