Synthesis
The general procedure for the synthesis of 7-methoxy-2,4(1H,3H)-quinazolinediones from urea and 2-amino-4-methoxybenzoic acid was as follows: 2-amino-4-methoxybenzoic acid (1 g, 5.98 mmol) was mixed with urea (7.18 g, 120 mmol), and the reaction was stirred for 16 hours at 155 °C. After the reaction was completed, the mixture was cooled to 100 °C and 3 mL of water was added. Continued cooling to room temperature was followed by filtration. To the filtrate, 30 mL of 1 mol/L NaOH aqueous solution was added to dissolve the precipitate. after 1 h, 4.2 mL of acetic acid was slowly added dropwise to produce a light brown precipitate, which was filtered and dried to afford the target product, 7-methoxy-2,4(1H,3H)-quinazolinedione (0.55 g, 2.9 mmol, 48% yield). The product characterization data were as follows: 1H NMR (500 MHz, DMSO) δ 11.10 (brs, 1H, NH), 10.55 (brs, 1H, NH), 7.8 (d, J = 8.63 Hz, 1H, Ar-H), 6.77 (dd, J = 2.44, 8.84 Hz, 1H, Ar-H), 6.64 (d, J = 2.43 Hz, 1H, Ar-H), 3.82 (s, 3H, OCH3).13C NMR (125 MHz, DMSO) δ 164.8, 162.8, 151.0, 143.3, 129.3, 111.0, 108.2, 98.8, 56.1. HRMS-ESI (m/z) Calculated Value C9H8N2O3 [M + H]+ : 193.0489, measured value: 193.0511.
References
[1] Patent: WO2016/151144, 2016, A1. Location in patent: Page/Page column 55; 56
[2] Journal of Medicinal Chemistry, 2014, vol. 57, # 12, p. 5141 - 5156
