Solid-phase synthesis of the 2-aminobenzoxazole library using thioether linkage as the safety-catch linker

An efficient solid-phase methodology has been developed for the synthesis of 2-aminobenzoxazole derivatives. The key step in this procedure involves preparation of polymer-bound 2-mercaptobenzoxazole resins 3 by reaction of the Merrifield resin with 2-aminophenols and CS(2) in the presence of DIC in MeCN. Oxidation of the resulting resins followed by treatment with amines gives the desired 2-aminobenzoxazole products 5. Further diversification can be introduced to the key resin 11, derived from the nitro group containing resin 3c. This process produces the corresponding amine, which upon reaction with acid chlorides and isocyanates can be used to generate various 6-functionalized 2-aminobenzoxazole analogues 13 and 15.     

Pyrido[2,3-c]furoxan as a probable intermediate in the reaction of 2-nitro-3-azidopyridine with amines

Two parallel reactions, viz., cyclization of 2-nitro-3-azidopyridine to pyrido-[2,3-c]furoxan, which is aminated in the 6 position of the pyridine ring with opening of the furoxan ring, and reduction of the azido group to form 2-nitro-3-aminopyridine, occur in the reaction of 2-nitro-3-azidopyridine with amines. It was established that pyrido[2,3-c]furoxan reacts with amines in aqueous media in the 1-oxide form.Deceased.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 5, pp. 654–657, May, 1981.     

Study on the reactions of 4-amino-5-nitro-6-phenylethynylpyrimidines with amines and thiols

Reactions of 4-amino-5-nitro-6-phenylethynylpyrimidines with amines and thiols have been investigated. Pyridine catalyzes rearrangement of the title compounds into 6-phenyl-7-oxo-7H-pyrrolo[3,2-d]pyrimidine-5-oxides. Primary and secondary amines and thiols take part in a regio- and stereoselective addition reaction to the triple bond of 5-nitro-6-phenylethynylpyrimidines to form the corresponding syn-addition (in the case of secondary amines) or anti-addition (in the case of primary amines or thiols) products.     

Synthesis of 2-Amino- and 2-Hydrazino-substituted 5-Nitro-4,6-diphenylpyrimidines

Nitrogen-containing derivatives of 5-nitro-4,6-diphenylpyrimidine have been synthesized by the reaction of 2-chloro-5-nitro-4,6-diphenylpyrimidine with amines or of 2-hydrazino-5-nitro-4,6-diphenylpyrimidine with carbonyl or -dicarbonyl compounds. Their structures were confirmed by data of IR spectroscopy and mass spectrometry.     

Synthesis and IR spectra of some 2-aminobenzoxazole derivatives

A large number of 5-nitro-, 6-nitro-, 5-chloro-, and 6-bromo-2-aminobenzoxazoles were synthesized by the reaction of benzoxazoline-2-thiones with various amines. It was shown by IR spectroscopy that all of the compounds exist in the amino form in solution, whereas the 5-substituted compounds exist in the imino form in the solid state, and the 6-substituted compounds exist simultaneously in the two forms.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 5, pp. 604–607, May, 1981.The authors thank T. Dukhova, P. Braikov, I. Nachev, and T. Georgieva for their assistance in carrying out several of the experiments.     

Formation of anilines from 5-nitro-2-phenylpyrimidine,amines, and acetone

The reaction of 5-nitro-2-phenylpyrimidine with aliphatic amines and acetone gaveN-substituted 4-nitroanilines. In addition, 2-methyl-5-nitropyridine was also obtained from ethylamine.Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 6, pp. 1102–1104, June, 1994.     

Synthesis of 5H-[1,3]thiazolo[3,2-a]pyrimidin-5-one derivatives

The reaction of 2-aminothiazoles with ethyl acetoacetate in acetic or polyphosphoric acid gave a series of 5H-[1,3]thiazolo[3,2-a]pyrimidin-5-one derivatives which were nitrated with a mixture of nitric and sulfuric acid to 6-nitro-5H-[1,3]thiazolo[3,2-a]pyrimidin-5-ones, and the latter were reduced to the corresponding amines.     

