5-Bromo-2-(3-methoxypropylamino)pyrimidine: Properties & Lab Guide

5-Bromo-2-(3-methoxypropylamino)pyrimidine is a brominated aminopyrimidine building block widely employed as a versatile intermediate in heterocyclic synthesis, cross-coupling reactions, and medicinal chemistry scaffold elaboration.

Product Name

5-Bromo-2-(3-methoxypropylamino)pyrimidine

SKU

B179989

Molecular Formula

C8H12BrN3O

Core Functional Groups

Aryl C–Br bond (C-5), secondary amine linkage (C-2), ether oxygen (methoxyethyl chain)

Primary Utility

Synthetic intermediate for Pd-catalyzed cross-coupling and nucleophilic aromatic substitution

Storage Recommendation

Cool, dry, well-ventilated area; away from moisture and incompatible oxidizers

Chemical Identity and Structural Features

5-Bromo-2-(3-methoxypropylamino)pyrimidine (SKU B179989) is a disubstituted pyrimidine derivative carrying two key functional handles. At the 5-position of the pyrimidine ring sits a carbon–bromine bond that serves as a classical electrophilic site for palladium-catalyzed cross-coupling reactions, including Suzuki–Miyaura, Negishi, and Buchwald–Hartwig protocols. At the 2-position, a secondary amine tether bearing a 3-methoxypropyl chain introduces both conformational flexibility and a hydrogen-bond donor/acceptor pair, elements frequently exploited in structure–activity relationship (SAR) campaigns.

The pyrimidine core itself is an electron-deficient six-membered nitrogen heterocycle that confers distinct physicochemical properties: moderate polarity, capacity for π-stacking interactions, and susceptibility to nucleophilic aromatic substitution (SNAr) at the 2- and 4-positions when appropriately activated. The combination of the bromine leaving group and the alkylamino donor at C-2 creates an electronically polarized ring that can participate in diverse two-step functionalisation sequences.

Handling, Safety, and Storage Guidelines

Personal Protective Equipment (PPE): Handle 5-Bromo-2-(3-methoxypropylamino)pyrimidine in a well-ventilated fume hood. Wear nitrile gloves, a laboratory coat, and appropriate eye protection (safety glasses or goggles). Avoid generating dust or aerosols when weighing solid material.

Storage: Store the compound in a tightly sealed container in a cool (≤25 °C), dry environment protected from light. Keep away from strong oxidising agents, strong acids, and sources of ignition. Segregate from incompatible materials in accordance with local chemical storage regulations.

Waste Disposal: Dispose of the compound and contaminated materials in accordance with applicable federal, state, and local regulations. Do not discharge to drains or the environment. Consult your institution's Environmental Health and Safety (EHS) office for specific disposal procedures for halogenated organic waste.

First Aid: In the event of skin contact, wash thoroughly with soap and water. For eye contact, rinse with copious water for at least 15 minutes and seek medical attention. If inhaled, move the affected individual to fresh air. Consult the full Safety Data Sheet (SDS) before use.

Research Applications and Synthetic Utility

Cross-Coupling Reactions: The C-5 aryl bromide is well-suited for a broad range of palladium-catalysed cross-coupling transformations. Suzuki–Miyaura coupling with aryl- or heteroarylboronic acids installs diverse (hetero)aryl groups at C-5, rapidly expanding molecular complexity. Negishi and Kumada couplings with organozinc or organomagnesium reagents offer complementary carbon–carbon bond-forming options. The electron-deficient ring moderately accelerates oxidative addition of Pd(0) into the C–Br bond relative to electron-rich aryl bromides.

Buchwald–Hartwig Amination: The C–Br bond can also serve as a substrate for palladium-catalysed C–N bond formation, enabling installation of secondary or tertiary amines at C-5, which is particularly valuable in generating aminopyrimidine libraries relevant to kinase inhibitor discovery programmes.

Nucleophilic Aromatic Substitution (SNAr): Although the bromine at C-5 is the primary reactive site for metal-catalysed chemistry, the electron-poor pyrimidine ring may also participate in SNAr at C-4 under appropriate conditions with strong nucleophiles such as amines or alkoxides, providing an orthogonal diversification strategy.

Medicinal Chemistry and Drug Discovery: Aminopyrimidine motifs are privileged scaffolds in kinase inhibitor drug design, featuring prominently in approved therapeutics. The 3-methoxypropyl chain on the exocyclic nitrogen may modulate solubility, metabolic stability, and binding interactions within target active sites, making this compound a useful starting point for SAR exploration.

