Synthesis of 2,3-Dihydroimidazo[1,2-a]pyridines from 1,3-Diketones

A series of 2-hydroxy-, 2-chloro-, and 2-(2-hydroxyethylamino)-6-aryl-4-polyfluoroalkyl-3-cyanopyridines has been synthesized. The latter react with phosphorus oxychloride to give fluorine containing 2,3-dihydroimidazo[1,2-a]pyridines.     

Kinetic resolution of alcohols using a 1,2-dihydroimidazo[1,2-a]quinoline enantioselective acylation catalyst

A new enantioselective acylation catalyst (Cl-PIQ), designed to provide enhanced pi-stacking with benzylic and cinnamyl alcohol substrates, was found to give considerably increased reaction rates and selectivities compared with the first-generation catalyst CF(3)-PIP. [reaction: see text]     

Influence of electronic and steric factors on 2,3-dihydroimidazo[1,2-a]pyridine-based enantioselective acylation catalysts

The catalytic activity and enantioselectivity of chiral 2,3-dihydroimidazo[1,2-a]pyridine (DHIP) derivatives was examined as a function of the steric environment of the nucleophilic nitrogen and the electronic properties of the pyridine ring. 2-Phenyl-6-trifluoromethyl-DHIP (CF₃-PIP) was confirmed to be the best catalyst in this series. In addition, three second-generation catalysts derived from the 1,2-dihydroimidazo[1,2-a]quinoline (DHIQ) core were tested and proved to be considerably more active than CF₃-PIP.     

Synthesis of 5-Phenyl-7-trifluoromethyl-2,3-dihydroimidazo[1,2-a]pyridines

Syntheses are reported for a series of 2-alkylamino-6-phenyl-4-trifluoromethylpyridines. The reaction of 3-cyano-2-(hydroxyalkylamino)-6-phenyl-4-trifluoromethylpyridines with thionyl chloride gave the corresponding 2-(chloroalkylamino)pyridines, 8-cyano-5-phenyl-7-trifluoromethyl-2,3-dihydro-imidazo[1,2-a]pyridines, and 9-cyano-6-phenyl-8-trifluoromethyl-2,3,4-trihydropyrido[1,2-a]-pyrimidines. X-ray diffraction structural analysis was used to study 8-cyano-5-phenyl-7-trifluoromethyl-2,3-dihydroimidazo[1,2-a]pyridine.     

Properties of 2,3-dihydro-imidazolo[1,2-a]pyridines. (Review)

Published data on the physical and chemical characteristics of 2,3-dihydroimidazo[1,2-a]pyridines to 1998 are reviewed.Riga Technical University, Riga, Latvia; e-mail: mara@ktf.rtu.lv. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 8, pp. 1011–1027, August, 2000.     

Investigations of Imidazoles. 101. Synthesis of 2,3-Dihydroimidazo[1,2-a]pyrimidine from 2-Aminopyrimidine

Two novel preparative methods have been developed for the synthesis of 2,3-dihydroimidazo[1,2-a]pyrimidine from 2-aminopyrimidine. These are the reaction with 1,2-dibromoethane and also the reaction with ethylene chloro(bromo)hydrin, subsequent treatment of 1--hydroxyethyl-2-imino-1,2-dihydropyrimidine with thionyl chloride, and cyclization of the intermediate 1--chloroethyl-2-imino-1,2-dihydropyrimidine in the presence of sodium hydroxide.     

Synthesis of 6-alkylthioimidazo[1,2-a]pyridines

A number of 6-alkylthio(and sulfonyl)-substituted imidazo[1,2-a]pyridines were synthesized by the reaction of 5-alkylthio- and 5-alkylsulfonyl-2-aminopyridines with -bromoacetophenone and -chlorocyclohexanone in order to search for new compounds that have fungicidal activity. 5-Alkylthio-2-aminopyridines were obtained from the double salt of 5-mercapto-2-aminopyridine with SnCl₂ and HCl by reaction with alkyl halides or tert-C₄H₉OH and 75% H₂SO₄. 5-tert-Butylthio-2-aminopyridine was oxidized by means of KMnO₄ to 5-tert-butylsulfonyl-2-aminopyridine. A double salt was synthesized from 2-aminopyridine-5-sulfonic acid.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 5, pp. 634–638, May, 1979.     

Properties of 8-Cyano-5-phenyl-7-trifluoromethyl-2,3-dihydroimidazo[1,2-a]pyridines

The alkylation, acylation, halogenation, nitration, oxidation, and hydrolysis reactions of 8-cyano-5-phenyl-7-trifluoromethyl-2,3-dihydroimidazo[1,2-a]pyridine have been studied. It was found that the 6-halo derivatives add alcohol to give covalent solvates. X-ray analysis has been carried out on one of the solvates (6-chloro-8-cyano-7-ethoxy-5-phenyl-7-trifluoromethyl-1,2,3,7-tetrahydroimidazo[1,2-a]pyridine) as well as on 8-cyano-5-phenyl-7-trifluoromethyl-2,3-dihydroimidazo[1,2-a]pyridine trifluoroacetate.     

An efficient access to 2,3-diarylimidazo[1,2-a]pyridines via imidazo[1,2-a]pyridin-2-yl triflate through a Suzuki cross-coupling reaction-direct arylation sequence

An efficient method to prepare 2,3-diarylimidazo[1,2-a]pyridines is described. The procedure involves a Suzuki cross-coupling reaction followed by a direct arylation at position 3. Imidazo[1,2-a]pyridin-2-yl triflate was identified as a suitable coupling partner, permitting access to a variety of highly functionalized 2,3-diarylimidazo[1,2-a]pyridines.     

