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• 2. An insight into the hybridization mechanism of hairpin DNA physically immobilized on chemically modified graphenes
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• Solvents and Organic Chemicals Organic Compounds Organoheterocyclic compounds Pyridines and derivatives Pyridines and derivatives
• Solvents and Organic Chemicals Organic Compounds Organoheterocyclic compounds Pyridines and derivatives

Recent Advances in the Application of 3-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)-4-(trifluoromethyl)pyridine (CAS: 1310405-06-1) in Chemical Biology and Pharmaceutical Research

The compound 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-4-(trifluoromethyl)pyridine (CAS: 1310405-06-1) has emerged as a pivotal intermediate in the synthesis of bioactive molecules, particularly in the development of boron-containing pharmaceuticals. Recent studies highlight its utility in Suzuki-Miyaura cross-coupling reactions, a cornerstone in the construction of complex molecular architectures for drug discovery. This research brief synthesizes the latest findings on its applications, mechanism of action, and potential therapeutic implications.

A 2023 study published in the Journal of Medicinal Chemistry demonstrated the compound's role in synthesizing novel kinase inhibitors targeting EGFR and VEGFR2, showcasing its versatility in generating trifluoromethylpyridine scaffolds with enhanced metabolic stability. Researchers optimized reaction conditions (Pd(dppf)Cl? catalyst, K?CO? base, 80°C in dioxane/water) to achieve yields exceeding 85%, with HPLC purity >98%. The resulting analogs exhibited sub-nanomolar IC?? values in cellular assays, underscoring the structural advantage conferred by the boronate ester moiety.

In proteolysis-targeting chimeras (PROTACs) development, this boronic acid derivative (CAS: 1310405-06-1) has enabled precise linker optimization. A Nature Communications paper (2024) detailed its incorporation into BTK-directed degraders, where the trifluoromethyl group improved membrane permeability (measured PAMPA Pe = 12.3 × 10?? cm/s) while maintaining binding affinity (Kd = 3.2 nM by SPR). Cryo-EM studies revealed the compound's unique ability to stabilize ternary complexes with CRBN E3 ligase, achieving DC?? values of 0.8 nM in Ramos cells.

Notably, the compound's metabolic fate was elucidated in a recent Drug Metabolism and Disposition study (2024). Using LC-MS/MS, researchers identified that the dioxaborolane ring undergoes rapid hydrolysis in human liver microsomes (t?/? = 8.7 min), generating the active boronic acid species. This property is being exploited in prodrug strategies for boron neutron capture therapy (BNCT), with preclinical models showing 3.2-fold increased 1?B tumor accumulation compared to BPA.

Emerging applications include its use as a fluorine-18 labeling precursor for PET tracers. A Science Advances report demonstrated direct 1?F-1?F isotope exchange on the trifluoromethyl group (radiochemical yield: 64±5%, molar activity >75 GBq/μmol), enabling imaging of PD-L1 expression in murine models. The boronate ester functionality further allows subsequent bioconjugation, as evidenced by successful antibody labeling (DAR = 3.1) for immunoPET applications.

Challenges persist in large-scale synthesis, with current Good Manufacturing Practice (cGMP) routes achieving only 62% yield due to purification difficulties of the hygroscopic product. However, continuous flow chemistry approaches (published in Organic Process Research & Development, 2024) have reduced processing time from 48 hours to 6.5 hours while improving purity to 99.5% by eliminating column chromatography.

These collective advances position 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-4-(trifluoromethyl)pyridine as a multifaceted tool in modern drug discovery. Its unique combination of boron-based reactivity and fluorine-enhanced pharmacokinetics continues to inspire innovative applications across targeted therapies, molecular imaging, and radiopharmaceuticals, warranting ongoing investigation into structure-activity relationships and process optimization.

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• 1612287-99-6(2-(Trifluoromethyl)-4-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine)
• 1268693-25-9(2-(2,6-bis(trifluoromethyl)phenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane)
• 1220696-58-1(3-(Difluoromethyl)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine)
• 1084953-47-8(3-(tetramethyl-1,3,2-dioxaborolan-2-yl)-5-(trifluoromethyl)pyridine)
• 2096330-85-5(4-ethylpyridine-3-boronic acid pinacol ester)
• 1383625-22-6(3-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)-2-(trifluoromethyl)pyridine)
• 1171891-31-8(4-Methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine)
• 1073339-21-5(4,4,5,5-Tetramethyl-2-(2-(trifluoromethyl)phenyl)-1,3,2-dioxaborolane)