5-Amino-4-Bromopyrimidine: Properties, Handling & Lab Use
5-Amino-4-Bromopyrimidine: Properties, Handling & Lab Use
5-Amino-4-bromopyrimidine is a halogenated aminopyrimidine building block widely employed in medicinal chemistry and heterocyclic synthesis as a versatile precursor for cross-coupling reactions and the construction of biologically active scaffolds.
- CAS Number
- 40494-91-5
- Molecular Formula
- C₄H₄BrN₃
- Molecular Weight
- 174.00 g/mol
- Appearance
- Off-white to pale yellow crystalline solid
- Key Functional Groups
- Aromatic bromide, primary amine on pyrimidine ring
- Primary Application
- Pharmaceutical intermediate and coupling partner in cross-coupling reactions
- Storage Condition
- Cool, dry, well-ventilated area; protect from moisture and light
Chemical Identity and Physical Properties
5-Amino-4-bromopyrimidine (CAS 40494-91-5; Aladdin SKU A186944) is a disubstituted pyrimidine bearing a bromine atom at the 4-position and a primary amino group at the 5-position of the six-membered diazine ring. Its molecular formula is C₄H₄BrN₃, giving a molecular weight of approximately 174.00 g/mol.
The compound typically presents as an off-white to pale yellow crystalline solid. The coexistence of an electron-withdrawing bromine and an electron-donating amino group on the pyrimidine ring creates a pronounced electronic asymmetry, which underpins its reactivity in nucleophilic and metal-catalysed transformations. The amino group is capable of participating in hydrogen-bonding interactions, influencing solubility in polar aprotic solvents such as DMSO and DMF, while the aryl bromide serves as the primary handle for palladium-catalysed cross-coupling chemistry.
Synthetic Applications and Reactivity
The aryl bromide moiety in 5-Amino-4-bromopyrimidine makes it an excellent electrophilic partner in transition-metal-catalysed cross-coupling reactions. Palladium-catalysed transformations such as Suzuki–Miyaura, Buchwald–Hartwig, and Sonogashira couplings can be performed at the C-4 position to install aryl, heteroaryl, amine, or alkynyl substituents with high selectivity.
The free amino group at C-5 provides an additional handle for further elaboration: it can be acylated, sulfonylated, or used in condensation reactions to form fused ring systems, making 5-Amino-4-bromopyrimidine a bifunctional building block that enables rapid construction of complex heterocyclic scaffolds. This dual reactivity has made it particularly attractive in the synthesis of kinase inhibitors, antiviral agents, and other pharmacologically relevant nitrogen-containing heterocycles.
When planning multi-step syntheses, chemists typically exploit the C-Br bond first (cross-coupling), followed by manipulation of the amino group, or vice versa depending on orthogonal protecting-group strategies.
Safe Handling, Storage, and Disposal
Personal Protective Equipment (PPE): Handle 5-Amino-4-bromopyrimidine in a well-ventilated fume hood. Wear appropriate chemical-resistant gloves (nitrile recommended), safety glasses or goggles, and a laboratory coat. Avoid inhalation of dust or aerosols.
Storage: Store in a tightly sealed container in a cool (2–25 °C), dry, and well-ventilated location away from direct light, heat sources, oxidising agents, and strong acids or bases. Prolonged exposure to moisture may lead to hydrolytic degradation of the aryl bromide or protonation of the amino group, affecting purity.
Stability: The compound is stable under recommended storage conditions. Monitor for discolouration as a practical indicator of decomposition.
Disposal: Dispose of waste in accordance with local, regional, and national regulations governing halogenated organic compounds. Do not pour down the drain. Consult your institution's chemical waste management programme.
First Aid: In case of skin or eye contact, flush immediately with copious water for at least 15 minutes and seek medical advice. If inhaled, move to fresh air.
Quality, Purity, and Analytical Characterisation
For research applications, the purity of 5-Amino-4-bromopyrimidine is typically assessed by high-performance liquid chromatography (HPLC) and confirmed by nuclear magnetic resonance (NMR) spectroscopy (¹H and ¹³C), and high-resolution mass spectrometry (HRMS). The characteristic isotope pattern of bromine (approximately 1:1 ratio of ⁷⁹Br:⁸¹Br) provides a reliable mass-spectrometric fingerprint.
Researchers should request a Certificate of Analysis (CoA) when placing an order to verify lot-specific purity data. For sensitive downstream applications such as asymmetric catalysis or biological assays, reagent purity of ≥97% is generally recommended to minimise the influence of impurities on reaction outcomes or assay signals.
Aladdin Scientific's A186944 is subject to quality control procedures to ensure consistent performance. Contact technical support or refer to the product CoA for lot-specific analytical data.
Frequently asked questions
What cross-coupling reactions are compatible with 5-Amino-4-bromopyrimidine?
The C-4 aryl bromide in 5-Amino-4-bromopyrimidine is compatible with palladium-catalysed Suzuki–Miyaura (with boronic acids), Buchwald–Hartwig (C–N coupling with amines), and Sonogashira (with terminal alkynes) reactions. Standard Pd(0)/Pd(II) catalyst systems and mild bases are typically employed. The amino group at C-5 is generally tolerated under these conditions but may require protection in certain sensitive protocols.
How should 5-Amino-4-bromopyrimidine be stored to maintain stability?
Store 5-Amino-4-bromopyrimidine in a tightly sealed container at a cool temperature (2–25 °C), away from moisture, direct light, and incompatible materials such as strong oxidising agents. Moisture exposure can promote degradation; therefore, desiccants are recommended for long-term storage. Always re-seal the container promptly after use.
Is 5-Amino-4-bromopyrimidine suitable for use as a pharmaceutical intermediate?
Yes, 5-Amino-4-bromopyrimidine is widely used as a pharmaceutical intermediate in the synthesis of biologically active compounds, including kinase inhibitors and antiviral agents. Its bifunctional nature—aryl bromide for cross-coupling and a free amino group for further functionalisation—makes it a versatile building block in drug discovery programmes. Researchers requiring material for GMP or regulated applications should contact Aladdin Scientific to discuss appropriate grade and documentation requirements.
What solvents are recommended for dissolving 5-Amino-4-bromopyrimidine?
5-Amino-4-bromopyrimidine is generally soluble in polar aprotic solvents such as DMSO and DMF, which are commonly used in both analytical and synthetic workflows. Solubility in aqueous media is limited and pH-dependent due to the basic amino group. Always confirm solubility empirically for your specific application and concentration requirements.
References
- Joule, J. A.; Mills, K. Heterocyclic Chemistry, 5th ed.; Wiley-Blackwell: Oxford, 2010. General reference for pyrimidine chemistry and reactivity.
- Miyaura, N.; Suzuki, A. Palladium-Catalyzed Cross-Coupling Reactions of Organoboron Compounds. Chem. Rev. 1995, 95, 2457–2483. doi:10.1021/cr00039a007
- Buchwald, S. L.; Mauger, C.; Mignani, G.; Scholz, U. Industrial-Scale Palladium-Catalyzed Coupling of Aryl Chlorides and Amines — A Personal Account. Adv. Synth. Catal. 2006, 348, 23–39. (General reference for Buchwald–Hartwig coupling applicability to halopyrimidines.) doi:10.1002/adsc.200505009
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