Compound Overview and Chemical Properties

7-Bromo-2,2-dimethyl-2H-pyrido[3,2-b][1,4]oxazin-3(4H)-one (SKU: B195659) is a bicyclic heterocyclic compound comprising a pyridine ring fused to a 1,4-oxazin-3(4H)-one (morpholinone-type) ring. The compound carries three chemically significant features: (1) an aryl bromide at the 7-position of the pyridine ring, which is highly amenable to transition-metal-catalyzed cross-coupling reactions such as Suzuki–Miyaura, Buchwald–Hartwig, and Negishi couplings; (2) a gem-dimethyl substitution at the C-2 position, which confers conformational rigidity and lipophilic character; and (3) a lactam-type carbonyl at the C-3 position, providing a hydrogen-bond acceptor site relevant to target binding in drug design.

This fused pyridine–oxazinone scaffold is of significant interest in drug discovery programs targeting kinases, GPCRs, and other therapeutic proteins, where constrained bicyclic fragments are used to improve selectivity and bioavailability. The aryl bromide handle allows direct elaboration of the core via C–C and C–N bond-forming reactions.

Materials and Safety Precautions

Materials required:

• 7-Bromo-2,2-dimethyl-2H-pyrido[3,2-b][1,4]oxazin-3(4H)-one (B195659)
• Appropriate anhydrous organic solvents (e.g., DMSO, DMF, dichloromethane, THF) for dissolution
• Inert gas supply (nitrogen or argon) for air-sensitive operations
• Analytical balance, volumetric glassware, magnetic stirrer
• Personal protective equipment (PPE): lab coat, chemical-resistant gloves, safety goggles

Safety precautions: As a brominated organic heterocycle, this compound should be handled with standard laboratory precautions. Avoid inhalation of dust or vapors. Work in a well-ventilated fume hood. Consult the current Safety Data Sheet (SDS) before use. Dispose of waste in accordance with local hazardous chemical regulations. This compound has not been fully toxicologically characterized; treat as potentially harmful.

Step-by-Step Protocol: Dissolution and Stock Solution Preparation

Follow these steps to prepare a stock solution of 7-Bromo-2,2-dimethyl-2H-pyrido[3,2-b][1,4]oxazin-3(4H)-one for use in synthetic or biological assay workflows:

1. Equilibrate to room temperature: Remove the vial from cold storage and allow it to equilibrate to ambient temperature for at least 15 minutes before opening to prevent moisture condensation on the solid.
2. Weigh accurately: Using an analytical balance and a tared vessel, weigh the desired amount of compound in a fume hood. Record the exact mass.
3. Select solvent: For general synthetic applications, anhydrous DMF or DMSO are recommended as primary solvents due to their ability to dissolve polar heterocycles. For reactions requiring non-polar media, THF or dichloromethane may be used. Confirm solubility empirically if using a novel solvent system.
4. Dissolve: Add solvent incrementally to the weighed compound with gentle swirling or stirring. Ensure complete dissolution before adjusting to final volume. Sonication at room temperature may assist dissolution if needed.
5. Prepare stock concentration: Calculate the required volume of solvent to achieve the desired molar concentration using the molecular formula and molecular weight of the compound. Prepare stock solutions typically in the range of 10–100 mM for synthetic use or 1–10 mM for biological screening.
6. Storage of stock solution: Aliquot stock solutions into single-use portions where possible. Store sealed vials under inert gas at −20 °C or below. Limit freeze–thaw cycles to preserve compound integrity.

Note: Confirm the molecular weight from the current product specification sheet available on the Aladdin Scientific website for accurate concentration calculations.

Applications in Synthesis and Drug Discovery

The aryl bromide functionality at C-7 makes this compound a highly useful electrophilic partner in a range of palladium- and copper-catalyzed transformations:

• Suzuki–Miyaura coupling: Reaction with aryl or heteroaryl boronic acids/esters in the presence of a Pd catalyst and base introduces biaryl or heteroaryl substituents at C-7, enabling rapid diversification of the pyridooxazinone core.
• Buchwald–Hartwig amination: The C–Br bond can be converted to a C–N bond using Pd catalysis with appropriate phosphine ligands and amine nucleophiles, yielding amino-substituted analogues valuable in medicinal chemistry SAR studies.
• Negishi and Kumada couplings: Organozinc or organomagnesium reagents can be employed to introduce alkyl or aryl groups at C-7 under Pd or Ni catalysis.
• Miyaura borylation: The aryl bromide can be converted to an aryl boronate ester using bis(pinacolato)diboron (B2pin2) under Pd catalysis, enabling the compound to be used subsequently as a coupling partner in Suzuki reactions.

The constrained bicyclic scaffold with embedded nitrogen and oxygen atoms provides favorable pharmacokinetic properties (e.g., moderate polarity, defined three-dimensional shape) relevant to CNS and kinase-targeted drug discovery programs. Researchers are encouraged to consult primary literature for specific reaction conditions optimized for pyridooxazinone substrates.

Troubleshooting and Quality Notes

Common issues and recommended actions:

• Poor solubility: If the compound does not dissolve readily, try warming the solvent gently (40–50 °C) with stirring, or switch to a higher-polarity solvent such as DMSO. Avoid prolonged heating, which may cause degradation.
• Discoloration of solid: The compound should appear as a solid (color consistent with supplier specification). Any unexpected darkening may indicate degradation due to moisture, heat, or light exposure. Contact Aladdin Scientific technical support if this is observed on first opening.
• Reduced reactivity in cross-coupling: Ensure reagents are anhydrous and reactions are run under inert atmosphere. Aged or poorly stored aryl bromides may exhibit reduced reactivity due to surface oxidation or trace moisture. Use freshly prepared solutions where possible.
• Purity verification: Before use in critical experiments, verify purity by HPLC or NMR in accordance with the certificate of analysis (CoA) provided. Report any discrepancies to Aladdin Scientific.

For technical support, batch-specific CoA, or SDS requests, contact Aladdin Scientific customer service with the product SKU (B195659) and batch number.