Synthesis
An aqueous solution (25 mL) of sodium cyanate (28 mmol) was added dropwise to an aqueous solution (50 mL) of N-methyl-phthalaminobenzoic acid (20 mmol) and acetic acid (0.2 mL) under stirring conditions. When the temperature of the reaction mixture rose to 40 °C, sodium hydroxide was added in batches until the reaction temperature reached 75 °C. The reaction temperature was maintained at this temperature with continuous stirring for 4 hours. This temperature was maintained and the reaction was stirred continuously for 4 hours without cooling. Upon completion of the reaction, the precipitated crystals were collected by filtration and dissolved in boiling water (50 mL). Subsequently, the above solution was acidified with 50% sulfuric acid solution to pH 1-2. The precipitated crystals were filtered, washed with water and finally recrystallized from 50% acetic acid solution to afford the target product 1-methyl-2,4(1H,3H)-quinazolinedione (2.92 g, 84% yield); the melting point was 278 °C. The reaction was carried out at a temperature of 75 °C for 4 hours.
References
[1] Chemistry of Heterocyclic Compounds, 2009, vol. 45, # 12, p. 1508 - 1514
[2] Spectrochimica Acta - Part A: Molecular and Biomolecular Spectroscopy, 2013, vol. 110, p. 324 - 332
[3] Patent: WO2016/92326, 2016, A1. Location in patent: Page/Page column 97; 113
[4] Patent: EP3299371, 2018, A1. Location in patent: Paragraph 0525; 0526
[5] Letters in Drug Design and Discovery, 2014, vol. 11, # 6, p. 712 - 720
