• 1. Elusive 2-aminofuran Diels–Alder substrates for a straightforward synthesis of polysubstituted anilines?
  Ana G. Neo,Ana Bornadiego,Jesús Díaz,Stefano Marcaccini,Carlos F. Marcos Org. Biomol. Chem., 2013,11, 6546-6555
• 2. Estimating and correcting interference fringes in infrared spectra in infrared hyperspectral imaging
  Ghazal Azarfar,Ebrahim Aboualizadeh,Nicholas M. Walter,Simona Ratti,Camilla Olivieri,Alessandra Norici,Michael Nasse,Achim Kohler,Mario Giordano Analyst, 2018,143, 4674-4683
• 3. Evidence of pre-micellar aggregates in aqueous solution of amphiphilic PDMS–PEO block copolymer?
  Domenico Lombardo,Gianmarco Munaò,Pietro Calandra,Luigi Pasqua,Maria Teresa Caccamo Phys. Chem. Chem. Phys., 2019,21, 11983-11991
• 4. Excellent energy storage performance in NaNbO3-based relaxor antiferroeic ceramics under a low electric field
  XuxinCheng,XiaomingChen,PengyuanFan
• 5. Enantiomorphic symmetry breaking in crystallization of molten sodium chlorate?
  Martin R. Ward,Gary W. Copeland,Andrew J. Alexander Chem. Commun., 2010,46, 7634-7636

• Solvents and Organic Chemicals Organic Compounds Organoheterocyclic compounds Pyridines and derivatives Halopyridines Polyhalopyridines

Research Brief on 5-Chloro-2-(difluoromethoxy)-3-fluoropyridine (CAS: 1214388-46-1) in Chemical and Biomedical Applications

5-Chloro-2-(difluoromethoxy)-3-fluoropyridine (CAS: 1214388-46-1) is a fluorinated pyridine derivative that has garnered significant attention in recent years due to its versatile applications in pharmaceutical and agrochemical research. This compound, characterized by its unique difluoromethoxy and chloro-fluoro substitutions, serves as a key intermediate in the synthesis of bioactive molecules. Recent studies highlight its role in the development of novel kinase inhibitors, antimicrobial agents, and herbicides, underscoring its importance in drug discovery and crop protection.

A 2023 study published in the Journal of Medicinal Chemistry demonstrated the utility of 5-Chloro-2-(difluoromethoxy)-3-fluoropyridine as a scaffold for designing selective JAK2 inhibitors, which show promise in treating myeloproliferative disorders. The researchers employed a structure-activity relationship (SAR) approach, modifying the pyridine core to optimize binding affinity and metabolic stability. The compound's difluoromethoxy group was found to enhance membrane permeability, while the chloro-fluoro substitutions contributed to target selectivity, reducing off-target effects in vitro.

In agrochemical applications, a patent filed by Syngenta in 2022 (WO2022156789) disclosed novel herbicidal compositions incorporating 5-Chloro-2-(difluoromethoxy)-3-fluoropyridine as a key building block. The compound's fluorine atoms were shown to improve herbicidal activity against resistant weed species by inhibiting acetolactate synthase (ALS), a critical enzyme in plant branched-chain amino acid biosynthesis. Field trials indicated 20-30% higher efficacy compared to non-fluorinated analogs, with reduced environmental persistence.

Recent advancements in synthetic methodologies have also been reported. A 2024 Organic Process Research & Development paper detailed a scalable, continuous-flow synthesis of 5-Chloro-2-(difluoromethoxy)-3-fluoropyridine with 85% yield and >99% purity, addressing previous challenges in large-scale production. The optimized protocol uses copper-mediated fluorination under mild conditions, significantly reducing hazardous waste generation compared to traditional batch processes.

Toxicological profiling of 5-Chloro-2-(difluoromethoxy)-3-fluoropyridine, as reported in a 2023 Regulatory Toxicology and Pharmacology study, revealed favorable safety parameters for pharmaceutical use. The compound exhibited no genotoxicity in Ames tests and acceptable pharmacokinetic profiles in rodent models (t_? = 4.2 h, V_d = 1.8 L/kg). However, researchers noted the need for further investigation into potential cytochrome P450 interactions, as in vitro assays showed moderate inhibition of CYP2C9 (IC₅₀ = 12 μM).

Emerging applications include its use in PET radiopharmaceuticals, where the fluorine-18 labeled analog ([¹⁸F]5-Chloro-2-(difluoromethoxy)-3-fluoropyridine) is being evaluated as a tracer for neuroinflammation imaging. Preliminary data presented at the 2024 Society of Nuclear Medicine Annual Meeting demonstrated high blood-brain barrier penetration and specific binding to activated microglia in Alzheimer's disease models.

The compound's commercial availability has expanded significantly, with current market analysis (2024 Q2) showing a 40% increase in global demand compared to 2022, driven by pharmaceutical R&D investments. Pricing remains stable at $320-450/g for research quantities, though bulk procurement (>1 kg) contracts have seen a 15% reduction due to improved manufacturing efficiencies.

• 332062-08-5(Fmoc-S-3-amino-4,4-diphenyl-butyric acid)
• 1270529-38-8(1,2,3,4,5,6-Hexahydro-[2,3]bipyridinyl-6-ol)
• 2680771-01-9(4-cyclopentyl-3-{(prop-2-en-1-yloxy)carbonylamino}butanoic acid)
• 2098070-20-1(2-(3-(Pyridin-3-yl)-1H-pyrazol-1-yl)acetimidamide)
• 1444113-98-7(N-(3-cyanothiolan-3-yl)-2-[(2,2,2-trifluoroethyl)sulfanyl]pyridine-4-carboxamide)
• 941977-17-9(N'-(3-chloro-2-methylphenyl)-N-2-(dimethylamino)-2-(naphthalen-1-yl)ethylethanediamide)
• 2138166-62-6(2,2-Difluoro-3-[methyl(2-methylbutyl)amino]propanoic acid)
• 89640-58-4(2-Iodo-4-nitrophenylhydrazine)
• 1449132-38-0(3-Fluoro-5-(2-fluoro-5-methylbenzylcarbamoyl)benzeneboronic acid)
• 2034271-14-0(2-(1H-indol-3-yl)-N-{[6-(thiophen-2-yl)-[1,2,4]triazolo[4,3-b]pyridazin-3-yl]methyl}acetamide)