Quality, Purity, and Analytical Verification

Research-grade 5-Bromo-2-(3-methoxypropylamino)pyrimidine (B179989) supplied by Aladdin Scientific is intended for laboratory research use. Researchers are encouraged to verify compound identity and purity upon receipt using standard analytical techniques prior to use in sensitive assays.

Recommended Analytical Methods:

• NMR Spectroscopy: ¹H and ¹³C NMR in DMSO-d₆ or CDCl₃ should confirm the pyrimidine ring proton pattern, the NH doublet (2-position amine), the methylene protons of the 3-methoxypropyl chain, and the methoxy singlet. The C-5 position (bearing Br) appears as a singlet in the aromatic region distinct from H-4 and H-6.
• HPLC: Reverse-phase HPLC (C18 column, UV detection at 254 nm) provides a quantitative purity assessment. A single symmetrical peak is expected for a high-purity batch.
• LC-MS: Electrospray ionisation mass spectrometry should yield [M+H]⁺ ions consistent with the molecular weight of C₈H₁₂BrN₃O, with the characteristic ⁷⁹Br/⁸¹Br isotope pattern (1:1 ratio) confirming the presence of bromine.
• TLC: Thin-layer chromatography on silica gel with an appropriate solvent system (e.g., ethyl acetate/hexane mixtures) provides a rapid identity check.

Contact Aladdin Scientific technical support for batch-specific Certificate of Analysis (CoA) documentation.

Frequently asked questions

What cross-coupling reactions is 5-Bromo-2-(3-methoxypropylamino)pyrimidine suitable for?

The C-5 aryl bromide makes this compound a suitable substrate for Suzuki–Miyaura, Negishi, Kumada, and Buchwald–Hartwig cross-coupling reactions. Pd(0) or Pd(II) pre-catalyst systems with appropriate phosphine ligands are typically employed. The electron-deficient pyrimidine ring may facilitate oxidative addition relative to electron-neutral aryl bromides.

How should 5-Bromo-2-(3-methoxypropylamino)pyrimidine be stored to maintain stability?

Store the compound in a tightly sealed container at room temperature or below (≤25 °C) in a cool, dry, well-ventilated area away from direct light, moisture, and strong oxidising agents. Under these conditions the compound is expected to remain stable for an extended period; however, verifying purity by HPLC or NMR before use in critical experiments is recommended.

Is 5-Bromo-2-(3-methoxypropylamino)pyrimidine relevant to kinase inhibitor research?

Yes. Aminopyrimidine scaffolds are extensively represented among kinase inhibitor pharmacophores, as the ring nitrogen atoms and the exocyclic amine can engage in key hydrogen-bonding interactions within ATP-binding sites. The 5-bromo handle provides a synthetic handle for further elaboration of the scaffold via cross-coupling, enabling rapid SAR exploration.

What solvents are recommended for dissolving 5-Bromo-2-(3-methoxypropylamino)pyrimidine?

Polar aprotic solvents such as DMSO, DMF, and acetonitrile are generally suitable for dissolving aminopyrimidine derivatives. For synthetic applications, THF, dioxane, and dichloromethane are commonly used. Aqueous solubility may be limited; addition of a small percentage of DMSO or organic co-solvent may be required for biological assay formulations.

How can I confirm the identity and purity of the received batch?

Identity can be confirmed by ¹H NMR (characteristic pyrimidine ring protons, NH signal, methoxypropyl chain protons) and LC-MS (molecular ion with the characteristic 1:1 ⁷⁹Br/⁸¹Br isotope pattern). Purity is best assessed by reverse-phase HPLC. A batch Certificate of Analysis (CoA) is available from Aladdin Scientific upon request.

References

1. General reference: Joule, J.A.; Mills, K. Heterocyclic Chemistry, 5th ed.; Wiley-Blackwell: Oxford, 2010. (Textbook-level source for pyrimidine chemistry.)
2. General reference: Miyaura, N.; Suzuki, A. Palladium-Catalyzed Cross-Coupling Reactions of Organoboron Compounds. Chem. Rev. 1995, 95, 2457–2483. doi:10.1021/cr00039a007
3. General reference: Buchwald, S.L. et al. Palladium-catalyzed C–N bond forming reactions. Acc. Chem. Res. (Review article – specific volume/page requires verification.)
4. General reference: Cohen, P. Protein kinases — the major drug targets of the twenty-first century? Nat. Rev. Drug Discov. 2002, 1, 309–315. (Context for kinase inhibitor relevance of aminopyrimidine scaffolds.) doi:10.1038/nrd773

Products are supplied for research and development use only. Not for use in humans, animals, diagnosis, or therapy.