Chemical Identity and Structure

2-Chloro-5-fluoro-4-methoxy-6-methylpyrimidine is a substituted pyrimidine heterocycle with the molecular formula C₆H₆ClFN₂O and a molecular weight of approximately 176.57 g/mol. The compound features a six-membered aromatic ring containing two nitrogen atoms at positions 1 and 3. Four distinct substituents decorate the ring: a chlorine atom at C-2, a fluorine atom at C-5, a methoxy group (–OCH₃) at C-4, and a methyl group (–CH₃) at C-6.

The co-presence of both a chloro and a fluoro leaving group on the electron-deficient pyrimidine ring endows the molecule with differential reactivity: the C-2 chloro position is generally more susceptible to nucleophilic aromatic substitution (S_NAr) under mild conditions, while the C-5 fluorine, activated by the flanking ring nitrogens, can participate in selective displacement or palladium-catalyzed cross-coupling reactions under appropriate conditions. The methoxy group at C-4 can be displaced under more forcing conditions, providing further synthetic flexibility.

Physicochemical Properties and Stability

As a low-molecular-weight halogenated heteroaromatic compound, 2-Chloro-5-fluoro-4-methoxy-6-methylpyrimidine is expected to be a solid or low-melting solid at ambient temperature, though researchers should consult the certificate of analysis (CoA) supplied with Aladdin product C734312 for confirmed physical state, melting point, and purity data.

The compound is likely soluble in common polar aprotic organic solvents such as dimethyl sulfoxide (DMSO), N,N-dimethylformamide (DMF), tetrahydrofuran (THF), and dichloromethane (DCM), and sparingly soluble in water due to the lipophilic methyl and methoxy substituents. The C–Cl and C–F bonds on the electron-poor ring are stable under standard storage conditions but are reactive toward nucleophiles under synthetic conditions.

For long-term stability, the compound should be stored under inert atmosphere (nitrogen or argon) in a sealed container, away from moisture and strong nucleophiles. Refrigerated storage (2–8 °C) or freezer storage (−20 °C) in a cool, dry, well-ventilated area is recommended to prevent degradation.

Synthetic Applications and Reactivity

Halogenated pyrimidines such as 2-Chloro-5-fluoro-4-methoxy-6-methylpyrimidine are highly valued as building blocks in medicinal chemistry, drug discovery, and agrochemical research. The differentiated leaving groups at C-2 (Cl) and C-5 (F) allow sequential, chemoselective functionalization of the ring in multi-step synthesis.

Nucleophilic Aromatic Substitution (S_NAr): The electron-withdrawing ring nitrogen atoms activate the C-2 chloro position toward S_NAr with amines, alkoxides, and thiolates. This reaction can typically be performed under mild to moderate conditions, providing access to 2-amino, 2-alkoxy, or 2-thioether pyrimidine analogs.

Cross-Coupling Reactions: The C-2 C–Cl bond is compatible with palladium-catalyzed cross-coupling reactions, including Suzuki-Miyaura, Buchwald-Hartwig amination, and Negishi couplings, enabling introduction of aryl, heteroaryl, or amino substituents at C-2.

Selective C-5 Fluorine Displacement: Under appropriate conditions, the C-5 fluorine can be selectively displaced, offering an orthogonal handle for further diversification of the pyrimidine scaffold.

These attributes make C734312 a useful intermediate for constructing libraries of pyrimidine-containing drug candidates, particularly in projects targeting kinases, GPCRs, or other therapeutically relevant protein classes where pyrimidine motifs are prevalent.

Safe Handling, Storage, and Regulatory Guidance

Personal Protective Equipment (PPE): When handling 2-Chloro-5-fluoro-4-methoxy-6-methylpyrimidine, wear appropriate PPE including chemical-resistant gloves (e.g., nitrile), safety goggles, and a laboratory coat. Handling should be performed in a fume hood to minimize inhalation exposure to dust or vapors.

Hazard Considerations: As a halogenated organic compound, it may be irritating to skin, eyes, and respiratory tract. Researchers must consult the Safety Data Sheet (SDS) provided by Aladdin Scientific for the specific hazard classification, GHS pictograms, first-aid measures, and disposal requirements applicable to C734312 before use.

Storage: Store in a tightly sealed container under inert gas at 2–8 °C (or −20 °C for extended storage), away from heat sources, light, moisture, and incompatible materials such as strong bases, strong nucleophiles, and oxidizing agents.

Waste Disposal: Dispose of waste material in accordance with local, regional, and national regulations governing halogenated organic waste. Do not pour into drains or water systems.