A facile large scale synthesis of optically active 3-amino-5-(2-pyridyl)-1,4-benzodiazepin-2-one derivatives

A facile method for the synthesis of 3-amino-5-(2-pyridyl)-1,4-benzodiazepin-2-ones (8) mediated by benzotriazole is described. The synthesis and optical resolution of the product by fractional crystallisation proceeds in high yield, under mild conditions and without recourse to toxic reagents or chromatographic separations and hence is amenable to the large scale preparation of these important precursors to potent CCK receptor ligands.     

A facile synthesis of 1,4-benzodiazepine derivatives via Ugi four-component condensation

A simple two-step route to 4,5-dihydro-3H-benzo[1,4]diazepin-5-ones is described. This synthesis, based on the isocyanide chemistry, allows a wide variety of substitution patterns starting from commercially available or easily obtainable reagents.     

A facile synthesis of 2-(N-alkylamino)-pyrimidin-4-one derivatives

Substituted 2-(N-alkylamino)-pyrimidin-4-ones were synthesized from N-alkyl β-amino acid esters starting with guanidinylation using Pbf-activated thiourea. The six-membered pyrimidinones were obtained in good yields via intramolecular cyclization during TFA cleavage of the Pbf protecting group.     

Regioselective synthesis of novel 2-chloroquinoline derivatives of 1,4-dihydropyridines

Highly regioselective reaction of some substituted 2,4-dichloroquinolines with symmetrical 1,4-dihydropyridines, leading to novel quinoline derivatives of DHPs, has been achieved in the presence of powdered K₂CO₃, as a mild and efficient base, at moderate temperature. All the synthesized compounds were characterized by use of IR, NMR, and mass spectral data.     

A facile reaction involving zwitterionic intermediates for the synthesis of 5-hydroxy-2H-pyrrol-2-one derivatives

The reaction of cyclohexyl isocyanide with various aldehydes and 1,3-dicarbonyl compounds catalyzed by piperidine is described. The protocol offers facile and efficient synthesis of 5-hydroxy-2H-pyrrol-2-one derivatives from readily available starting materials in high yields.     

Solid-phase synthesis of tetrahydro-1,4-benzodiazepine-2-one derivatives as a beta-turn peptidomimetic library

The beta-turn has been implicated as an important conformation for biological recognition of peptides or proteins. We adapted the concept of general Calpha atom positioning from the cluster analysis and recombination of each ideal beta-turn conformation pattern by Garland and Dean (J. Comput.-Aided Mol. Des. 1999, 13, 469) as one strategy of designing non-peptide beta-turn scaffolds. Herein, the Calpha positions of tetrahydro-1,4-benzodiazepin-2-one scaffold were analyzed after the calculation of the low-energy conformer using a semiempirical protocol. Three points of corresponding Calpha carbons for diverse substitutions in the scaffold were designated, and an efficient solid-phase synthesis of the peptidomimetic library was developed. The scaffold itself was synthesized in solution phase starting from 5-hydroxy-2-nitrobenzaldehyde and loaded to the 4-formyl-3,5-dimethoxyphenoxy (PL-FDMP) resin with high efficiency of reductive amination. Various building blocks for the derivatization of the 7-hydroxyl and N-1 amide nitrogen could be introduced via selective alkylation. Cleavage, parallel column chromatography, and NMR analysis of 62 final compounds confirmed the feasibility of this peptidomimetic library synthesis.     

Saturated heterocycles. Part 216 . Synthesis,structure and ring opening of trans-perhydro-1,4-benzoxazepin-3-one derivatives

trans-Perhydro-1,4-benzoxazepin-3-ones 2a-c were synthesized and transformed to condensed-skeleton perhydro-trans-1,4-benzoxazepines 3a,b , the thiones 4a,b , the urea derivatives 5a,b , and N-acylated compounds 6a-e . Compounds 6b,d were ring-opened by hydrochloric acid in ethanol to yield trans-2-(1-carbethoxyethoxy)-1-acylaminomethylcyclohexane derivatives 7b,d . The ¹H- and ¹³C-nmr investigation and X-ray analysis of 5b and 6c,d proved that the expected N-acylated derivatives were formed and that both rings of the trans anellated compounds have a chair conformation.     

A simple and facile synthesis of novel 1,2,3-triazole substituted pyrimidine derivatives

A series of novel indole and pyrimidine scaffolds bearing 1,2,3-triazoles have been designed and synthesized using click chemistry reaction conditions. Target compounds 9a-j were synthesized in the multi-step process. In the first step 5-substituted-1-methyl-1H-indole-3-carbaldehyde 2a-b reacted with ethyl cyanoacetate 3 and guanidine hydrochloride 4 in presence of L-Proline in ethanol undergoes cyclisation to form 5a-b . Further, 5a-b condensed with various benzaldehydes to form Schiff's base 6a-f , which further proporgylated with propargyl bromide to form 7a-f . Finally, 7a-f was subjected to click-chemistry with various azides in the presence of CuSO₄.5H₂O + sodium ascorbate mixture in Dimethylformamide at room temperature to obtain 2 + 3 cycloaddition products 9a-j in high yield. All these synthetic methods are mostly green and inexpensive with excellent yields.     

A novel and facile synthesis of 2,3-dihydrofuran derivatives containing trifluoromethyl group

A series of CF₃-containing 2,3-dihydrofuran derivatives were prepared via the reaction of arsonium bromides 1 with β,β-di(trifluoroacetyl)ethylene derivatives 2 in the presence of K₂CO₃, usually in a stereoselective manner with moderate yields. The structures of these compounds were confirmed by ¹H NMR, ¹³C NMR, IR, MS and HRMS as well.     

