6-Chloro-2-methylpyrimidin-4-amine: Properties & Lab FAQ

6-Chloro-2-methylpyrimidin-4-amine is a halogenated aminopyrimidine building block widely used in medicinal chemistry and heterocyclic synthesis as a versatile electrophilic scaffold for the preparation of biologically active compounds.

CAS Number

5734-64-5

Molecular Formula

C5H6ClN3

Molecular Weight

143.57 g/mol

IUPAC Name

6-chloro-2-methylpyrimidin-4-amine

Appearance

White to off-white crystalline solid

Aladdin SKU

C174984

What Is 6-Chloro-2-methylpyrimidin-4-amine?

6-Chloro-2-methylpyrimidin-4-amine (CAS 5734-64-5, MW 143.57 g/mol, molecular formula C₅H₆ClN₃) is a difunctional pyrimidine derivative bearing an amino group at the 4-position, a chloro substituent at the 6-position, and a methyl group at the 2-position. This combination of functional groups makes the compound a particularly versatile intermediate in synthetic organic chemistry.

The electron-withdrawing chlorine atom activates the ring toward nucleophilic aromatic substitution (S_NAr), while the primary amine provides an additional handle for acylation, reductive amination, or condensation reactions. As a result, this scaffold is frequently employed in the construction of kinase inhibitors, antiviral agents, and other pharmacologically relevant heterocyclic architectures.

Physicochemical Properties and Solubility

6-Chloro-2-methylpyrimidin-4-amine is typically obtained as a white to off-white crystalline solid. Key physicochemical characteristics relevant to laboratory handling include:

• Molecular Weight: 143.57 g/mol
• Molecular Formula: C₅H₆ClN₃
• LogP (estimated): Moderately lipophilic due to the chloro and methyl substituents
• Solubility: Soluble in polar aprotic solvents such as DMSO, DMF, and acetonitrile; sparingly soluble in water; slightly soluble in ethanol and methanol

For stock solution preparation, DMSO is generally recommended as the primary solvent. When aqueous solubility is required for biological assays, it is advisable to prepare a concentrated DMSO stock and dilute into aqueous buffer immediately before use, keeping the final DMSO concentration below 0.1% to minimize cytotoxicity artifacts.

Storage, Stability, and Handling Precautions

Storage: Store 6-Chloro-2-methylpyrimidin-4-amine in a tightly sealed container at room temperature (15–25 °C) in a cool, dry, well-ventilated location away from light, moisture, and incompatible materials such as strong oxidizers and strong acids. Long-term storage at 2–8 °C under inert atmosphere (argon or nitrogen) is recommended to maximize shelf life.

Stability: The compound is generally stable under recommended storage conditions. The C–Cl bond may be susceptible to hydrolysis under strongly acidic or basic aqueous conditions; avoid prolonged exposure to such environments.

Handling Precautions: As with all aromatic amines and halogenated heterocycles, handle with appropriate personal protective equipment (PPE) including nitrile gloves, laboratory coat, and eye protection. Work in a fume hood when weighing or dissolving the compound. Consult the Safety Data Sheet (SDS) before use and follow all applicable local regulations for disposal of chemical waste.

Synthetic Applications and Reactivity

The dual functionality of 6-Chloro-2-methylpyrimidin-4-amine makes it a highly sought-after building block in medicinal and process chemistry:

• Nucleophilic Aromatic Substitution (S_NAr): The 6-chloro group undergoes facile displacement by amines, thiols, alcohols, and carbon nucleophiles under mild to moderate conditions, enabling rapid library synthesis of 4-amino-2-methylpyrimidin-6-yl derivatives.
• Transition-Metal-Catalyzed Cross-Coupling: The aryl chloride participates in Buchwald–Hartwig amination, Suzuki–Miyaura coupling (after boronate formation or with suitable partners), and Ullmann-type reactions, broadening the accessible chemical space.
• Acylation and Sulfonylation of the Amino Group: The 4-amino group can be acylated with acid chlorides or anhydrides, or sulfonylated with sulfonyl chlorides, to yield amide and sulfonamide derivatives relevant to drug discovery programs.
• Heterocycle Annulation: Condensation of the amino group with bifunctional electrophiles (e.g., β-keto esters, aldehydes) can furnish fused bicyclic or polycyclic heterocyclic systems.

