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A two-step synthetic strategy toward difluoromethyl ethers via a CuI-catalyzed reaction of the alcohols, bearing additional protected functionalities, with FSO2CF2CO2H has been developed. The high potential of the developed protocol has been shown by preparing novel OCF2H-analogues of GABA and l-proline. The described transformation has good functional group compatibility and can serve as a powerful synthetic tool for late-stage preparation of complex OCF2H-containing organic compounds as well as building blocks for drug discovery.

Starting from readily accessible cyclic enaminoesters, arylisothiocyanates and α-haloketones, a facile method for the synthesis of ω-aminoalkylthiophene hydrobromides was developed. It was shown that in the first step cyclic enaminoesters react with arylisothiocyanates exclusively at the enamine position. Upon treatment with base, free 5-aminopentylthiophenes were prepared. In the case of shorter alkyl substituents (4-aminobutyl and 3-aminopropyl) the free ω-aminoalkylthiophenes undergo intramolecular condensation of the amino and ketone groups affording novel fused heterocycles—thieno[2,3-c]azepine and thieno[2,3-c]azocine.

In the presence of acetic acid anhydride (III), cyclic thioimidates with five-membered ring [e.g. (II)] react with compounds containing activated methylene group [e.g. (I)] to give aminopropanes [e.g. (IV)] as the major products.

A new method is proposed for obtaining 3,4-polymethylene-1,2,4-benzothiadiazine 1,1-dioxides by reacting o-halobenzenesulfonamides with lactim ethers. Attempts were undertaken to synthesize quaternary salts of the heterocycles obtained.

The reactions of cyclic nitroenamines with isocyanates were investigated. It was found that two different products could be obtained: in inert media β-carbamoyl products were observed and when a strong base was used 1,6-polymethylene-6-nitromethyl-1,3,5-triazine-2,4-dione derivatives were isolated.

New N-substituted 7-amino-1-nitro-2-heptanone derivatives have been obtained starting from readily accessible 2-(nitromethylidene)hexahydro-1H-azepine. These compounds have been further used as starting materials for the synthesis of some heterocycles with 5-aminopentyl fragment.

A study on the stepwise hydrolysis of hetarene- and cycloalkenecarboxamidophosphoryl dichlorides afforded the synthesis of hitherto unknown hetarene- and cycloalkene-carboxamidophosphoric acids as well as allowing the introduction of unsubstituted carbamoyl group in the molecules of pyrroles, indoles, indolizines, and some enamines.

Electron-rich N-substituted pyrazoles smoothly reacted with trifluoroacetic anhydride in pyridine to form the corresponding trifluoromethyl ketones in good yields.

A convenient and efficient route for the chemoselective synthesis of carbohydrazide, arenesulfonylhydrazide, and thiosemicarbazone derivatives of 5 H -pyrrolo[3,4- b ]pyrazine and 1 H -pyrrolo[3,4- b ]quinoxaline from the corresponding dinitriles and substituted hydrazines was elaborated. The synthesis of starting pyrazine-2,3-dicarbonitrile was sufficiently improved by using concentrated HCl as a catalyst.

The uncatalyzed title reaction produces various derivatives of the title heterocycle in good yields.

A wide range of imidazole-containing N-heterocycles is prepared via intramolecular C—H/C—Hal and C—H/C—H coupling reactions.

6,7,8,9-Tetrahydro-5H-[1,2,4]triazolo[4,3-a]azepin-3-ylacetonitrile reacts with carboxylic acid anhydrides and chlorides to afford acylation products at the nitrogen atom in the heteroring or methylene carbon atom, depending on the conditions and nature of the acylating agent. Heating of the N-acyl derivatives leads to migration of the acyl group with formation of C-acyl derivatives.

The synthesis of 3-acylated cyclic enones (III) is developed and their regioselective reaction with aminopyrazoles and 1,2,4-triazoles is studied.

An efficient method for the synthesis of dicarbonitrile (IV) and its conversion into pyrrolopyridinylidene carbohydrazides such as (VI) are described.

The reaction of 3-aminoisoquinolinone derivatives with aromatic aldehydes in the presence of Tms-Cl leads to the formation of fused naphthyridine and isoquinolinone derivatives.

5-Aminoimidazoles, prepared in situ from formimidate (II) and amines, react with title compound (I) to give the pharmaceutically important title skeleton (IV).

1-H-imidazole-5-amines, generated in situ from formimidate (II) and primary amines, react with chromenone (I) to produce imidazopyridines (IV) which represent potential adenosine deaminase inhibitors.

The reaction of 2-(cyanomethyl)benzoic acid (I) with hetarylamines (II) leads selectively to 3-aminoisoquinolinones (III).

N-Ethylcarbazole is electrophilically phosphorylated by phosphorus tribromide to give 9-ethylcarbazolyl-3-dibromophosphine under more forcing conditions than for pyrrole and indole.

