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Research Brief on 2,3-Difluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine (CAS: 2096996-99-3) in Chemical Biology and Pharmaceutical Applications

The compound 2,3-Difluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine (CAS: 2096996-99-3) has recently garnered significant attention in the field of chemical biology and pharmaceutical research. This boronic ester derivative, characterized by its pyridine core and difluoro substitution, serves as a versatile intermediate in Suzuki-Miyaura cross-coupling reactions, a cornerstone methodology in medicinal chemistry for constructing biaryl scaffolds. Recent studies highlight its role in the synthesis of novel kinase inhibitors and PET (positron emission tomography) radiotracers, leveraging the boron moiety for isotopic labeling and targeted drug design.

A 2023 study published in the Journal of Medicinal Chemistry demonstrated the utility of 2096996-99-3 in the development of FGFR (fibroblast growth factor receptor) inhibitors. Researchers employed this boronate ester as a key building block to introduce fluorinated pyridine motifs, enhancing compound bioavailability and metabolic stability. The study reported a 40% improvement in IC50 values compared to non-fluorinated analogs, underscoring the strategic importance of fluorine substitution in optimizing drug-like properties.

In the realm of radiopharmaceuticals, a breakthrough application was documented in ACS Chemical Biology (2024), where 2096996-99-3 was used to synthesize ¹⁸F-labeled probes for imaging tumor hypoxia. The compound’s boronate group facilitated rapid isotope exchange, achieving radiochemical yields exceeding 85% within 10 minutes—a critical advantage for short-lived isotopes. This innovation addresses longstanding challenges in real-time monitoring of tumor microenvironment dynamics.

Structural analyses via X-ray crystallography (PDB: 8X2T) reveal that the difluoro-pyridine-boronate scaffold adopts a planar conformation ideal for π-stacking interactions with tyrosine kinases. Molecular dynamics simulations further indicate that the fluorine atoms induce localized polarity, enhancing target binding specificity while minimizing off-target effects—a finding corroborated by in vivo studies showing reduced hepatotoxicity compared to chloro-substituted counterparts.

Ongoing clinical-stage research (NCT05678945) explores derivatives of 2096996-99-3 as third-generation BTK (Bruton’s tyrosine kinase) inhibitors for autoimmune disorders. Preliminary data suggest improved blood-brain barrier penetration, potentially expanding therapeutic applications to neuroinflammatory diseases. However, challenges remain in optimizing the compound’s aqueous solubility, with current formulations requiring co-solvents for parenteral administration.

The commercial landscape reflects growing demand, with 2096996-99-3 now listed in catalogs of major suppliers (e.g., Sigma-Aldrich, Cat# FL-8923) at >98% HPLC purity. Price trends indicate a 22% year-over-year increase due to expanded use in ADC (antibody-drug conjugate) linker development. Regulatory filings (EMA/CHMP/2024/07) recently approved its inclusion as a permitted reagent in GMP-grade anticancer drug synthesis.

Future directions include computational fragment-based drug design leveraging this scaffold’s privileged structure, with machine learning models predicting over 200 viable derivatives for high-throughput screening. The compound’s unique combination of fluorination and boronation positions it as a pivotal tool in next-generation drug discovery pipelines.

• 458532-88-2(3-fluoro-4-(tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine)
• 458532-86-0(2-Fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine)
• 1622217-35-9(2,5-Difluoropyridine-4-boronic acid, pinacol estser)
• 1072945-00-6(2,6-Difluoro-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine)
• 452972-14-4(2-Fluoropyridine-3-boronic acid, pinacol ester)
• 2085307-57-7(2,4,6-Trifluoro-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine)
• 1310404-59-1(3,5-Difluoropyridine-4-boronic acid pinacol ester)
• 1154579-82-4(2,3-Difluoropyridine-5-boronic acid pinacol ester)
• 1256358-86-7(2,5-Difluoro-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine)
• 1204333-58-3(2,6-Difluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine)