Acetic Acid → 4-Hydroxypyrimidine-5-carbonitrile

Participants

Reaction Steps

First, 22.5 g (0.187 mol) of 1-amidino-4,4-dimethylimidazolidin-2-one are introduced as a suspension in 300 ml of absolute DME with stirring and exclusion of moisture. Next, 56 g (0.119 mol) of ethoxymethylene-N-(2,2,3,3,4,4,4-heptafluorobutyl)-N-[(3-trifluoromethyl)phenyl]cyanoacetamide in 300 ml of absolute DME are slowly added dropwise at 0° C. After addition, the mixture is stirred at room temperature for 2 hours. After this time the reaction has ended (TLC checking). 125 ml of glacial acetic acid are added dropwise with stirring to this solution and it is stirred for 2 hours at a temperature of 50° C. After allowing to stand overnight at room temperature, the cyclization to the pyrimidine derivative has ended. For working-up, the precipitated 5-cyano-4-pyrimidone derivative formed as a by-product is filtered off. The filtrate is concentrated, the glacial acetic acid is evaporated with toluene, and the semisolid residue is taken up in ethyl acetate. Additionally precipitated amounts of the 5-cyano-4-pyrimidone derivative formed are removed again by filtration. The ethyl acetate phase is then washed 2× with 2N aqueous NaOH solution and 2× with saturated sodium chloride solution, dried using MgSO4, filtered and concentrated on a rotary evaporator, after which, as a residue, 51 g of crude product remain as a dark oil. Purification is carried out by means of column chromatography using silica gel and ethyl acetate as eluent. After evaporating the solvent, 12.56 g of 4-amino-2-(4,4-dimethylimidazolidin-2-on-1-yl)pyrimidine-5-N-(2,2,3,3,4,4,4-heptafluorobutyl)-N-[(3-trifluoro- methyl)phenyl]carboxamide remain as yellowish crystals (18% of theory).

Provenance & Evidence