2,6-Dichloropyrimidine-4,5-diamine: Properties & Applications

2,6-Dichloropyrimidine-4,5-diamine is a bifunctionally activated pyrimidine building block widely employed in medicinal chemistry and heterocyclic synthesis due to its dual electrophilic chloro substituents and nucleophilic diamine moiety.

IUPAC Name

2,6-Dichloropyrimidine-4,5-diamine

Molecular Formula

C₄H₄Cl₂N₄

Molecular Weight

179.00 g/mol

CAS Number

Needs review — not confirmed in source material

Key Functional Groups

Two electrophilic C–Cl bonds at positions 2 and 6; two primary amine groups at positions 4 and 5

Primary Research Use

Synthetic intermediate for purines, fused heterocycles, and bioactive small molecules

SKU

D696710

Chemical Structure and Properties

2,6-Dichloropyrimidine-4,5-diamine possesses a pyrimidine ring substituted at the 2- and 6-positions with chlorine atoms and at the 4- and 5-positions with primary amine groups. This combination of electron-withdrawing chloro substituents and electron-donating amine groups creates a molecule with amphoteric reactivity, making it exceptionally versatile in organic synthesis.

The two chlorine atoms render the ring highly electron-deficient, activating these positions toward nucleophilic aromatic substitution (SNAr) reactions. The vicinal 4,5-diamine arrangement facilitates cyclization reactions with electrophilic coupling partners, providing direct access to fused bicyclic systems such as purines and imidazopyrimidines.

The compound is typically a solid at room temperature. It should be stored in a cool, dry environment away from moisture and strong oxidizing agents to maintain reagent integrity. Specific melting point and solubility data should be confirmed from the product certificate of analysis.

Synthesis and Reactivity

The dual electrophilic positions of 2,6-Dichloropyrimidine-4,5-diamine make it an outstanding scaffold for sequential or selective functionalization. Under controlled reaction conditions, one chlorine can be selectively displaced by an amine, thiol, or alkoxide nucleophile, leaving the second chlorine available for a subsequent transformation. This stepwise approach is frequently exploited in medicinal chemistry programs targeting kinase inhibitors and other bioactive heterocycles.

The 4,5-diamine unit readily undergoes condensation with carbonyl compounds, acid chlorides, orthoesters, or nitriles to form five- or six-membered fused rings. For example, reaction with formate equivalents or formamidine derivatives yields the purine skeleton, the core scaffold of numerous nucleoside analogues and antiviral agents. Reaction with alpha-ketoaldehydes or beta-dicarbonyl compounds can furnish imidazo[4,5-d]pyrimidine or related fused systems.

Researchers should note that amine groups may require protection in multi-step sequences to control chemoselectivity. Standard amine protecting groups such as Boc, Cbz, or acyl groups are compatible with this scaffold under appropriate conditions.

Research and Pharmaceutical Applications

2,6-Dichloropyrimidine-4,5-diamine is a valued intermediate in the synthesis of purine analogues, which form the structural basis of adenine, guanine, and their derivatives. Many clinically significant drugs — including antivirals, antineoplastics, and immunosuppressants — incorporate a purine or deazapurine core that can be accessed via this diaminodichloropyrimidine precursor.

In kinase inhibitor discovery, the pyrimidine scaffold is a privileged motif for binding to the ATP-binding site of protein kinases. The chlorine atoms of this compound serve as handles for introducing diverse pharmacophoric groups through cross-coupling reactions (e.g., Buchwald-Hartwig amination, Suzuki-Miyaura coupling) or direct nucleophilic displacement, enabling rapid exploration of structure-activity relationships (SAR).

Beyond pharmaceutical research, this compound finds utility in agrochemical development and materials science contexts where nitrogen-rich heterocycles are required. Its bifunctional reactivity supports the creation of dendrimers, coordination polymers, and ligands for transition-metal catalysis.

Handling, Storage, and Safety Considerations

As with all fine chemical reagents containing aromatic amines and reactive chloro groups, 2,6-Dichloropyrimidine-4,5-diamine should be handled with appropriate personal protective equipment (PPE), including nitrile gloves, safety glasses, and a laboratory coat. Operations generating dust or aerosols should be conducted in a well-ventilated fume hood.

The compound should be stored in a tightly sealed container under cool and dry conditions, protected from light, heat, and moisture. Incompatibility with strong acids, strong bases, and oxidizing agents should be observed. Researchers are advised to consult the Safety Data Sheet (SDS) provided by Aladdin Scientific before use for detailed hazard information, first-aid measures, and disposal procedures.

Specific toxicological data for this compound are limited in the open literature; handle as a potentially irritating substance until full characterization data are available. All waste should be disposed of in accordance with local institutional and regulatory guidelines for chemical waste.

Frequently asked questions

What is 2,6-Dichloropyrimidine-4,5-diamine used for in research?

It is primarily used as a versatile synthetic building block for constructing purine analogues, fused heterocyclic systems, and pharmacologically active small molecules. Its dual chloro substituents and diamine functionality allow sequential functionalization, making it valuable in medicinal chemistry, particularly for kinase inhibitor and antiviral compound development.

How should 2,6-Dichloropyrimidine-4,5-diamine be stored to maintain stability?

The compound should be stored in a tightly sealed container under cool, dry conditions, away from light, moisture, strong acids, strong bases, and oxidizing agents. Always consult the product's Safety Data Sheet and certificate of analysis for specific storage temperature recommendations.

Can both chlorine atoms in 2,6-Dichloropyrimidine-4,5-diamine be selectively substituted?

Yes. Under carefully controlled reaction conditions — including temperature, choice of nucleophile, and solvent — it is possible to achieve mono-substitution at one chlorine position while leaving the other intact for a subsequent reaction step. This selectivity is routinely exploited in multi-step synthesis to introduce different substituents at the 2- and 6-positions.

What is the molecular formula and molecular weight of 2,6-Dichloropyrimidine-4,5-diamine?

The molecular formula is C₄H₄Cl₂N₄ and the molecular weight is approximately 179.00 g/mol. Researchers should verify these values against the certificate of analysis supplied with each batch.

Is 2,6-Dichloropyrimidine-4,5-diamine suitable for cross-coupling reactions?

Yes, the C–Cl bonds at positions 2 and 6 can participate in palladium-catalyzed cross-coupling reactions such as Buchwald-Hartwig amination and Suzuki-Miyaura coupling, as well as direct nucleophilic aromatic substitution. These reactions are commonly used to diversify the pyrimidine scaffold in drug discovery programs.

References

1. March, J. Advanced Organic Chemistry: Reactions, Mechanisms, and Structure. Wiley-Interscience. General reference for nucleophilic aromatic substitution chemistry.
2. Joule, J.A.; Mills, K. Heterocyclic Chemistry, 5th ed. Wiley-Blackwell. General reference for pyrimidine and purine chemistry.
3. Aladdin Scientific. Product information for 2,6-Dichloropyrimidine-4,5-diamine, SKU D696710. Aladdin Scientific internal source.

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