Bromination and diazo-coupling of pyridinethiones; microwave assisted synthesis of isothiazolopyridine, pyridothiazine and pyridothiazepines

Isothiazolopyridines, pyridothiazines and pyridothiazepines are important compounds that possess valuable biological activities. This paper reports on the synthesis of these compounds using both conventional chemical methods and modern microwave techniques. 3-Bromo-6-hydroxy-4-methyl-2-thioxo-2,3-dihydropyridine-3-carboxamide, 5-arylazo-6-hydroxy-4-methyl-2-thioxo-1,2-dihydropyridine-3-carboxamides, 3,5-bis-arylazo-6-hydroxy-4-methyl-2-thioxo-2,3-dihydropyridine-3-caboxamide, 4-methyl-2,3,6,7-tetra-hydroisothiazolo[5,4-b]-pyridine-3,6-dione, 2,2'-(methylene-bis-(sulfanediyl))bis(4-methyl-6-oxo-1,6-dihydropyridine-3-carboxamide), 2-hydroxy-5-methyl-4H-pyrido[3,2-e][1,3]-thiazine-4,7(8H)-dione and 2-arylmethylene-8-hydroxy-6-methyl-2,3,4,5-tetrahydropyrido-[3,2-f][1,4]thiazepine-3,5-diones have been prepared from 6-hydroxy-4-methyl-2-thioxo-2,3-dihydropyridine-3-carboxamide. Some of these compounds were prepared using microwave-assisted reaction conditions, that provided higher yields in shorter times than the conventional methods.     

Synthesis,Bioactivity and Crystal Structure Analysis of Novel Benzo[d]isothiazol-3（2H）-ones

Two compounds,3-oxo-N-o-tolylbenzo[d]isothiazole-2(3H)-carboxamide (1) and N-(2-methoxyphenyl)-3-oxobenzo[d]isothiazole-2(3H)-carboxamide (2),were synthesized from the initial compound benzo[d]isothiazol-3(2H)-one (BIT) and characterized by 1 H NMR,IR and elemental analysis,respectively.The single crystals of compounds 1 and 2 were obtained and determined by X-ray diffraction analysis.The preliminary results of biological activity experiment show that some of the title compounds exhibited a favorable antimicrobial activity.     

Synthesis,Crystal Structure,and DFT Study of a New Derivative of Pyrido[2,3-d]pyrimidine

Russian Journal of General Chemistry - N-{4-[(6-bromopyrido[2,3-d]pyrimidin-4-yl)oxy]phenyl}morpholine-4-carboxamide has been synthesized as a derivative of pyrido[2,3-d]pyrimidine that...     

Synthesis of C-Nucleoside Analogues： 2-[2-（Hydroxymethyl）-1, 3-dioxolan-5-yl]1, 3-thiazole-4-carboxamide and 2-[2-（Mercaptometh-yl）-1, 3-dioxolan-5-yl] 1, 3-thiazole-4-carboxamide

Novel C-nucleosides of tiazofurin analogue (2-[2-(hydroxymethyl)-1,3-dioxolan-5-yl] 1,3-thiazole-4-carboxamide) and its thiol-substituted derivative (2-[2-(mercaptomethyl)-1,3-dioxolan-5-yl] 1, 3-thiazole-4-carboxamide) were synthesized from methyl acrylate through a multistep procedure. Their structures were confirmed by IR, ^1HNMR, ^13CNMR and elemental analysis.     

Nukleophile Addition von Lithiumorganylen an das N,N-Diethyl-10-(trimethylsilyl)-1, 6-methano[10]annulen-2-carboxamid

Nucleophilic Addition of Lithiumorganyles to N,N-Diethyl-10-(trimethylsilyl)-1,6-methano[10]annulene-2-carboxamide Reaction of lithiumorganyles with N,N-diethyl-10-(trimethylsilyl)-1,6-methano[10]annulene-2-carboxamide followed by quenching with H₂O or MeI yields 2,3-dihydro derivatives of 1,6-methano[10]annulene.     

