A facile synthesis of a novel family of heterotricyclic hybrids: Spiro-pyrrolopyridazines

Abstract

An efficient strategy for the synthesis of spiro-pyrrolopyridazines has been developed. When reacted with hydrazine monohydrate, spiro-2H-pyrroles with a 1,4-diketone functionality produced a novel family of heterotricyclic hybrids, spiro-pyrrolopyridazines, specifically spiro{cyclohexane-1,5'-pyrrolo[3,4-d]pyridazine} systems. The condensation reaction of spiro-2H-pyrroles with hydrazine monohydrate in refluxing 1-butanol proceeded well and afforded spiro-pyrrolopyridazines in good to high yields. The reaction was found to be general for variety of spiro-2H-pyrroles and demonstrated good tolerance to a variety of aromatic and heteroaromatic groups with electron-withdrawing and electron-donating substituents. The synthesis of heterotricyclic spiro-pyrrolopyridazine hybrids may exhibit potential to deliver diverse structural motifs that aid the drug discovery efforts.

Graphical Abstract

Keywords:

• Pyridazine
• pyrrole
• 2H-pyrrole
• N-propargylic β-enaminone
• spiro compounds
• condensation reaction

Additional information

Funding

We thank the Scientific and Technological Research Council of Turkey [TUBITAK, Grant No. 114Z811] and the Research Fund of Middle East Technical University [METU, Grant No. GAP-103-2018-2770] for financial support of this research.