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.     

Ugi four-component condensation with two cleavable components: the easiest synthesis of 2,N-diarylglycines

The Ugi four-component condensation between anilines, aromatic aldehydes, isocyanides, and α-oxoacids afforded the expected adducts which were cleaved in mild conditions to give 2,N-diarylglycines in high yields.     

Aldehyde components for use in four-component condensation (“4CC”) Ugi reaction peptide synthesis

The use of 9-formylfluorene as the aldehyde component in four-component condensation (4CC) fragment strategy peptide synthesis has been investigated in the synthesis of model dipeptides.     

Solvent-free Ugi four-component condensation: application to synthesis of philanthotoxins-12 analogues

Philanthotoxins-12 analogues was synthesized by a highly convergent approach, utilizing an efficient, simple, and convenient one-pot Ugi four-component solvent-free method as key step, followed by removal of the protecting groups in the presence of trifluoroacetic acid.     

Liquid-phase combinatorial synthesis of alicyclic beta-lactams via Ugi four-component reaction

[reaction: see text] Alicyclic beta-lactams were successfully synthesized via a parallel liquid-phase Ugi four-center three-component reaction (U-4C-3CR), starting from alicyclic beta-amino acids such as cis-2-aminocyclohexanecarboxylic acid, cis-2-aminocyclopentanecarboxylic acid, 2,3-diexo-3-aminobicyclo[2.2.1]heptane-2-carboxylic acid and some of their partially unsaturated analogues. A six-membered mixture-based combinatorial library of beta-lactams was also generated.     

Synthesis of diverse phenylglycine derivatives via transformation of Ugi four-component condensation primary adducts

3-(N-Substituted)amino-4-arylamino-1H-isochromenones (isocoumarins) which can be regarded as the enediamine tautomers of the Ugi four-component condensation primary adducts between 2-formylbenzoic acids, arylamines, and isocyanides undergo a facile ring cleavage with amines to give a series of phenylglycine derivatives. Thus, a synthetically useful post-condensation transformation of Ugi four-component condensation primary adducts is described for the first time.     

A versatile approach to hybrid thiadiazine-based molecules by the Ugi four-component reaction

Aiming at developing a versatile method for the generation of hybrid heterocyclic molecules, we describe a sequential approach comprising the formation of carboxy-functionalized 1,3,5-thiadiazines followed by the Ugi reaction with variation of the amino and the isonitrile components. The method enables the generation of structurally diverse molecular hybrids including peptide, lipid, steroidal and sugar moieties linked to the 1,3,5-thiadiazine scaffold.     

A simple synthesis of ferrocenyl bis-amides by a Ugi four-component reaction

An efficient and simple synthesis of ferrocenyl bis-amides by the Ugi four-component reaction of ferrocenecarboxaldehyde, carboxylic acids, isocyanides and amines in methanol at room temperature is reported.     

Practical preparation of ethyl 2-methylthiophene-3-carboxylate

A safe and efficient process for the preparation of ethyl 2-methylthiophene-3-carboxylate (5) was devised. This process provides several advantages over the precedents, involving operational simplicity, avoidance of the use of strong bases such as n-butyllithium and application of noncryogenic conditions, and enabled to prepare 5 in 52% overall yield from commercially available 2-methylthiophene on a multikilogram scale.     

6-氯-2-氯甲基-3-喹啉甲酸乙酯与胺的反应研究

以6-氯-2-氯甲基-3-喹啉甲酸乙酯(1)为底物,在溶剂无水乙醇中与胺及胺的衍生物2a-p反应,以较好的收率(64.8-77.7%)得到7-氯-2,3-二氢-1H-吡咯并[3,4-b]喹啉-1-酮衍生物,其中与芳胺反应生成N-芳基取代的化合物3a-i,与氨水、甲胺、乙胺和苄胺反应生成N-烷基取代的化合物3j-m,与乙二胺、丙二胺及丁二胺反应生成具有对称结构的化合物3n-p.该反应具有操作简便、条件温和等特点.所有化合物均为新化合物,其结构经IR、1H NMR、13C NMR、MS和HRMS得以证实.     

