Synthesis
To a freshly prepared sodium ethanolate solution [made by reacting ethanol (250 mL) with sodium metal (9.02 g, 392.55 mmol)], ethyl 2-cyano-4,4-diethoxybutyrate (45 g, 196.27 mmol) and thiourea (14.94 g, 196.27 mmol dissolved in 200 mL of ethanol) were added sequentially. The reaction mixture was heated to reflux for 3.5 hours with stirring. Upon completion of the reaction, the mixture was cooled to room temperature and stirring was continued overnight. Subsequently, the reaction was quenched with water (100 mL) and the ethanol was removed by vacuum concentration. The residue was dissolved in water (100 mL) and neutralized with dilute aqueous hydrochloric acid (3N) to pH 7 at a temperature below 10 °C. The resulting solid was collected by filtration and dried under vacuum to afford 6-amino-5-(2,2-diethoxyethyl)-2-mercapto-pyrimidin-4-ol (30.6 g, 60.19% yield) as a light yellow solid. The product was confirmed by 1HNMR, IR, MS, HPLC and elemental analysis.
References
[1] Patent: WO2010/14930, 2010, A2. Location in patent: Page/Page column 60
[2] Bioorganic and Medicinal Chemistry, 2012, vol. 20, # 22, p. 6770 - 6789
[3] Patent: WO2006/46023, 2006, A1. Location in patent: Page/Page column 122-123
[4] Patent: WO2008/75109, 2008, A1. Location in patent: Page/Page column 112
[5] Patent: WO2006/46024, 2006, A1. Location in patent: Page/Page column 117
