6-Bromoquinazolin-4-ol

White powder

General procedure: In a 10 mL glass tube 2-iodobenzoic acid (1.0 mmol), acetamidine hydrochloride (1.2 mmol), CuClIn a 100 mL round bottom flask, 2.16 g (10 mmol) of 2-amino-5-bromobenzoic acid was added.Formamidine acetate 1.04g (10mmol), isopropanol 30ml, Stir at 100 ° C for 8 hours, cool, Precipitated white solid was filtered off with suction, and dried to give 6-bromo -4 (3H) - quinazolinone 2.1g, 94percent yield.2-amino-5-Bromobenzamide (107 mg, 0.5 mmol), [Cp * Ir (2, 2'-bpyO) (H2O)](5.4 mg, 0.005 mmol, 1 molpercent), Cesium carbonate (49 mg, 0.15 mmol, 0.3 equiv.) And methanol (0.5 ml) were sequentially added to a dried 5 mL microwave reaction tube.The tube was nitrogen protected and placed in a single mode pressure microwave synthesizer (Discover CEM, USA). After the reaction mixture was reacted at 130 ° C for 2 hours, it was cooled to room temperature. Rotary evaporation to remove the solvent, Pure target compound was then obtained by column chromatography (developing solvent: petroleum ether / ethyl acetate), yield: 82percentIn short, 2-Amino-5-bromobenzoic acid (A, 50.0 g, 0.233 mmol, 1.0 equiv)Add formamide (50.0 mL, d = 1.133, 56.7 g, 1.26 mmol)The mixture was heated under reflux for 12 hours, The solution was lowered to 70 ° C, Add 100 ml of ethanol.The resulting precipitate was filtered and washed with 50 ml of ethanol, And dried to give 6-bromo-3H-quinazolin-4-one (B, 42.5 g, 0.189 mol)Yield 81percent5-bromoisigo anhydride (III) (20.0 g, 82.64 mmol) and formamidine acetate (17.04 g, 165.27 mmol)Dispersed in 1-methoxy-2-propanol (300mL) solution, stirred and heated to reflux for 2h, TLC The reaction is complete. The 1-methoxy-2-propanol was removed under reduced pressure, the residue was beaten with 50 ml of water for 0.5 h, Washed with water and dried to give the title compound (IV) (16.55 g, 89percent).