Synthesis of 3-[(aryl)-1,2,4-oxadiazol-5-yl]propionic acids

Seven 3,5-disubstituted oxadiazole derivatives, 3a-g , have been prepared by direct condensation of appropriate benzamidoxime with succinic anhydride. Spectroscopic properties, especially uv, ir and mass spectra confirmed the cyclic 1,2,4-oxadiazole structure. No ring-opened intermediate or side product could be observed. The ¹H-nmr assignments of the two CH₂ groups were unequivocally made by acid- and base-induced shifts.     

Synthesis and reactions of β-(5-halo-3-uracyl) propionic acids

The reaction of elementary bromine and iodine with -(3-uracyl)-propionic acid has given the corresponding -(5-bromo-3-uracyl) and -(5-iodo-3-uracyl)propionic acids. The methyl esters and amides of the acids have also been synthesized for the first time.     

Synthesis of α-methyl-β-(3-methylpyrazol-1-yl)-and α-methyl-β-(5-methylpyrazol-1-yl)propionic acids and their esterification with vinyl acetate

α-Methyl-β-(3-methylpyrazol-1-yl)-and α-methyl-β-(5-methylpyrazol-1-yl)propionic acids were synthesized by reaction of 3(5)-methylpyrazole with methyl methacrylate, followed by separation of the resulting isomeric esters and their hydrolysis. Esterification of the title acids was performed via vinyl exchange reaction with vinyl acetate in the catalytic system mercury acetate-trifluoroacetic acid.     

Synthesis of 2-(5-hydroxymethyl-2-formylpyrrol-1-yl)propionic acid lactone

2-(5-Hydroxymethyl-2-formylpyrrol-1-yl)propionic acid lactone was synthesized in six steps with a 17.0% overall yield, starting from L-alanine. The synthetic route involved the Clauson-Kaas reaction, Vilsmeier reaction, and transesterification. The transesterification was the key step in the formation of the target compound.     

Synthesis of 1,3-diketones from 3-(4-R-phenyl)propionic acids

Self-acylation of 3-(4-R-phenyl)propionic acids (R = H, Br, 1-adamantyl) in trifluoroacetic anhydride catalyzed by trifluoromethanesulfonic acid provides a simple and efficient synthesis of 1,3-diketones. Indan-1-ones formed in the first step undergo acylation to give the corresponding 2-(3-phenyl-1-oxopropyl) indan-1-ones as the major products. One-pot synthesis of polysubstituted pyrazoles directly from 3-(4-R-phenyl)propionic acids is described.     

Synthesis of 3- and 5-amino-5-(3)-(pyrrol-2-yl)isoxazoles

5-Amino-3-(pyrrol-2-yl)isoxazoles were selectively prepared by the reaction of 2-(2,2-dicyano-1-ethylthioethenyl)pyrroles with hydroxylamine in methanol. Under analogous conditions, 2-(2-carbamoyl-2-cyano-1-ethylthioethenyl) pyrroles with hydroxylamine gave 5-aminoisoxazoles and their structural isomers, 3-aminoisoxazoles (3-5% yield). The latter were selectively prepared by reacting 2-(2-carbamoyl-2-cyano-1-ethylthioethenyl)pyrroles with hydroxylamine in the presence of aqueous NaOH and from the products of intramolecular cyclization of 2-(2-carbamoyl-2-cyano-1-ethylthioethenyl)pyrroles, 1-ethylthio-3-iminopyrrolizines and hydroxylamine.     

Synthesis of 2-alkyl-2-(3-cyanopyridin-2-ylthio)propionic acids

Derivatives of 2-alkyl-2-mercaptopropionic acid were synthesized based on the substituted 3-cyanopyridin-2(1H)-thiones. The synthesis was carried out by the heating of a mixture of thione, alkyl methyl ketone, and chloroform in the presence of a base. The reaction proceeds readily for acetone, whereas alkyl methyl ketones require a prolonged heating in the presence of a phase-transfer catalyst. Methyl esters were prepared from the acids obtained. Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 10, pp. 1967–1970, October, 2007.     

Synthesis and crystal structure of 3-{(2-carboxyethyl)-[2-(3-methylpyrazol-1-yl)-ethyl]amino}- and 3-{(2-carboxyethyl)[2-(5- methylpyrazol-1-yl)-ethyl]amino} propionic acids

Russian Journal of General Chemistry -     

Synthesis of Derivatives of 2-(Indol-1-yl)propionic Acids

We have developed a method for synthesis of N-substituted derivatives of indole from N-phenylalanine, including Fischer cyclization of the corresponding arylalkylhydrazones. The starting hydrazines were obtained by reduction of the corresponding nitrosamines. We have established that the optimum reduction method is to use metallic zinc in a methanol-hydrochloric acid system at low temperatures.     

利用Pummerer反应合成2-(2,6-二卤苯基)-3-(4,5,6-三甲基-2-嘧啶基)-5-酯酰氧基-1,3-噻唑烷-4-酮衍生物

利用Pummerer反应,以有机酸为反应原料、溶剂和催化剂,简便、高效地合成了一系列2-(2,6-二卤苯基)-3-(4,5,6-三甲基-2-嘧啶基)-5-酯酰氧基-1,3-噻唑烷-4-酮(7a～7g和8a～8g),产率为62%～85%.X衍射确证化合物主要异构体的构型为噻唑烷-4-酮环C-5与C-2位取代基处于反式构型,顺反异构体比例通过1H NMR确定.化合物7a和8a具有中等强度的抗HIV-RT活性.     

