A novel synthesis of thioxo-quinazolino[3,4-a]quinazolinone framework was developed through a four-step reaction starting from isatoic anhydride. The resulting 2-aminobenzamides from the reaction of isatoic anhydride and different amines underwent coupling-cyclization reaction with 2-nitrobenzaldehydes, reduction of nitro group, and then cyclization reaction with carbon disulfide (CS 2 ). All steps were carried out under easy and user-friendly conditions in a short time without using expensive catalysts or reagents.[Supplementary materials are available for this article. Go to the publisher's online edition of Synthetic Communications 1 for the following free supplemental resource(s): Full experimental and spectral details.]