Methyl 2-aminonicotinate
[CAS# 14667-47-1]

Identification

• Classification: Pharmaceutical intermediate >> Heterocyclic compound intermediate >> Pyridine compound >> Aminopyridine
• Name: Methyl 2-aminonicotinate
• Synonyms: Methyl 2-aminopyridine-3-carboxylate
• Molecular Formula: C₇H₈N₂O₂
• Molecular Weight: 152.15
• CAS Registry Number: 14667-47-1
• EC Number: 681-092-5
• SMILES: COC(=O)C1=C(N=CC=C1)N

Properties

• Density: 1.2±0.1 g/cm³, Calc.^*
• Melting point: 82-86 ºC (Expl.)
• Index of Refraction: 1.571, Calc.^*
• Boiling Point: 251.3±20.0 ºC (760 mmHg), Calc.^*
• Flash Point: 105.8±21.8 ºC, Calc.^*

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

Safety Data

• Hazard Symbols: GHS07 Warning
• Hazard Statements: H302-H312-H315-H319-H332-H335
• Precautionary Statements: P261-P264-P264+P265-P270-P271-P280-P301+P317-P302+P352-P304+P340-P305+P351+P338-P317-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.	2	H319
Specific target organ toxicity - single exposure	STOT SE	3	H335
Acute toxicity	Acute Tox.	4	H332
Acute toxicity	Acute Tox.	4	H302
Acute toxicity	Acute Tox.	4	H312
Eye irritation	Eye Irrit.	2A	H319

Discovory and Applicatios

Methyl 2-aminonicotinate is a chemical compound with the molecular formula C₇H₈N₂O₂, consisting of a pyridine ring substituted at the 2-position with an amino group (–NH₂) and at the 3-position with a methyl ester (–COOCH₃). It is categorized as an aminopyridine ester and is structurally related to 2-aminonicotinic acid, from which it can be derived through esterification. The compound is a solid under standard conditions and exhibits chemical properties typical of aminopyridine derivatives.

The synthesis of methyl 2-aminonicotinate is well-documented in the chemical literature. A common method involves the esterification of 2-aminonicotinic acid with methanol in the presence of an acid catalyst such as sulfuric acid. This Fischer esterification proceeds under reflux conditions and results in the conversion of the carboxylic acid moiety to the methyl ester. The reaction is typically followed by neutralization and purification via crystallization or solvent extraction to isolate the target compound in good yield.

Methyl 2-aminonicotinate is used as an intermediate in organic synthesis, particularly in the pharmaceutical and agrochemical industries. Its functional groups offer versatile sites for further derivatization. The amino group can participate in a range of chemical transformations, including acylation, sulfonation, and coupling reactions, while the ester group can undergo hydrolysis or transesterification. These features make the compound valuable in the preparation of more complex heterocyclic systems and in the synthesis of bioactive molecules.

In medicinal chemistry, methyl 2-aminonicotinate has been employed as a starting material or building block for the development of compounds with potential biological activity. It serves as a precursor in the synthesis of pyridine-based scaffolds that are part of pharmacologically relevant structures, including kinase inhibitors, anti-inflammatory agents, and antimicrobial compounds. Although methyl 2-aminonicotinate itself is not used as a therapeutic agent, its derivatives have been studied for activity in various biological assays.

The compound is also of interest in coordination chemistry due to the ability of the pyridine nitrogen and the amino group to coordinate with metal ions. It can form chelating ligands for transition metals, and such complexes have been investigated for their structural properties and reactivity. Metal complexes involving substituted aminonicotinates, including methyl 2-aminonicotinate, have been prepared and characterized using spectroscopic and crystallographic techniques.

In the synthesis of dyes and pigments, methyl 2-aminonicotinate may be used as a functional intermediate. The introduction of the amino group into the aromatic pyridine ring contributes to electronic effects that can influence the optical properties of chromophoric systems. Derivatives of aminonicotinates have been incorporated into dye structures for applications in textiles and biological staining.

Analytically, methyl 2-aminonicotinate is characterized using techniques such as nuclear magnetic resonance (NMR) spectroscopy, infrared (IR) spectroscopy, mass spectrometry (MS), and elemental analysis. In NMR spectra, the pyridine protons and the methoxy group provide distinctive chemical shifts, while IR spectroscopy confirms the presence of ester and amine functionalities. High-performance liquid chromatography (HPLC) and gas chromatography (GC) are commonly employed for purity assessment and quantitative analysis.

The physical properties of methyl 2-aminonicotinate include a moderate melting point and limited solubility in water, but it is soluble in common organic solvents such as ethanol, methanol, and dichloromethane. The compound is stable under normal laboratory conditions and can be stored in closed containers protected from moisture and strong oxidizing agents.

Methyl 2-aminonicotinate continues to serve as a useful intermediate in chemical synthesis, with established roles in the preparation of pharmaceuticals, coordination complexes, and other functional organic compounds. Its reactivity and ease of modification support its ongoing use in research and industrial applications.

References

2023. Coordination of Distal Carboxylate Anion Alters Metal Ion Specific Binding in Imidazo[1,2-a]pyridine Congeners. Journal of Fluorescence, 33(4).
DOI: 10.1007/s10895-022-03122-x

2022. Electrophilic Fluorination of Imidazoheterocycles by Selectfluor. Russian Journal of General Chemistry, 92(7).
DOI: 10.1134/s1070363222070234

1973. Research on naphthyridines. Chemistry of Heterocyclic Compounds, 9(10).
DOI: 10.1007/bf00477465