325142-95-8

Usage

Uses

Used in Organic Synthesis:
2,6-Dimethylpyridine-4-boronic acid, pinacol ester is utilized as a reagent in organic synthesis for its ability to form stable complexes with transition metals. This property is particularly advantageous in cross-coupling reactions, facilitating the formation of carbon-carbon bonds and contributing to the synthesis of complex organic molecules.
Used in Pharmaceutical Research:
In the pharmaceutical industry, 2,6-Dimethylpyridine-4-boronic acid, pinacol ester is employed as a key intermediate in the development of various pharmaceuticals. Its unique reactivity and metal-binding properties allow for the creation of novel drug candidates with potential therapeutic applications.
Used in Agrochemical Development:
Similarly, in agrochemical research, 2,6-Dimethylpyridine-4-boronic acid, pinacol ester is used as a building block for the synthesis of new agrochemicals. Its reactivity in cross-coupling reactions aids in the development of innovative compounds with improved pesticidal or herbicidal properties.
Used in Chemistry Research for Novel Materials:
2,6-Dimethylpyridine-4-boronic acid, pinacol ester also shows promise as a tool in the development of new materials and functional molecules in chemistry research. Its capacity to engage in metal-catalyzed reactions opens up possibilities for the creation of advanced materials with unique properties and potential applications in various industries.

Upstream product

• 108-48-5 2,6-dimethylpyridine 
• 25015-63-8 4,4,5,5-tetramethyl-[1,3,2]-dioxaboralane 
• 73183-34-3 bis(pinacol)diborane 
• 96901-96-1 4-D-2,6-dimethylpyridine 
• 5093-70-9 4-bromo-2,6-dimethylpyridine 

Downstream Products

• 3512-75-2 4-chloro-2,6-lutidine 
• 5093-70-9 4-bromo-2,6-dimethylpyridine 
• 39965-81-6 2,6-dimethylisonicotinonitrile 
• 848088-52-8 4-(2,6-dimethyl-[4]pyridyl)-aniline 
• 1358811-13-8 [(2,6-Me₂)(4-Bpin)C₅H₂NH][HB(C₆F₅)3] 
• 1321513-76-1 6-(2,6-dimethylpyridin-4-yl)-5-phenyl-1,2,4-triazin-3-amine 
• 1321514-97-9 5-(3,5-difluorophenyl)-6-(2,6-dimethylpyridin-4-yl)-1,2,4-triazin-3-amine 
• 1321515-01-8 6-(2,6-dimethylpyridin-4-yl)-5-(3-fluorophenyl)-1,2,4-triazin-3-amine 
• 1394909-42-2 5-chloro-2-(2,6-dimethyl-4-pyridinyl)-benzonitrile 
• 1394909-81-9 3-bromo-6-(2,6-dimethyl-4-pyridinyl)-2-fluoro-benzonitrile 
• 1394908-05-4 N-[[5-[(2R,6S)-2,6-dimethyl-4-morpholinyl]-2-(2,6-dimethyl-4-pyridinyl)phenyl]methyl]-cyclopropaneacetamide 
• 1394908-06-5 N-[[5-[(2R,6S)-2,6-dimethyl-4-morpholinyl]-2-(2,6-dimethyl-4-pyridinyl)phenyl]methyl]-2-methyl-propanamide 
• 1394909-82-0 3-[(2R,6S)-2,6-dimethyl-4-morpholinyl]-6-(2,6-dimethyl-4-pyridinyl)-2-fluoro-benzonitrile 
• 1394909-84-2 6-(2,6-dimethyl-4-pyridinyl)-2-fluoro-3-[(2S)-2-(trifluoromethyl)-4-morpholinyl]-benzonitrile 

Relevant academic research and scientific papers

Mechanistic Studies of Cobalt-Catalyzed C(sp2)-H Borylation of Five-Membered Heteroarenes with Pinacolborane

Studies into the mechanism of cobalt-catalyzed C(sp2)-H borylation of five-membered heteroarenes with pinacolborane (HBPin) as the boron source established the catalyst resting state as the trans-cobalt(III) dihydride boryl, (iPrPNP)Co(H)2(BPin) (iPrPNP = 2,6-(iPr2PCH2)2(C5H3N)), at both low and high substrate conversions. The overall first-order rate law and observation of a normal deuterium kinetic isotope effect on the borylation of benzofuran versus benzofuran-2-d1 support H2 reductive elimination from the cobalt(III) dihydride boryl as the turnover-limiting step. These findings stand in contrast to that established previously for the borylation of 2,6-lutidine with the same cobalt precatalyst, where borylation of the 4-position of the pincer occurred faster than the substrate turnover and arene C-H activation by a cobalt(I) boryl is turnover-limiting. Evaluation of the catalytic activity of different cobalt precursors in the C-H borylation of benzofuran with HBPin established that the ligand design principles for C-H borylation depend on the identities of both the arene and the boron reagent used: electron-donating groups improve catalytic activity of the borylation of pyridines and arenes with B2Pin2, whereas electron-withdrawing groups improve catalytic activity of the borylation of five-membered heteroarenes with HBPin. Catalyst deactivation by P-C bond cleavage from a cobalt(I) hydride was observed in the C-H borylation of arene substrates with C-H bonds that are less acidic than those of five-membered heteroarenes using HBPin and explains the requirement of B2Pin2 to achieve synthetically useful yields with these arene substrates.

