7-(Benzyloxy)-2,4-dichloro-6-methoxyquinazoline: FAQs
7-(Benzyloxy)-2,4-dichloro-6-methoxyquinazoline: FAQs
7-(Benzyloxy)-2,4-dichloro-6-methoxyquinazoline is a halogenated quinazoline building block widely employed in medicinal chemistry as a versatile intermediate for the synthesis of kinase inhibitors and other biologically active quinazoline derivatives.
- Chemical Name
- 7-(Benzyloxy)-2,4-dichloro-6-methoxyquinazoline
- Aladdin SKU
- D730195
- Core Scaffold
- Quinazoline (bicyclic nitrogen-containing heterocycle)
- Key Functional Groups
- 2,4-dichloro substituents (electrophilic handles), 6-methoxy group, 7-benzyloxy protecting group
- Primary Application
- Intermediate in the synthesis of EGFR and other tyrosine kinase inhibitors
- Recommended Storage
- Cool, dry, well-ventilated area; away from moisture and incompatible materials
What Is 7-(Benzyloxy)-2,4-dichloro-6-methoxyquinazoline?
7-(Benzyloxy)-2,4-dichloro-6-methoxyquinazoline (Aladdin SKU: D730195) is a functionalized quinazoline derivative bearing two chlorine atoms at the 2- and 4-positions, a methoxy group at the 6-position, and a benzyloxy protecting group at the 7-position. The quinazoline ring system is a bicyclic aromatic heterocycle consisting of fused benzene and pyrimidine rings, recognized for its broad relevance in pharmaceutical research.
The 2,4-dichloro substitution pattern makes this compound a highly reactive electrophilic intermediate: the chlorine atoms at C-2 and C-4 can be selectively displaced by nucleophiles such as amines, thiols, and alkoxides under mild conditions. The benzyloxy group at C-7 serves as a removable protecting group that can be cleaved by hydrogenolysis to reveal a free hydroxyl, enabling further structural diversification.
Applications in Medicinal Chemistry and Synthesis
The primary utility of 7-(Benzyloxy)-2,4-dichloro-6-methoxyquinazoline lies in its role as a key building block for the preparation of quinazoline-based kinase inhibitors. Quinazoline scaffolds are prominent in oncology drug discovery; several approved therapeutics targeting the epidermal growth factor receptor (EGFR) and related receptor tyrosine kinases are built on the 4-aminoquinazoline core. This compound's dichloro pattern allows sequential or regioselective functionalization, enabling researchers to introduce different pharmacophoric groups at each reactive position.
Typical synthetic transformations include nucleophilic aromatic substitution (SNAr) at C-4 with aniline derivatives to install the anilino pharmacophore characteristic of many EGFR inhibitors, followed by further modification at C-2. Hydrogenolytic removal of the benzyloxy group post-coupling provides access to the free 7-hydroxy species, which can then be re-alkylated or used as a hydrogen-bond donor in structure–activity relationship (SAR) studies.
Handling, Storage and Safety Considerations
As with all halogenated organic intermediates, 7-(Benzyloxy)-2,4-dichloro-6-methoxyquinazoline should be handled with appropriate personal protective equipment (PPE), including nitrile gloves, safety glasses, and a laboratory coat. Work in a well-ventilated fume hood to minimize inhalation exposure. Avoid contact with skin, eyes, and mucous membranes.
Store the compound in a tightly sealed container in a cool, dry, and well-ventilated location, away from moisture, strong oxidizers, and incompatible reagents. Extended exposure to moisture or elevated temperatures may lead to hydrolysis or decomposition of the reactive chloro groups. Consult the Safety Data Sheet (SDS) provided by Aladdin Scientific for complete hazard classification, first-aid measures, and disposal guidance before use.
Ordering, Purity and Specifications
7-(Benzyloxy)-2,4-dichloro-6-methoxyquinazoline is available from Aladdin Scientific under SKU D730195. Researchers should confirm the current purity specification, available pack sizes, and pricing by visiting the product page on the Aladdin Scientific website or by contacting customer service directly.
For sensitive synthetic applications, it is recommended to verify purity by HPLC or NMR prior to use, particularly for reactions requiring high regioselectivity. If specific certificate of analysis (CoA) documentation is required for regulatory or quality-management purposes, please request it at the time of ordering.
Frequently asked questions
What is 7-(Benzyloxy)-2,4-dichloro-6-methoxyquinazoline used for?
This compound is primarily used as a synthetic intermediate in medicinal chemistry, particularly for preparing quinazoline-based kinase inhibitors such as EGFR-targeting agents. The two chlorine atoms at the 2- and 4-positions serve as electrophilic handles for sequential nucleophilic substitution reactions, while the benzyloxy group at the 7-position acts as a protecting group that can be removed by hydrogenolysis.
How should 7-(Benzyloxy)-2,4-dichloro-6-methoxyquinazoline be stored?
The compound should be stored in a tightly sealed container in a cool, dry, and well-ventilated area, away from moisture and strong oxidizing agents. Prolonged exposure to moisture or elevated temperatures may compromise the integrity of the reactive chloro groups through hydrolysis or decomposition.
Can I selectively functionalize only one of the two chloro positions?
Yes, selective functionalization is generally achievable due to the differential reactivity of the C-4 and C-2 chloro groups on the quinazoline ring. The C-4 position is typically more electrophilic and reacts preferentially with amine nucleophiles under mild conditions, while the C-2 position can be addressed subsequently under more forcing conditions or with different nucleophiles. Optimization of reaction conditions (temperature, solvent, and nucleophile choice) is recommended for each specific transformation.
How do I remove the benzyloxy protecting group at the 7-position?
The benzyloxy (OBn) group is most commonly removed by catalytic hydrogenolysis, typically using hydrogen gas and a palladium catalyst (e.g., Pd/C) in an appropriate solvent such as ethanol or ethyl acetate at ambient temperature and pressure. This cleanly affords the free 7-hydroxy quinazoline derivative. Ensure that other functional groups present in the molecule are compatible with hydrogenolysis conditions before proceeding.
What Aladdin SKU should I use to order this compound?
7-(Benzyloxy)-2,4-dichloro-6-methoxyquinazoline is listed under Aladdin Scientific SKU D730195. Please visit the Aladdin Scientific website or contact our customer service team for current availability, pack sizes, purity specifications, and pricing.
References
- Traxler, P.; Furet, P. Strategies toward the design of novel and selective protein tyrosine kinase inhibitors. Pharmacology & Therapeutics, 1999, 82(2-3), 195-206.
- Rewcastle, G. W.; Denny, W. A.; Bridges, A. J. et al. Tyrosine kinase inhibitors. 5. Synthesis and structure-activity relationships for 4-[(phenylmethyl)amino]- and 4-(phenylamino)quinazolines as potent adenosine 5'-triphosphate binding site inhibitors of the tyrosine kinase domain of the epidermal growth factor receptor. Journal of Medicinal Chemistry, 1995, 38(18), 3482-3487.
Products are supplied for research and development use only. Not for use in humans, animals, diagnosis, or therapy.
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