6-Bromo-3-methylisoquinolin-1(2H)-one: Properties & Applications

6-Bromo-3-methylisoquinolin-1(2H)-one is a halogen-functionalized isoquinolinone heterocycle valued in synthetic and medicinal chemistry as a versatile building block for the preparation of pharmacologically relevant compounds.

Product Name

6-Bromo-3-methylisoquinolin-1(2H)-one

SKU

B691995

Core Scaffold

Isoquinolin-1(2H)-one (isoquinolinone)

Key Substituents

6-Bromo, 3-Methyl

Primary Use

Synthetic building block for medicinal chemistry and drug discovery

Halogen Handle

C-6 bromine enables cross-coupling reactions (e.g., Suzuki, Buchwald-Hartwig)

Chemical Identity and Structure

6-Bromo-3-methylisoquinolin-1(2H)-one belongs to the isoquinolinone family of nitrogen-containing bicyclic heterocycles. The parent isoquinolin-1(2H)-one scaffold consists of a benzene ring fused to a pyridinone ring, providing a planar, aromatic-rich framework commonly encountered in natural products and pharmaceuticals.

This compound carries two key substitutions relative to the unsubstituted parent: a bromine atom at the C-6 position on the benzene ring, and a methyl group at the C-3 position of the lactam ring. The C-6 bromine is an electrophilic handle that renders the molecule highly amenable to transition-metal-catalyzed cross-coupling chemistry. The C-3 methyl group modulates the electronic density of the heterocyclic system and influences physicochemical properties such as lipophilicity and metabolic stability in drug candidates derived from this scaffold.

The lactam (cyclic amide) nitrogen at the N-2 position can participate in hydrogen bonding, an important consideration when this scaffold is incorporated into target molecules intended to interact with biological macromolecules.

Synthetic Utility and Reactivity

The defining synthetic feature of 6-Bromo-3-methylisoquinolin-1(2H)-one is the aryl C–Br bond at C-6. This bond is well-suited for a range of palladium- and nickel-catalyzed cross-coupling reactions that are central to modern medicinal chemistry library synthesis:

• Suzuki–Miyaura coupling: Allows replacement of the bromine with aryl, heteroaryl, or vinyl boronic acids and esters, enabling rapid diversification of the biaryl or aryl-heteroaryl pharmacophore.
• Buchwald–Hartwig amination: Facilitates introduction of primary or secondary amine groups at C-6, expanding structural diversity toward aminoisoquinolinone derivatives.
• Negishi and Kumada couplings: Permit installation of alkyl, aryl, or heteroaryl groups via organozinc or Grignard reagents.
• Miyaura borylation: Converts the C–Br bond to a boronic ester, yielding a complementary coupling partner for further transformations.

The N-H of the lactam can also be alkylated or acylated under standard conditions to provide N-substituted isoquinolinone derivatives with distinct biological profiles. The combination of these orthogonal handles makes this compound a high-value starting material for parallel synthesis and medicinal chemistry campaigns.

Relevance to Medicinal Chemistry and Drug Discovery

The isoquinolinone scaffold is a privileged structure in drug discovery, appearing in a diverse array of bioactive natural products and synthetic drug candidates. Compounds bearing this core have been investigated for a wide range of biological activities, including inhibition of poly(ADP-ribose) polymerase (PARP), kinase inhibition, antifungal activity, and modulation of various receptor systems.

The introduction of a bromine at C-6 is a strategic design element: bromine is comparable in size to a methyl group but substantially more electronegative, and it can engage in halogen bonding interactions with protein residues. These properties can influence binding affinity and selectivity when the compound is used as a starting point for structure-activity relationship (SAR) studies.

The C-3 methyl group is another common medicinal chemistry modification employed to block metabolic soft spots, improve membrane permeability, and fine-tune potency. Together, the bromine and methyl substitutions make 6-Bromo-3-methylisoquinolin-1(2H)-one a strategically designed fragment-like building block suitable for fragment-based drug discovery (FBDD) or as an advanced intermediate in total synthesis programs targeting isoquinolinone-containing natural products.

Handling, Storage, and Laboratory Safety

As with all research reagents containing an aryl bromide and a lactam functional group, proper laboratory practice should be observed when handling 6-Bromo-3-methylisoquinolin-1(2H)-one. Researchers should consult the Safety Data Sheet (SDS) provided by Aladdin Scientific before use.

General guidelines:

• Wear appropriate personal protective equipment (PPE), including nitrile gloves, laboratory coat, and safety glasses.
• Handle the compound in a well-ventilated area or fume hood to minimize inhalation exposure to fine powder or aerosols.
• Store in a cool, dry location, away from strong oxidizing agents and incompatible materials, in a tightly sealed container.
• Dispose of waste in accordance with local institutional and governmental regulations governing halogenated organic compounds.

Specific hazard classifications, first-aid measures, and transport information should be verified against the current SDS. Aladdin Scientific provides SDS documentation for all catalog compounds upon request and via the product page.

Frequently asked questions

What cross-coupling reactions can be performed with 6-Bromo-3-methylisoquinolin-1(2H)-one?

The aryl C–Br bond at C-6 is compatible with a wide range of palladium- and nickel-catalyzed cross-coupling reactions, including Suzuki–Miyaura, Buchwald–Hartwig amination, Negishi, Kumada, and Miyaura borylation. These reactions allow chemists to introduce diverse aryl, heteroaryl, amino, and alkyl groups at the C-6 position, enabling rapid structural diversification.

What is the significance of the bromine substituent at C-6 in medicinal chemistry applications?

The C-6 bromine serves dual purposes: it acts as a synthetic handle for transition-metal-catalyzed diversification reactions, and it can participate in halogen bonding interactions with protein residues when the compound is evaluated in biological assays. Bromine's size and electronegativity profile can positively influence binding affinity and selectivity in structure-activity relationship studies.

How should 6-Bromo-3-methylisoquinolin-1(2H)-one be stored to maintain its integrity?

The compound should be stored in a tightly sealed container in a cool, dry environment, away from strong oxidizing agents. Consult the Aladdin Scientific Safety Data Sheet and product page for specific storage temperature recommendations and shelf-life information relevant to your lot.

Is 6-Bromo-3-methylisoquinolin-1(2H)-one suitable for fragment-based drug discovery (FBDD)?

Yes. The isoquinolinone core is a privileged scaffold with documented biological relevance, and the relatively low molecular weight of this brominated derivative, combined with its multiple orthogonal reactive handles (C–Br bond and N–H lactam), makes it a suitable fragment-like starting material for FBDD programs or as an advanced intermediate for SAR exploration.

References

1. Joule, J. A.; Mills, K. Heterocyclic Chemistry, 5th ed.; Wiley-Blackwell: Oxford, 2010. General reference for isoquinolinone scaffold chemistry.
2. Roughley, S. D.; Jordan, A. M. The medicinal chemist's toolbox: an analysis of reactions used in the pursuit of drug candidates. J. Med. Chem. 2011, 54, 3451–3479. doi:10.1021/jm200187y
3. Aladdin Scientific. Product page: 6-Bromo-3-methylisoquinolin-1(2H)-one, SKU B691995.

Products are supplied for research and development use only. Not for use in humans, animals, diagnosis, or therapy.