Pyrazolo[1,5-a]pyridine-5-carboxylic acid
[CAS# 104468-87-3]

Identification

• Classification: Pharmaceutical intermediate >> Heterocyclic compound intermediate >> Pyridine compound
• Name: Pyrazolo[1,5-a]pyridine-5-carboxylic acid
• Molecular Formula: C₈H₆N₂O₂
• Molecular Weight: 162.15
• CAS Registry Number: 104468-87-3
• EC Number: 874-973-2
• SMILES: C1=CN2C(=CC=N2)C=C1C(=O)O

Properties

• Solubility: Slightly soluble (3.9 g/L) (25 °C), Calc.^*
• Density: 1.41±0.1 g/cm³ (20 °C 760 Torr), Calc.^*

^* Calculated using Advanced Chemistry Development (ACD/Labs) Software V11.02 (©1994-2016 ACD/Labs)

Safety Data

• Hazard Symbols: GHS07 Warning
• Risk Statements: H302-H315-H319-H335
• Safety Statements: P261-P264-P264+P265-P270-P271-P280-P301+P317-P302+P352-P304+P340-P305+P351+P338-P319-P321-P330-P332+P317-P337+P317-P362+P364-P403+P233-P405-P501

Hazard Classification

Hazard	Class	Category Code	Hazard Statement
Skin irritation	Skin Irrit.	2	H315
Eye irritation	Eye Irrit.	2A	H319
Specific target organ toxicity - single exposure	STOT SE	3	H335
Acute toxicity	Acute Tox.	4	H302

Discovery and Applications

Pyrazolo[1,5-a]pyridine-5-carboxylic acid is a heterocyclic compound consisting of a fused pyrazole and pyridine ring system with a carboxylic acid functional group at the 5-position. This bicyclic aromatic system is part of the broader class of pyrazolopyridines, which have been studied for their structural and electronic properties and have found significant applications in the development of biologically active molecules.

The synthesis of pyrazolo[1,5-a]pyridine-5-carboxylic acid has been reported in the literature through several established routes. One common method involves the cyclocondensation of hydrazines with appropriately substituted pyridine derivatives, followed by oxidation and carboxylation steps to introduce the carboxylic acid moiety. The introduction of a carboxyl group at the 5-position is facilitated by the electronic characteristics of the ring system, which can stabilize intermediates during functionalization reactions.

The compound has attracted interest due to its role as an intermediate in the preparation of pharmacologically active molecules. Derivatives of the pyrazolo[1,5-a]pyridine core have been extensively investigated for their potential as kinase inhibitors, anti-inflammatory agents, and modulators of central nervous system receptors. The presence of a carboxylic acid group allows for enhanced solubility and provides a reactive site for the formation of amides, esters, or other conjugates used in drug development.

In medicinal chemistry, pyrazolopyridine frameworks, including those bearing a carboxylic acid group, have been incorporated into screening libraries to identify lead compounds with selective activity. The fused heterocycle offers a rigid and planar scaffold, which can be functionalized at multiple positions to fine-tune the physicochemical properties and receptor-binding characteristics of candidate molecules. Pyrazolo[1,5-a]pyridine-5-carboxylic acid has thus been employed in structure-activity relationship studies where its core structure serves as a key pharmacophore.

Applications of this compound extend to synthetic organic chemistry as well. The carboxylic acid group provides a versatile functional handle for derivatization via peptide coupling reactions or conversion into acid chlorides, amides, and esters. These derivatives are often used as intermediates in the synthesis of more complex heterocyclic structures. The ability to introduce various substituents on the pyrazolopyridine ring system makes this compound a useful starting material for diversity-oriented synthesis strategies.

In the field of material science, pyrazolopyridine-based compounds have been examined for their photophysical properties, particularly their fluorescence behavior and electron-transporting capabilities. Although pyrazolo[1,5-a]pyridine-5-carboxylic acid itself has not been widely used in material applications, its structural motifs have been incorporated into organic electronic materials due to their planarity and conjugation.

From an analytical standpoint, pyrazolo[1,5-a]pyridine-5-carboxylic acid can be characterized using standard techniques such as nuclear magnetic resonance (NMR) spectroscopy, infrared (IR) spectroscopy, and mass spectrometry. The carboxylic acid group typically shows a broad absorption band in the IR spectrum, while the fused aromatic protons give distinct chemical shifts in the NMR spectrum, confirming the structure.

In conclusion, pyrazolo[1,5-a]pyridine-5-carboxylic acid is a well-established compound in heterocyclic chemistry. It serves both as a building block in the synthesis of biologically active compounds and as a versatile intermediate in functionalization reactions. Its applications in medicinal chemistry, supported by its chemical stability and reactivity, underscore its continued relevance in research and development.

References

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