These reaction pathways have been exploited in the preparation of various kinase inhibitor scaffolds, antimicrobial agents, and other bioactive small molecules documented in the primary literature.

Ordering, Purity, and Quality Specifications

Aladdin Scientific offers 6-Chloro-2-methylpyrimidin-4-amine under SKU C174984. When placing an order or evaluating the reagent, consider the following quality-related points:

• Purity: Confirm the certificate of analysis (CoA) for the specific lot; typical analytical methods include HPLC, GC, or ¹H NMR. Contact Aladdin technical support for lot-specific purity data.
• Available Pack Sizes: Multiple pack sizes may be available to suit both small-scale discovery and larger process chemistry needs. Check the product page for current stock and pricing.
• Documentation: CoA, SDS, and structural confirmation data (NMR, MS) are available upon request or via the product page.
• Custom Quantities: For bulk requirements beyond standard pack sizes, contact Aladdin's custom synthesis or bulk procurement team for a quotation.

To place an order, visit the Aladdin Scientific website, search for SKU C174984, or contact your regional sales representative. For technical enquiries regarding reaction conditions, compatibility, or analytical data, the Aladdin technical support team is available to assist.

Frequently asked questions

What is the CAS number for 6-Chloro-2-methylpyrimidin-4-amine?

The CAS registry number for 6-Chloro-2-methylpyrimidin-4-amine is 5734-64-5. It is available from Aladdin Scientific under SKU C174984.

What solvents are recommended for dissolving 6-Chloro-2-methylpyrimidin-4-amine?

6-Chloro-2-methylpyrimidin-4-amine dissolves well in polar aprotic solvents such as DMSO, DMF, and acetonitrile. It has limited water solubility; for aqueous-based assays, prepare a concentrated DMSO stock and dilute into buffer just before use, keeping the final DMSO content below 0.1%.

How should 6-Chloro-2-methylpyrimidin-4-amine be stored to maintain stability?

Store the compound in a tightly sealed container at room temperature (15–25 °C) in a cool, dry, dark location. For long-term storage, 2–8 °C under inert atmosphere (nitrogen or argon) is recommended. Avoid exposure to strong acids, strong bases, moisture, and prolonged light.

Can the chloro group of 6-Chloro-2-methylpyrimidin-4-amine be selectively substituted?

Yes. The 6-chloro substituent is activated toward nucleophilic aromatic substitution (SᵊAr) due to the electron-deficient pyrimidine ring, enabling selective displacement with amines, thiols, and other nucleophiles under mild conditions. The 4-amino group can be independently functionalized via acylation or sulfonylation, offering orthogonal reactivity for sequential elaboration of the scaffold.

What personal protective equipment (PPE) is required when handling this compound?

Use nitrile gloves, a laboratory coat, and chemical splash goggles when handling 6-Chloro-2-methylpyrimidin-4-amine. All weighing and dissolution operations should be performed in a well-ventilated fume hood. Consult the Safety Data Sheet (SDS) for complete hazard information and emergency procedures.

What is the molecular weight and molecular formula of 6-Chloro-2-methylpyrimidin-4-amine?

The molecular formula is C5H6ClN3 and the molecular weight is 143.57 g/mol. These values are important for calculating molar quantities when preparing reaction mixtures or stock solutions.

References

1. CAS Registry. 6-Chloro-2-methylpyrimidin-4-amine. CAS RN 5734-64-5. SciFinder / CAS Common Chemistry.
2. March, J. Advanced Organic Chemistry: Reactions, Mechanisms, and Structure, 4th ed.; Wiley: New York, 1992. (General reference for SᵊAr reactions of halopyrimidines.)
3. Joule, J. A.; Mills, K. Heterocyclic Chemistry, 5th ed.; Wiley-Blackwell: Oxford, 2010. (Reference for pyrimidine reactivity and synthetic applications.)

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