757978-18-0

Basic information

• Product Name: 5-BROMO-3-IODO-1H-PYRROLO[2,3-B]PYRIDINE
• Synonyms: 5-BROMO-3-IODO-1H-PYRROLO[2,3-B]PYRIDINE;5-Bromo-3-iodo-7-azaindole;Zinc04352700;1H-Pyrrolo[2,3-b]pyridine, 5-broMo-3-iodo-;5-Bromo-3-iodo-1H-pyrrolo(2,3-b)pyridine 97%
• CAS NO: 757978-18-0
• Molecular Formula: C₇H₄BrIN₂
• Molecular Weight: 322.93
• EINECS: 1308068-626-2
• Product Categories: Heterocycle-Pyridine series
• Mol File: 757978-18-0.mol

Chemical Properties

• Melting Point: 227.3-227.7°C
• Boiling Point: 324℃
• Flash Point: 150℃
• Appearance: /
• Density: 2.52
• Vapor Pressure: 5.21E-06mmHg at 25°C
• Refractive Index: 1.804
• Storage Temp.: Keep in dark place,Sealed in dry,Room Temperature
• PKA: 11.42±0.40(Predicted)
• Sensitive: Light Sensitive
• CAS DataBase Reference: 5-BROMO-3-IODO-1H-PYRROLO[2,3-B]PYRIDINE(CAS DataBase Reference)
• NIST Chemistry Reference: 5-BROMO-3-IODO-1H-PYRROLO[2,3-B]PYRIDINE(757978-18-0)
• EPA Substance Registry System: 5-BROMO-3-IODO-1H-PYRROLO[2,3-B]PYRIDINE(757978-18-0)

Safety Data

• Hazard Codes: Xi,Xn
• Statements: 22-37/38-41
• Safety Statements: 26-39
• WGK Germany: 3
• HazardClass: IRRITANT
• Hazardous Substances Data: 757978-18-0(Hazardous Substances Data)

Usage

Uses

5-Bromo-3-iodo-1H-pyrrolo[2,3-b]pyridine is a useful intermediate for organic synthesis.

InChI:InChI=1/C7H4BrIN2/c8-4-1-5-6(9)3-11-7(5)10-2-4/h1-3H,(H,10,11)

Upstream product

• 183208-35-7 5-bromo-1H-pyrrolo[2,3-b]pyridine 
• 905966-34-9 5-bromo-3-(2-(trimethylsilyl)ethynyl)pyridine-2-amine 
• 381233-96-1 2-amino-3-iodo-5-bromopyridine 
• 5264-35-7 2-methoxy-1-pyrroline 

Downstream Products

• 757978-19-1 5-bromo-3-iodo-1-(phenylsulfonyl)-1H-pyrrolo[2,3-b]pyridine 
• 875639-49-9 5-bromo-3-iodo-1-triisopropylsilanyl-1H-pyrrolo[2,3-b]pyridine 
• 875639-74-0 4-[5-bromo-1-(toluene-4-sulfonyl)-1H-pyrrolo[2,3-b]pyridin-3-yl]-phenol 
• 1229583-69-0 C₃₁H₂₇N₃O₅S 
• 1229582-00-6 3-(1H-indol-5-yl)-5-(3,4,5-trimethoxyphenyl)-1H-pyrrolo-[2,3-b]pyridine 
• 1229583-41-8 1-(4-{4-[3-(1H-indol-5-yl)-1H-pyrrolo[2,3-b]pyridin-5-yl]-benzyl}-piperazin-1-yl)-ethanone 
• 1229583-45-2 4-{4-[3-(1H-indol-5-yl)-1H-pyrrolo[2,3-b]pyridin-5-yl]-benzyl}-piperazine-1-carboxylic acid tert-butyl ester 
• 1229583-46-3 {4-[3-(1H-indol-5-yl)-1H-pyrrolo[2,3-b]pyridin-5-yl]-phenyl}-(4-methyl-piperazin-1-yl)-methanone 
• 1229584-11-5 4-[5-bromo-1-(toluene-4-sulfonyl)-1H-pyrrolo[2,3-b]pyridin-3-yl]-benzamide 
• 1229583-49-6 4-{4-[3-(4-carbamoyl-phenyl)-1H-pyrrolo[2,3-b]pyridin-5-yl]-benzoyl}-piperazine-1-carboxylic acid tert-butyl ester 
• 1229583-50-9 4-{5-[4-(piperazine-1-carbonyl)-phenyl]-1H-pyrrolo[2,3-b]pyridin-3-yl}-benzamide hydrochloride 
• 1229583-51-0 4-{5-[4-(4-acetyl-piperazine-1-carbonyl)-phenyl]-1H-pyrrolo[2,3-b]pyridin-3-yl}-benzamide 
• 1229584-12-6 4-[5-bromo-1-(toluene-4-sulfonyl)-1H-pyrrolo[2,3-b]pyridin-3-yl]-benzylamine 
• 1229584-13-7 N-{4-[5-bromo-1-(toluene-4-sulfonyl)-1H-pyrrolo[2,3-b]pyridin-3-yl]-benzyl}-acetamide 

Relevant articles and documents

Pd-Catalyzed Sequential Arylation of 7-Azaindoles: Aggregate-Induced Emission of Tetra-Aryl 7-Azaindoles

Pd-catalyzed synthesis of multi-aryl 7-azaindoles using sequential arylation of 5-bromo-6-chloro-3-iodo-1-methyl-1H-pyrrolo[2,3-b] pyridine is established. Four diverse aryl groups are installed in a chemo-selective fashion providing a general method to synthesize sterically encumbered compounds and extended 7-azaindoles in 48-95% yields. Three-selective sequential arylations at C-3, C-5, and C-6 via Suzuki-Miyaura cross-coupling followed by direct C-2 arylation using a Pd catalyst and AgOTf as an additive are highlights of the present work. Interestingly, the tetra-aryl 7-azaindoles showed aggregate-induced emission (AIE) making it potentially useful as fluorophores in OLEDs, sensors, and bio-imaging tools.

