Purines, pyrimidines, and imidazoles. Part 61. Reaction of 6-alkylamino-4-chloro-5-nitropyrimidines with diethyl malonate, ethyl cyanoacetate, and ethyl acetoacetate and some derived pyrrolo[3,2-d]pyrimidines related to the cytokinins

Abstract

Reaction of 4-chloro-6-methylamino-5-nitropyrimidine (3d) with diethyl malonate and sodium hydroxide afforded diethyl 6-methylamino-5-nitropyrimidin-4-ylmalonate which was reduced to diethyl 5-amino-6-methylaminopyrimidin-4-ylmalonate and this, with sodium carbonate, produced ethyl 6,7-dihydro-4-methylamino-6-oxo-5H-pyrrolo[3,2-d]pyrimidine-7-carboxylate. Ethyl cyano-acetate and ethyl acetoacetate with (3d) and alkali similarly afforded ethyl 6-methylamino-5-nitro-pyrimidin-4-ylcyano (or aceto) acetate respectively. The latter compound when reduced afforded ethyl 5-amino-6-methylaminopyrimidin-4-ylacetate (4e) which was also obtained by treatment of ethyl α-(6-methylamino-5-nitropyrimidin-4-yl)acetoacetate with aqueous ammonia to give ethyl g-methylamino-5-nitropyrimidin-4-ylacetate, followed by subsequent hydrogenation of this compound. Cyclisation of (4e) with phosphoryl trichloride and dimethylformamide gave, after hydrolysis, 4-methylamino-5H-pyrrolo[3,2-d]pyrimidine-7-carboxylic acid (2g). 4-[(trans)-4-t-Butoxy-3-methylbut-2-enylamino)-6-chloro-5-nitropyrimidine in a similar sequence of reactions gave the cytokinin analogue 4-(4-hydroxy-3-methylbutylamino)-5H-pyrrolo[3,2-d]pyrimidine-7-carboxylic acid (2j)