A novel and facile synthesis of mesoionic 1,2,4-triazolium-3-thiolate derivatives

Mesoionic 1,2,4-triazolium-3-thiolate derivatives were synthesized from the reaction of N-substituted-2-phenylhydrazinocarbothioamides with tetracyanoethylene (TCNE) to give tricyanovinyl intermediates, followed by heterocyclization to afford 5-(1-amino-2,2-dicyano-vinyl)-4-substituted-1-phenyl-4H-1,2,4-triazol-1-ium-3-thiolates in 67–76% yields. The structures of the products have been confirmed unambiguously by single crystal X-ray structure analyses. A rationale for the formation of the products is presented.     

A facile synthesis of 2-deoxy-2,3-didehydroneuraminic acid derivatives

The 2-thio- or 2-selenoglycosides of N-acetylneuraminic acid methyl ester were transformed by successive treatment with dimethyl(methylthio)sulfonium triflate (DMTST) and 1,8-diazabicyclo[5.4.0]-7-undecene (DBU) to give the corresponding methyl 2-deoxy-2,3-didehydroneuraminates in excellent yields. Their acids and their analogues are sialidase inhibitors of pharmaceutical interest.     

A facile synthesis of novel cyclodextrin derivatives incorporating one beta-(1,4)-glucosidic bond and their unique inclusion ability

Novel cyclodextrin derivatives incorporating one (1,4)-glucosidic bond are easily synthesized in three steps from permethylated alpha- and beta-cyclodextrins, and such host molecules show inclusion selectivity for sodium m-nitrobenzoate over the corresponding p-isomer, in contrast to the cases of the parent permethylated alpha- and beta-cyclodextrins.     

Stereoselective synthesis of 4-hydroxymethyl-1,3-oxazolidin-2-one derivatives from novel 2-hydroxymethylaziridines

A stereoselective and simple method for the synthesis of trans-2-hydroxymethyl-N-alkyl-1,3-oxazolidin-2-ones is described. The synthesis involved the reduction of trans-aziridine-2-carboxylates with LiAlH₄, followed by a ring opening and a cyclization reaction in the presence of methyl chloroformate to afford the target trans-oxazolidinones in completely regio- and stereoselective process. A plausible reaction mechanism has been proposed involving an S_N1 pathway and a detailed computational study of this mechanistic process has been carried out using theoretical calculations.     

Synthesis and NMR spectral assignments of novel 1,4-benzothiazepine-5-one derivatives

The one-pot reaction between 2-aminobenzo[d]isothiazol-3-one and alkyl propiolates in presence of triphenylphosphine leads to the corresponding alkyl 4-amino-5-oxobenzo[f][1,4]thiazepine-3-carboxylates. A plausible mechanism of the reaction is proposed and unambiguous evidence for the structures is obtained from a detailed magnetic resonance spectral analysis. 1D and 2D NMR spectra such as COSY, ¹H-¹³C and ¹H-¹⁵N HSQC and HMBC heteronuclear correlations and an INADEQUATE experiment are reported and discussed.     

Chemoselective synthesis and cytotoxic activity of a series of novel benzo[1,4]oxazin-3-one derivatives

That tetraacetonitrile copper perchlorate catalyzes intramolecular amidation of arenes was found to be a new strategy for construction of nitrogen-containing heterocycles and resulted in the formation of a series of novel benzo[1,4]oxazin-3-one derivatives from N-(1,3-diphenyl-1H-1,2,4-triazol-5-yl)-2-phenoxyacetamides.This approach of heterocyclic construction proceeds in a chemoselective manner in which only benzo[1,4]oxazin-3-one derivatives were obtained by C—N bonds formation with cheap and simple copper salt catalyst under mild conditions in moderate to good yields.The biological assay of some of benzo[1,4]oxazin-3-one derivatives showed that they had moderate antiproliferative activity toward MDA-MB231 and HeLa cancer cell lines.     

One-pot synthesis of some 2H-Pyran-2-one derivatives

A one-pot synthesis of various 2H-pyran-2-one derivatives 5–19 starting from methyl ketones 1 , N,N-dimethylformamide dimethyl acetal and N-acylglycines 3 in acetic anhydride is described.     

A novel highly stereoselective synthesis of 2,3-disubstituted 3H-quinazoline-4-one derivatives

[structure: see text]. An efficient three-step synthesis of chiral 3H-quinazoline-4-one derivatives from commercial materials is disclosed. The Mumm reaction of imidoyl chloride with alpha-amino acids followed by reductive cyclization affords enantiomerically pure (ee >93%) quinazoline-4-ones in good overall yield. A comparison with existing approaches indicates that this method is superior for hindered substrates.     

Communication: polymer-assisted solution-phase synthesis of 4,5-dihydro-1,4-benzoxazepin-3(2H)-ones

The polymer assisted solution phase (PASP) synthesis of 4,5-dihydro-1,4-benzoxazepin-3(2H)-ones is described. Using salicylic aldehydes, alpha-bromo acetic acid esters, and primary amines as broadly variable building blocks, the target molecules were obtained in a straightforward manner. The use of polymer bound reagents and scavengers greatly simplified workup, and avoided the use of protecting groups. A small library was prepared, showing the feasibility of the synthetic concept for the generation of larger sets of screening compounds.     

Synthesis of novel 1,3-dithiolan-2-one derivatives

Novel 1,3-dithiolan-2-one derivatives were prepared starting from α, β- or β, γ-dichlorinated carboxylic esters and potassium O-ethyl dithiocarbonate. The scope and the mechanism of this reaction were investigated. The biological uses of the compounds obtained here were examined.