Synthesis
Sodium methanolate (540 g, 9.98 mol) was dissolved in 2 L of methanol, followed by the sequential addition of thiourea (190 g, 2.50 mol) and malononitrile (412 g, 6.24 mol). The reaction mixture was stirred at 40 °C for 30 hours. After completion of the reaction, the mixture was cooled to room temperature and the solid was collected by filtration. The filter cake was dissolved in 3.5 L of water and the pH of the solution was adjusted with acetic acid to about 7. The solid product was collected by filtration again and dried to give 334 g of light yellow solid in 94% yield.
References
[1] Patent: CN107973798, 2018, A. Location in patent: Paragraph 0113-0114; 0119; 0122; 0123-0125; 0128
[2] Patent: CN107973832, 2018, A. Location in patent: Paragraph 0066; 0108-0125
[3] Arzneimittel-Forschung/Drug Research, 2002, vol. 52, # 11, p. 792 - 796
[4] Chemical and Pharmaceutical Bulletin, 2012, vol. 60, # 1, p. 70 - 78
[5] Patent: CN103709164, 2016, B. Location in patent: Paragraph 0034; 0086; 0106
