Pyrimidine derivatives and related compounds. Part 47. A new synthesis of xanthines and pyrrolo[3,2-d]pyrimidines by intramolecular cyclisation of 6-substituted 5-nitrouracil derivatives

Abstract

6-Arylalkylamino-1,3-dimethyl-5-nitrouracils (2a–f) were prepared by reaction of 6-chloro-1,3-dimethyl-5-nitrouracil (1) with arylalkylamines in the presence of triethylamine. Among them, the 6-arylalkylaminouracils (2a–d), possessing no substituent at the nitrogen and the benzylic position in the 6-arylalkylamino moiety, were converted into the corresponding 8-aryl-1,3-dimethylxanthines (3a–d) when heated under reflux in dimethylformamide (DMF). The reaction of the sodium salt (7) of 1,3,6-trimethyl-5-nitrouracil (6) with alkyl and arylalkyl halides in dry DMF gave the corresponding 6-(substituted methyl)-1,3-dimethyl-5-nitrouracils (8a–j). Among them, 6-(2-arylethyl)uracils (8b–f) underwent base-catalysed cyclisation to afford 8-aryl-7-hydroxy-9-deazaxanthines (9a–e). On the other hand, treatment of 6-[2-(ethoxycarbonyl, acetyl, and cyano) ethyl] uracil (8h–j) with triethylamine led to the formation of the corresponding 6-vinyluracil (11 a–c). A one-step synthesis of the 7-hydroxy-9-deazaxanthines (9a–e) was accomplished by the treatment of the sodium salt (7) with arylalkyl chlorides in the presence of potassium carbonate in dry DMF. Deoxygenation of the 7-hydroxy-9-deazaxanthines (9a–e) smoothly occurred upon heating them in DMF to give the corresponding 8-aryl-9-deazaxanthines (l0a–e) in high yield.