Production Method 1

100-48-1

878194-91-3

Reaction Conditions

1.1 Reagents: Piperidine, 2,2,6,6-tetramethyl-, lithium salt (1:1) Solvents: Tetrahydrofuran ;  0.5 h, -80 °C
1.2 Reagents: Triisopropyl borate ;  0.5 h, -80 °C; -80 °C → rt
1.3 Reagents: Hydrochloric acid Solvents: Water ;  pH 6, rt
2.1 Reagents: Sulfuric acid magnesium salt (1:1) Solvents: Toluene ;  overnight, rt

Reference

Synthesis of ortho-cyanopyridylboronic acids and esters toward cyano-functionalized bipyridines

Cailly, Thomas; et al, Synlett, 2006, (1), 53-56

Production Method 2

76-09-5

874290-90-1

878194-91-3

Reaction Conditions

1.1 Reagents: Sulfuric acid magnesium salt (1:1) Solvents: Toluene ;  overnight, rt

Reference

Synthesis of ortho-cyanopyridylboronic acids and esters toward cyano-functionalized bipyridines

Cailly, Thomas; et al, Synlett, 2006, (1), 53-56

Production Method 3

76-09-5

100-48-1

878194-91-3

Reaction Conditions

1.1 Reagents: Butyllithium ,  2,2,6,6-Tetramethylpiperidine Solvents: Tetrahydrofuran ,  Hexane ;  -30 °C; -30 °C → 0 °C; 15 min, 0 °C; 0 °C → -80 °C
1.2 Reagents: Triisopropyl borate ;  5 min, -80 °C
1.3 Solvents: Tetrahydrofuran ;  15 min, -80 °C; overnight, -80 °C → rt
1.4 Reagents: Acetic acid ;  2 h, rt
1.5 Reagents: Monopotassium phosphate Solvents: Water ;  rt
1.6 Reagents: Hydrochloric acid Solvents: Dichloromethane ,  Water ;  rt

Reference

Straightforward access to ethyl 3-aminofuropyridine-2-carboxylates from 1-chloro-2-cyano- or 1-hydroxy-2-cyano-substituted pyridines

Cailly, Thomas; et al, Synthesis, 2007, (20), 3247-3251

3-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)isonicotinonitrile Raw materials

• 2,3-Dimethylbutane-2,3-diol
• (4-Cyanopyridin-3-yl)boronic acid
• 4-Cyanopyridine

3-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)isonicotinonitrile Preparation Products

• 3-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)isonicotinonitrile (878194-91-3)

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• Other Chemical Reagents Derivatization Reagents
• Solvents and Organic Chemicals Organic Compounds Acids/Esters

Recent Advances in the Application of 3-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)isonicotinonitrile (CAS: 878194-91-3) in Chemical Biology and Drug Discovery

The compound 3-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)isonicotinonitrile (CAS: 878194-91-3) has recently garnered significant attention in the field of chemical biology and medicinal chemistry due to its versatile applications in drug discovery and development. This boronic ester derivative serves as a key intermediate in Suzuki-Miyaura cross-coupling reactions, enabling the synthesis of complex heterocyclic compounds with potential therapeutic properties. Recent studies have highlighted its role in the development of novel kinase inhibitors and proteolysis-targeting chimeras (PROTACs), underscoring its importance in modern drug design.

One of the most notable applications of 3-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)isonicotinonitrile is in the synthesis of targeted cancer therapies. Researchers have utilized this compound to develop inhibitors targeting the epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK), both of which are implicated in various malignancies. The boronic ester moiety facilitates efficient coupling with aryl halides, yielding high-purity compounds with improved pharmacokinetic properties. Recent preclinical studies have demonstrated the efficacy of these inhibitors in suppressing tumor growth in xenograft models, paving the way for further clinical evaluation.

In addition to its role in kinase inhibitor development, this compound has been employed in the design of PROTACs, a groundbreaking therapeutic modality that selectively degrades disease-causing proteins. By incorporating 3-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)isonicotinonitrile into the linker region of PROTAC molecules, researchers have achieved enhanced binding affinity and specificity for target proteins. Recent publications have reported successful degradation of oncogenic proteins such as BRD4 and ERα, highlighting the potential of this compound in advancing targeted protein degradation strategies.

Recent advancements in synthetic methodology have also expanded the utility of 3-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)isonicotinonitrile. A 2023 study published in the Journal of Medicinal Chemistry described a novel one-pot synthesis route that significantly improves yield and reduces purification steps. This innovation has streamlined the production of boronic ester derivatives, making them more accessible for high-throughput screening and combinatorial chemistry applications. Furthermore, computational studies have provided insights into the structural determinants of its reactivity, enabling more rational design of derivatives with tailored properties.

The compound's stability under physiological conditions has been another area of active investigation. Recent pharmacokinetic studies have shown that 3-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)isonicotinonitrile exhibits favorable metabolic stability in human liver microsomes, with a half-life exceeding 120 minutes. This property, combined with its moderate lipophilicity (LogP ≈ 2.1), makes it an attractive scaffold for developing orally bioavailable drugs. Several research groups are currently exploring its incorporation into CNS-penetrant molecules for neurodegenerative disease treatment.

Looking forward, the unique chemical properties of 3-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)isonicotinonitrile position it as a valuable tool in emerging areas such as covalent inhibitor design and bioorthogonal chemistry. Its ability to participate in diverse chemical transformations while maintaining stability in biological systems makes it particularly suited for these applications. As research continues to uncover new synthetic applications and biological activities, this compound is expected to remain at the forefront of innovative drug discovery efforts in the coming years.

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• 944401-73-4(2-amino-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)isonicotinonitrile)
• 1326714-81-1(3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-indole-6-carbonitrile)
• 1309982-23-7(2-Bromo-4-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine)
• 1622217-32-6(4,6-Dimethylpyridine-3-boronic Acid Pinacol Ester)
• 878194-93-5(3-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)picolinonitrile)
• 402718-29-0(5-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)nicotinonitrile)
• 1421252-89-2(2,4-dimethyl-3-(tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine)
• 868944-72-3(3-(5,5-dimethyl-1,3,2-dioxaborinan-2-yl)pyridine-4-carbonitrile)
• 1171891-31-8(4-Methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine)