SYNTHESIS OF 7-ALKYL-6-AMINO-7H-PYRROLO[2,3-d]PYRIMIDINE-6-CARBONITRILES BY THE COPPER-CATALYZED REACTION OF 4-(ALKYLAMINO)-5-IODOPYRIMIDINES WITH PROPANEDINITRILE

摘要

A convenient sequence for the first general preparation of 6-aminopyrrolo[2,3-d]pyrimidine-5-carbonitrile derivatives has been developed. Thus, treatment of 4-chloro-6-methoxypyrimidines with lithium diisopropylamide in THF at -78 degrees C lithiated the 5-position to generate 4-chloro-5-lithio-6-methoxypyrimidines, which were allowed to react with iodine to give 4-chloro-5-iodo-6-methoxypyrimidines in good yields. Substitution of the 4-chloro group of these compounds with primary amines in the presence of triethylamine in refluxing THF afforded 4-(alkylamino)-5-iodo-6-methoxypyrimidines. The reaction of these aminated compounds with propanedinitrile (malononitrile) in the presence of a catalytic amount of copper(I) iodide and excess potassium carbonate in dimethyl sulfoxide at 100 degrees C provided 7-alky1-6-amino-4-methoxypyrrolo[2,3-d]pyrimidine-5-carbonitriles in moderate yields.