Synthesis of 2-substituted 7,7-dimethyl-5-oxo-5,6,7,8-tetrahydroquinoline-4-carboxylic acids

2-Substituted 7,7-dimethyl-5-oxo-5,6,7,8-tetrahydroquinoline-4-carboxylic acids were synthesized by reaction of acyl- and aroylpyruvic acids with 3-amino-5,5-dimethylcyclohex-2-en-1-one. A plausible mechanism of their formation was proposed on the basis of ab initio quantum-chemical calculations.     

Synthesis and stereochemistry of 5-substituted quinuclidine-2-carboxylic acids with semicyclic double bonds

Esters of 5-methylene- and 5-ethylidenequinuclidine-2-carboxylic acid were synthesized using the Wittig reaction. Using NMR spectra, the stereochemistry of the 5-substituted quinuclidine-2-carboxylic acids with semicyclic double bonds was studied.     

Epimerization at C-2 of 2-substituted thiazolidine-4-carboxylic acids

2(R,S)-5,5-Trimethylthiazolidine-4-(S)-carboxylic acid ( 1a ), with a 3.3 to 1 predominance of the 2S (cis) isomer, was shown to epimerize at the C-2 position in neutral, protic solvents. This was manifested by mutarotation concomitant to changes in the ratios of the C-4 methine proton resonances in the nmr spectrum. Compound 1a was stable in dilute sodium carbonate solution, but underwent rapid equilibration in 1N hydrochloric acid. Acetylation of 1a gave an acetyl derivative ( 2a ) with exclusively 2S,4S stereochemistry. Chiral integrity at C-2 was proved by conversion of both 2a and its enantiomer 2b via their munchnone derivatives to enantiomeric dimethyl 1,1,3,5-tetramethyl-1H,2H-pyrrolo[1,2-c]thiazole-6,7-dicarboxylates ( 4a and 4b ). Acetylation of 2-(R,S)-phenyl-5,5-dimethylthiazolidine-4(S)-carboxylic acid, afforded both the 2 S ,4S ( 6a ) and 2R,4S ( 6b ) epimers. Epimerization of 6a at C-4 gave the 2S,4R isomer ( 6c ) which was enantiomeric with 6b .     

Conversion of amino hydroxyacids to oxazolidine-4-carboxylic acids,oxazolidine-5-carboxylic acids and tetrahydrooxazine-4-carboxylic acids

The title compounds are stable in aqueous solution above pH 7, and can be isolated following N-acylation.     

Synthesis of 2,4-substituted 3-oxo-1-phenylcyclopentane-1-carboxylic acids

A procedure has been developed for the synthesis of 2,4-substituted 3-oxo-1-phenylcyclopentan-1-carboxylic acids, and substituent effects on particular steps of the synthesis have been studied.     

Synthesis and antitumor activities of novel 2-substituted pyrimidinone-5-carboxylic acid benzylamides

The title compounds were synthesized via N-benzylmalonamic acid methyl ester (3). As the key intermediate, 3 was prepared from methyl malonyl chloride and benzylamine. Then, compound 3 was reacted with dimethyl-formamide dimethyl acetal yielding vinylogue amides 4 and 5. Isomers 4 and 5 were respectively treated with amidine and guanidine to afford the title compounds 2-substituted pyrimidinone-5-carboxylic acid benzylamides 6 and 7. All of the new compounds were characterized by ¹H-NMR (nuclear magnetic resonance), ¹³C-NMR, MS and High Resolution Mass Spectrometer (HRMS). The antitumor activities of the compounds were tested in vitro against LoVo cells and Hep3B cells. Both compounds 6 and 7 show activity against these two cell lines. Translated from Huaxue Tongbao (Chemistry), 2006, 69(8): 623–626 (in Chinese)     

2-carbaldoximes of pyridine-4- and 5-carboxylic acids

A series of pyridine-2-carbaldoximes, all of which are substituted at the 4- or 5-position with derivatives of the corresponding carboxylic acids, have been prepared via the corresponding pyridine-2-carbaldehydes.     

Synthesis of ω-substituted 5-alkylorotic acids

The lactone of 5 - -hydroxyethylorotic acid, the thiolactone of 5-(-mercaptoethyl)orotic acid, and 5-(-benzamidobutyl)orotic acid were synthesized from substituted 5-carb-ethoxymethylenehydantoins obtained by the condensation of urea with -ethoxalyl derivatives of -butyrolactone, -thiobutyrolactone, and ethyl -benzamidocaproate. The lactam of 5-(-aminoethyl)orotic acid was synthesized by the ammonolysis of the lactone of 5 -(-hydroxyethyl)orotic acid. The acid hydrolysis of 5-(-benzamidobutyl)orotic acid gave 5-(-aminobutyl)orotic acid.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 9, pp. 1280–1282, September, 1971.     

Optimized synthesis of 2-substituted 1-halocyclopropane-1-carboxylic acids

The reaction of gem-dichloro- and gem-dibromocyclopropanes with n-butyllithium in THF under argon at–78°С followed by purging the reaction mixture with dry CO₂ was used to synthesize cis- and/or trans-1-halocyclopropane-1-carboxylic acids in 30–56% yields. The yields of the target products could be increased to 76–83% by the addition of an equimolar amount of LiCl to the reaction mixture. The highest salt effect was obtained with lithium chloride generated in situ (88–96%).     

