Dedicated to Prof. Scott E. Denmark on the occasion of his 60th birthday
Abstract
Strategies for carrying out the reaction of 4,6-dichloropyrimidine-5-carboxaldehyde
with both aromatic and aliphatic hydrazines to generate 1-substituted 4-chloropyrazolo[3,4-d]pyrimidines in a selective, high-yielding, and operationally simple manner are presented.
For aromatic hydrazines, the reaction is performed at a high temperature in the absence
of an external base. For aliphatic hydrazines, the reaction proceeds at room temperature
in the presence of an external base. The observed selectivity and reactivity trends
are rationalized through consideration of the proposed reaction mechanism. The 1-substituted
4-chloropyrazolo[3,4-d]pyrimidine products serve as versatile synthetic intermediates, through further functionalization
of the 4-chloride moiety, enabling the rapid generation of a structurally diverse
array of 1,4-disubstituted pyrazolo[3,4-d]pyrimidines.
Key words
condensation - hydrazines - hydrazones - nucleophilic aromatic substitution - pyrazolo[3,4-
d]pyrimidines
