Methyl 2-Bromopyrimidine-4-Carboxylate: Properties & Lab Guide

Methyl 2-bromopyrimidine-4-carboxylate is a versatile halogenated pyrimidine building block widely employed in medicinal chemistry and heterocyclic synthesis, offering a reactive C–Br bond and an electrophilic ester handle for diverse chemical transformations.

Chemical Name

Methyl 2-bromopyrimidine-4-carboxylate

Molecular Formula

C6H5BrN2O2

Molecular Weight

217.02 g/mol

Key Functional Groups

Aryl bromide, methyl ester, pyrimidine ring

Primary Applications

Palladium-catalyzed cross-coupling (Suzuki, Negishi), nucleophilic aromatic substitution, pharmaceutical intermediate synthesis

Storage Recommendation

Store in a cool, dry, well-ventilated area away from light and moisture; sealed container recommended

Aladdin SKU

M734855

Chemical Identity and Physicochemical Properties

Methyl 2-bromopyrimidine-4-carboxylate is a halogenated pyrimidine derivative with the molecular formula C₆H₅BrN₂O₂ and a molecular weight of approximately 217.02 g/mol. The compound features a six-membered pyrimidine ring bearing a bromine substituent at the 2-position and a methyl ester group at the 4-position.

The presence of two ring nitrogen atoms renders the pyrimidine ring electron-deficient, which significantly activates the C–Br bond toward oxidative addition in transition-metal-catalyzed reactions and also facilitates nucleophilic aromatic substitution at the 2-position. The methyl ester at the 4-position serves as an additional electrophilic handle, enabling condensation, hydrolysis to the corresponding carboxylic acid, or conversion to amides and other derivatives.

The compound is typically a solid at room temperature. It is soluble in common organic solvents such as dichloromethane, tetrahydrofuran, dimethyl sulfoxide (DMSO), and N,N-dimethylformamide (DMF), and has limited solubility in water due to its hydrophobic character.

Note: Specific melting point, boiling point, and density values should be verified against the certificate of analysis (CoA) supplied with each lot.

Synthetic Applications and Reaction Protocols

Methyl 2-bromopyrimidine-4-carboxylate is a valuable building block in modern synthetic chemistry, particularly in the construction of complex nitrogen-containing heterocycles relevant to pharmaceutical discovery.

1. Palladium-Catalyzed Cross-Coupling Reactions
The aryl bromide functionality participates readily in Suzuki–Miyaura, Negishi, Stille, and Buchwald–Hartwig coupling reactions. Typical Suzuki conditions employ a palladium source (e.g., Pd(PPh₃)₄ or Pd(dppf)Cl₂), an aryl or heteroaryl boronic acid partner, an inorganic base (e.g., K₂CO₃ or Cs₂CO₃), and a polar solvent system such as DMF/water or dioxane/water, typically at 80–100 °C under inert atmosphere.

2. Nucleophilic Aromatic Substitution (SNAr)
The electron-deficient pyrimidine ring is amenable to SNAr at the 2-position. Amines, alkoxides, and thiolates can displace the bromide under mild to moderate conditions, providing access to 2-amino, 2-alkoxy, and 2-thioether pyrimidine-4-carboxylate derivatives without the need for a metal catalyst.

3. Ester Transformations
The methyl ester can be hydrolyzed to the corresponding carboxylic acid using aqueous lithium hydroxide or sodium hydroxide, followed by acidification. The acid can subsequently be converted to amides via coupling reagents (e.g., HATU, EDC/HOBt), enabling the synthesis of pyrimidine-4-carboxamides that are prevalent scaffolds in kinase inhibitor programs.

All reaction conditions should be optimized at the laboratory scale before scale-up. Conduct reactions under inert atmosphere where moisture or oxygen sensitivity is a concern.

Safe Handling, Storage, and Disposal

Handling Precautions
Methyl 2-bromopyrimidine-4-carboxylate should be handled with appropriate personal protective equipment (PPE), including chemical-resistant gloves, safety goggles, and a laboratory coat. Operations that may generate dust or aerosols should be conducted in a fume hood. Avoid inhalation of dust or vapors and contact with skin, eyes, and clothing.

