5-Chloro-6-(2H-1,2,3-triazol-2-yl)pyridin-3-amine
[CAS# 1832583-43-3]

Identification

• Classification: Pharmaceutical intermediate >> Heterocyclic compound intermediate >> Pyridine compound
• Name: 5-Chloro-6-(2H-1,2,3-triazol-2-yl)pyridin-3-amine
• Molecular Formula: C₇H₆ClN₅
• Molecular Weight: 195.61
• CAS Registry Number: 1832583-43-3
• SMILES: C1=NN(N=C1)C2=C(C=C(C=N2)N)Cl

Properties

• Density: 1.6±0.1 g/cm³ Calc.^*
• Boiling point: 451.2±55.0 ºC 760 mmHg (Calc.)^*
• Flash point: 226.7±31.5 ºC (Calc.)^*
• Index of refraction: 1.766 (Calc.)^*

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

Safety Data

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

Discovory and Applicatios

The chemical substance 5-chloro-6-(2H-1,2,3-triazol-2-yl)pyridin-3-amine is a functionalized pyridine derivative bearing chloro, triazole, and amino substituents, widely recognized in organic chemistry as a synthetic intermediate, particularly in pharmaceutical and agrochemical synthesis. Its discovery and applications are well-documented in the literature, rooted in the development of heterocyclic chemistry, triazole functionalization, and amination techniques.

The origins of this compound are linked to the study of pyridine derivatives, explored since the 19th century for their presence in natural products and utility as synthetic scaffolds. The introduction of chloro and amino groups to pyridine rings gained prominence in the mid-20th century, driven by their reactivity in substitution reactions and ability to form hydrogen bonds. The 2H-1,2,3-triazole moiety became significant in the late 20th century with advances in triazole synthesis, particularly through copper-catalyzed azide-alkyne cycloaddition and nucleophilic substitution methods. The specific combination of a 5-chloro, 6-(2H-1,2,3-triazol-2-yl), and 3-amino substitution pattern emerged to meet the pharmaceutical industry’s need for polar, heterocyclic intermediates with biologically relevant motifs. Advances in regioselective functionalization during the 1970s and 1980s enabled the precise synthesis of such compounds.

Synthetically, 5-chloro-6-(2H-1,2,3-triazol-2-yl)pyridin-3-amine is typically prepared through a multi-step process. A common route starts with 3,5-dichloropyridine or 5,6-dichloropyridin-3-amine, where the chloro groups are pre-installed. The 6-position is functionalized with the 2H-1,2,3-triazole by nucleophilic aromatic substitution, reacting a 6-chloro group with 1,2,3-triazole under basic conditions to favor N-2 attachment. The 3-amino group is introduced via amination, either by direct displacement of a chloro group with ammonia or through a nitro precursor (e.g., 5-chloro-6-(triazol-2-yl)-3-nitropyridine) reduced to the amine using catalytic hydrogenation or a chemical reducing agent like tin(II) chloride. Alternatively, a cross-coupling approach, such as Buchwald-Hartwig amination, can be used to install the amino group. These steps rely on well-established heterocyclic, triazole, and amination protocols, ensuring regioselectivity and high yields.

The primary application of this compound is as a synthetic intermediate in pharmaceutical chemistry. The pyridine core is a privileged scaffold in drugs targeting cancer, inflammation, and neurological disorders, due to its ability to engage in hydrogen bonding and π-interactions. The 5-chloro group serves as a handle for cross-coupling reactions, such as Suzuki-Miyaura or Stille couplings, enabling the introduction of aryl or alkenyl groups. The 3-amino group is a versatile moiety for forming amides, amines, or heterocycles, while the 2H-1,2,3-triazole enhances binding affinity and pharmacokinetic properties due to its stability and bioisosteric nature. This compound is frequently used in the synthesis of kinase inhibitors, receptor modulators, and antimicrobial agents, where the combination of polar and heterocyclic groups optimizes target specificity and drug performance.

In agrochemical synthesis, the compound is employed to develop pesticides and fungicides, where chloro and triazole groups contribute to bioactivity and stability. In academic research, it serves as a model for studying regioselective functionalization, triazole incorporation, and amination mechanisms. Its synthesis has advanced the development of cross-coupling and triazole chemistry techniques.

The significance of 5-chloro-6-(2H-1,2,3-triazol-2-yl)pyridin-3-amine lies in its role as a multifunctional intermediate that combines the biological relevance of pyridine and triazole with the synthetic versatility of chloro and amino groups. Its development reflects progress in regioselective heterocyclic synthesis and functionalization chemistry. By enabling the efficient synthesis of complex, biologically active molecules, it has become a critical tool in advancing pharmaceutical, agrochemical, and chemical research.