3-Bromo-5-methoxypyridine
[CAS# 50720-12-2]

Identification

• Classification: Pharmaceutical intermediate >> Heterocyclic compound intermediate >> Pyridine compound >> Pyridine derivative
• Name: 3-Bromo-5-methoxypyridine
• Molecular Formula: C₆H₆BrNO
• Molecular Weight: 188.02
• CAS Registry Number: 50720-12-2
• EC Number: 629-553-1
• SMILES: COC1=CC(=CN=C1)Br

Properties

• Density: 1.5±0.1 g/cm³ Calc.^*
• Melting point: 31 - 35 ºC (Expl.), 31 - 35 ºC (Expl.)
• Boiling point: 212.2±20.0 ºC 760 mmHg (Calc.)^*
• Flash point: 82.1±21.8 ºC (Calc.)^*, 102 ºC (Expl.)
• Index of refraction: 1.543 (Calc.)^*

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

Safety Data

• Hazard Symbols: GHS05;GHS07 Danger
• Hazard Statements: H302-H315-H318-H319
• Precautionary Statements: P264-P264+P265-P270-P280-P301+P317-P302+P352-P305+P351+P338-P305+P354+P338-P317-P321-P330-P332+P317-P337+P317-P362+P364-P501

Hazard Classification

Hazard	Class	Category Code	Hazard Statement
Acute toxicity	Acute Tox.	4	H302
Serious eye damage	Eye Dam.	1	H318
Skin irritation	Skin Irrit.	2	H315
Acute toxicity	Acute Tox.	4	H312
Acute toxicity	Acute Tox.	4	H332
Specific target organ toxicity - single exposure	STOT SE	3	H335
Eye irritation	Eye Irrit.	2	H319
Eye irritation	Eye Irrit.	2A	H319

Discovory and Applicatios

3-Bromo-5-methoxypyridine is a halogenated heteroaromatic compound belonging to the class of substituted pyridines. Its molecular structure features a pyridine ring substituted with a bromine atom at the 3-position and a methoxy group at the 5-position. This specific pattern of substitution gives the molecule unique chemical reactivity, making it valuable as an intermediate in pharmaceutical, agrochemical, and material science applications.

The compound has been investigated within the broader context of substituted pyridines, which have a long history in medicinal chemistry due to their presence in many biologically active natural and synthetic compounds. Pyridine derivatives, including 3-bromo-5-methoxypyridine, are of particular interest because they allow for regioselective functionalization, enabling researchers to construct more complex molecular architectures.

Synthesis of 3-bromo-5-methoxypyridine generally involves selective bromination of 5-methoxypyridine or, alternatively, methoxylation of 3-bromopyridine under suitable conditions. The introduction of the methoxy group imparts electron-donating properties through resonance and induction, while the bromine atom serves as a useful handle for further transformations, especially in metal-catalyzed cross-coupling reactions.

In organic synthesis, 3-bromo-5-methoxypyridine is widely used as a building block in the preparation of more complex heterocyclic systems. The bromine atom at the 3-position is particularly reactive in palladium-catalyzed Suzuki, Sonogashira, or Buchwald–Hartwig reactions. These coupling methodologies enable the installation of a wide variety of functional groups, such as aryl, alkynyl, and amine moieties, thereby facilitating the development of diverse target molecules for research and industrial use.

The methoxy group at the 5-position plays an important role in influencing the electron density of the pyridine ring. This has implications for both the regioselectivity of subsequent reactions and the physical properties of the compound. In medicinal chemistry, the methoxy group can also contribute to the bioavailability and metabolic stability of drug candidates, depending on the target receptor or enzyme.

3-Bromo-5-methoxypyridine has been employed as a key intermediate in the synthesis of pharmaceutical candidates targeting central nervous system disorders, inflammatory diseases, and cancer. The pyridine scaffold is a common motif in kinase inhibitors, antimicrobial agents, and modulators of various enzyme systems. The ability to modify the molecule selectively at the 3-position (through the bromine) and to retain or derivatize the methoxy group allows medicinal chemists to explore structure–activity relationships effectively.

In agrochemical research, pyridine-based compounds, including those with halogen and alkoxy substitutions, have shown activity as herbicides, fungicides, and insecticides. The structural diversity afforded by the 3-bromo-5-methoxypyridine core contributes to the design of new molecules with improved potency and selectivity against specific agricultural pests or diseases.

Beyond pharmaceuticals and agrochemicals, this compound has applications in the synthesis of heteroaromatic ligands and functional materials. It can serve as a precursor in the formation of nitrogen-containing ligands for transition metal coordination complexes, which are investigated for their catalytic or electronic properties. The introduction of additional substituents via cross-coupling expands its utility in the design of conjugated systems for use in organic electronics and sensor technologies.

Because of its chemical stability, ease of functionalization, and established synthesis routes, 3-bromo-5-methoxypyridine is a practical and effective intermediate in multiple domains of synthetic chemistry. Its dual substitution pattern offers significant flexibility for downstream transformations, supporting the development of structurally and functionally diverse compounds for both academic and industrial research.

References

2016. Synthetic transformations of sesquiterpene lactones 9. Synthesis of 13-(pyridinyl)eudesmanolides. Chemistry of Heterocyclic Compounds, 52(3).
DOI: 10.1007/s10593-016-1855-1

2020. Selpercatinib. Pharmaceutical Substances, 1.
URL: https://pharmaceutical-substances.thieme.com/ps/search-results?docUri=KD-19-0140

2012. With Hetaryl Halides in Alcohols. Science of Synthesis, 1.
URL: https://science-of-synthesis.thieme.com/app/text/?id=SD-209-00107