The reaction of ethyl 4H-pyran-4-one-2-carboxylate with 1,2-diaminobenzene

Ethyl 4H-pyran-4-one-2-carboxylate was allowed to react with 1,2-diaminobenzene and related diamines. The resulting products were found to be 8H-5,6-dihydro-6,8-dioxopyrido[1,2-a]quinoxaline and derivatives. The synthesis 3H-5,6-dihydrobenzo[g]pyrido[1,2-a]quinoxaline-3,5-dione ( 2c ) constitutes the synthesis of a derivative of previously unknown benzo[g]pyrido[1,2-a]quinoxaline ring system.     

Direct synthesis of the arylboronic acid analogues of phenylglycine via microwave-assisted four-component Ugi reaction

A four-component Ugi reaction (Ugi-4CR) utilizing formylphenyl boronic acids under mild condition was developed for the synthesis of arylboronic acid analogs. The reactions were performed in methanol and accelerated by microwave irradiation, which makes this strategy suitable for constructing boronic-containing chemical libraries. Two of the synthesized analogs were found to have cytotoxic activity against HepG2, MDA-MB231, and A549 cancer cell lines, demonstrating the potential application of this approach in developing novel boron-containing pharmaceuticals.     

Studies on isocyanides: synthesis of tetrazolyl-isoindolinones via tandem Ugi four-component condensation/intramolecular amidation

The Ugi four-component condensation between methyl o-formylbenzoates 1, anilines 2a-c, isocyanides 3, and trimethylsilyl azide (4) afforded the expected Ugi adducts 5a-d, which were cyclized to the title compounds 6a-d upon treatment with sodium ethoxide in ethanol. Starting from aralkyl- or alkylamines 2d-g the Ugi adducts underwent a spontaneous cyclization to tetrazolyl-isoindolinones 6e-j.     

Skeletal diversity by allylation/RCM on Ugi four-component coupling reaction products

Here, we report a diversity-oriented synthetic approach toward skeletally diverse, cyclized peptidomimetics with diverse appendages. Starting from α-(N-acylamino)amides with various appendages, 12 to 16-membered lactams with defined olefin geometry were synthesized by a common synthetic sequence. We also synthesized the macrocycle in a liquid phase directed toward a construction of the peptidomimetics library.     

Synthesis of tetrazolodiazepines by a five-centered four-component azide Ugi reaction. Scope and limitations

Tetrazolo[1,5-a][1,4]benzodiazepines were obtained by an efficient azide five-centered four-component Ugi reaction, which used ketones, sodium azide, ammonium chloride, and the corresponding isonitrile. Scope and limitations of this multi-component reaction were considered.     

Direct aldol condensation reaction of ethyl diazoacetate with trifluoromethyl ketones

An efficient and direct aldol-type condensation of ethyl diazoacetate with trifluoromethyl ketones was developed in the presence of dialkyl zinc. A series of trifluoromethylated products were obtained in good to excellent yields (60-95%). A preliminary extension to a catalytic enantioselective aldol reaction of ethyl diazoacetate to trifluoromethyl ketones (up to 72% ee) is also described.     

Lewis acid-catalyzed formation of Ugi four-component reaction product from Passerini three-component reaction system without an added amine

In the presence of a Lewis acid the phenol-Passerini three-component reaction (phenol-P-3CR) system is found to deliver a product of the phenol-Ugi four-component reaction (phenol-U-4CR). It is the first demonstration of an isocyanide as an amine equivalent in isocyanide-based multicomponent reactions (IMCRs). In general, by using Ti(O-i-Pr)₄ in MeOH both phenol-U-4CR and U-4CR products are synthesized from an aromatic aldehyde, a phenolic or carboxylic acid, and an isocyanide. Moreover, by using MeCN as the solvent, the phenol-P-3CR products can be obtained in good yields without contamination of the phenol-U-4CR products.     

The condensation of ethyl phenylpropiolale with 3-pyridylacetonitrile

The reaction of 3-pyridylacetonitrile with ethyl phenylpropiolate gave not only the expected 3-hydroxy-5-phenyl-2-(3-pyridyl)pent-2-en-4-ynenitrile (IX) but also a di-Michael addition product of one molecule of the pyridylacetonitrile and two molecules of the acetylenic ester, ethyl 4-earbethoxy-3,5-diphenyl-6-(3-pyridyl) anthranilate (IV). Moreover, 2-elhoxy-6-phenyl-3-(3-pyridyl)pyrid-4-one (XIV) was also isolated as the eyclization product obtained after the addition of a molecule of ethanol to compound IX. Ir and ninr spectra arc reported for all products.