Production Method 1

13939-06-5

3932-97-6

176214-12-3

2375204-83-2

958452-21-6

Reaction Conditions

1.1 Solvents: Acetonitrile ,  Water ;  16 h, pH 9.5, rt → 45 °C
1.2 Reagents: Sodium chloride Solvents: Ethanol ;  overnight, -20 °C
1.3 Reagents: Cesium hydroxide Catalysts: Palladate(1-), [2′-(amino-κN)[1,1′-biphenyl]-2-yl-κC]chloro[2′-(dicyclohexylphos… Solvents: 1-Methoxy-2-propanol ,  Water ;  15 h, 80 °C

Reference

Palladium-Catalyzed Hydroxycarbonylation of (Hetero)aryl Halides for DNA-Encoded Chemical Library Synthesis

Li, Jian-Yuan; Miklossy, Gabriella; Modukuri, Ram K.; Bohren, Kurt M.; Yu, Zhifeng; et al, Bioconjugate Chemistry, 2019, 30(8), 2209-2215

5-(Trifluoromethyl)pyrimidine Raw materials

• Hexacarbonylmolybdenum
• 2,4-Dichloro-5-(trifluoromethyl)pyrimidine

5-(Trifluoromethyl)pyrimidine Preparation Products

• 5-(Trifluoromethyl)pyrimidine-4-carboxylic acid (2375204-83-2)
• 4-Chloro-5-(trifluoromethyl)pyrimidine (958452-21-6)
• 5-(Trifluoromethyl)pyrimidine (176214-12-3)

• 1. Heterocyclic polyfluoro-compounds. Part XIX. Synthesis of and nucleophilic substitution in some 2,4,6-trifluoropyrimidines; formation of trifluoromethylpyrimidines by pyrolysis of tetrafluoropyrimidine
  R. E. Banks,D. S. Field,R. N. Haszeldine J. Chem. Soc. C 1970 1280
• 2. Lead tetraacetate mediated one pot oxidative cleavage and acetylation reaction: an approach to apio and homologated apio pyrimidine nucleosides and their anticancer activity
  Amarendra Panda,Sehbanul Islam,Manas Kumar Santra,Shantanu Pal RSC Adv. 2015 5 82450
• 3. Electrochemical Minisci-type trifluoromethylation of electron-deficient heterocycles mediated by bromide ions
  Gui-Yuan Dou,Yang-Ye Jiang,Kun Xu,Cheng-Chu Zeng Org. Chem. Front. 2019 6 2392

Introduction to 5-(Trifluoromethyl)pyrimidine (CAS No. 176214-12-3) and Its Emerging Applications in Chemical Biology and Medicine

5-(Trifluoromethyl)pyrimidine, a fluorinated heterocyclic compound with the CAS number 176214-12-3, has garnered significant attention in the field of chemical biology and medicinal chemistry due to its versatile structural framework and functional properties. The presence of a trifluoromethyl group at the 5-position of the pyrimidine ring imparts unique electronic and steric characteristics, making it a valuable scaffold for the design of novel bioactive molecules. This introduction explores the compound’s chemical properties, synthetic methodologies, and its latest applications in drug discovery, emphasizing recent advancements that highlight its potential in addressing complex biological challenges.

The trifluoromethyl group is a well-documented pharmacophore in medicinal chemistry, renowned for its ability to modulate metabolic stability, lipophilicity, and binding affinity. In 5-(Trifluoromethyl)pyrimidine, this moiety enhances the compound’s interaction with biological targets, particularly enzymes and receptors involved in disease pathways. Recent studies have demonstrated that fluorinated pyrimidines exhibit improved pharmacokinetic profiles compared to their non-fluorinated counterparts, owing to the electron-withdrawing nature of the trifluoromethyl group. This property is particularly advantageous in developing small-molecule inhibitors with enhanced bioavailability and prolonged half-life.

From a synthetic perspective, 5-(Trifluoromethyl)pyrimidine can be accessed through multiple routes, including nucleophilic substitution reactions of halogenated pyrimidines or condensation reactions involving trifluoromethyl-substituted precursors. Advanced methodologies such as transition-metal-catalyzed cross-coupling reactions have further streamlined its synthesis, enabling access to derivatives with diverse substituents. These synthetic strategies are crucial for generating libraries of compounds for high-throughput screening (HTS), a cornerstone of modern drug discovery efforts aimed at identifying lead candidates for therapeutic development.

In recent years, 5-(Trifluoromethyl)pyrimidine has been extensively investigated as a key building block in the development of antiviral, anticancer, and anti-inflammatory agents. For instance, fluorinated pyrimidines have shown promise in inhibiting viral polymerases by disrupting nucleotide incorporation into growing chains. A notable example involves derivatives of 5-(Trifluoromethyl)pyrimidine that exhibit potent activity against RNA viruses, including those responsible for emerging infectious diseases. The trifluoromethyl group’s ability to stabilize transition states during enzymatic reactions makes these compounds particularly effective in targeting viral replication mechanisms.

Moreover, the incorporation of 5-(Trifluoromethyl)pyrimidine into kinase inhibitors has yielded compounds with improved selectivity and efficacy against cancer-related enzymes. Kinases are critical regulators of cellular processes, and their dysregulation is often implicated in tumor growth and progression. By leveraging the steric and electronic properties of the trifluoromethyl group, researchers have designed inhibitors that bind tightly to kinase active sites while minimizing off-target effects. Such developments underscore the compound’s significance in oncology research and highlight its potential as a therapeutic agent.

Emerging evidence also suggests that 5-(Trifluoromethyl)pyrimidine derivatives possess anti-inflammatory properties by modulating signaling pathways involved in immune responses. For example, certain analogs have been shown to inhibit Janus kinases (JAKs), which play a pivotal role in inflammatory cascades. By targeting JAKs, these compounds can attenuate excessive immune responses associated with chronic inflammatory diseases such as rheumatoid arthritis and inflammatory bowel disease. This therapeutic potential is further enhanced by the compound’s ability to cross the blood-brain barrier, offering avenues for treating neuroinflammatory conditions.

The role of computational chemistry in optimizing 5-(Trifluoromethyl)pyrimidine-based drug candidates cannot be overstated. Molecular modeling techniques enable researchers to predict binding affinities, assess metabolic stability, and identify structural modifications that enhance drug-like properties. These computational approaches are complemented by experimental validation through X-ray crystallography and nuclear magnetic resonance (NMR) spectroscopy, which provide insights into molecular interactions at an atomic level. Such integrative strategies are essential for translating laboratory discoveries into clinical applications.

Future directions in the study of 5-(Trifluoromethyl)pyrimidine include exploring its applications in targeted therapy and combination regimens. The compound’s versatility allows for further functionalization at various positions on the pyrimidine ring or through linkers connecting it to other pharmacophores. Such modifications can lead to multivalent inhibitors that engage multiple targets simultaneously, potentially overcoming resistance mechanisms observed in single-agent therapies. Additionally, advances in prodrug technology may enhance the delivery and bioavailability of these compounds, expanding their therapeutic reach.

In conclusion,5-(Trifluoromethyl)pyrimidine (CAS No. 176214-12-3) represents a promising scaffold with broad applications in chemical biology and medicine. Its unique structural features enable the development of bioactive molecules with improved pharmacokinetic profiles and target specificity. Recent research highlights its potential in antiviral, anticancer, and anti-inflammatory therapies, driven by innovative synthetic methodologies and computational approaches. As scientific understanding evolves,5-(Trifluoromethyl)pyrimidine-based compounds are poised to play an increasingly significant role in addressing unmet medical needs through targeted drug design.

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