Ringöffnung von Nitrothiazolen

The reaction between 2-halogeno-5-nitro-thiazoles and amines has been studied. Especially the sterically hindered strongly basic secondary aliphatic amines tend to cause opening of the thiazole ring system, resulting in the formation of the heretofore unknown (1-nitro-2-amino-vinyl)-thiocyanates. The ring opening is favored by a highly polar solvent, such as dimethyl sulfoxide. A simple reaction mechanism is proposed and some properties of these new compounds are discussed.     

Nucleophilic amination of 2-iodo-3-nitro-1-(phenylsulfonyl)indole

The reaction of 2-iodo-3-nitro-1-(phenylsulfonyl)indole (2) with amines affords the corresponding 2-amino-3-nitroindoles in excellent yields via nucleophilic aromatic substitution.     

Synthesis of benzoxazole sulfanilamide derivatives

A number of hitherto undescribed 2-(p-aminobenzenesulfamide) benzoxazoles are prepared by treating 2-aminobenzoxazole or its 6-substituted compounds with p-carbomethoxyaminobenzenesulfochloride or p-acetylaminobenzenesulfochloride, followed by alkaline hydrolysis. A similar reaction with 6-amino-2-hydroxy- and 2-mercaptobenzoxazoles gives 6-(p-aminobenzenesulfamido)-2-hydroxy- and 2-mercaptobenzoxazoles.The work was done by E. N. Padeiska of the Chemotherapy Division of VNIKhFI (All-Union Pharmaceutical Chemistry Research Institute).     

Synthesis of 3-nitro- and 3-aminoquinoline-2,4-diones. An unexpected route to 3-hydroxyquinoline-2,4-diones

Nitration of 3-substituted-4-hydroxy-2(1H)-quinolones 1 with nitric acid leads either to 3-nitro- 2 or 3-hydroxyquinolinediones 3 , depending on the reaction conditions. 3-Substituted-3-hydroxyquinolinediones 3 are also obtained by oxidative hydroxylation with peracetic acid. Amination of 3-substituted-3-chloroquinolinediones 4 with ammonium hydroxide predominantly leads again to 3-substituted-3-hydroxyquinolinediones 3 , only in one case the 3-aminoquinolinedione 5 could be isolated. With morpholine or pyridine as amines the expected 3-aminoquinolinediones 6 and 7 were obtained.     

含可聚合基团的萘酰亚胺衍生物的合成

以4-溴-1,8-萘酐和4-硝基-1,78-萘酐为起始原料,与各种芳胺经亚胺化,再与脂肪胺经取代反应,最后与丙烯酰氯经酯化得到一系列具有强烈荧光的含丙烯酰氧乙基氨基的1,8-萘酰亚胺衍生物,它们可作为一种聚合荧光色素的单体。     

Facile solid phase synthesis of 1,2-disubstituted-6-nitro-1,4-dihydroquinazolines using a tetrafunctional scaffold

Solid phase synthesis of 1, 2-disubstituted-6-nitro-1,4-dihydroquinazolines is described. The new tetrafunctional scaffold N-Alloc-3-amino-3-(2-fluoro-5-nitrophenyl)propionic acid was prepared by nitration of 3-amino-3-(2-fluorophenyl)propionic acid. The scaffold was anchored to Rink resin via its carboxylic group and treated with primary amines to displace the arylfluorine followed by cyclization with aryl isothiocyanates in the presence of DIC upon Alloc deprotection to afford 1,2-disubstituted-6-nitro-1,4-dihydroquinazolines in high yield.     

Synthesis of substituted diazines,diazoles, and condensed thia- and oxadiazoles

The corresponding 2-arylhydrazono-3-oxoimidazo[1,2-a]pyridines, 3-arylhydrazono-2-oxoimidazo [1,2-a]benzothiazoles, 2-oxoimidazolidino[3,2-a]benzimidazoles, 2-oxoimidazo[1,2-a]benzoxazoles, and 2-arylhydrazono-3-oxothiazolo[2,3-a]benzimidazoles were obtained by the condensation of arylazochloroacetyl chlorides with 2-aminopyridine, 2-aminobenzothiazole, 2-aminobenzoxazole, 2-aminobenzimidazole, and 2-mercaptobenzimidazole. 5-Arylhydrazono-1,2-diphenylimidazole-4-ones and 5-arylhydrazono-3,4-diaryl-1,2,4-oxidiazine-6-ones were synthesized by the reaction of arylazochloroacetyl chlorides with N-phenylbenzamidine and N-phenylamidoxime.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 7, pp. 930–936, July, 1971.     

