4-Hydroxy-2-(methylthio)pyrimidine-5-carbonitrile synthesis

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]