Synthesis of 4-(pyrazol-5-yl)-1,2,4-triazole-3-thiones

Condensation of pyrazolyl isothiocyanates 2 with N-substituted hydrazines provided the 2-methyl/phenyl-4-(pyrazol-5-yl)thiosemicarbazides 3 . Cyclization of 3 with formic acid-acetic anhydride or with triethyl orthoacetate-acetic anhydride provided 4-(pyrazol-5-yl)-l,2,4-triazole-3-thiones 4a-f and 5-methyl-4-(pyrazol-5-yl)-1,2,4-triazole-3-thiones 4g-I respectively.     

Short Synthesis of 1-(3-tert-Butyl-1-phenyl-1H-pyrazol-5-yl)-3-(5-(2-morpholinoethoxy)-2H-chromen-8-yl) Urea Derivatives

A short and efficient synthesis of 1-(3-tert-butyl-1-phenyl-1H-pyrazol-5-yl)-3-(5-(2-morpholinoethoxy)-2H-chromen-8-yl) urea derivatives (1a–c), a novel type of p38 MAPK inhibitors, is described. The Claisen thermal rearrangement of arylpropargyl ethers was employd as a key step to synthesize the chromene core. The solvent effect on the ratio of the resultant two isomers of Claisen thermal rearrangement, namely 2-methylbenzofuran and 2H-chromen, was also investigated.     

Synthesis of 3-(5-Aryl-1,3,4-oxadiazol-2-yl)chromones

A general method was proposed for the synthesis of 3-(5-aryl-1,3,4-oxadiazol-2-yl)chromones starting from 3-formylchromone. This aldehyde yields acylhydrazones, from which the corresponding unstable nitrile imines are generated. These intermediates undergo intramolecular 1,3-dipolar cycloaddition.     

4-(5-喹啉-3-基-四氮唑-2-基)丁胺的合成

三苯基膦钯催化3-溴喹啉完成氰化取代制得3-氰喹啉(1);1与叠氮化钠经[2+3]环加成合成了3-(2H-四氮唑-5-基)喹啉(2);2与N-(4-溴丁基)邻苯二甲酰亚胺反应制得2-[4-(5-喹啉-3-基-四氮唑-2-基)丁基]异吲哚-1,3-二酮(3);3经肼解合成了4-(5-喹啉-3-基-四氮唑-2-基)丁胺(4...     

Synthesis and anticancer activity evaluation of 3-(4-oxo-2-thioxothiazolidin-5-yl)-1H-indole-carboxylic acids derivatives

Abstract

A mild and efficient method for the synthesis of 1-oxo-9H-thiopyrano[3,4-b]indole-3-carboxylic acids and dimerized 3-(4-carboxy-1H-3-indolyl)-2-propenoic acids via alkaline hydrolysis of 3-(rhodanin-5-yl)-1H-indole-2-carboxylic acids derivatives was elaborated. Anticancer activity screening in NCI60-cell lines assay allowed identification of 5-fluoro-3-(4-oxo-2-thioxothiazolidin-5-ylidenemethyl)-1H-indole-2-carboxylic acid methyl ester 2a with significant antimitotic activity at micromolar and submicromolar concentrations.     

Synthesis of 3-(5-Aryl-1,3,4-oxadiazol-2-yl)chromones

A general procedure was proposed for the synthesis of 3-(5-aryl-1,3,4-oxadiazol-2-yl)chromones by reaction of 3-formylchromone with aroylhydrazines, transformation of the corresponding acylhydrazones into 1,3-dipoles by the action of bromine in the presence of sodium acetate, and intramolecular ring closure.     

Synthesis of 2-(5′-substituted isoxazol-3′-yl)-4-oxo-3-thiazolidinylalkanoic acids

A series of 2-substituted 4-oxo-3-thiazolidinylalkanoic acids bearing an isoxazole nucleus in the 2-position have been prepared. None of the compounds synthesised showed antibacterial activity in vitro.     

Synthesis of 5-(thiazol-5-yl)-4,5-dihydroisoxazoles from 3-chloropentane-2,4-dione

Condensation of 3-chloropentane-2,4-dione with thioamides gives 1-(thiazol-5-yl)ethanones and subsequent Wittig olefination, followed by nitrile oxide 1,3-dipolar cycloaddition to the resulting prop-1-en-2-yl moiety, delivers racemic 5-(thiazol-5-yl)-4,5-dihydroisoxazoles. When this thiazole and isoxazoline diheterocyclic scaffold has a carboethoxy substituent at C2 of the thiazole ring, aminolysis provides for effective diversification. A 50-member library of various 5-(thiazol-5-yl)-4,5-dihydroisoxazoles is reported.     

2-芳基-5-(6-哒嗪酮-3-基)-1,3,4-噁二唑的合成

1,4,5,6-四氢-6-哒嗪酮-3-甲酰肼(1)和1,6-二氢-6-哒嗪酮-3-甲酰肼(2)与芳香醛反应得到相应的芳香醛腙3a～3g和5a～5g, 再将3a～3g, 5a～5g在溴的作用下, 合环得到一系列1,3,4-噁二唑的衍生物4a～4g和6a～6g. 化合物的结构经1H NMR, IR, MS和元素分析得以证实.