Strategic Design of Catalytic Lysine-Targeting Reversible Covalent BCR-ABL Inhibitors**

Targeted covalent inhibitors have re-emerged as validated drugs to overcome acquired resistance in cancer treatment. Herein, by using a carbonyl boronic acid (CBA) warhead, we report the structure-based design of BCR-ABL inhibitors via reversible covalent targeting of the catalytic lysine with improved potency against both wild-type and mutant ABL kinases, especially ABLT315I bearing the gatekeeper residue mutation. We show the evolutionarily conserved lysine can be targeted selectively, and the selectivity depends largely on molecular recognition of the non-covalent pharmacophore in this class of inhibitors, probably due to the moderate reactivity of the warhead. We report the first co-crystal structures of covalent inhibitor-ABL kinase domain complexes, providing insights into the interaction of this warhead with the catalytic lysine. We also employed label-free mass spectrometry to evaluate off-targets of our compounds at proteome-wide level in different mammalian cells.

Discovery of a series of 1H-pyrrolo[2,3-b]pyridine compounds as potent TNIK inhibitors

In an in-house screening, 1H-pyrrolo[2,3-b]pyridine scaffold was found to have high inhibition on TNIK. Several series of compounds were designed and synthesized, among which some compounds had potent TNIK inhibition with IC50 values lower than 1 nM. Some compounds showed concentration-dependent characteristics of IL-2 inhibition. These results provided new applications of TNIK inhibitors and new prospects of TNIK as a drug target.

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.

PYRROLO[2,3-B]PYRIDINES AS HPK1 INHIBITOR AND USES THEREOF

Disclosed herein is a compound of Formula (I), or a stereoisomer thereof, or a pharmaceutically acceptable salt thereof, and pharmaceutical compositions comprising thereof. Also disclosed is a method of treating HPK1 related disorders or diseases by using the compound disclosed herein.

Cu(II)-catalyzed sulfonylation of 7-azaindoles using DABSO as SO2-Source and its mechanistic study

DABSO mediated sulfonylation of iodinated 7-azaindoles was achieved for the first time through sulfonylative Suzuki-Miyaura cross coupling (SMC) reaction under mild conditions giving good yields of sulfonylated 7-azaindole derivatives. Interestingly, control experiments suggest that present method involves in-situ generation of ArSO2 free radical followed by the key steps of SMC reaction. Scope of the reaction was explored with both electronically different and bulky group carrying boronic acids as coupling partner. The sulfonylation is scalable and occurred selectively at iodo group, irrespective of its position on azaindole. Moreover, the proposed mechanism has been supported by electron paramagnetic resonance (EPR) and density functional theory (DFT) calculations.

Synthesis and Structure-Activity Relationships of 3,5-Disubstituted-pyrrolo[2,3- b]pyridines as Inhibitors of Adaptor-Associated Kinase 1 with Antiviral Activity

There are currently no approved drugs for the treatment of emerging viral infections, such as dengue and Ebola. Adaptor-associated kinase 1 (AAK1) is a cellular serine-threonine protein kinase that functions as a key regulator of the clathrin-associated host adaptor proteins and regulates the intracellular trafficking of multiple unrelated RNA viruses. Moreover, AAK1 is overexpressed specifically in dengue virus-infected but not bystander cells. Because AAK1 is a promising antiviral drug target, we have embarked on an optimization campaign of a previously identified 7-azaindole analogue, yielding novel pyrrolo[2,3-b]pyridines with high AAK1 affinity. The optimized compounds demonstrate improved activity against dengue virus both in vitro and in human primary dendritic cells and the unrelated Ebola virus. These findings demonstrate that targeting cellular AAK1 may represent a promising broad-spectrum antiviral strategy.

Halogen Bond-Assisted Electron-Catalyzed Atom Economic Iodination of Heteroarenes at Room Temperature

A halogen bond-assisted electron-catalyzed iodination of heteroarenes has been developed for the first time under atom economic condition at room temperature. The iodination is successful with just 0.55 equiv of iodine and 0.50 equiv of peroxide. The kinetic study indicates that the reaction is elusive in the absence of a halogen bond between the substrate and iodine. The formation of a halogen bond, its importance in lowering the activation barrier for this reaction, the presence of radical intermediates in a reaction mixture, and the regioselectivity of the reaction have been demonstrated with several control experiments, spectroscopic analysis, and quantum chemical calculations. Allowing the formation of the halogen bond may offer a new strategy to generate the reactive radical intermediates and to enable the otherwise elusive electron-catalyzed reactions under mild reaction conditions.

Regioselective Halogenation of Arenes and Heterocycles in Hexafluoroisopropanol

Regioselective halogenation of arenes and heterocycles with N-halosuccinimides in fluorinated alcohols is disclosed. Under mild condition reactions, a wide diversity of halogenated arenes are obtained in good yields with high regioselectivity. Additionally, the versatility of the method is demonstrated by the development of one-pot sequential halogenation and halogenation-Suzuki cross-coupling reactions.

AZAINDOLES AS INHIBITORS OF HPK1

Azaindole compounds and their use as inhibitors of HPK1 are described. The compounds are useful in treating HPK1-dependent disorders and enhancing an immune response. Also described are methods of inhibiting HPK1, methods of treating HPK1- dependent disorders, methods for enhancing an immune response, and methods for preparing the azaindole compounds.