A. Yahyazadeh, Babak Pourrostam, Mahdi Rabiee
Apr 27, 2004
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ChemInform
Abstract
Purine, purine nucleosides and their analogues have been extremely useful as anti-cancer agents. Robines, in 1964, reviewed the anti-tumour activity of purine and purine nucleosides from a structure-activity stand-point. Subsequently, several reviews on this subject have been published. The chemotherapeutic uses of purines and purine analogues have prompted tremendous efforts towards their synthesis, both in academia and in the pharmaceutical industry. As the purine ring system is a fusion of two aromatic heterocyclces, pyrimidine and imidazole, a logical starting point for ring synthesis is an appropriately substituted pyrimidine or imidazole from which the second ring can be constructed by a cyclization process. 5-amino-4-cyanoimidazoles are useful intermediates for purine synthesis. There are few reports of 9-aminopurine derivatives and most of the routes described are from 5amino-4-hydrazinopyrimidine precursors, substituted in the 2and 6-position. We therefore decided to investigate the reactions of 9benzyl-6-aminopurines 5a-b were prepared via a multistep synthesis from ethyl (Z)-N-(2-amino-1,2-dicyanovinyl)formimidate 1, by treatment with a benzyl-amine in a 1 : 1 molar ratio in ethanol in the presence of a catalytic amount of aniline hydrochloride to give the corresponding formamidine. (Scheme 1). Cyclisation of the formamidines in the presence of a strong base, aqueous KOH solution, provided the corresponding 5-amino-1-benzyl-4-cyanoimidazoles 3a-b, which are readily converted to 1-amino-9benzyl-6-aminopurines 5a-b by treatment with HC(OEt)3 and Ac2O followed by reaction with ammonia. The initial step involved conversion of the 5-amino-4cyanoimidazoles 3 to the corresponding ethoxyimidates 4. These were achieved by a modification of the procedure