C(sp2)-H Borylation of Heterocycles by Well-Defined Bis(silylene)pyridine Cobalt(III) Precatalysts: Pincer Modification, C(sp2)-H Activation, and Catalytically Relevant Intermediates

Well-defined bis(silylene)pyridine cobalt(III) precatalysts for C(sp2)-H borylation have been synthesized and applied to the investigation of the mechanism of the catalytic borylation of furans and 2,6-lutidine. Specifically, [(ArSiNSi)CoH3]·NaHBEt3 {ArSiNSi = 2,6-[EtNSi(NtBu)2CAr]2C5H3N, where Ar = C6H5 (1-H3·NaHBEt3) or 4-MeC6H4 (2-H3·NaHBEt3)} and trans-[(ArSiNSi)Co(H)2BPin] {Ar = C6H5 [1-(H)2BPin] or 4-MeC6H4 [2-(H)2BPin], and Pin = pinacolato} were prepared and employed as single-component precatalysts for the C(sp2)-H borylation of 2-methylfuran, benzofuran, and 2,6-lutidine. The cobalt(III) precursors, 2-H3·NaHBEt3 and 2-(H)2BPin, also promoted C(sp2)-H activation of benzofuran, yielding [(ArSiNSi)CoH(Bf)2] {Ar = 4-MeC6H4 [2-H(Bf)2], and Bf = 2-benzofuranyl}. Monitoring the catalytic borylation of 2-methylfuran and 2,6-lutidine by 1H NMR spectroscopy established the trans-dihydride cobalt(III) boryl as the catalyst resting state at low substrate conversions. At higher conversions, two distinct pincer modification pathways were identified, depending on the substrate and the boron source.

Mono-Phosphine Metal-Organic Framework-Supported Cobalt Catalyst for Efficient Borylation Reactions

We report a metal-organic framework (MOF) supported monoligated phosphine-cobalt complex, which is an active heterogeneous catalyst for aromatic C?H borylation and alkene hydroboration. The mono(phosphine)-Co catalyst (MOF?P?Co) was prepared by metalation of a porous triarylphosphine-functionalized MOF (MOF?P) with CoCl2 followed by activation with NaEt3BH. The MOF catalyst has a broad substrate scope with excellent functional group tolerance to afford arene- and alkyl-boronate esters in excellent yields and selectivity. MOF?P?Co gave a turnover number (TON) of 30,000 and could be recycled and reused at least 13 times in arene C?H borylation. Importantly, the attempt to prepare the homogeneous control (Ph3P?Co) using triphenylphosphine was unsuccessful due to the facile disproportionation reactions or intermolecular ligand exchanges in the solution. In contrast, the site isolation of the active mono(phosphine)-Co species within the MOF affords the robust and coordinatively unsaturated metal complexes, allowing to explore their catalytic properties and the reaction mechanism.

Sequential Ir/Cu-Mediated Method for the Meta-Selective C-H Radiofluorination of (Hetero)Arenes

This article describes a sequential Ir/Cu-mediated process for the meta-selective C-H radiofluorination of (hetero)arene substrates. In the first step, Ir-catalyzed C(sp2)-H borylation affords (hetero)aryl pinacolboronate (BPin) esters. The intermediate organoboronates are then directly subjected to copper-mediated radiofluorination with [18F]tetrabutylammonium fluoride to afford fluorine-18 labeled (hetero)arenes in high radiochemical yield and radiochemical purity. This entire process is performed on a benchtop without Schlenk or glovebox techniques and circumvents the need to isolate (hetero)aryl boronate esters. The reaction was automated on a TracerLab FXFN module with 1,3-dimethoxybenzene and a meta-tyrosine derivative. The products, [18F]1-fluoro-3,5-dimethoxybenzene and an 18F-labeled meta-tyrosine derivative, were obtained in 37 ± 5% isolated radiochemical yield and >99% radiochemical purity and 25% isolated radiochemical yield and 99% radiochemical purity, and 0.52 Ci/μmol (19.24 GBq/μmol) molar activity (Am), respectively.

