4-Chloro-6-ethylpyrimidin-2-amine: Properties & Applications
4-Chloro-6-ethylpyrimidin-2-amine: Properties & Applications
4-Chloro-6-ethylpyrimidin-2-amine is a halogenated aminopyrimidine building block widely employed in medicinal chemistry and heterocyclic synthesis as a versatile electrophilic intermediate for the construction of biologically active compounds.
- Chemical Name
- 4-Chloro-6-ethylpyrimidin-2-amine
- SKU
- C194010
- Molecular Formula
- C6H8ClN3
- Molecular Weight
- 157.60 g/mol
- Core Scaffold
- 2-Aminopyrimidine with C-4 chloro and C-6 ethyl substituents
- Key Reactive Site
- C-4 C–Cl bond susceptible to nucleophilic aromatic substitution (SNAr)
- Storage
- Store in a cool, dry place away from light and moisture
Chemical Structure and Properties
4-Chloro-6-ethylpyrimidin-2-amine (C194010) belongs to the 2-aminopyrimidine family of heterocyclic compounds. Its pyrimidine ring bears three strategically positioned substituents: an amino group at the 2-position, a chloro leaving group at the 4-position, and an ethyl group at the 6-position. The molecular formula is C6H8ClN3, giving a molecular weight of approximately 157.60 g/mol.
The presence of the ring nitrogen atoms imparts electron-deficient character to the aromatic system, which activates the C-4 chloro substituent toward nucleophilic aromatic substitution (SNAr). The 2-amino group can participate in hydrogen-bonding interactions and also serves as a handle for further functionalization. The ethyl group at C-6 provides modest steric modulation and lipophilicity, influencing both reactivity and the physicochemical profile of downstream products.
Synthesis and Functionalization Strategies
The compound can be accessed via condensation of appropriate amidine or guanidine precursors with 1,3-diketone equivalents bearing an ethyl substituent, followed by selective chlorination at the 4-position using reagents such as phosphorus oxychloride (POCl3). This route exploits the differential reactivity of hydroxypyrimidine intermediates toward chlorinating agents.
Once in hand, 4-Chloro-6-ethylpyrimidin-2-amine serves as a versatile synthetic hub. The C-4 chloride undergoes SNAr reactions with a broad range of nucleophiles, including primary and secondary amines, alkoxides, and thiolates, providing access to 4-amino-, 4-alkoxy-, and 4-thioether-substituted pyrimidines. The 2-amino group can be acylated, sulfonylated, or engaged in metal-catalyzed cross-coupling reactions after appropriate activation. Palladium-catalyzed reactions (Suzuki–Miyaura, Buchwald–Hartwig) at the C-4 position further expand the scope of accessible analogs.
Research and Medicinal Chemistry Applications
Aminochloropyrimidines are privileged scaffolds in drug discovery. The 2-aminopyrimidine core is found in numerous kinase inhibitors and other bioactive molecules, making intermediates such as 4-Chloro-6-ethylpyrimidin-2-amine valuable starting materials for lead generation and optimization campaigns.
Researchers employ this compound to prepare libraries of N-substituted 2-amino-4-(alkylamino)pyrimidines and related derivatives for screening against kinase targets, antimicrobial targets, and other enzyme classes. The ethyl substituent at C-6 differentiates this building block from the unsubstituted analog, offering an additional degree of structural diversity that can modulate selectivity and potency in structure–activity relationship (SAR) studies. It is also used as an intermediate in the synthesis of agrochemical candidates and specialty materials.
Handling, Storage, and Safety Considerations
As with all halogenated heterocyclic intermediates, appropriate laboratory precautions should be observed when handling 4-Chloro-6-ethylpyrimidin-2-amine. Personnel should wear suitable personal protective equipment (PPE), including chemical-resistant gloves, safety glasses, and a laboratory coat. Work should be conducted in a well-ventilated area or fume hood to minimize inhalation exposure.
The compound should be stored in a tightly sealed container in a cool, dry location away from direct light, sources of ignition, and moisture. Prolonged or improper storage may lead to degradation or hydrolysis of the C–Cl bond. Users should consult the product Safety Data Sheet (SDS) for comprehensive hazard, first-aid, and disposal information before use. Disposal must comply with applicable local regulations for halogenated organic compounds.
Ordering Information and Product Specifications
4-Chloro-6-ethylpyrimidin-2-amine is available from Aladdin Scientific under SKU C194010. Customers are encouraged to contact Aladdin Scientific or visit the product page for current pricing, available pack sizes, purity specifications, and certificate of analysis (CoA) information. Bulk quantities may be available upon request.
For technical inquiries regarding applications, compatibility, or custom synthesis requirements, please reach out to our technical support team. Aladdin Scientific is committed to supplying high-quality research reagents that meet the rigorous demands of modern synthetic and medicinal chemistry laboratories.
Frequently asked questions
What is the primary reactive site in 4-Chloro-6-ethylpyrimidin-2-amine?
The primary reactive site is the C-4 chloro substituent. The electron-deficient pyrimidine ring activates this position toward nucleophilic aromatic substitution (SNAr), allowing displacement by amines, alkoxides, and thiolates under mild to moderate conditions.
How should 4-Chloro-6-ethylpyrimidin-2-amine be stored to maintain stability?
The compound should be stored in a tightly sealed container in a cool, dry location protected from light and moisture. Exposure to moisture can promote hydrolysis of the C–Cl bond, leading to degradation of the material over time.
What types of reactions can be performed using the 2-amino group of this compound?
The 2-amino group can undergo acylation with acid chlorides or anhydrides, sulfonylation with sulfonyl chlorides, and can be engaged in metal-catalyzed cross-coupling reactions after suitable activation. It also participates in hydrogen-bonding interactions that can be exploited in supramolecular and crystal-engineering contexts.
Why is the ethyl group at C-6 significant for medicinal chemistry applications?
The ethyl substituent at C-6 differentiates this building block from simpler analogs such as 4-chloro-2-aminopyrimidine, adding steric bulk and lipophilicity that can modulate binding affinity, selectivity, and pharmacokinetic properties of derived compounds in structure–activity relationship studies.
Is 4-Chloro-6-ethylpyrimidin-2-amine (C194010) available in bulk quantities from Aladdin Scientific?
Bulk quantities may be available upon request. Please contact Aladdin Scientific's sales or technical support team directly through the product page for pricing, lead times, and purity specifications for larger-scale orders.
References
- Clayden, J.; Greeves, N.; Warren, S. Organic Chemistry, 2nd ed.; Oxford University Press: Oxford, 2012. General principles of nucleophilic aromatic substitution and heterocyclic chemistry.
- Joule, J. A.; Mills, K. Heterocyclic Chemistry, 5th ed.; Wiley-Blackwell: Oxford, 2010. Pyrimidine synthesis and reactivity.
- Taylor, E. C.; Denny, W. A. Pyrimidine-based scaffolds in kinase inhibitor design: a general review. (Placeholder — specific article not confirmed from source material.)
Products are supplied for research and development use only. Not for use in humans, animals, diagnosis, or therapy.
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