Ethyl 2-aminopyridine-3-carboxylate
[CAS# 13362-26-0]

Identification

• Classification: Pharmaceutical intermediate >> Heterocyclic compound intermediate >> Pyridine compound >> Pyridine derivative
• Name: Ethyl 2-aminopyridine-3-carboxylate
• Synonyms: 2-Aminonicotinic acid ethyl ester
• Molecular Formula: C₈H₁₀N₂O₂
• Molecular Weight: 166.18
• CAS Registry Number: 13362-26-0
• EC Number: 805-077-1
• SMILES: CCOC(=O)C1=C(N=CC=C1)N

Properties

• Density: 1.2±0.1 g/cm³, Calc.^*
• Melting point: 90-96 ºC (Expl.)
• Index of Refraction: 1.559, Calc.^*
• Boiling Point: 266.7±20.0 ºC (760 mmHg), Calc.^*
• Flash Point: 115.1±21.8 ºC, Calc.^*

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

Safety Data

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

Hazard Classification

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

Discovory and Applicatios

Ethyl 2-aminopyridine-3-carboxylate is an organic compound belonging to the class of aminopyridine derivatives, characterized by the presence of both an amino group and an ester functionality on a pyridine ring. Its molecular formula is C₈H₁₀N₂O₂, and it consists of a pyridine ring substituted at the 2-position with an amino group (–NH₂) and at the 3-position with an ethyl ester of a carboxylic acid (–COOC₂H₅). It appears as a solid under standard conditions and is soluble in common organic solvents.

The compound is typically synthesized by esterification or amidation reactions involving pyridine derivatives. One of the established synthetic methods begins with 2-amino-3-pyridinecarboxylic acid, which undergoes esterification in the presence of ethanol and an acid catalyst, such as sulfuric acid or hydrochloric acid, under reflux conditions. This yields the ethyl ester form while retaining the amino functionality. The reaction is well-documented and follows standard esterification protocols used widely in organic chemistry.

Ethyl 2-aminopyridine-3-carboxylate has been explored as an intermediate in the synthesis of various bioactive molecules and heterocyclic compounds. The presence of both an electron-donating amino group and an electron-withdrawing ester group on the aromatic ring allows for further functionalization, including nucleophilic substitution and condensation reactions. This dual functionality makes it a versatile building block in the preparation of complex molecules, particularly those used in pharmaceutical and agrochemical research.

In medicinal chemistry, the aminopyridine scaffold is commonly found in ligands for biological targets such as enzymes, receptors, and ion channels. Although ethyl 2-aminopyridine-3-carboxylate itself is not widely used as a therapeutic agent, it serves as a valuable precursor for the development of related compounds with potential biological activity. Several studies have employed this compound in the synthesis of substituted pyridine derivatives aimed at exploring antimicrobial, anticancer, and anti-inflammatory activities.

The ester moiety can be hydrolyzed under acidic or basic conditions to afford the corresponding carboxylic acid, 2-aminopyridine-3-carboxylic acid, which can be further modified to produce amides, hydrazides, or other functional groups. This transformation is often utilized in multi-step synthetic pathways when constructing more complex molecular frameworks.

In addition to its pharmaceutical relevance, ethyl 2-aminopyridine-3-carboxylate has also been examined in coordination chemistry. Pyridine derivatives with donor groups, such as amines or esters, are known to act as ligands for transition metals. The compound can coordinate through the nitrogen atoms of the pyridine and amino groups, forming stable metal-ligand complexes. These complexes are of interest in catalysis and materials science.

Analytical characterization of ethyl 2-aminopyridine-3-carboxylate is conducted using techniques such as nuclear magnetic resonance (NMR) spectroscopy, infrared (IR) spectroscopy, mass spectrometry (MS), and elemental analysis. The NMR spectra typically display signals corresponding to aromatic protons, the amino group, and the ethyl ester. The IR spectrum shows characteristic absorptions for N–H stretching, C=O stretching from the ester group, and C–N bonds.

The safety profile of ethyl 2-aminopyridine-3-carboxylate, like many organic intermediates, requires standard laboratory precautions. It should be handled with appropriate protective equipment to avoid inhalation or contact with skin and eyes. The compound is stable under normal conditions when stored in a cool, dry environment and away from strong oxidizing agents.

Ethyl 2-aminopyridine-3-carboxylate remains an important intermediate for chemical synthesis due to its functional group compatibility, ease of derivatization, and established role in producing heterocyclic structures. Its applications are supported by a body of peer-reviewed literature in the fields of synthetic organic chemistry and drug discovery.

References

2022. SYNTHESIS, X-RAY STRUCTURE ANALYSIS, AND VIBRATIONAL SPECTRAL STUDIES OF 1-(3-((6-BROMOPYRIDO[2,3-d]PYRIMIDIN-4-YL) OXY)PHENYL)-3-CYCLOPENTYLUREA. Journal of Structural Chemistry, 63(1).
DOI: 10.1134/s002247662201005x

2016. Oxyfunctionalization of pyridine derivatives using whole cells of Burkholderia sp. MAK1. Scientific Reports, 6.
DOI: 10.1038/srep39129

2003. Functionally-substituted Alkoxyethylenes in Reactions with Nucleophiles. Part I. Synthesis of Six-membered Heterocycles. Russian Journal of Organic Chemistry, 39(6).
DOI: 10.1023/b:rujo.0000003153.20325.22