Selective Synthesis of 1‑Substituted 4‑Chloropyrazolo[3,4‑<i>d</i>]pyrimidines

Strategies for carrying out the reaction of 4,6-dichloropyrimidine-5-carboxaldehyde with various hydrazines to generate 1-substituted 4-chloropyrazolo[3,4-<i>d</i>]pyrimidines in a selective and high-yielding manner are presented. For aromatic hydrazines, the reaction is performed in the absence of an external base, which promotes exclusive hydrazone formation. The hydrazones subsequently cyclize at an elevated temperature to form the desired pyrazolo[3,4-<i>d</i>]pyrimidine products. For aliphatic hydrazines, the reaction sequence proceeds as a single step in the presence of an external base