Lead Optimization of 3,5-Disubstituted-7-Azaindoles for the Treatment of Human African Trypanosomiasis

Neglected tropical diseases such as human African trypanosomiasis (HAT) are prevalent primarily in tropical climates and among populations living in poverty. Historically, the lack of economic incentive to develop new treatments for these diseases has meant that existing therapeutics have serious shortcomings in terms of safety, efficacy, and administration, and better therapeutics are needed. We now report a series of 3,5-disubstituted-7-azaindoles identified as growth inhibitors of Trypanosoma brucei, the parasite that causes HAT, through a high-throughput screen. We describe the hit-to-lead optimization of this series and the development and preclinical investigation of 29d, a potent antitrypanosomal compound with promising pharmacokinetic (PK) parameters. This compound was ultimately not progressed beyond in vivo PK studies due to its inability to penetrate the blood-brain barrier (BBB), critical for stage 2 HAT treatments.

Understanding the Activation of Air-Stable Ir(COD)(Phen)Cl Precatalyst for C-H Borylation of Aromatics and Heteroaromatics

A newly developed robust catalyst [Ir(COD)(Phen)Cl] (A) was used for the C-H borylation of three dozen aromatics and heteroaromatics with excellent yield and selectivity. Activation of the catalyst was identified by the use of catalytic amounts of water, alcohols, etc., when B2pin2 was used in noncoordinating solvents, while for THF catalytic use of HBpin was required. The results were on par with the in situ based expensive system [Ir(OMe)(COD)]2/dtbbpy or Me4Phen.

Single-Site Cobalt-Catalyst Ligated with Pyridylimine-Functionalized Metal-Organic Frameworks for Arene and Benzylic Borylation

We report a highly active single-site heterogeneous cobalt-catalyst based on a porous and robust pyridylimine-functionalized metal-organic frameworks (pyrim-MOF) for chemoselective borylation of arene and benzylic C-H bonds. The pyrim-MOF having UiO-68 topology, constructed from zirconium-cluster secondary building units and pyridylimine-functionalized dicarboxylate bridging linkers, was metalated with CoCl2 followed by treatment of NaEt3BH to give the cobalt-functionalized MOF-catalyst (pyrim-MOF-Co). Pyrim-MOF-Co has a broad substrate scope, allowing the C-H borylation of halogen-, alkoxy-, alkyl-substituted arenes as well as heterocyclic ring systems using B2pin2 or HBpin (pin = pinacolate) as the borylating agent to afford the corresponding arene- or alkyl-boronate esters in good yields. Pyrim-MOF-Co gave a turnover number (TON) of up to 2500 and could be recycled and reused at least 9 times. Pyrim-MOF-Co was also significantly more robust and active than its homogeneous control, highlighting the beneficial effect of active-site isolation within the MOF framework that prevents intermolecular decomposition. The experimental and computational studies suggested (pyrim?-)CoI(THF) as the active catalytic species within the MOF, which undergoes a mechanistic pathway of oxidative addition, turnover limiting σ-bond metathesis, followed by reductive elimination to afford the boronate ester.

Pyridine N-oxidation derivative as well as preparation method and application thereof

The invention relates to a pyridine N-oxidation derivative as well as a preparation method and an application thereof, in particular to a compound shown in a general formula (I), a preparation methodof the compound, pharmaceutical composition containing the compound and an application of the compound as a BRD4 inhibitor in treating related diseases such as cancer, inflammation, chronic liver diseases, diabetes, cardiovascular diseases, AIDS and the like, wherein in the general formula (I), all substituent groups are the same as definitions in the description.

meta-Nitration of Arenes Bearing ortho/para Directing Group(s) Using C?H Borylation

Herein, we report the meta-nitration of arenes bearing ortho/para directing group(s) using the iridium-catalyzed C?H borylation reaction followed by a newly developed copper(II)-catalyzed transformation of the crude aryl pinacol boronate esters into the corresponding nitroarenes in a one-pot fashion. This protocol allows the synthesis of meta-nitrated arenes that are tedious to prepare or require multistep synthesis using the existing methods. The reaction tolerates a wide array of ortho/para-directing groups, such as ?F, ?Cl, ?Br, ?CH3, ?Et, ?iPr ?OCH3, and ?OCF3. It also provides regioselective access to the nitro derivatives of π-electron-deficient heterocycles, such as pyridine and quinoline derivatives. The application of this method is demonstrated in the late-stage modification of complex molecules and also in the gram-scale preparation of an intermediate en route to the FDA-approved drug Nilotinib. Finally, we have shown that the nitro product obtained by this strategy can also be directly converted to the aniline or hindered amine through Baran's amination protocol.

Sterically controlled C-H/C-H homocoupling of arenes: Via C-H borylation

A mild one-pot protocol for the synthesis of symmetrical biaryls by sequential Ir-catalyzed C-H borylation and Cu-catalyzed homocoupling of arenes is described. The regiochemistry of the biaryl formed is sterically controlled as dictated by the C-H borylation step. The methodology is also successfully extended to heteroarenes. Some of the products obtained by this approach are impossible to obtain via the Ullmann or the Suzuki coupling protocols. Finally, we have shown a one-pot sequence describing C-H borylation/Cu-catalyzed homocoupling/Pd-catalyzed Suzuki coupling to obtain π-extended arene frameworks.