An unexpected cyclization discovered during the synthesis of 8-substituted purines from a 4,5-diaminopyrimidine

Attempted conversion of 4-chloro-5-(N-4-bromobutanoyl)amino-6-phenethylaminopyrimidine (2) to 6-chloro-8-[1-(3-bromo)propyl]-9-phenethylpurine (1) under standard cyclization conditions did not give the targeted product. Instead, an unexpected cyclization occurred to give 6-chloro-5-[1-(3-hydroxy)propyl]-9-phenethylpurine (3), which can be viewed as a hydrolysis product of the resulting halide. The cyclization reaction was optimized and compound 3 was prepared in excellent yield. A mechanism involving transient generation of a spiro-tetrahydrofuran is also proposed.