Synthesis and transformations of polysubstituted diastereomeric 5-oxomorpholin-2-carboxylic acids

A series of trans- and cis-3,4-disubstituted 5-oxomorpholine-2-carboxylic acids 5 were prepared by a cyclocondensation between diglycolic anhydride 3 and arylideneamines 4. Transformations of the carboxylic group leading to a peptide bond in the side chain to the morpholinone ring were effected. The relative configurations and the preferred conformations of the substituents at the morpholinone ring in some of the newly prepared derivatives were determined by means of ¹H NMR and X-ray analysis.     

Synthesis of methyl esters of 5-aroyl-6-aryl-2-oxo-1,2,3,6-tetra-hydropyrimidine-4-carboxylic acids

Methyl esters of 5-aroyl-6-aryl-2-oxo-1,2,3,6-tetrahydropyrimidine-4-carboxylic acids were synthesized from three component mixtures of methyl esters of aroylpyruvic acids, urea, and substituted benzaldehydes. 8-Hydroxy-4,5-diphenyl-3,4-dihydropyrimido[4,5-d]pyridazin-2(1H)-one was synthesized by the reaction of 5-benzoyl-2-oxo-6-phenyl-1,2,3,6-tetrahydropyrimidin-4-carboxylate with hydrazine hydrate.     

Synthesis and exchange reactions of 5-alkyl-2-oxo-6-thioxo-1,2,3,6-hexahydropyrimidine-4-carboxylic acids

An improved preparation of 2-oxo-6-thioxo-1,2,3,6-hexahydropyrimidine-4-carboxylic acid 3, a potent inhibitor of dihydroorotase is presented. Trans-5-alkyl-2-oxo-6-thioxohexahydropyrimidine-4-carboxylic acids 12a-c were synthesised via the thiation of the p-methoxybenzyl esters of 5-alkyldihydroorotic acids with Lawesson's reagent followed by subsequent de-protection. The corresponding cisisomers were prepared by reduction of 5-alkyl-6-thioxoorotic acids with zinc in acetic acid. The stability and exchange reactions of 12a-c under physiological conditions were investigated by ultra-violet and ¹H nmr spectroscopy. The attempted synthesis of 16 , a fused cyclopentyl derivative of 3 is also presented.     

Synthesis and reaction of 5-amino-3-trifluoromethylisoxazole and -pyrazole-4-carboxylic acids

5-Amino-3-trifluoromethylisoxazole- and -pyrazole-4-carboxylic acids were prepared by the reactions ot trifluoroacetonitrile oxide or -imines with cyanoacetic acid derivatives, respectively. The behavior of thus obtained aminoazole-4-carboxylic acids toward some electrophiles was examined. In acylation with acyl chlorides, the aminoisoxazole-4-carboxylate 2a was diacylated to give the (diacylamino)isoxazole-4-carboxylate 7 , whereas the analogous aminopyrazole 5a produced the cyclized pyrazolooxazinone 13 . Moreover, carbamoylation of 2a with isocyanates gave the trifluoromethylisoxazolouracils 10 .     

Synthesis of ethynyl-3-hydroxyquinoline-4-carboxylic acids

Russian Chemical Bulletin - 3-Hydroxyquinoline-4-carboxylic acids containing ethynyl moiety in the 6th and 8th positions were obtained for the fi rst time. A synthetic approach to aforementioned...     

Synthesis of substituted 1,2,3,4-tetrahydroquinoline-4-carboxylic acids

Reduction of some substituted quinoline-4-carboxylic acids was studied. The reduction of 2-alkylquinoline-4-carboxylic acids with Raney nickel in aqueous alkali was stereoselective, and the resulting 2-alkyl-1,2,3,4-tetrahydroquinoline-4-carboxylic acids were individual cis isomers. Original Russian Text ? Yu.A. Zhuravleva, A.V. Zimichev, M.N. Zemtsova, Yu.N. Klimochkin, 2009, published in Zhurnal Organicheskoi Khimii, 2009, Vol. 45, No. 4, pp. 622–625.     

Synthesis of 5-substituted 4-methylthio-1,3-thiazoline-2-thiones

Translated from Khimiya Geterotsiklicheskih Soedinenii, No. 2, pp. 276–277, February, 1989.     

Synthesis and antibacterial activity of new 5-substituted 1-cyclopropyl-6-fluoro-7-piperazinyl-1,4-dihydro-4-oxo-1,8-naphthyridine-3-carboxylic acids

The 5-hydroxymethyl and the 5-formyl-1-cyclopropyl-6-fluoro-7-piperazinyl-1,4-dihydro-4-oxo-1,8-naphthyridine-3-carboxylic acids have been prepared via a 5-trimethylsilyl group and were tested in vitro as potential antibacterials.     

Synthesis of 5-substituted benzyl-2,4-diamino pyrimidine derivatives as c-Fms kinase inhibitors

<正>A serials of novel 5-substituted benzyl-2,4-diamino pyrimidine derivatives have been synthesized and evaluated as inhibitors of c-Fms kinase by the standard MTT method.The results showed that compound 15,5-[3-methoxy-4-(pyridine-3-yl)benzyl]-2,4-diamino pyrimidine,had an IC_(50) of 1.45μmol/L in inhibiting the proliferation of M-CSF-dependent myeloid leukemia cells in mice (NFS-60),which was similar with GW2580,a selective inhibitor of c-Fms kinase.