Chemical Identity and Structure

6-Bromo-2-methyl-3,4-dihydroisoquinolin-1(2H)-one belongs to the dihydroisoquinolinone family of bicyclic lactams. The core bicyclic system consists of a benzene ring fused to a six-membered lactam ring. The N-2 position bears a methyl group, conferring greater metabolic stability compared with the N-unsubstituted analogue, while the bromine substituent at C-6 of the aromatic ring provides a reactive handle for further chemical elaboration.

The aryl bromide is particularly valuable in transition-metal-catalysed cross-coupling chemistry, enabling introduction of aryl, heteroaryl, vinyl, alkyl, amino, and other functional groups at the C-6 position via Suzuki–Miyaura, Buchwald–Hartwig, Negishi, Sonogashira, and related protocols. The lactam carbonyl at C-1 further offers opportunities for nucleophilic addition, amide bond manipulation, or reduction chemistry.

Research Applications

The dihydroisoquinolinone scaffold is a privileged heterocyclic motif encountered in numerous bioactive natural products and pharmaceutical agents. 6-Bromo-2-methyl-3,4-dihydroisoquinolin-1(2H)-one serves primarily as an advanced intermediate and building block in the following research contexts:

• Drug Discovery: Researchers use this compound as a starting point for library synthesis targeting kinase inhibitors, G-protein-coupled receptor (GPCR) modulators, and central-nervous-system (CNS) active agents, exploiting the aryl bromide for rapid diversification.
• Total Synthesis: The pre-formed dihydroisoquinolinone ring system simplifies retrosynthetic analysis and reduces step count when constructing more complex natural product-like frameworks.
• Medicinal Chemistry SAR Studies: Systematic replacement of the bromine via cross-coupling enables structure–activity relationship (SAR) exploration around the C-6 position with minimal synthetic overhead.
• Fragment-Based Drug Design (FBDD): The compact bicyclic lactam framework is suitable as a fragment hit for elaboration and fragment-linking strategies.

Because the N-methyl group locks the lactam nitrogen conformation and reduces H-bond donor count, compounds derived from this scaffold often display improved membrane permeability and oral bioavailability profiles relative to NH-lactam analogues.

Handling, Storage, and Safety Guidelines

General Handling: Handle in a well-ventilated fume hood using standard laboratory personal protective equipment (PPE): nitrile gloves, lab coat, and safety glasses. Avoid generating dust or aerosols. Wash hands thoroughly after handling.

Storage Conditions: Store in a tightly sealed container in a cool (recommended 2–8 °C or as indicated on the Certificate of Analysis), dry environment protected from light and moisture. Prolonged storage at ambient temperature may lead to gradual degradation; always check for discolouration or off-odour before use.

Stability Considerations: As an aryl bromide and lactam, the compound is generally stable under standard laboratory conditions. However, exposure to strong bases, strong nucleophiles, or moisture over extended periods should be avoided to prevent hydrolysis of the lactam ring or competitive reactions at the aryl bromide.

First Aid: In case of skin or eye contact, rinse immediately with copious water for at least 15 minutes and seek medical advice. If inhaled, move to fresh air. Consult the Safety Data Sheet (SDS) for complete hazard information before use.

Waste Disposal: Dispose of in accordance with applicable local, regional, and national regulations for organic halide-containing chemical waste.

Recommended Reaction Protocols

The aryl C–Br bond in 6-Bromo-2-methyl-3,4-dihydroisoquinolin-1(2H)-one is the primary site for synthetic diversification. The following general protocols represent textbook-level best practices for common transformations:

Suzuki–Miyaura Cross-Coupling

Combine the aryl bromide (1.0 equiv) with an aryl- or heteroarylboronic acid (1.2–1.5 equiv), Pd(PPh₃)₄ or Pd(dppf)Cl₂ (2–5 mol%), and K₂CO₃ or Cs₂CO₃ (2–3 equiv) in a degassed mixture of toluene/EtOH/H₂O or DMF/H₂O. Heat at 80–100 °C under nitrogen or argon for 12–18 h. Monitor by TLC or LC-MS.

Buchwald–Hartwig Amination

Combine the aryl bromide (1.0 equiv) with the desired amine (1.2–2.0 equiv), Pd₂(dba)₃ or Pd(OAc)₂ (2–5 mol%), an appropriate phosphine ligand (BINAP, XPhos, or RuPhos; 4–10 mol%), and Cs₂CO₃ or NaO^tBu (1.5–2.5 equiv) in anhydrous toluene or 1,4-dioxane under inert atmosphere. Heat at 80–110 °C for 12–24 h.

General Tips

• Degas all solvents thoroughly by freeze–pump–thaw or sparging with inert gas before use.
• Perform reactions under strictly anhydrous conditions when using organometallic reagents.
• Quench and purify products by column chromatography (silica gel) or preparative HPLC as appropriate.
• Confirm product identity by ¹H NMR, ¹³C NMR, and HRMS.

Quality, Purity, and Certificate of Analysis

Aladdin Scientific supplies 6-Bromo-2-methyl-3,4-dihydroisoquinolin-1(2H)-one (SKU: B589997) with purity verified by HPLC and/or NMR analysis. A Certificate of Analysis (CoA) is available for each lot and includes the following information:

• Lot-specific purity (HPLC area %)
• ¹H NMR confirmation of structure
• Appearance (typically a white to off-white solid)
• Molecular formula and molecular weight confirmation

Researchers are advised to request and retain the CoA corresponding to the specific lot received, as purity can vary between lots. For highly sensitive applications (e.g., biological assays, asymmetric catalysis), additional in-house characterisation by NMR and HRMS is recommended prior to use.

If the material does not meet stated specifications, contact Aladdin Scientific customer service to initiate a return or replacement per the standard returns policy.