N2,N2,6-trimethyl-3,6-dihydro-1,3,5-triazine-2,4-diamine
[CAS# 757178-57-7]

Identification

• Classification: Pharmaceutical intermediate >> Heterocyclic compound intermediate >> Pyrimidine compound >> Amine
• Name: N2,N2,6-trimethyl-3,6-dihydro-1,3,5-triazine-2,4-diamine
• Synonyms: 6-N,6-N,4-trimethyl-1,4-dihydro-1,3,5-triazine-2,6-diamine; imeglimin
• Molecular Formula: C₆H₁₃N₅
• Molecular Weight: 155.20
• CAS Registry Number: 757178-57-7
• SMILES: CC1N=C(NC(=N1)N(C)C)N

Properties

• Density: 1.3±0.1 g/cm³ Calc.^*
• Boiling point: 239.9±23.0 ºC 760 mmHg (Calc.)^*
• Flash point: 98.9±22.6 ºC (Calc.)^*
• Index of refraction: 1.622 (Calc.)^*

^* Calculated using Advanced Chemistry Development (ACD/Labs) Software.

Discovory and Applicatios

N₂,N₂,6-trimethyl-3,6-dihydro-1,3,5-triazine-2,4-diamine is a synthetic heterocyclic compound belonging to the class of substituted triazines. Its molecular structure consists of a 1,3,5-triazine ring partially saturated at the 3 and 6 positions, with amino groups at positions 2 and 4. The nitrogen at the 2-position is further substituted with two methyl groups (N₂,N₂-dimethyl), and the 6-position of the triazine ring bears a single methyl group. This configuration gives the compound a distinct chemical identity as a methylated diaminodihydrotriazine.

The triazine ring system is a six-membered heterocycle composed of three nitrogen atoms and three carbon atoms arranged alternately. Substituted triazines are widely studied and utilized in both chemical and pharmaceutical contexts due to their structural stability and ability to engage in a wide variety of reactions. Diaminotriazines in particular are known for their bioactivity and serve as important intermediates or pharmacophores in drug design, especially in antiviral, anticancer, and antimicrobial research.

N₂,N₂,6-trimethyl-3,6-dihydro-1,3,5-triazine-2,4-diamine is most prominently recognized as a key intermediate in the synthesis of the antimalarial drug pyrimethamine. Pyrimethamine is a 2,4-diaminopyrimidine derivative that inhibits dihydrofolate reductase (DHFR), thereby interfering with folic acid metabolism in Plasmodium species. During its industrial preparation, the triazine compound serves as a precursor that undergoes condensation and ring transformation reactions to yield the final pyrimidine-based therapeutic.

The synthesis of this triazine compound typically involves the cyclization of appropriate amidine or guanidine derivatives with formaldehyde or other one-carbon electrophiles, under controlled acidic or basic conditions. The presence of methyl groups on both the nitrogen and carbon positions enhances the lipophilicity and alters the electronic properties of the molecule, which can influence both its reactivity and potential interactions in biological systems.

Though not widely applied on its own in clinical or commercial products, the compound is important in chemical research and development due to its utility in heterocycle synthesis. It has been used in laboratories studying structure-activity relationships (SAR) of triazine analogs and is referenced in patents and scientific literature dealing with antifolate drug development.

The triazine core’s similarity to natural purine and pyrimidine bases allows for potential binding to enzymes and receptors involved in nucleic acid synthesis, which is why related structures often show activity against proliferative diseases or pathogens. However, the biological activity of N₂,N₂,6-trimethyl-3,6-dihydro-1,3,5-triazine-2,4-diamine itself has not been widely characterized or reported beyond its synthetic applications.

In summary, N₂,N₂,6-trimethyl-3,6-dihydro-1,3,5-triazine-2,4-diamine is a methylated diaminotriazine compound primarily used as a synthetic intermediate in the preparation of pharmaceutical agents such as pyrimethamine. It represents an example of functionalized triazines with significance in medicinal chemistry and heterocyclic synthesis due to its stable ring system and versatile reactivity.

References

2008. Towards Metformin Prodrugs. Synthesis, 2008(20).
DOI: 10.1055/s-0028-1083603