3-Ethynylimidazolo[1,2-b]pyridazine
[CAS 943320-61-4]

Identification

• Classification: Pharmaceutical intermediate >> Heterocyclic compound intermediate >> Pyridazine
• Name: 3-Ethynylimidazolo[1,2-b]pyridazine
• Molecular Formula: C₈H₅N₃
• Molecular Weight: 143.15
• CAS Registry Number: 943320-61-4
• SMILES: C#CC1=CN=C2N1N=CC=C2

Properties

• Solubility: Slightly soluble (1.2 g/L) (25 $degree$C), Calc.^*
• Density: 1.15$+/-$0.1 g/cm³ (20 $degree$C 760 Torr), Calc.^*
• Index of refraction: 1.634 (Calc.)^*

^* Calculated using Advanced Chemistry Development (ACD/Labs) Software.

Safety Data

• Hazard Symbols: GHS07 Warning
• Risk Statements: H302-H315-H319-H335
• Safety Statements: P261-P305+P351+P338

Discovery and Applications

3-Ethynylimidazolo[1,2-b]pyridazine is a fused heteroaromatic compound consisting of an imidazole ring fused to a pyridazine ring with an ethynyl substituent at the 3-position. Compounds of this type are important in medicinal chemistry and synthetic heterocyclic chemistry due to the combination of electron-rich and electron-deficient nitrogen-containing rings, which can serve as hydrogen-bond donors and acceptors, and the ethynyl group, which provides a site for further chemical functionalization or conjugation. The rigid planar structure of the fused ring system allows for defined molecular geometry, which is advantageous for interactions with biological targets or in the construction of extended π-conjugated systems.

Structurally, the imidazolo[1,2-b]pyridazine framework comprises a five-membered imidazole ring fused at the 1,2-positions to a six-membered pyridazine ring. The ethynyl group attached at the 3-position of the imidazole ring introduces a linear, sp-hybridized carbon–carbon triple bond, which is reactive toward nucleophilic addition, cycloaddition, or coupling reactions. The nitrogen atoms in the fused heterocycles provide sites for hydrogen bonding, coordination with metal centers, and electronic modulation of the aromatic system. This combination of features makes the molecule versatile for both synthetic and biological applications.

The synthesis of 3-ethynylimidazolo[1,2-b]pyridazine is typically accomplished via palladium-catalyzed Sonogashira cross-coupling reactions. A halogenated imidazolo[1,2-b]pyridazine precursor is reacted with a terminal alkyne under inert atmosphere and basic conditions to introduce the ethynyl group selectively. Reaction parameters such as temperature, solvent, and catalyst loading are optimized to prevent polymerization or decomposition of the fused heterocycle. The final product is generally isolated as a stable solid suitable for further chemical transformations.

In medicinal chemistry, fused imidazolo-pyridazine derivatives bearing ethynyl groups are explored as kinase inhibitors, nucleic acid ligands, and receptor modulators. The ethynyl substituent can act as a handle for introducing additional functional groups, enabling the synthesis of derivatives with improved binding affinity, selectivity, or pharmacokinetic properties. The nitrogen-rich fused system allows for interactions with polar residues or coordination with metal ions in biological macromolecules, providing opportunities for designing bioactive compounds with precise molecular recognition.

Beyond pharmaceutical applications, 3-ethynylimidazolo[1,2-b]pyridazine is a useful intermediate in heterocyclic chemistry and materials science. The ethynyl group can participate in cycloaddition reactions such as click chemistry, enabling the construction of complex molecular scaffolds or conjugation with other functional moieties. The fused heterocyclic core can be further functionalized through substitution, oxidation, or metal-catalyzed coupling, facilitating the preparation of libraries of derivatives or π-conjugated systems for electronic or photophysical applications.

Overall, 3-ethynylimidazolo[1,2-b]pyridazine is a multifunctional fused heteroaromatic compound combining the imidazole and pyridazine rings with a reactive ethynyl substituent. Its planar, nitrogen-rich framework and alkyne functionality make it a versatile intermediate for organic synthesis, medicinal chemistry, and the development of bioactive molecules or functional materials.

References

2014. Ponatinib. Pharmaceutical Substances.
PubChem Literature ID: 906196375