Synthesis of istradefylline / 军事医学

ABSTRACT

Objective To optimize the synthesis process of istradefylline 1 for industrial production.Methods Istrade-fylline was synthesized from dimethyl carbonate and ethylamine through a series reactions including condensation,cycliza-tion,nitrosation,and reduction to produce 1,3-diethyl-5,6-diaminouracil(6),which was subjected to amidation with (E)-3,4-dimethoxycinnamic acid (8),followed by cyclization and methylation reaction.Compound 8 was prepared from veratr-aldehyde and propanedioic acid by Knoevenagel condensation.The structures of intermediate and target compounds were confirmed by MS and 1 H-NMR.Results and Conclusion The quality control points of each key process were optimized so that the total yield was 26.2% and the purity of the product was 99.76%.This improved synthesis method has some advan-tages,such as mild reaction conditions,simple operation,and applicability to industrial production.