Synthesis of substituted 4-oxo-2-thioxo-1,2,3,4-tetrahydroquinazolines and 4-oxo-3,4-dihydroquinazoline-2-thioles

We have developed a liquid-phase synthesis of combinatorial libraries of new disubstituted 4-oxo-2-thioxo-1,2,3,4-tetrahydroquinazolines and trisubstituted 4-oxo-3,4-dihydroquinazoline-2-thioles. The former were prepared using two general procedures: (i) cyclization of substituted methyl anthranilates with isothiocyanates, or (ii) cyclization of substituted 2-(methylcarboxy)benzeneisothiocyanates with primary amines or hydrazines. 4-Oxo-3,4-dihydroquinazoline-2-thioles were prepared by S-alkylation of disubstituted 4-oxo-2-thioxo-1,2,3,4-tetrahydroquinazolines with alkyl or aryl halides. The hydrolysis of methyl benzimidazo[1,2-c]quinazoline-6(5H)-thione-3-carboxylate led to the corresponding acid. This acid was utilized in the synthesis of new benzimidazo[1,2-c]quinazoline-6(5H)-thione-3-carboxamide and S-substituted 6-mecaptobenzimidazo[1,2-c]quinazoline-3-carboxamide libraries.     

1-β-D-呋喃核糖基-1,2,4-三唑-3-酰胺铂(II)配合物的合成

在缓冲液中，利用1-β-D-呋喃核糖基-1，2，4-三唑-3-酰胺(ribavirin)和1- （2'-脱氧-β-D-呋喃核糖基）-1，2，4-三唑-3-酰胺(deoxyribavirin)作为配体 ，分别与cis-[Pt(DMSO)_2Cl_2]或K[Pt(DMSO)Cl_3]进行配位反应，得到了高产率 的[Pt-(N~4,N~7-ribavirin)(DMSO)Cl] (1)和[Pt(N~4,N~7-deoxyribavirin) (DMSO)Cl] (2)两种配合物。1-（2'-脱氧-β-D呋喃核糖基）-1，2，4-三唑-3-酰 胺的合成是由1-β-D-呋喃核糖基-1，2，4-三唑-3-酰胺与1，3-二氯-1，1，3，3- 四异丙基二硅氧烷保护，在1-甲基咪唑存在下与硫代苯氧基碳酰氯反应，再用tri- n-butyltin hydride和AIBN还原，四丁基氟化铵的四氢呋喃溶液脱去保护基四步反 应完成的。     

Discovery of novel 2-anilinopyrazolo[1,5-a]pyrimidine derivatives as c-Src kinase inhibitors for the treatment of acute ischemic stroke

We synthesized a series of novel 2-anilinopyrazolo[1,5-a]pyrimidine derivatives and evaluated their ability to inhibit c-Src kinase; 7-(2-amino-2-methylpropylamino)-5-cyclopropyl-2-(3,5-dimethoxyphenylamino)pyrazolo[1,5-a]pyrimidine-3-carboxamide 7o and 7-(2-amino-2-methylpropylamino)-2-(3,5-dimethoxyphenylamino)-5-methylpyrazolo[1,5-a]pyrimidine-3-carboxamide 7f showed potent inhibitory activity. Compound 7f inhibited c-Src selectively and exhibited satisfactory central nervous system (CNS) penetration. Furthermore, 7f.HCl reduced the infarct volume in vivo in a rat middle cerebral artery (MCA) occlusion model when administrated intraperitoneally.     

The synthesis of pyrimido[4,5-c]pyridazines and pyrimido[5,4-c]pyridazines

The Hofmann reaction on 6-methylpyridazine-3,4-dicarboxamide (1) gave a mixture of 3-methylpyrimido[4,5-c]pyridazine-5,7-dione (2), 3-methylpyrimido[5,4-c]pyridazine-6,8-dione (3) and an acid (4) of unknown structure. The Hofmann reaction on pyridazine-3,4-dicarboxamide (9) gave a mixture of pyrimido[4,5-c]pyridazine-5,7-dione ( 10 ) and an acid ( 11 ) of unknown structure. The reaction of 3-amino-6-methylpyridazine-4-carboxamide ( 18 ) with ethyl orthoformate gave 3-methylpyrimido[4,5-c]pyridazin-5-one ( 21 ). 4-Aminopyridazine-3-carboxamide ( 36 ) upon fusion with urea gave pyrimido[5,4-c]pyridazine-6,8-dione ( 37 ) while with ethyl orthoformate 36 gave pyrimido[5,4-c]pyridazin-8-one ( 38 ). Pyrimido[5,4-c]-pyridazine-8-thione ( 39 ) was obtained by the action of phosphorus pentasulfide on 38. 4-Amino-3-cyanopyridazine ( 16 ) when treated with formamide produced 8-aminopyrimido[5,4-c]-pyridazine ( 41 ). The synthesis of 4-aminopyridazine-3-carboxamide ( 36 ) and 4-amino-3-cyanopyridazine ( 16 ), both key intermediates in the synthesis of the novel pyrimido[5,4-c]pyridazine ring system was accomplished by the Reissert reaction of 4-aminopyridazine-2-oxides and subsequent conversion of the nitrile to the amide.     

