Electron-rich Aminoheterocycles Research Articles

Trifluoromethyl Vinamidinium Salt as a Promising Precursor for Fused β-Trifluoromethyl Pyridines

An efficient chlorotrimethylsilane-promoted synthetic protocol for the preparation of functionalized fused β-trifluoromethyl pyridines by cyclization of electron-rich aminoheterocycles or substituted anilines with a trifluoromethyl vinamidinium salt was developed. The efficient and scalable approach for producing represented trifluoromethyl vinamidinium salt demonstrated huge prospects for further use. The structure specificities of the trifluoromethyl vinamidinium salt and their impact on the reaction progress were determined. The procedure's scope and alternative ways of the reaction were investigated. The possibility of increasing the reaction scale up to 50 g and further modification of obtained products was shown. A minilibrary of potential fragments for 19F NMR-based fragment-based drug discovery (FBDD) was synthesized.

Triethylammonium Hydrogen Sulfate [Et3NH][HSO4]-Catalyzed Rapid and Efficient Multicomponent Synthesis of Pyrido[2,3-d]pyrimidine and Pyrazolo[3,4-b]pyridine Hybrids.

An operationally simple, one-pot multicomponent reaction has been developed for the assembly of pyrido[2,3-d]pyrimidine and pyrazolo[3,4-b]pyridine derivatives (4a–4am) in excellent yields (92–94%) with high purity. The reactions were easy to perform simply by mixing of electron-rich amino heterocycles (including aminouracils and aminopyrazoles), aldehyde, and acyl acetonitrile in the presence of [Et3NH][HSO4] under solvent-free conditions. The remarkable feature of the present approach is that the ionic liquid possesses dual solvent-catalytic engineering capability. Results of this study revealed that 1 mmol of the ionic liquid catalyst under solvent-free conditions at 60 °C is the best reaction parameter for the construction of fused pyridine and pyrimidine derivatives in excellent yields. The present methodology showed good results under gram-scale conditions, thereby indicating its applicability in industrial as well as academic settings in the near future.

A domino reaction of 3-chlorochromones with aminoheterocycles. Synthesis of pyrazolopyridines and benzofuropyridines and their optical and ecto-5'-nucleotidase inhibitory effects.

A new and efficient domino reaction of 3-chlorochromones with electron-rich aminoheterocycles was developed which allows for a convenient synthesis of a variety of pyrazolo[3,4-b]pyridines, pyrrolo[2,3-b]pyridines, pyrido[2,3-d]pyrimidines and benzofuro[3,2-b]pyridines. The products exhibit strong fluorescence. In addition, they exhibit significant ecto-5'-nucleotidase inhibition properties and cytotoxic behavior.

Synthesis of fused pyridines in the presence of thiamine hydrochloride as an efficient and reusable catalyst in aqueous conditions

Efficient and straightforward synthesis of fused pyridine derivatives was achieved from electron-rich amino heterocycles and Knoevenagel products derived from aldehyde and malononitrile under aqueous media at 90 °C in the presence of thiamine hydrochloride as a reusable, green catalyst. The strategy in this protocol involves addition on an activated olefinic bond formed in situ by Knoevenagel condensation between an aromatic aldehyde and an active methylene compound. The Michael product on subsequent cyclo condensation yielded fused pyridine in high yield. It offers several advantages such as inexpensive, easily available and recyclable catalyst, simple operational procedure, excellent yield and use of aqueous medium that is considered to be relatively eco-friendly. Vitamin B1 was recovered and reused thrice.

ChemInform Abstract: Synthesis of Heteroannulated 3‐Nitro‐ and 3‐Aminopyridines by Cyclocondensation of Electron‐Rich Aminoheterocycles with 3‐Nitrochromone.

Abstract 3-Nitrochromone reacts with electron-rich aminoheterocycles (in glacial acetic acid at reflux) and anilines (in a mixture of DMF and TMSCl at 100–140 °C) to give a variety of hetero(carbo)annulated 3-nitropyridines. The reaction, involving a formal [3+3] cyclocondensation, proceeds in high yields and appears not to be influences greatly by the nature of the 1,3-C,N-dinucleophile as seen from the thorough scope study. The synthetic utility of the products was demonstrated by their conversion into the corresponding 3-aminopyridine derivatives. An NMR study and X-ray crystallographic analysis are reported.

Aqua mediated indium(III) chloride catalyzed synthesis of fused pyrimidines and pyrazoles

The utilization of water as solvent and indium trichloride as promoter for the three-component combinatorial synthesis of a variety of bioactive pyrimidine and pyrazole derivatives (2–10) from aldehydes, 1,3-dicarbonyl compounds, and electron-rich amino heterocycles like 6-amino-1,3-dimethyl uracil and 3-methyl-1-phenyl-1H-pyrazol-5-amine catalyzed by indium trichloride under reflux has been studied. A new class of pyrimidine derivatives (2) has also been synthesized and the structure was confirmed by single crystal X-ray analysis. The reactions are environmentally benign, reaction product could be isolated easily and the catalyst could be recycled, which makes it an appealing synthetic protocol.

ChemInform Abstract: 4‐Chloro‐3‐(trifluoroacetyl)‐ and 4‐Chloro‐3‐(methoxalyl)coumarins as Novel and Efficient Building Blocks for the Regioselective Synthesis of 3,4‐Fused Coumarins.

