A new four-component domino reaction has been discovered. The reaction is easy to perform simply by mixing four common reactants and K2CO3 in ethylene glycol under microwave irradiation. The reaction proceeds rapidly and can be finished within 10-24 min with water as the major byproduct, making workup convenient. Four stereogenic centers with one quaternary carbon-amino function are controlled very well; the stereochemistry was unequivocally determined by X-ray structural analysis. The resulting pyrido[3,4-i]quinazoline derivatives are of importance for organic and medicinal research.