Determination of the anxiolytic agent 8-chloro-6-(2-chlorophenyl)-4H-imidazo-[1,5-alpha] [1,4]-benzodiazepine-3-carboxamide in whole blood, plasma or urine by high-performance liquid chromatography

A rapid, sensitive and specific high-performance liquid chromatographic (HPLC) assay was developed for the determination of 8-chloro-6-(2-chlorophenyl)-4H-imidazo-[1,5-alpha]-[1,4]-benzodiazepine-3-carboxamide [I] and its 4-hydroxy metabolite, 8-chloro-6-(2-chlorophenyl)-4-hydroxy-4H-imidazo-[1,5-alpha] [1,4]-benzodiazepine-3-carboxamide [II] in whole blood, plasma or urine. The assay for both compounds involves extraction into diethyl ether-methylene chloride (70:30) from blood, plasma, or urine buffered to pH 9.0. The overall recoveries of [I] and [II] are 92.0 +/- 5.4% (S.D.) and 90.3 +/- 4.9% (S.D.), respectively. The sensitivity limit of detection is 50 ng/ml of blood, plasma, or urine using a UV detector at 254 nm. The HPLC assay was used to monitor the blood concentration-time fall-off profiles, and urinary excretion profiles in the dog following single 1 mg/kg intravenous and 5 mg/kg oral doses, and following multiple oral doses of 100 mg/kg/day of compound [I].     

New (S)-proline derivatives as catalysts for the enantioselective aldol reaction

(2S)-N- 2-[(R)-Hydroxy(phenyl)methyl]phenylpyrrolidine-2-carboxamide, (2 S)-N-{2-[(S)-hydroxy(phenyl)methyl]phenyl}pyrrolidine-2-carboxamide, and (S)-N-{2-[hydroxy-(diphenyl)methyl]phenyl}pyrrolidine-2-carboxamide were obtained and tested as catalysts for an asymmetric aldol reaction of 4-nitrobenzaldehyde with acetone.     

Synthesis,Structure, and Spectroscopic Properties of Isotianil as a Bactericide

Russian Journal of Organic Chemistry - Isotianil [N-(2-cyanophenyl)-3,4-dichloro-1,2-thiazole-5-carboxamide] has been synthesized in a good yield with high purity by reaction of the key...     

Synthesis,structural and conformational study of some amides derived from 3,7-dimethyl-9-amino-3,7-diazabicyclo[3.3.1]nonane-9-carboxamide

A series of 3,7-dimethyl-9-amino-3,7-diazabicyclo[3.3.1]nonane-9-carbonitrile and 3,7-dimethyl-9-amino-3,7-diazabicyclo[3.3.1]nonane-9-carboxamide N-substituted have been synthesized and studied by ¹ H and ¹³C nmr spectroscopy and the crystal structure of 3,7-dimethyl-9-benzylamino-3,7-diazabicyclo[3.3.1]nonane-9-carboxamide dihydrochloride ( IVb· 2HCl) has been determined by X-ray diffraction. The compounds studied display in deuteriochloroform, dimethyl sulfoxide-d₆ and methanol-d₄ the same preferred flattened chair-chair conformation with the methyl groups in equatorial position. The carboxamido group lies in a plane nearly perpendicular to the bispidine skeleton. The conformation and protonation sites of IVb· 2HCl in the crystal state and in deuterium oxide solution are discussed.     

Some transformations of the substitutive recyclization product obtained from tetrachlorocyclopentadiene dimer and diethylamine

1, 1a,2,3,3a,4,5-Heptachloro-N,N-diethyl-6-oxo-1,1a,3a,6-tetrahydrocyclopropa[c]pentalene-1-carboxamide reacts with hydroxide ion and N-centered nucleophiles following exclusively the Ad_NE scheme with replacement of the 4-chlorine atom. Its reactions with methylmagnesium iodide and diethyl malonate sodium salts involve simultaneous substitution, 1,2-addition at the carbonyl group, and aromatization. Oxidation of 1,1a,2,3,3a,4,5-heptachloro-N,N-diethyl-6-oxo-1,1a,3a,6-tetrahydrocyclopropa[c]pentalene-1-carboxamide with potassium permanganate under conditions of phase-transfer catalysis is accompanied by cleavage of the cyclopentenone fragment with formation of 2,3,4,5,6-pentachloro-6-diethylcarbamoylbicyclo[3.1.0]hex-3-ene-1,2-dicarboxylic acid.     

