7-Bromo-1,5-naphthyridin-2(1H)-one: Properties & Applications
7-Bromo-1,5-naphthyridin-2(1H)-one: Properties & Applications
7-Bromo-1,5-naphthyridin-2(1H)-one is a halogenated bicyclic lactam building block belonging to the 1,5-naphthyridine family, valued in medicinal chemistry and drug discovery for its reactive bromo substituent and rigid heteroaromatic scaffold.
- Chemical Name
- 7-Bromo-1,5-naphthyridin-2(1H)-one
- Product SKU
- B590862
- Compound Class
- Halogenated naphthyridinone (bicyclic lactam)
- Key Functional Groups
- C–Br bond (C-7), lactam carbonyl (C-2), two ring nitrogen atoms (N-1, N-5)
- Primary Research Use
- Synthetic intermediate and scaffold in medicinal chemistry and drug discovery
- Reactivity Highlight
- Bromo group amenable to cross-coupling reactions (e.g., Suzuki, Buchwald–Hartwig)
Chemical Structure and Key Properties
7-Bromo-1,5-naphthyridin-2(1H)-one features a fused bicyclic ring system composed of two pyridine-like nitrogen-containing six-membered rings. The lactam carbonyl at position 2 imparts partial aromatic character and hydrogen-bond acceptor/donor capability, while the bromine substituent at position 7 provides a versatile handle for further chemical elaboration.
The 1,5-naphthyridine core is a well-established pharmacophore known for its ability to engage biological targets through π-stacking and hydrogen-bonding interactions. The presence of two ring nitrogen atoms increases the polarity and water solubility of derivatives relative to purely carbocyclic analogs, making this scaffold attractive for the design of drug-like molecules.
The C–Br bond at position 7 exhibits typical aryl bromide reactivity, rendering the compound suitable as a substrate in transition-metal-catalyzed cross-coupling reactions and nucleophilic aromatic substitution under appropriate conditions.
Synthesis and Functionalization Strategies
The naphthyridinone core can generally be accessed through classical heterocyclic condensation routes, including the cyclization of appropriately substituted aminopyridine precursors with carbonyl-containing partners. The introduction of the bromine atom at the 7-position can be achieved via directed electrophilic bromination of the parent 1,5-naphthyridin-2(1H)-one or through de novo synthesis starting from pre-brominated building blocks.
Once in hand, 7-Bromo-1,5-naphthyridin-2(1H)-one serves as a divergent synthetic intermediate. The aryl bromide is readily engaged in Suzuki–Miyaura cross-coupling to install aryl or heteroaryl groups, Buchwald–Hartwig amination to introduce amino substituents, and Sonogashira coupling to append alkyne functionalities. These transformations enable rapid generation of structural diversity from a single brominated precursor.
The lactam NH can additionally be alkylated or acylated under standard conditions, providing a second site of diversification and allowing fine-tuning of physicochemical properties such as lipophilicity and membrane permeability.
Research and Drug Discovery Applications
Naphthyridinone-containing compounds have attracted sustained interest in drug discovery programs targeting a range of therapeutically relevant enzymes and receptors. The bicyclic heteroaromatic scaffold is found in molecules with reported activity against kinases, integrase enzymes, and other nucleotide-binding proteins, reflecting the ability of the naphthyridine core to mimic purine-like binding interactions.
7-Bromo-1,5-naphthyridin-2(1H)-one (SKU: B590862) is therefore employed by research groups as a key intermediate for preparing focused libraries aimed at target-based drug discovery. The compound is also used in structure–activity relationship (SAR) studies where systematic variation of the substituent at the 7-position is required to map binding interactions with a biological target.
Beyond pharmaceutical research, brominated naphthyridinones may find utility in materials science contexts, for example as ligands in coordination chemistry or as components of functional organic materials, although these applications remain predominantly exploratory at the research stage.
Handling, Storage, and Safety Considerations
As with most halogenated heterocyclic intermediates, 7-Bromo-1,5-naphthyridin-2(1H)-one should be handled with appropriate laboratory precautions. Personnel should wear suitable personal protective equipment including chemical-resistant gloves, eye protection, and a laboratory coat when weighing or manipulating the compound.
The compound should be stored in a cool, dry, well-ventilated area away from incompatible materials such as strong oxidizers and strong bases. Containers should be kept tightly sealed to prevent moisture uptake, which can affect compound integrity over time.
Researchers are advised to consult the Safety Data Sheet (SDS) specific to product B590862 prior to use, as it contains detailed hazard classifications, first-aid measures, disposal guidance, and regulatory information applicable to their jurisdiction.
Frequently asked questions
What cross-coupling reactions are compatible with 7-Bromo-1,5-naphthyridin-2(1H)-one?
The aryl bromide functionality at position 7 is compatible with a range of palladium-catalyzed cross-coupling reactions, including Suzuki–Miyaura (boronic acid/ester coupling), Buchwald–Hartwig (C–N bond formation), and Sonogashira (alkyne coupling) protocols. Standard conditions used for activated aryl bromides are generally applicable, though optimization may be required depending on the specific coupling partner.
How should 7-Bromo-1,5-naphthyridin-2(1H)-one be stored to maintain stability?
The compound should be stored in a tightly sealed container under cool, dry conditions away from moisture, light, and incompatible reagents such as strong oxidizers. Consulting the product-specific SDS for B590862 is recommended for precise storage temperature requirements and shelf-life guidance.
What is the significance of the 1,5-naphthyridine scaffold in medicinal chemistry?
The 1,5-naphthyridine scaffold is a privileged heteroaromatic framework that mimics purine binding interactions, enabling engagement with kinases, integrases, and other nucleotide-binding proteins. Its two nitrogen atoms enhance polarity and hydrogen-bonding capacity compared to purely carbocyclic systems, making derivatives more drug-like and facilitating interactions with biological targets.
Can the lactam NH of 7-Bromo-1,5-naphthyridin-2(1H)-one be further modified?
Yes, the lactam NH at position 1 can be alkylated using alkyl halides in the presence of a suitable base, or acylated under standard acylation conditions, providing an additional site for structural diversification and modulation of physicochemical properties. Care should be taken to avoid competing reactions at other nucleophilic or electrophilic sites under the chosen reaction conditions.
References
- Comprehensive Heterocyclic Chemistry III; Katritzky, A. R.; Ramsden, C. A.; Scriven, E. F. V.; Taylor, R. J. K., Eds.; Elsevier: Oxford, 2008. (General reference on naphthyridine chemistry.)
- Miyaura, N.; Suzuki, A. Palladium-Catalyzed Cross-Coupling Reactions of Organoboron Compounds. Chem. Rev. 1995, 95, 2457–2483. doi:10.1021/cr00039a007
- Aladdin Scientific product page for 7-Bromo-1,5-naphthyridin-2(1H)-one, SKU B590862.
Products are supplied for research and development use only. Not for use in humans, animals, diagnosis, or therapy.
危险品化学品经营许可证（带存储）