4,6-Dichloro-5-(4-bromophenyl)pyrimidine
[CAS# 146533-41-7]

Identification

• Classification: Pharmaceutical intermediate >> Heterocyclic compound intermediate >> Pyrimidine compound
• Name: 4,6-Dichloro-5-(4-bromophenyl)pyrimidine
• Synonyms: 5-(4-bromophenyl)-4,6-dichloropyrimidine
• Molecular Formula: C₁₀H₅BrCl₂N₂
• Molecular Weight: 303.97
• CAS Registry Number: 146533-41-7
• EC Number: 807-547-1
• SMILES: C1=CC(=CC=C1C2=C(N=CN=C2Cl)Cl)Br

Properties

• Solubility: Practically insoluble (0.064 g/L) (25 °C), Calc.^*
• Density: 1.677±0.06 g/cm³ (20 °C 760 Torr), Calc.^*
• Index of Refraction: 1.630, Calc.^*
• Boiling Point: 368.7±42.0 °C (760 mmHg), Calc.^*
• Flash Point: 176.8±27.9 °C, Calc.^*

^* Calculated using Advanced Chemistry Development (ACD/Labs) Software V11.02 (©1994-2013 ACD/Labs)

Safety Data

• Hazard Symbols: GHS07 Warning
• Risk Statements: H315-H317-H319
• Safety Statements: P261-P264-P264+P265-P272-P280-P302+P352-P305+P351+P338-P321-P332+P317-P333+P317-P337+P317-P362+P364-P501

Hazard Classification

Hazard	Class	Category Code	Hazard Statement
Skin irritation	Skin Irrit.	2	H315
Skin sensitization	Skin Sens.	1	H317
Eye irritation	Eye Irrit.	2	H319

Discovery and Applications

4,6-Dichloro-5-(4-bromophenyl)pyrimidine is a chemical compound that belongs to the class of substituted pyrimidines, which are known for their diverse applications in pharmaceuticals and organic synthesis. This particular compound features two chlorine atoms at positions 4 and 6 of the pyrimidine ring, and a bromophenyl group attached at position 5. The combination of halogen substituents and an aromatic group in its structure makes 4,6-dichloro-5-(4-bromophenyl)pyrimidine an interesting molecule for a variety of synthetic and medicinal purposes.

The discovery of 4,6-dichloro-5-(4-bromophenyl)pyrimidine is part of ongoing research into the synthesis of bioactive pyrimidine derivatives. Pyrimidines are a well-known class of heterocyclic compounds with wide-ranging biological activity, including antiviral, anticancer, and anti-inflammatory properties. Researchers have long been interested in modifying the pyrimidine ring to create derivatives with improved selectivity or potency. The introduction of halogens, like chlorine and bromine, is a common strategy to modify the electronic properties of the molecule, potentially enhancing its biological activity or enabling specific interactions with biological targets.

4,6-Dichloro-5-(4-bromophenyl)pyrimidine has found applications in medicinal chemistry, especially in the development of kinase inhibitors. Kinases are enzymes that play critical roles in cellular signaling, and their dysregulation is a hallmark of many diseases, including cancer. By introducing halogens and a phenyl group, this compound can be tuned to interact with the ATP-binding sites of certain kinases, making it a useful scaffold for designing targeted therapies. It has been studied for its potential in developing drugs that can selectively inhibit cancer cell growth by targeting specific kinases involved in the disease's progression.

Beyond its pharmaceutical applications, 4,6-dichloro-5-(4-bromophenyl)pyrimidine is also valuable in the field of organic synthesis. The halogenated pyrimidine structure is a useful intermediate for the preparation of other bioactive molecules. Its reactivity, particularly in nucleophilic substitution reactions, makes it a versatile building block for the construction of more complex compounds. Additionally, the bromophenyl group can be employed in cross-coupling reactions, such as Suzuki or Heck reactions, to create new compounds with desired functional groups or structural features.

This compound also plays a role in the development of agrochemicals, particularly herbicides and pesticides. The pyrimidine backbone is found in a variety of agrochemical agents, and halogenated derivatives like 4,6-dichloro-5-(4-bromophenyl)pyrimidine are often incorporated into herbicide formulations to enhance their efficacy. The ability to selectively target specific biochemical pathways in plants or pests is crucial for the development of effective and environmentally friendly agrochemicals, and this compound's properties make it an attractive candidate for further research.

In summary, 4,6-dichloro-5-(4-bromophenyl)pyrimidine is a compound of significant interest due to its potential applications in pharmaceuticals, organic synthesis, and agrochemicals. Its halogenated structure, particularly the combination of chlorine and bromine atoms, provides opportunities for designing new, bioactive molecules with enhanced selectivity and potency. Its utility in synthetic chemistry and drug development continues to drive research in these areas, with promising applications in the treatment of cancer and other diseases.

References

2014. Macitentan. Pharmaceutical Substances.
URL: https://pharmaceutical-substances.thieme.com/ps/search-results?docUri=KD-13-0200

2018. Improved and single-pot process for the synthesis of macitentan, an endothelin receptor antagonist, via lithium amide-mediated nucleophilic substitution. Monatshefte für Chemie - Chemical Monthly, 149(2).
DOI: 10.1007/s00706-017-2098-2