Synthesis of 5-aminothiazoles as building blocks for library synthesis

A convenient route to 4-phenyl-5-aminothiazoles is described, which offers control over substitution at the 2-position. 2-N-Acylglycinamides were dithionated and a subsequent TFAA-mediated cyclisation step was followed by removal of the 5-N-trifluoroacetyl group providing the free amines. Though applicable generally the method was found to be most effective when introducing aromatic substituents at the 2-position, whereupon moderate overall yields of the 5-amino compounds were obtained.     

A simple synthesis of 2,4-diaryl-1,3,5-triazines

Summary Arylamidines2 react with 5-methoxymethylen-2,2-dimethyl-1,3-dioxan-4,6-dione5 to give 2,4-diaryl-1,3,5-triazines in moderate to good yields.5 can be comprehended as a formic acid derivative which transfers a C₁-building block. Other formic acid derivatives give only poor to moderate yields of triazines by treatment with amidines. The synthetic method is applicable to aromatic amidines.

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Eine einfache Synthese von 2,4-Diaryl-1,3,5-triazinen

Zusammenfassung Die Arylamidine2 reagieren mit 5-Methoxymethylen-2,2-dimethyl-1,3-dioxan-4,6-dion5 in guten Ausbeuten zu 2,4-Diaryl-1,3,5-triazinen. Verbindung5 kann als Derivat der Ameisensäure aufgefaßt werden, welches einen C₁-Baustein überträgt. Andere Derivate der Ameisensäure ergeben bei Umsetzung mit Amidinen nur schlechte Ausbeuten an Triazinen. Die beschriebene Methode ist auf aromatische Amidine anwendbar.

     

A general synthesis of 2-substituted-5-aminooxazoles: building blocks for multifunctional heterocycles

Condensation of unsubstituted isocyanoacetamides with aldehydes and ketones, or their derived iminium ions, leads to 2-substituted-5-aminooxazoles, which are useful compounds for drug discovery programs.     

A practical approach to the synthesis of 2,4-disubstituted oxazoles from amino acids

[reaction: see text] A new sequence for the synthesis of various 2,4-disubstituted oxazoles from alpha-amino acids is reported. The method is shown to be general and incorporates the reagent combination, triphenylphosphine/hexachloroethane, for cyclodehydration of intermediate alpha-acylamino aldehydes. Implementation of this reagent system for the conversion of alpha-acylamino ketones to oxazoles is briefly investigated.     

A practical synthesis of （-）fosfomycin from its enantiomer

（＋）-cis-（1S, 2R）-Epoxypropylphosphonic acid, the enantiomer of fosfomycin, which is the industrial side-product in the preparation of the antibiotic fosfomycin, was converted into （-）fosfomycin by a seven-step procedure. The esterification of the dihydroxyphosphonic intermediate was the key step. The title compound was obtained in good yield and its optical purity was up to the medicine quality standard of Chinese Pharmacopoeia.     

A simple synthesis of 5-substituted-thiophene-2 (3H)-thiones

Treatment of 1-alkyne and allene derivatives successively with two equivalents of n-Buli, one equivalent of CS₂ and then an electrophile yielded novel 5-substituted-thiophene-2 (3H)-thiones $\text{4}$.     

Domino electrocyclization/azide-capture/schmidt rearrangement of dienones: one-step synthesis of dihydropyridones from simple building blocks

Simple 1,4-dien-3-ones undergo Lewis acid-catalyzed Nazarov electrocyclization and intermolecular trapping by various azides to furnish 3,4-dihydropyridin-2-ones in moderate to good yields. The reaction is proposed to proceed via nucleophilic trapping of the 2-oxidocyclopentenyl intermediate, followed by Schmidt-type rearrangement to give a transient 1,4-dipole. In unsymmetrical examples, complete regioselectivity in favor of attack on the less substituted side was observed. The 1,4-dipole intermediate then rearranges to the observed dihydropyridone, via either proton transfer or 1,5-hydride shift.     

Macrocycles from simple building blocks by a multifold Heck-type coupling reaction

Diiodobenzenes and bisallylic alcohols—two equivalents of each—were coupled under palladium catalysis to give oxofunctionalized macrocycles as 2:2 products. The 1:1 products as medium sized rings were disfavoured and not observed.     

