Synthesis
GENERAL METHOD: 2-Amino-3-methylbenzoic acid (5.0 g, 33.1 mmol) was mixed with urea (20 g) and the reaction was stirred at 160°C for 6 hours. Upon completion of the reaction, the reaction mixture was cooled to 100 °C and an equal volume of water was slowly added with continuous stirring for 5 min. Subsequently, the precipitate formed was collected by filtration and washed with cold water to obtain a solid filter cake. This filter cake was suspended in 0.5 N NaOH aqueous solution, heated to boiling and held for 5 minutes, then cooled to room temperature. The pH of the suspension was adjusted to 2 with concentrated hydrochloric acid and the quinazoline dione product was collected by filtration. The product was washed with a mixture of water: methanol (1:1) and dried under vacuum to give 4.50 g (25.5 mmol, 77% yield) of 2,4-dihydroxy-8-methylquinazoline solid. The 1H-NMR (CDCl3) data of the product were as follows: δ (ppm) 7.78-7.74 (m, 1H), 7.49-7.46 (m, 1H), 7.11-7.05 (m, 1H), 2.31 (s, 3H).
References
[1] Bioorganic and Medicinal Chemistry Letters, 2012, vol. 22, # 1, p. 461 - 467
[2] Synthesis (Germany), 2016, vol. 48, # 8, p. 1226 - 1234
[3] ACS Medicinal Chemistry Letters, 2015, vol. 6, # 3, p. 254 - 259
[4] Journal of Medicinal Chemistry, 2014, vol. 57, # 12, p. 5141 - 5156
[5] Patent: US2016/90374, 2016, A1. Location in patent: Paragraph 0170; 0171
