889877-77-4

(7R)-2-Chloro-7-ethyl-7,8-dihydro-8-(1-methylethyl)-6(5H)-pteridinone is used as a reactant in the synthetic preparation of dihydroimidazolo-pteridine derivatives as novel Polo-like kinase-1 (PLK1) inhibitors and potential antitumor agents.

General procedure for the synthesis of (R)-2-chloro-7-ethyl-8-isopropyl-7,8-dihydropteridin-6(5H)-one from (R)-2-((2-chloro-5-nitropyrimidin-4-yl)(isopropyl)amino)butanoic acid methyl ester: 50 g of (R)-2-((2-chloro-5-nitropyrimidin-4-yl)(isopropyl)amino)butanoic acid methyl ester was dissolved in 375 mL of in tetrahydrofuran and hydrogenation was carried out in the presence of 5 g of platinum carbon catalyst (5% loading) at 3 bar hydrogen pressure and 35 °C until hydrogen consumption ceased. Subsequently, 2.5 g of vanadium oxyacetylacetonate was added and the hydrogenation reaction was continued. Upon completion of the reaction, the reaction mixture was filtered to remove the catalyst. The solvent was removed by distillation under reduced pressure. To the residue was added 150 mL of 2-propanol and heated to reflux. Then 300 mL of deionized water was added and the resulting suspension was slowly cooled to 2°C. The precipitate was collected by filtration and washed with a cold 2-propanol and deionized water mixture. Finally, the product was dried in a vacuum drying oven at 50 °C to give 36 g of (R)-2-chloro-7-ethyl-8-isopropyl-7,8-dihydropteridin-6(5H)-one in 90% of the theoretical yield.

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