The Synthesis And Methodology Of One New Fused-Pyrazoles

Fused pyrazoles are structural motifs increasingly found in a wide array of medicinal chemistry programs. For example, A class of 3-arylbenzofuropyrazolesn has been developed as inhibitors of certain tyrosine kinases for the treatment of diseases and disorders associated with abnormal cell proliferation. Fused pyrazoles, including benzothieno-and benzofuropyrazoles, have been identified as selective histamine H3 antagonists, which are potentially useful in the treatment of a host of CNS disorders such as ADHD, Parkinson's disease, memory, Alzheimer's, narcolepsy, sleep apnea, insomnia, etc. The synthesis of fused pyrazoles remains of great interest due to the wide applications of such heterocycles in the pharmaceutical and agrochemical industry. The most important methods for preparing this class of heterocycles are the reaction between hydrazines with a-difunctional compounds and 1,3-dipolar cycloadditions of diazo compounds onto triple bonds. A novel intramolecular 1,3-dipolar cycloaddition strategy and the reaction between hydrazines with a-difunctional compounds for a rapid entry into a new fused pyrazoles are described. By careful choice of solvent, base, and reaction conditions, the two entire sequences can be carried out with moderate yields. New synthetic methods that allow efficient access to this class of fused heterocycles is therefore of great value especially in the early stages of drug discovery and structure-activity studies. These compounds can then be further elaborated by substitution using palladium catalyzed coupling strategies. To demonstrate this utility, we investigated crosscoupling reactions to expand our compounds.