The synthesis of compounds with potential antitubercular activity

A number of new N-(2-benzoxazolyl)-N-phenylthioureas have been prepared by the reaction of 2-aminobenzoxazole and of its 6-substituted derivatives with phenyl and p-alkoxyphenyl isothiocyanates.For part XII, see [5].     

Solid phase synthesis of 6-acylamino-1-alkyl/aryl-4-oxo-1,4-dihydrocinnoline-3-carboxamides

6-Acylmino-1-alkyl/aryl-4-oxo-1,4-dihydrocinnoline-3-carboxamides were synthesized in parallel from 6-nitro-4-oxo-1,4-dihydrocinnoline-3-carboxylic acid. The latter formed amides with amines bound to polystyrene-based resins via acid-labile linkers. N1 and N2-alkylation, followed by alkyl migration yielded only N1-alkylated products. Reduction of the 6-nitro group and acylation concluded the synthesis.     

Competitive nucleophilic substitution reactions of methylsulfonyl and nitro derivatives of polychloropyridines

2,6-Di(methylsulfonyl)-3,4,5-trichloropyridine (II) and 4-nitro-2,6-di(methyl-sulfonyl)-3, 5-dichloropyridine (IX) were synthesized, and their reactions with nucleophilic reagents were studied. It was found that the methylsulfonyl groups are replaced on reaction with alkali and sodium alkoxides; on reaction with amines, the chlorine atoms are replaced in the case of II and the nitro group is replaced in the case of IX. The nitro and methylsulfonyl groups are simultaneously replaced in the reaction of excess sodium methoxide with IX.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 6, pp. 802–806, June, 1975.     

Synthesis and reactions of 1-(2-oxopropyl)pyridazin-6-ones

Oxopropylation of 4,5-dihalopyridazin-6-ones with chloroacetone afforded the corresponding 1-(2-oxo-propyl) derivatives. Reaction of title compound with nucleophiles such as amines, alkoxides were investigated. In addition, selective reduction of 3-nitro-1-(2-oxopropyl)pyridazin-6-ones with iron/ammonium chloride in two phase solutions or zinc in acetic acid gave the corresponding 3-amino or 3-hydroxyimino derivatives.     

Azolyl derivatives of nitrohalobutadienes: IV. Synthesis of 4-amino derivatives of 1-azolyl-1-arylamino-2-nitrotrihalo-1,3-butadienes

Reactions of l-(benzotriazol-l-yl)-l-(4-R-phenylamino)- and l-(3,5-dimethylpyrazol-l-yl)-l-(4-R-phenylamino)-2-nitro-3,4,4-trichloro-l, 3-butadienes and also l-(benzotriazol-l-yl)-l-(4-R-phenylamino)- and l-(3,5-dimethylpyrazol-l-yl)-l-(4-R-phenylamino)-2-nitro-4-bromo-3,4-dichloro-l,3-butadienes (R = EtO, MeO, Me) with amines proceed with replacement of the terminal chlorine in the trichlorovinyl group or of bromine in the bromodichlorovinyl group by an amine rest to yield the corresponding l-azolyl-4-amino-l-arylamino-2-nitro-3,4-dichloro-l,3-butadienes. When binucleophilic reagents (ethylenediamine and 2-aminoethanol) are used only one N-nucleophilic site of the nucleophile takes part in the reaction. For communication III, see [1].     

Nucleophilic substitution in 1-alkyl-4,5-dichloro-3-nitropyridazin-6-ones

Treatment of 1-alkyl-4,5-dichloro-3-nitropyridazin-6-one with C-nucleophiles and with ambident nucleophiles (2-azahetarylacetonitriles) leads to a selective substitution of a chorine atom by the quaternary carbon atom of the carbanion formed from a substituted acetonitrile. The pK_a of the CH-acid 2-(1-alkyl-5-chloro-3-nitro-6-oxo-1,6-dihydro-4-pyridazinyl)malononitrile was determined by potentiometric titration. Reaction of 2-(1-alkyl-5-chloro-3-nitro-6-oxo-1,6-dihydro-4-pyridazinyl)-2-hetarylacetonitriles with primary amines gives 6,7-dihydro-1H-pyrrolo[2,3-d]pyridazin-7-ones. __________ Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 4, pp. 556–564, April, 2006.