4-Chloro-2,6-diaminopyrimidine
[CAS# 156-83-2]

Identification

• Classification: Pharmaceutical intermediate >> Heterocyclic compound intermediate >> Pyrimidine compound >> Chloropyrimidine
• Name: 4-Chloro-2,6-diaminopyrimidine
• Synonyms: 2,6-Diamino-4-chloropyrimidine; 6-Chloropyrimidine-2,4-diamine
• Molecular Formula: C₄H₅ClN₄
• Molecular Weight: 144.56
• CAS Registry Number: 156-83-2
• EC Number: 205-863-9
• SMILES: C1=C(N=C(N=C1Cl)N)N

Properties

• Melting point: 198 °C
• Boiling point: 199-202 °C
• Water solubility: slightly soluble

Safety Data

• Hazard Symbols: GHS07 Warning
• Risk Statements: H302-H315-H319-H332-H335
• Safety Statements: P261-P264-P264+P265-P270-P271-P280-P301+P317-P302+P352-P304+P340-P305+P351+P338-P317-P319-P321-P330-P332+P317-P337+P317-P362+P364-P403+P233-P405-P501

Hazard Classification

Hazard	Class	Category Code	Hazard Statement
Acute toxicity	Acute Tox.	4	H302
Skin irritation	Skin Irrit.	2	H315
Eye irritation	Eye Irrit.	2	H319
Specific target organ toxicity - single exposure	STOT SE	3	H335
Eye irritation	Eye Irrit.	2A	H319

Discovery and Applications

The discovery of 4-chloro-2,6-diaminopyrimidine dates back to the mid-20th century when pyrimidine derivatives were being investigated for medicinal chemistry. The synthesis usually involves chlorination of 2,6-diaminopyrimidine using reagents such as phosphorus oxychloride (POCl3) or sulfonyl chloride (SO3Cl3). This process introduces a chlorine atom at the 4-position of the pyrimidine ring, forming 4-chloro-2,6-diaminopyrimidine. 4-Chloro-2,6-diaminopyrimidine consists of a six-membered pyrimidine ring with chlorine at the 4-position and amino groups at the 2- and 6-positions. This arrangement confers unique chemical reactivity and the potential for a variety of modifications. It typically occurs as a white to off-white crystalline powder that is soluble in organic solvents such as ethanol, methanol, and dimethyl sulfoxide (DMSO), but slightly soluble in water. The presence of electron-donating amino groups and electron-withdrawing chlorine atoms makes it reactive in substitution and addition reactions, facilitating the synthesis of more complex molecules.

4-Chloro-2,6-diaminopyrimidine is a key intermediate in the synthesis of antiviral drugs. It is involved in the construction of nucleoside analogs and other molecules that inhibit viral replication by targeting viral enzymes or interfering with viral DNA/RNA synthesis. The compound is used to develop antimetabolites used in cancer chemotherapy. These antimetabolites mimic natural substrates in cellular processes, disrupt DNA synthesis and induce death of rapidly dividing cancer cells. Its derivatives inhibit bacterial growth by targeting bacterial enzymes or interfering with nucleic acid synthesis, helping to develop new antibiotics.

4-Chloro-2,6-diaminopyrimidine is used in the synthesis of herbicides and fungicides. These compounds disrupt important biological pathways in weeds and fungal pathogens, protect crops and increase agricultural productivity. 4-Chloro-2,6-diaminopyrimidine derivatives are studied for their insecticidal properties. They act by interfering with neurotransmission or other important processes in insect pests, helping to manage pest populations in agricultural and urban environments.

In organic synthesis, 4-chloro-2,6-diaminopyrimidine is a versatile building block. Its reactivity enables the construction of different chemical entities through nucleophilic substitutions, coupling reactions and other transformations.

Ongoing research aims to discover new applications and optimize 4-chloro-2,6-diaminopyrimidine derivatives with enhanced biological activities and is directed toward developing more sustainable and efficient synthetic methods.

References

1962. D. J. Brown and N. W. Jacobsen. J. Chem. Soc. 1962, 3172.

2022. Nano-CoCr2O4 Catalysts Promote the Synthesis of Diamino Pyrimidine Oxide Derivatives. Russian Journal of General Chemistry.
DOI: https://doi.org/10.1134/s1070363222120271

2006. Minoxidil. Pharmaceutical Substances.
URL: https://pharmaceutical-substances.thieme.com/ps/search-results?docUri=KD-13-0156