4-Hydroxy-2-(methylthio)pyrimidine-5-carbonitrile synthesis
- Product Name:4-Hydroxy-2-(methylthio)pyrimidine-5-carbonitrile
- CAS Number:89487-99-0
- Molecular formula:C6H5N3OS
- Molecular Weight:167.19
2986-19-8
94-05-3
89487-99-0
2-Methyl-2-isothiourea (5 mmol) and ethyl ethoxycarbonylcyanoacetate (5 mmol) were dissolved in 20 mL of ethanol. Potassium carbonate (10 mmol) was added to the solution. The reaction mixture was refluxed for 48 hours, followed by cooling to room temperature and filtration. The filtrate was concentrated under reduced pressure and purified by column chromatography to afford 4-hydroxy-2-(methylthio)pyrimidine-5-carbonitrile in 65% yield.
Yield:-
Reaction Conditions:
with potassium carbonate in ethanol;water at 85;
Steps:
4.3.1. 4-Hydroxy-2-(methylthio)pyrimidine-5-carbonitrile (8)
To a solution of 2-Methyl-2-thiopseudourea sulfate (19 g, 100 mmol) and (E)-ethyl 2-cyano-3-ethoxyacrylate (17 g, 100 mmol) in ethanol (380 ml), the K2CO3 solution (276 g, 200 mmol in 100 mL water) was added at room temperature. The reaction mixture was stirred at 85 °C overnight. The solvents were distilled on a rota-evaporator. The crude mixture was dissolved in water (100 ml) and adjusted the pH = 7-8 by using 6 N HCl. During the acidification, a buff solid was formed and collected by filtration. The filter cake was washed with a small amount of water and dried in a vacuum oven to give the product 8(10.8 g). Yield: 65%; Purity: 92%; LC-MS m/z: 168.0 [M + H]+.
References:
Yang, Ling-Ling;Li, Guo-Bo;Yan, Heng-Xiu;Sun, Qi-Zheng;Ma, Shuang;Ji, Pan;Wang, Ze-Rong;Feng, Shan;Zou, Jun;Yang, Sheng-Yong [European Journal of Medicinal Chemistry,2012,vol. 56,p. 30 - 38]