Synthesis of 6,8-disubstituted purines

Abstract

Condensations of 4,5,6-triaminopyrimidine with ethyl glycolate, cinnamamide, crotonic anhydride, and benzyl cyanide led to 8-hydroxymethyl-(I), 8-styryi-(II), N(6)-crotonoyl-8-propenyl-(III), and 8-benzyl-adenine (IV), respectively. Ring closure of the appropriate diamino-pyrimidine with ethyl glycolate afforded 6-hydroxy-8-hydroxymethyl-(V) and 8-hydroxymethyl-6-methylpurine (VI). Adenine-8-carboxylic acid (VII) was obtained by oxidation of compounds (II) and (III). Adenine was the sole product of the alkaline hydrolysis of 8-trifluoromethyladenine (VIII). The methyl group of 8-methyladenine was unreactive towards a variety of reagents.