Efficient and practical synthesis of 4(5)-aryl-1H-imidazoles and 2,4(5)-diaryl-1H-imidazoles via highly selective palladium-catalyzed arylation reactions

4(5)-aryl-1H-imidazoles can be efficiently and selectively prepared by PdCl2(dppf)-catalyzed Suzuki-Miyaura reaction of commercially available 4(5)-bromo-1H-imidazole with arylboronic acids under phase-transfer conditions. On the other hand, N-unprotected 4(5)-aryl-1H-imidazoles can undergo highly selective Pd(OAc)2-catalyzed and CuI-mediated direct C-2-arylation with a variety of aryl bromides and iodides under base-free and ligandless conditions to produce 2,4(5)-diaryl-1H-imidazoles in modest to good yields. No N-arylation byproducts are observed under the experimental conditions used to prepare 2,4(5)-diaryl-1H-imidazoles.     

Design and synthesis of macromolecular structures from self-assembling building blocks

The self-assembling properties of a variety of building-blocks are used to generate different types of nanostructures, e.g. molecular golfballs, molecular tubes, and molecular braids.     

Organocatalytic asymmetric synthesis of 5-(trialkylsilyl)cyclohex-2-enones and the transformation into useful building blocks

A simple organocatalytic approach to highly attractive chiral building blocks is presented. By the reaction of beta-ketoesters with alpha,beta-unsaturated aldehydes using a chiral TMS-protected prolinol as the catalyst, optically active 5-(trialkylsilyl)cyclohex-2-enones are formed in good yields and with 98-99% ee. The applications of 5-(trialkylsilyl)cyclohex-2-enones for the formation of 5-(hydroxy)cyclohex-2-enones and the A-ring of 19- nor-1alpha,25-dihydroxyvitamin D3 are also presented.     

A simple one-step synthesis of 3-amino-2,4(1H,3H)quinazolinediones

Anthranilic acids and alkyl carbazates in refluxing quinoline give high yields of 3-arnino-2,4(1H,3H)-quinazolinediones.     

Versatile building blocks from disaccharides: glycosylated 5-hydroxymethylfurfurals

A practical protocol for the elaboration of O-glycosyl-HMF’s from glycosyl-(1→6)-glucoses is reported, the two steps involving aluminate-promoted isomerization to the respective 6-O-glycosyl-fructoses and subsequent selective dehydration of the fructose portion. Accordingly, melibiose, gentiobiose, and primeverose are converted into the corresponding 2-uloses and, then, into α-GalMF 11, β-GMF 12, and β-XylMF 13. Pt/C-catalyzed oxidation with oxygen in NaOH at 25 °C efficiently generated the respective furoic acids from α-GalMF and α-GMF, whilst Pt/O₂ in water at 50 °C also oxidizes the primary OH to give the dicarboxylic acids 15 and 17–key building blocks for the generation of novel types of polyesters and polyamides.     

An efficient and practical synthesis of 2,4-substituted pyrido[4,3-d]pyrimidin-5(6H)-ones

We describe an efficient synthesis of 2,4-substituted pyrido[4,3-d]pyrimidin-5(6H)-ones, which involves the acid-promoted cyclization of cyano enamine 15 to afford 2,4-bis(methylthio)pyrido[4,3-d]pyrimidin-5(6H)-one 17 as a key intermediate. Selective displacement of the 4-methylthio group by a wide range of anilines followed by oxidation of the 2-methylthio group and subsequent substitution by amines enabled the synthesis of a variety of 2,4-disubstituted pyrido[4,3-d]pyrimidin-5(6H)-ones.     

A practical synthesis of (±)-thienamycin

An efficient and operationally simple synthesis of (±)-thienamycin is described.     

Novel synthesis of 5-halouracils from 5-mercuri-2,4-dimethoxypyrimidines

Direct C-mercuration of 2,4-dimethoxypyrimidine with mercury (II) acetate has been shown to give the 5-mercuri-derivative, which is readily converted, either directly or via 5,5 -mercuribis (2,4-dimethoxypyrimidine), into the 5-halo derivatives. Hydrolysis of the latter with hydrochloric acid affords the 5-halouracils.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 2, pp. 249–252, February, 1989.