Synthesis
General procedure for the synthesis of 7-chloro-4-hydroxy-6-nitroquinazoline from 7-chloro-4(3H)-quinazolinone: Concentrated sulfuric acid (10 mL) and concentrated nitric acid (5 mL) were added to a 100 mL round-bottomed flask, followed by 7-chloro-4(3H)-quinazolinone (10 g, 55.4 mmol). The reaction mixture was stirred at 0 °C, then slowly heated to 90 °C and stirred continuously at this temperature for 3 hours. After completion of the reaction, the mixture was cooled to room temperature and carefully poured into ice water. The precipitate was collected by filtration, washed well with water and then dried. The crude product was purified by recrystallization from acetic acid to give 7-chloro-6-nitroquinazolin-4(3H)-one (6c) as a light yellow solid (9 g, 72% yield). The melting point of the product was 315-316 °C; 1H NMR (DMSO-d6, ppm): δ 12.79 (broad peak, 1H), 8.67 (single peak, 1H), 8.31 (single peak, 1H), 8.01 (single peak, 1H).
References
[1] Medicinal Chemistry Research, 2013, vol. 22, # 9, p. 4096 - 4109
[2] European Journal of Medicinal Chemistry, 2018, vol. 147, p. 227 - 237
[3] Patent: CN108484574, 2018, A. Location in patent: Paragraph 0133; 0134; 0135
[4] Patent: CN103382182, 2016, B. Location in patent: Paragraph 0272; 0273; 0276; 0277
[5] Patent: WO2008/33747, 2008, A2. Location in patent: Page/Page column 129
