General procedure: 2-amino-3-chlorobenzoic acid (1 eq.) and an excess of formamide (6 eq.) were added to a three-necked flask. The reaction mixture was heated at 140 °C for 4-6 h. The progress of the reaction was monitored by thin layer chromatography (TLC). After completion of the reaction, ice water was added to the mixture. The precipitated solid was filtered, washed with water and subsequently dissolved in ethyl acetate, dried over anhydrous magnesium sulfate and concentrated to give pure 8-chloroquinazolin-4-ol. If the product did not precipitate, the reaction mixture was extracted with ethyl acetate, dried over anhydrous magnesium sulfate and concentrated to give quinazolin-4(3H)-one derivatives 1-9,11-15,17-21 and 23.
Generic method for the preparation of amino derivatives 10,16 and 22: Substituted nitroquinazolin-4(3H)-one derivatives (0.3 g, 1.56 mmol), 6 mL of ethyl acetate and stannous chloride dihydrate (2.12 g, 9.42 mmol) were added to a reaction flask and the mixture was refluxed for 8 hours. After cooling to room temperature, the reaction was quenched with saturated sodium bicarbonate solution and subsequently extracted with ethyl acetate (3 x 50 mL). The organic layers were combined, dried over anhydrous magnesium sulfate and concentrated to afford the target amino-substituted quinazolin-4(3H)-one derivatives 10,16 and 22.
The substituted o-aminobenzoic acid (1 g) was dissolved in excess acetic anhydride (10 mL) and stirred at room temperature for 4-7 h. The reaction progress was monitored by TLC. After removal of the solvent under vacuum, the residue was stirred with aqueous ammonia solution for 7 hours. After completion of the reaction, it was extracted with ethyl acetate (3 x 10 mL), the organic phases were combined, dried and concentrated with anhydrous magnesium sulfate to give compounds 26-30,31a and 32.
The reduction of 2-methyl-8-nitroquinazolin-4(3H)-one intermediate (31a) to compound 31 was carried out in the same manner as described above for the synthesis of compounds 10,16 and 22.