Pyrroles, indoles, indolizines, and 2-methylfuran are vigorously C-acylated with isocyanatophosphoryl dichloride. The resulting heteroaryl-substituted isocyanatophosphoryl dichlorides provide a convenient access to a variety of products.© 1999 John Wiley & Sons, Inc. Heteroatom Chem 10: 343–348, 1999

Novel pyrazolo[5,4-b]azaphosphinine and pyrazolo[4,5-e]diazaphosphinine ring systems have been synthesised from 4-phospho-rylated 5-form-amidinopyrazoles.

A preparative approach towards 1-desazapurines, start- ing from 4(5)-aminoimidazoles and polyfluoroalkyl-containing 1,3- CCC-biselectrophiles was developed. As a result, a set of fluorinat- ed 1-desazapurines was synthesized. Additionally, a synthetic route to 1-desazapurines bearing a sugar-mimicking group is proposed.

Starting from 5-amino-1-(2,3-O-isopropylidene-b-D-ri- bofuranosyl)-1H-pyrazole, fluorine-containing 1,3-CCC-, 1,3-CNC- dielectrophiles and 2,4,6-tris(trifluoromethyl)-1,3,5-triazine, a set of fluorinated pyrazolo(3,4-b)pyridine and pyrazolo(3,4-d)pyrimi- dine nucleosides was obtained. Synthetic access to stable 4-(poly- fluoroalkyl)-4,7-dihydro-1H-pyrazolo(3,4-b)pyridin-4-ole was elaborated, which can be considered to be mimetics of the putative transition state involved in adenosine deaminase activity.

Isothiocyanatophosphonium salts bearing an aroxy group at the phosphorus atom have been obtained for the first time. As found, these compounds undergo an intramolecular heterocyclization to give hitherto unknown benzoxazaphosphininethiones or cyanoiminophosphoranes, according to the nature of the substituents on the aryl ring. © 2008 Wiley Periodicals, Inc. Heteroatom Chem 19:667–670, 2008; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/hc.20491

The reaction of 2-aminothiazol-4(5H)-iminium salts with various 1,3-CCC-dielectrophiles was investigated. As a result, a set of diverse thiazolo[4,5-d]pyridines were obtained. The scope and limitation of the approach is described.

A new method based on the reaction of 4-bromo-1,3-diphenyl-2-buten-1-one with imidazoles and benzimidazoles was proposed to obtain imidazo[1,2-a]pyridinium and pyrido[2,1-b]benzimidazolium salts.

In situ generated benzofuran-2-amine reacts with 1,3-CCC-dielectrophiles, such as CF 3 -containing β-diketones, 3-formylchromone, methyl-2,4-dioxopentanoate and pentafluoro-benzaldehyde, and the reaction leads to the formation of benzofuro[2,3- B]pyridine ring system. By using a similar approach 4-trifluoromethyl-α-carbolines were synthesized starting from indole-2-amine.

The reaction of 2-(dialkylamino)-1,3-thiazol-4-amines and 1,2-dimethyl-1 H-imidazol-5-amine with aryl isocyanates, α-chloroalkyl isocyanates, N-(alkoxycarbonyl)imidoyl chlorides and 2,4,6-tris(trifluoromethyl)-1,3,5-triazine leads to thiapurines and purines containing trifluoromethyl groups in the 2- and 6-positions of the pyrimidine ring.

N,N'-Diarylureas having electron-donating substituents at appropriate positions react with phosphorus(III) bromide forming the new heterocyclic system 2,4,1-benzodiazaphosphinan-3-one. N-(5-Pyrazolyl), N'-arylureas, and N,O-diarylcarbamates also undergo an analogous heterocyclization affording 1H-pyrazolo[4,3c][1,5,2]diazaphosphinan-3-one and 2,4,1-benzoxazaphosphinan-3-one ring systems.

A method was developed for preparation of 5-amino-4-(4-aryl-2-thiazolyl)-2,3-dihydro-2-pyrrolones by alkylation of 4-aryl-2-thiazolylacetonitriles by N-substituted chloroacetamides in the presence of K2CO3. In 1-(1-naphthyl)-substituted pyrrolones atropoisomerism was observed.

A reaction of cyclohexanone phenylhydrazone with (het)aryldihalogenophosphines has been studied. As shown, cyclohexanone phenylhydrazone reacts with phenyldibromophosphine and 5-methyl-2-furyldibromophosphine to provide the corresponding 1,2,3-diazaphospholines in high yields. The diazaphospholines thus obtained have been derivatized. © 2005 Wiley Periodicals, Inc. Heteroatom Chem 16:81–83, 2005; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/hc.20074

At room temperature, N-(1-chloro-2,2,2-trihaloethylidene)-O-methyl urethanes react with 2-aminothiophenes to form N-(2-thienyl)-N'-(methoxycarbonyl)trihaloacetamidines, which when heated in boiling toluene undergo ring closure to form 2-trihalomethyl-3,4-dihydrothieno[2,3-d]pyrimidin-4-ones.