HCID 66611504, compound → HCID 135443732, compound

Participants

Reaction Conditions

Reaction Steps

3-Methoxy-2-nitrobenzoic acid (2000 mg, 10.15 mmol) was dissolved under argon in abs. tetrahydrofuran (10 ml), and oxalyl chloride (1288 mg, 10.15 mmol) and a catalytic amount of DMF were added. The resulting reaction mixture was stirred at 60° C. for 2 h and then concentrated under reduced pressure. The crude product was dissolved directly in abs. dioxane (8 ml) under argon and the solution was cooled to 0° C. Thereafter, ammonia gas was introduced for 10 min. After the introduction of gas had ended, the reaction solution was poured onto ice-water and extracted repeatedly with ethyl acetate. The combined organic phases were dried over magnesium sulfate, filtered and concentrated under reduced pressure. The 3-methoxy-2-nitrobenzamide (1950 mg, 9.94 mmol) thus prepared was then dissolved in abs. methanol (60 ml). After the addition of catalytic amounts of palladium on activated carbon (content of 10% in water-moist form; 543 mg, 0.51 mmol), hydrogen was introduced at room temperature until conversion was complete. The catalyst was then filtered off and the solvent was concentrated under reduced pressure. The crude product was used without further purification in the next reaction step, and the 2-amino-3-methoxybenzamide (350 mg, 2.11 mmol) thus obtained was dissolved in abs. tetrahydrofuran (5 ml). After addition of triethylamine (0.32 ml, 2.32 mmol) and stirring at room temperature for a further 10 minutes, 4-fluorobenzoyl chloride (0.28 ml, 2.32 mmol) was added. The resulting reaction mixture was stirred at room temperature for 3 h, then the solvent was removed under reduced pressure, and water and ethyl acetate were added to the residue. The aqueous phase was extracted repeatedly with ethyl acetate, and the combined organic phases were then dried over magnesium sulfate, filtered and concentrated under reduced pressure. Column chromatography purification (ethyl acetate/n-heptane gradient) of the crude product gave 2-[(4-fluorobenzoyl)amino]-3-methoxybenzamide (550 mg, 91% of theory) as a colorless solid. 2-[(4-Fluorobenzoyl)amino]-3-methoxybenzamide (500 mg, 1.73 mmol) was dissolved in aqueous sodium hydroxide solution (2M, 5 ml) and stirred at 60° C. for 5 h. After cooling to room temperature, filtration with suction and thorough drying gave 2-(4-fluorophenyl)-8-methoxyquinazolin-4(3H)-one (462 mg, 98% of theory) as a colorless solid. 1H NMR (400 MHz, d6-DMSO δ, ppm) 12.60 (br. s, 1H, NH), 8.24 (m, 2H), 7.70 (dd, 1H), 7.46 (d, 1H), 7.42 (d, 1H), 7.38 (m, 2H), 3.96 (s, 3H).

Provenance & Evidence