37388-07-1

Usage

Type of compound

Fused heterocyclic compound

Constituent elements

Carbon (C), Hydrogen (H), Nitrogen (N)

Contains rings

Pyridine and pyrrole rings

Common use

Building block in organic synthesis

Pharmaceutical potential

Possible applications in drug development

Research utility

Used as a research tool for studying biological processes

Molecular structure

Versatile and valuable for various chemical and pharmaceutical applications

Upstream product

• 504-24-5 4-aminopyridine 
• 54629-90-2 4-nitro-3-(2-phenylethenyl)pyridine N-oxide 
• 449173-31-3 4-amino-3-(2-phenylethynyl)pyridine 
• 98-81-7 1-bromovinylbenzene 
• 536-74-3 phenylacetylene 
• 88511-27-7 3-iodopyridin-4-amine 
• 13534-98-0 3-bromopyridin-4-amine 
• 407623-72-7 tert-butyl N-[3-(hydroxymethyl)pyridin-4-yl]carbamate 
• 7418-65-7 4-aminonicotinic acid 
• 16135-36-7 methyl 4-aminonicotinate 
• 98-86-2 acetophenone 
• 180253-65-0 (3-methylpyridin-4-yl)carbamic acid tert-butyl ester 
• 98400-69-2 N-(4-pyridyl) t-butyl carbamate 
• 627511-07-3 4-nitro-3-[(E)-2-phenylethenyl]pyridine 

Relevant academic research and scientific papers

Application of Fluorine- And Nitrogen-Walk Approaches: Defining the Structural and Functional Diversity of 2-Phenylindole Class of Cannabinoid 1 Receptor Positive Allosteric Modulators

Cannabinoid 1 receptor (CB1R) allosteric ligands hold a far-reaching therapeutic promise. We report the application of fluoro- and nitrogen-walk approaches to enhance the drug-like properties of GAT211, a prototype CB1R allosteric agonist-positive allosteric modulator (ago-PAM). Several analogs exhibited improved functional potency (cAMP, β-arrestin 2), metabolic stability, and aqueous solubility. Two key analogs, GAT591 (6r) and GAT593 (6s), exhibited augmented allosteric-agonist and PAM activities in neuronal cultures, improved metabolic stability, and enhanced orthosteric agonist binding (CP55,940). Both analogs also exhibited good analgesic potency in the CFA inflammatory-pain model with longer duration of action over GAT211 while being devoid of adverse cannabimimetic effects. Another analog, GAT592 (9j), exhibited moderate ago-PAM potency and improved aqueous solubility with therapeutic reduction of intraocular pressure in murine glaucoma models. The SAR findings and the enhanced allosteric activity in this class of allosteric modulators were accounted for in our recently developed computational model for CB1R allosteric activation and positive allosteric modulation.

Exploring the reactivity of halogen-free aminopyridines in one-pot palladium-catalyzed C–N cross-coupling/C–H functionalization

Aminopyridines are key building blocks for the synthesis of bioactive N-heterocyclic compounds such as azaindoles and imidazopyridines. However, the functionalization of aminopyridines is challenging, due to their electronic properties and coordination with metals. Herein we describe a reactivity study of aminopyridines under palladium-catalyzed reaction conditions. Several aminopyridines underwent a one-pot Pd-catalyzed C–N cross coupling reaction/C–H functionalization sequence affording azaindoles. The role of additives, ligands, and bases was investigated. This work consists of a platform for future studies on aminopyridines involving metal-catalyzed reactions and represents the first report on the direct conversion of non-halogenated aminopyridines into azaindoles via Pd-catalyzed C–H functionalization reactions.

One-pot synthesis of 1, 2-disubstituted 4-, 5-, 6-, and 7-azaindoles from amino-o-halopyridines via n-arylation/sonogashira/cyclization reaction

A direct synthesis of several 1, 2-disubstituted 4-, 5-, 6-, and 7-azaindoles from available amino-o-halopyridines is described. This procedure involves a palladium-catalyzed N-arylation followed by a Sonogashira reaction and subsequent cyclization in a one-pot manner, exhibiting a wide scope and compatibility with electron-withdrawing and electron-donating groups. The strategy represents an advancement in azaindole chemistry with a straightforward approach toward 1, 2-disubstituted azaindoles, while avoiding complex N-arylations of hindered 2-substituted azaindoles and difficult purification steps of intermediates.

