2,4-Diamino-6-hydroxypyrimidine
[CAS# 56-06-4]

Identification

• Classification: Pharmaceutical intermediate >> Heterocyclic compound intermediate >> Pyrimidine compound >> Hydroxypyrimidine
• Name: 2,4-Diamino-6-hydroxypyrimidine
• Synonyms: 2,6-Diamino-4-pyrimidinol; 2,6-Diamino-4-pyrimidinone
• Molecular Formula: C₄H₆N₄O
• Molecular Weight: 126.11
• CAS Registry Number: 56-06-4
• EC Number: 200-254-4
• SMILES: C1=C(N=C(NC1=O)N)N

Properties

• Solubility: 50mM (water), 100 mM (DMSO) (Expl.)
• Density: 1.6±0.1 g/cm³, Calc.^*
• Melting point: 285-286 °C (Decomp.) (Expl.)
• Index of Refraction: 1.770, Calc.^*
• Boiling Point: 524.0±53.0 °C (760 mmHg), Calc.^*
• Flash Point: 270.7±30.9 °C, Calc.^*

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

Safety Data

• Hazard Symbols: GHS09 Warning
• Risk Statements: H400-H410
• Safety Statements: P273-P391-P501

Hazard Classification

Hazard	Class	Category Code	Hazard Statement
Acute hazardous to the aquatic environment	Aquatic Acute	1	H400
Chronic hazardous to the aquatic environment	Aquatic Chronic	1	H410
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
Acute toxicity	Acute Tox.	4	H302

Discovery and Applications

2,4-Diamino-6-hydroxypyrimidine (C5H6N4O) is a heterocyclic compound featuring a pyrimidine ring with two amino groups at positions 2 and 4 and a hydroxyl group at position 6. It is a derivative of pyrimidine, an important class of compounds in both natural and synthetic chemistry. The discovery of 2,4-diamino-6-hydroxypyrimidine can be traced back to the broader study of pyrimidine derivatives and their applications in biochemistry, pharmacology, and medicine. Pyrimidines, due to their involvement in essential biological processes, have been of great interest to researchers for many decades.

The synthesis of 2,4-diamino-6-hydroxypyrimidine is part of the ongoing exploration of pyrimidine analogs as potential therapeutics. Pyrimidine derivatives are known for their ability to interact with biological molecules, especially in DNA and RNA synthesis, making them vital for the development of drugs targeting various diseases. 2,4-Diamino-6-hydroxypyrimidine is synthesized through the modification of the pyrimidine ring structure, allowing it to incorporate functional groups that are crucial for its biological activity.

One of the most important applications of 2,4-diamino-6-hydroxypyrimidine is in the field of medicinal chemistry. Its structural resemblance to purines and pyrimidines, key components of nucleic acids, makes it a valuable intermediate in the synthesis of antimetabolites, which are compounds that interfere with normal metabolic processes. Specifically, 2,4-diamino-6-hydroxypyrimidine can be utilized in the synthesis of antifolate drugs that inhibit folate metabolism. Folate is essential for DNA and RNA synthesis, and its inhibition has been shown to be an effective strategy for treating cancer and bacterial infections. By blocking folate-dependent enzymes, these drugs prevent the proliferation of cancer cells or pathogenic microorganisms.

In the pharmaceutical industry, 2,4-diamino-6-hydroxypyrimidine is also used as a precursor in the synthesis of compounds that target specific enzymes involved in the folate pathway. These compounds have been developed as chemotherapy agents, targeting fast-growing cancer cells, and as antibiotics for bacterial infections that rely on folate for survival. Additionally, some derivatives of 2,4-diamino-6-hydroxypyrimidine are being studied for their potential antiviral properties, particularly against RNA viruses that rely on the synthesis of nucleic acids for replication.

Another application of 2,4-diamino-6-hydroxypyrimidine is in the development of herbicides. Pyrimidine derivatives have shown promise in controlling weed growth by disrupting the biosynthesis of essential metabolites in plants. By targeting enzymes involved in the folate pathway, herbicides based on 2,4-diamino-6-hydroxypyrimidine can inhibit plant growth and proliferation, offering an efficient means of controlling unwanted vegetation in agricultural settings.

In addition to its role in the pharmaceutical and agricultural industries, 2,4-diamino-6-hydroxypyrimidine also has potential in biochemical research. Its structural characteristics make it a useful tool for studying enzyme inhibition, DNA synthesis, and other metabolic processes. Researchers can use this compound to explore the mechanisms of folate-dependent enzymes and to test new drugs designed to interact with these enzymes. Furthermore, its ability to act as an intermediate in organic synthesis makes it a valuable reagent in the laboratory, especially for the preparation of complex molecules.

In conclusion, 2,4-diamino-6-hydroxypyrimidine is a versatile chemical compound with significant applications in the pharmaceutical, agricultural, and research sectors. Its discovery and synthesis have contributed to the development of antimetabolites, antibiotics, and herbicides, with ongoing research exploring its potential in treating diseases and improving agricultural productivity.

References

2017. Synthesis of pyrido[2,3-d]pyrimidines in the reaction of 6-amino-2,4-dihydroxypyrimidine with chalcones. Synthesis, 49(5).
DOI: 10.1055/s-0036-1588757

2021. A high-throughput screen identifies small molecule modulators of alternative splicing by targeting RNA G-quadruplexes. Proceedings of the National Academy of Sciences, 118(12).
DOI: 10.1073/pnas.2005463117

1988. Effects of 2,4-diamino-6-hydroxypyrimidine, a dihydrofolate reductase inhibitor, on neurotransmitter amine biosynthesis in the rat. Brain Research, 446(2).
DOI: 10.1016/0006-8993(88)91290-5