What Is 7-Bromo-2,4-Dichloro-6,8-Difluoro-quinazoline?

7-Bromo-2,4-dichloro-6,8-difluoro-quinazoline (Aladdin SKU: B632433) is a polyhalogenated derivative of quinazoline, a bicyclic heteroaromatic system composed of a benzene ring fused to a pyrimidine ring. The compound bears four halogen substituents: two chlorine atoms at the 2- and 4-positions of the pyrimidine ring, one bromine atom at the 7-position, and two fluorine atoms at the 6- and 8-positions of the benzene ring.

This unique substitution pattern makes the molecule a highly reactive and versatile synthetic intermediate. The electron-withdrawing halogen atoms collectively activate the ring toward nucleophilic aromatic substitution (SNAr), while the C–Br bond at the 7-position provides a handle for transition-metal-catalyzed cross-coupling reactions such as Suzuki–Miyaura, Buchwald–Hartwig, and Sonogashira couplings.

Chemical Properties and Reactivity

The reactivity of 7-bromo-2,4-dichloro-6,8-difluoro-quinazoline is governed by the interplay of its four halogen substituents on the electron-deficient quinazoline core.

• Nucleophilic Aromatic Substitution (SNAr): The C-4 chlorine is the most electrophilic position due to the combined activating effect of the adjacent ring nitrogen atoms and the flanking fluorine atoms. It reacts preferentially with amines, alcohols, and thiols under mild conditions. The C-2 chlorine can be displaced under more forcing conditions or with selected nucleophiles, enabling sequential functionalization.
• Cross-Coupling Reactions: The C-7 bromo substituent participates readily in palladium- or copper-catalyzed coupling reactions, allowing introduction of aryl, heteroaryl, alkynyl, or amino groups at that position.
• Fluorine Effects: The 6,8-difluoro pattern on the benzene ring further withdraws electron density, enhancing electrophilicity at C-4 and influencing the lipophilicity and metabolic stability of downstream analogs.

Applications in Drug Discovery and Synthesis

Quinazoline derivatives are a privileged scaffold in medicinal chemistry, appearing in numerous approved kinase inhibitor drugs. The polyhalogenated nature of 7-bromo-2,4-dichloro-6,8-difluoro-quinazoline makes it a particularly attractive starting material or intermediate for:

• Kinase Inhibitor Synthesis: The 2,4-dichloroquinazoline core is a classical precursor to 4-anilinoquinazoline-type inhibitors targeting receptor tyrosine kinases such as EGFR, HER2, and VEGFR. Sequential substitution at C-4 (with an aniline) and C-2 (with a second amine or heterocycle) provides access to diverse analogs.
• Fragment-Based Drug Discovery: The compact, functionally dense structure is suited for fragment elaboration via SNAr and cross-coupling to explore structure–activity relationships (SAR).
• Fluorine-Containing Drug Analogs: Incorporation of fluorine atoms is a common strategy to improve metabolic stability, membrane permeability, and binding affinity; this compound enables direct installation of the 6,8-difluoro motif.
• Heterocyclic Library Synthesis: High-throughput parallel synthesis of compound libraries for biological screening.

Handling, Safety, and Storage

As a reactive polyhalogenated aromatic compound, 7-bromo-2,4-dichloro-6,8-difluoro-quinazoline should be handled with appropriate laboratory precautions:

• Personal Protective Equipment (PPE): Wear chemical-resistant gloves, a laboratory coat, and safety glasses. Use a fume hood when weighing or handling the compound.
• Storage: Store in a tightly sealed container in a cool, dry, and well-ventilated area, away from moisture, heat, and incompatible reagents (strong nucleophiles, bases, and reducing agents). Moisture can hydrolyze the reactive C–Cl bonds.
• Disposal: Dispose of waste in accordance with local institutional and governmental regulations for halogenated organic waste.
• First Aid: In case of skin or eye contact, flush immediately with copious water and seek medical attention. Consult the Safety Data Sheet (SDS) for complete hazard information before use.

Note: Always consult the current SDS provided by Aladdin Scientific for authoritative safety information specific to this product (B632433).

Ordering and Specifications

7-Bromo-2,4-dichloro-6,8-difluoro-quinazoline is available from Aladdin Scientific under catalog number B632433. When placing an order or evaluating the product, consider the following:

• Purity: Confirm the purity grade required for your application (e.g., for biological assays, higher purity is recommended). Refer to the current Certificate of Analysis (CoA) available on the product page for lot-specific analytical data including HPLC purity, NMR, and MS confirmation.
• Available Pack Sizes: Contact Aladdin Scientific or check the product listing for available quantities and pricing.
• Lead Time: Availability and lead times may vary; consult Aladdin Scientific customer service for current stock status.
• Custom Synthesis: For larger quantities or custom specifications, Aladdin Scientific may offer custom synthesis options — contact the sales team for details.