Synthesis of New 2′-(2- and 3-Aminopropanoyl)-6′,7′-dimethoxy-2′,3′-dihydro-1′H-spiro[cyclopentane-1,4′-isoquinoline]-1′-carboxamides

Russian Journal of Organic Chemistry - 6′,7′-Dimethoxy-N-methyl-2′,3′-dihydro-1′H-spiro[cyclopentane-1,4′-isoquinoline]-1′-carboxamide reacted with...     

Synthesis,Crystal Structure,and Spectral Study of a Novel Indenoimidazole Carboxylic Acid Amide

Russian Journal of Organic Chemistry - 3a,8a-Dihydroxy-2,8-dioxo-1,3a,8,8a-tetrahydro-2H-indeno[1,2-d]imidazole-3-carboxamide has been synthesized in 85% yield from ninhydrin and biuret via a green...     

Reactions of 3,4-Dichloro-N-R-maleimides with Substituted 2-Thiouracils

Reactions of 3,4-dichloro-N-R-maleimides with substituted thiouracils at 40°C gave a 1:1 mixture of isomers of pyrrolothiazolopyrimidinetriones. Under conditions of thermodynamic control (100°C, 5 h) only pyrrolo[3',4':4,5]thiazolo[3,2-a]pyrimidine-4,6,8-triones were formed, hydrolysis of which followed by decarboxylation gave 5-oxo-5H-thiazolo[3,2-a]pyrimidine-2-carboxamide. The structure of N²-phenyl-6-methyl-5-oxo-5H-thiazolo[3,2-a]pyrimidine-2-carboxamide was confirmed by X-ray crystallography. Analogous cyclization of 3,4-dichloro-N-R-maleimides with 2-thioxoquinazol-4-one also gave a mixture of two isomers which were successfully separated by fractional crystallization.     

The synthesis of novel polycyclic heterocyclic ring systems via photocyclization. 8 . [1]Benzothieno[2,3-c]naphtho[1,2-h]quinoline and [1]benzothieno[2,3-c]naphtho[1,2-h][1,2,4]triazolo[4,3-a]quinoline

The previously unknown polycyclic heterocyclic ring systems, namely, [1]benzothieno[2,3-c]naphtho[1,2-h]-quinoline and [1]benzothieno[2,3-c]naphtho[1,2-h][1,2,4]triazolo[4,3-a]quinoline were synthesized via photocyclization of 3-chloro-N-(1′-phenanthryl)benzo[b]thiophene-2-carboxamide.     

Synthesis of thio- and furan-fused heterocycles: furopyranone,furopyrrolone, and thienopyrrolone derivatives

We report herein the synthesis of a novel class of compounds, ethyl 4-oxo-4H-furo[3,2-c]pyran-6-yl carbonate, (7E)-7-[(dimethylamino)methylene]-4H-furo[3,2-c]pyran-4,6(7H)-dione, 5-oxo-N-phenyl-2,5-dihydro-4H-furo[3,2-b]pyrrole-4-carboxamide, and 5-oxo-N-phenyl-5,6-dihydro-4H-thieno[3,2-b]pyrrole-4-carboxamide starting from the corresponding acid derivatives. Intramolecular cyclization in the presence of thionyl chloride formed the target fused ring systems. Additional transformation was seen in the cyclization of furan-fused heterocycle. A mechanism was proposed based on experimental and computational findings.     

Synthesis and properties of analogs of 5(4)-aminoimidazole-4(5)-carboxamide (AICA)

A new analog of AICA — 5(4)-hydrazinoimidazole-4(5)-carboxamide — forms the corresponding hydrazones with carbonyl-containing compounds and reacts with sodium nitrite to give 5(4)-azidoimidazole-4(5)-carboxamide, the structure of which was proved on the basis of IR spectroscopic data.See [1] for communication I.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 1, pp. 94–95, January, 1973.