Regiospecific synthesis of 3-substituted imidazo[1,2-a]pyridines,imidazo[1,2-a]pyrimidines,and imidazo[1,2-c]pyrimidine

3-Substituted imidazo[1,2-a]pyridines, imidazo[1,2-a]pyrimidines, and imidazo[1,2-c]pyrimidine were obtained regiospecifically in yields of 35-92% in one pot by reaction of 2-aminopyridines or 2-(or 4-)aminopyrimidines, respectively, with 1,2-bis(benzotriazolyl)-1,2-(dialkylamino)ethanes.     

Efficient syntheses of imidazolo[1,2-a]pyridines and -[2, 1-a]isoquinolines

2-Aminopyridines 1a-c and 1-aminoisoquinoline with 1-chloromethylbenzotriazole give 2-amino-1-[alpha-benzotriazol-1-ylmethyl]pyridinium chlorides 2a-c and 1-amino-2-(alpha-benzotriazol-1-ylmethyl)isoquinolinium++ + chloride 12, respectively. Compounds 2a-c and 12 react with aryl aldehydes 3a-h to afford imidazolo[1,2-a]pyridines 7a-k and imidazolo[2, 1-a]isoquinolines 13a,b in good yields.     

Reactions of 1-Substituted Benzo[4,5]imidazo[1,2-a]pyridines

Bromination of 1-oxo(imino, amino)benzo[4,5]imidazo[1,2-a]pyridines gave the corresponding 2-bromo derivatives. Acylation using the Vilsmeier complex in acetic anhydride gave the N-formyl and N-acetyl derivatives. The reaction of the amine with the Vilsmeier complex, acetyl acetone, ethyl acetoacetate, and 2,5-dimethoxytetrahydrofuran occurs at the amino group.     

Transformations of the pyrido[1,2-a]pyrazine ring system into imidazo[1,2-a]pyridines,imidazo[1,2-a]pyrimidines and 2-oxa-6a, 10c-diazaaceanthrylenes

Transformations of methyl 3-dimethylamino-2-(1-methoxycarbonyl-4-oxo-4H-pyrido[1,2-a]pyrazin-3-yl)acrylate with some cyanomethylenecarbonyl group containing compounds or cyanamide into imidazo-[1,2-a]pyridines, irmdazo[1,2-a]pyrimidines and 2-oxa-6a, 10c-diazaaceanthrylenes are described.     

Manifestation of felkin-anh control in enantioselective acyl transfer catalysis: kinetic resolution of carboxylic acids

Under control: The classical polar Felkin-Anh model has been applied for the first time to the analysis of diastereoselectivity in acylation reactions. Computational studies demonstrate that stereoelectronic effects control the enantioselectivity in asymmetric catalytic alcoholysis of acyclic anhydrides.     

Synthesis of imidazo[1,2- a] pyridines directly from methyl or methylene ketones. iodination of imidazo[1,2-a] pyridines

Imidazo[1,2-a]pyridines were obtained by direct reaction of acetophenone, propiophenone, and their furan analogs and ring-substituted derivatives with an equimolar amount of iodine and and excess 2-aminopyridine or its substituted derivatives. The effect of substituents in the ketones and 2-aminopyridine, the reagent molar ratios, the character of the solvents, and replacement of iodine by other halogenating agents on the course of the reaction and the yields of products was studied. The formation of 3-iodo- and 6-iodoimidazopyridines as side products was noted in the case of ketones that do not have electron-acceptor substituents in the ring. These and other iodo-substituted imidazopyridines were synthesized for chromatographic comparison.Deceased.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 10, pp. 1396–1405, October, 1976.     

Synthesis of Structurally Related Purines: Benzimidazo[1,2-a]pyridines, Benzimidazo-[1,2-c]pyrimidines, and Pyrazolo-[1,5-a]pyrimidines

Summary.  Reactions of sodium salts of 3-hydroxymethylene-2-alkanones with 2-cyanomethylbenzimidazole afforded benzimidazo[1,2-a]pyridines. Analogues reactions with 2-aminobenzimidazole and 5-aminopyrazoles afforded benzimidazo[1,2-c]pyrimidines and pyrazolo[1,5-a]pyrimidines. Received December 12, 1999. Accepted (revised) February 12, 2000     

Selection of enantioselective acyl transfer catalysts from a pooled peptide library through a fluorescence-based activity assay: an approach to kinetic resolution of secondary alcohols of broad structural scope.

An assay employing a fluorescently labeled split and pool peptide library has been applied to the discovery of a new class of octapeptide catalysts for the kinetic resolution of secondary alcohols. A highly diverse library of peptide-based catalysts was synthesized on solid-phase synthesis beads such that each individual bead was co-functionalized with (i) a uniform loading of a pH-sensitive fluorophore and (ii) a unique peptide-based catalyst. The library was then screened for activity in acylation reactions employing (+/-)-sec-phenylethanol as the substrate and acetic anhydride as the acylation agent. From the most active catalysts, a lead peptide (4) was identified that provides a selectivity-factor (k(rel)) of 8.2 upon resynthesis and evaluation under homogeneous conditions. A "directed" second-generation split and pool peptide library was synthesized such that the new peptide sequences in the library were biased toward the lead structure. Random samples of the second generation library were screened in single bead assays that revealed several new peptide-based catalysts that afford improved selectivities in kinetic resolutions. Peptide catalyst 13 proves effective for the kinetic resolution of sec-phenylethanol (k(rel) = 20), as well as eight other secondary alcohols of a broad substrate scope (k(rel) = 4 to >50).     

Pyrimido[1,2-a]benzimidazoles: synthesis and perspective of their pharmacological use

Chemistry of Heterocyclic Compounds - The review presents data on the synthesis as well as studies of biological activity of new derivatives of pyrimido[1,2-a]benzimidazoles published over the last...