Abstract 4-Chloro-3-(trifluoroacetyl)- and 4-chloro-3-(methoxalyl)coumarins react with electron-rich aminoheterocycles, dimethyl 1,3-acetonedicarboxylate, hydrazines, alkyl thioglycolates, and methyl sarcosinate to give a variety of 3,4-heteroannulated coumarins. The starting materials were prepared by the reaction of 4-hydroxycoumarin with trifluoroacetic anhydride and methyl 2-chloro-2-oxoacetate in the presence of trimethylsilylchloride. An NMR study and X-ray crystallographic analysis are reported.

4-Chloro-3-(trifluoroacetyl)- and 4-chloro-3-(methoxalyl)coumarins as novel and efficient building blocks for the regioselective synthesis of 3,4-fused coumarins

4-Chloro-3-(trifluoroacetyl)- and 4-chloro-3-(methoxalyl)coumarins react with electron-rich aminoheterocycles, dimethyl 1,3-acetonedicarboxylate, hydrazines, alkyl thioglycolates, and methyl sarcosinate to give a variety of 3,4-heteroannulated coumarins. The starting materials were prepared by the reaction of 4-hydroxycoumarin with trifluoroacetic anhydride and methyl 2-chloro-2-oxoacetate in the presence of trimethylsilylchloride. An NMR study and X-ray crystallographic analysis are reported.

Synthesis of heteroannulated 3-nitro- and 3-aminopyridines by cyclocondensation of electron-rich aminoheterocycles with 3-nitrochromone

3-Nitrochromone reacts with electron-rich aminoheterocycles (in glacial acetic acid at reflux) and anilines (in a mixture of DMF and TMSCl at 100–140 °C) to give a variety of hetero(carbo)annulated 3-nitropyridines. The reaction, involving a formal [3+3] cyclocondensation, proceeds in high yields and appears not to be influences greatly by the nature of the 1,3-C,N-dinucleophile as seen from the thorough scope study. The synthetic utility of the products was demonstrated by their conversion into the corresponding 3-aminopyridine derivatives. An NMR study and X-ray crystallographic analysis are reported.

3-Acylindoles as versatile starting materials for pyridine ring annulation: synthesis of 1-deazapurine isosteres

The reaction of electron-rich aminoheterocycles with 3-acyl- and 3-formylindoles results in indole ring opening and cyclocondensation to give heteroannulated pyridines, which can be regarded as purine isosteres. The transformations reported herein represent rare examples of domino reactions, which include the cleavage of an indole moiety.

Efficient One-Pot Three-Component Synthesis of Fused Pyridine Derivatives in Ionic Liquid

An efficient one-pot synthesis of fused pyridine derivatives (including pyrazolo[3,4-b]pyridine and pyrido[2,3-d]pyrimidine) by three-component reaction of aldehyde, acyl acetonitrile, and electron-rich amino heterocycles (including aminopyrazole and aminouracils) in ionic liquid is reported. This new protocol has the advantages of environmental friendliness, higher yields, shorter reaction times, and convenient operation.

3-Formylchromones, Acylpyruvates, and Chalcone as Valuable Substrates for the Syntheses of Fused Pyridines

The reaction of electron-rich aminoheterocycles with 1,3-CCC -dielectrophiles, such as 3-formylchromones,acylpyruvates, and chalcone, provided diversely fused pyridines.Starting from 5-amino-1-(2,3- O-isopropylidene-β- D-ribofuranosyl)-1 H-pyrazole,nucleosides containing a pyrazolo[3,4- B]pyridinefragment were obtained, which can be considered as adenosine deaminase(ADA) inhibitors.

Approach to the Library of Fused Pyridine-4-carboxylic Acids by Combes-Type Reaction of Acyl Pyruvates and Electron-Rich Amino Heterocycles

A library of fused pyridine-4-carboxylic acids (including pyrazolo[3,4-b]pyridines, isoxazolo[5,4-b]pyridines, furo[2,3-b]pyridines, thieno[2,3-b]pyridines, and pyrido[2,3-d]pyrimidines) was generated by Combes-type reaction of acyl pyruvates and electron-rich amino heterocycles followed by hydrolysis of the ester. The library members were also demonstrated to undergo the standard combinatorial transformations including amide coupling and esterification, as well as less common heterocyclizations to 1,2,4-triazoles and 1,2,4-oxadiazoles.

3-Methoxalylchromone—a novel versatile reagent for the regioselective purine isostere synthesis

The first synthesis of 3-methoxalylchromone was described. The reaction of the latter with electron-rich aminoheterocycles afforded a set of heteroannelated pyridines bearing a CO(2)Me substituent located at the α-position of the pyridine core.

Chlorotrimethylsilane‐Mediated Synthesis of Functionalized Fused Pyridines: Reaction of 3‐Formylchromones with Electron‐Rich Aminoheterocycles.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.

Chlorotrimethylsilane-Mediated Synthesis of Functionalized Fused Pyridines: Reaction of 3-Formylchromones with Electron-Rich Aminoheterocycles

The reaction of 3-formylchromones with aminoheterocycles was investigated. A simple and flexible general procedure for annulation of 5-(2-hydroxybenzoyl)pyridines was proposed. The best reaction conditions were found to be heating the reaction mixture in DMF in the presence of Me 3 SiCl as a promoter and water as scavenger.

Electron-Rich Amino Heterocyclesfor Regiospecific Synthesis of Trifluoro­methyl-ContainingFused Pyridines

The reaction of 4,4,4-trifluoro-3-oxobutanoates with the corresponding electron-rich amino heterocycles was investigated. A simple and flexible general procedure for the regiospecific annulation of the trifluoromethylpyridine ring to electron-rich amino heterocycles was proposed. A set of CF3-containing fused pyridines in almost quantitative yield was obtained.