Storage Conditions
Store in a tightly sealed container in a cool (recommended: 2–8 °C or room temperature per CoA specification), dry, and well-ventilated location, protected from light and moisture. Keep away from incompatible materials including strong oxidizers, strong bases, and strong acids. Observe the expiry date stated on the label.

Stability
The compound is generally stable under recommended storage conditions. Prolonged exposure to moisture may lead to hydrolysis of the ester group. Re-seal containers promptly after use.

Disposal
Dispose of waste material in accordance with applicable local, regional, and national regulations for halogenated organic compounds. Do not discharge into drains or the environment. Consult the Safety Data Sheet (SDS) for full hazard information and emergency procedures before use.

The SDS and CoA for Aladdin product M734855 should be reviewed before working with this compound.

Quality, Purity, and Analytical Verification

For sensitive synthetic applications, verifying the purity and identity of Methyl 2-bromopyrimidine-4-carboxylate prior to use is strongly recommended. The following analytical techniques are applicable:

HPLC Purity Analysis
Reverse-phase HPLC (C18 column, UV detection at 254 nm or appropriate wavelength) is the standard method for purity determination. The Aladdin Certificate of Analysis (CoA) states the guaranteed purity for each lot of M734855; researchers should request the CoA before use.

NMR Spectroscopy
¹H NMR and ¹³C NMR in deuterated solvents (e.g., CDCl₃ or DMSO-d₆) confirm compound identity. Key signals include aromatic/heteroaromatic protons on the pyrimidine ring and the methyl ester singlet (typically ~3.9–4.0 ppm in CDCl₃).

Mass Spectrometry
ESI-MS or APCI-MS provides the molecular ion confirming the molecular weight of 217.02 g/mol, with the characteristic isotope pattern of a monobrominated compound (M and M+2 peaks in approximately 1:1 ratio).

Melting Point
Determination of the melting point and comparison against the specification range on the CoA is a simple and effective identity check for this solid compound.

Contact Aladdin Scientific technical support for lot-specific analytical data or custom purity requirements.

Frequently asked questions

What are the main uses of Methyl 2-bromopyrimidine-4-carboxylate in organic synthesis?

Methyl 2-bromopyrimidine-4-carboxylate is primarily used as a building block in palladium-catalyzed cross-coupling reactions (such as Suzuki–Miyaura coupling), nucleophilic aromatic substitution, and as a precursor for pyrimidine-4-carboxylic acid and carboxamide derivatives. These transformations make it a key intermediate in pharmaceutical and agrochemical research.

How should Methyl 2-bromopyrimidine-4-carboxylate be stored to maintain its stability?

The compound should be stored in a tightly sealed container in a cool, dry, and well-ventilated location away from light and moisture. Prolonged exposure to moisture can promote hydrolysis of the methyl ester group. Always reseal the container promptly after use and consult the Aladdin CoA for lot-specific storage temperature recommendations.

Can Methyl 2-bromopyrimidine-4-carboxylate undergo nucleophilic aromatic substitution without a metal catalyst?

Yes. The electron-withdrawing pyrimidine ring nitrogen atoms activate the 2-position C–Br bond toward SNAr reactions. Nucleophiles such as primary and secondary amines, alkoxides, and thiolates can displace the bromide under relatively mild conditions without requiring a palladium or other transition-metal catalyst, providing a metal-free route to 2-substituted pyrimidine-4-carboxylate derivatives.

What solvents are recommended for reactions involving Methyl 2-bromopyrimidine-4-carboxylate?

Common solvents include DMF, DMSO, THF, dioxane, and dichloromethane, depending on the reaction type. For Suzuki coupling, DMF/water or dioxane/water mixtures are typically preferred. For SNAr reactions with amines, DMSO or DMF at elevated temperatures often give good results. Avoid protic solvents that may promote ester hydrolysis under basic conditions.

References

1. Miyaura, N.; Suzuki, A. Palladium-Catalyzed Cross-Coupling Reactions of Organoboron Compounds. Chemical Reviews, 1995, 95, 2457–2483. doi:10.1021/cr00039a007
2. Clayden, J.; Greeves, N.; Warren, S. Organic Chemistry, 2nd ed.; Oxford University Press: Oxford, 2012. Chapter on Nucleophilic Aromatic Substitution.
3. Aladdin Scientific. Product Certificate of Analysis: Methyl 2-bromopyrimidine-4-carboxylate, SKU M734855.

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