Synthesis of Substituted 4-, 5-, 6-, and 7-Azaindoles from Aminopyridines via a Cascade C-N Cross-Coupling/Heck Reaction

A practical palladium-catalyzed cascade C-N cross-coupling/Heck reaction of alkenyl bromides with amino-o-bromopyridines is described for a straightforward synthesis of substituted 4-, 5-, 6-, and 7-azaindoles using a Pd2(dba)3/XPhos/t-BuONa system. This procedure consists of the first cascade C-N cross-coupling/Heck approach toward all four azaindole isomers from available aminopyridines. The scope of the reaction was investigated and several alkenyl bromides were used, allowing access to different substituted azaindoles. This protocol was further explored for N-substituted amino-o-bromopyridines.

Azaindole synthesis through dual activation catalysis with N-heterocyclic carbenes

A convergent, transition-metal-free synthesis of 2-aryl-azaindoles has been developed. The interception of a reactive aza-ortho-azaquinone methide intermediate by an acyl anion equivalent generated through carbene catalysis provides high yields, a wide substrate scope, and the synthesis of previously inaccessible azaindoles.

Microwave-assisted synthesis of indole- and azaindole-derivatives in water via cycloisomerization of 2-alkynylanilines and alkynylpyridinamines promoted by amines or catalytic amounts of neutral or basic salts

An efficient methodology is described and exploited for the preparation of differently substituted indoles and azaindoles via microwave-assisted cycloisomerization in water of 2-alkynylanilines and alkynylpyridinamines, which is promoted by catalytic amounts of neutral or basic salts or by stoichiometric weak organic bases. Good to high yields in the cyclization can be achieved for a variety of 2-amino(hetero)aryl alkynes. Reactions are run without any added metal catalyst. A comparison with the cycloisomerization conducted under conventional heating is also described. An efficient methodology is described for the preparation of differently substituted 1H-indoles and 1H-azaindoles via microwave-assisted cycloisomerization in water of 2-alkynylanilines and alkynylpyridinamines, promoted by catalytic amounts of neutral or basic salts or by weak organic bases.

Palladium-catalyzed reductive N-heterocyclization of alkenyl-substituted nitroarenes as a viable method for the preparation of bicyclic pyrrolo-fused heteroaromatic compounds

Palladium-catalyzed, carbon monoxide-mediated reductive N-heterocyclization of nitro-heteroaromatic compounds having an alkene adjacent to the nitro-group affords bicyclic pyrrolo-fused heteroaromatic molecules. This type of reaction was used to prepare the fused bicyclo[3.3.0] ring-system: thieno[3,2-b]pyrrole, thieno[2,3-b]pyrrole, furo[2,3-b]pyrrole, pyrrolo[3,2-d]thiazole, and pyrrolo[2,3-d]imidazole and the bicyclo[4.3.0] ring-systems: pyrrolo[3,2-b]pyridine, pyrrolo[2,3-b]pyridine, pyrrolo[3,2-c]pyridine, pyrrolo[2,3-c]pyridine, pyrrolo[3,2-c]pyridazine, and pyrrolo[3,2-d]pyrimidine in 32-94% yield.

One-pot synthesis of azaindoles via palladium-catalyzed α-heteroarylation of ketone enolates

(Figure presented) A convenient, one-pot method for the construction of a variety of azaindoles using simple ketones and haloaminopyridines is described.

Synthesis of 2-aryl-1-hydroxyazaindoles and 2-arylazaindoles via oxidation of o-hydroxyaminostyrylpyridines

2-Aryl-1-hydroxyazaindoles (pyrrolopyridin-1-ols) are prepared via an oxidation/cyclization of o-hydroxyaminostyrylpyridines with DDQ. Reduction of the N-OH bond affords the corresponding 2-arylazaindoles (1H-pyrrolopyridines). The scope of the cyclization is explored via (i) the condensation of 4-methyl-3-nitropyridine with various aryl aldehydes to afford 2-aryl substituted 6-azaindoles and, (ii) the synthesis of 2-phenyl-4-, 5- and 7-azaindoles.

Catalytic dehydrocyclization of azomethines. Synthesis of substituted indoles and 4(5)-azaindoles

Catalytic dehydrocydization of azomethines obtained by condensation of p-toluidine and also 3(4)-aminopyridines with methyl aryl ketones leads to substituted indoles and pyrrolopyridine isomers with the nitrogen atom at different positions in the six-memb