Synthesis and antimicrobial activity of some derivatives of (7-hydroxy-2-oxo-2H-chromen-4-yl)-acetic acid hydrazide

(7-Hydroxy-2-oxo-2H-chromen-4-yl)-acetic acid hydrazide (2) was prepared from (7-hydroxy-2-oxo-2H-chromen-4-yl)-acetic acid ethyl ester (1) and 100% hydrazine hydrate. Compound 2, is the key intermediate for the synthesis of several series of new compounds such as Schiff's bases 3a-l, formic acid N'-[2-(7-hydroxy-2-oxo-2H- chromen-4-yl)acetyl] hydrazide (4), acetic acid N'-[2-(7-hydroxy-2-oxo-2H-chromen-4- yl)-acetyl] hydrazide (5), (7-hydroxy-2-oxo-2H-chromen-4-yl)-acetic acid N'-[2-(4- hydroxy-2-oxo-2H-chromen-3-yl)-2-oxoethyl] hydrazide (6), 4-phenyl-1-(7-hydroxy-2- oxo-2H-chromen- 4-acetyl) thiosemicarbazide (7), ethyl 3-{2-[2-(7-hydroxy-2-oxo-2H- chromen-4-yl)-acetyl]hydrazono}butanoate (8), (7-hydroxy-2-oxo-2H-chromen-4-yl)- acetic acid N'-[(4-trifluoromethylphenylimino)methyl] hydrazide (9) and (7-hydroxy-2- oxo-2H-chromen-4-yl)acetic acid N'-[(2,3,4-trifluorophenylimino)-methyl] hydrazide (10). Cyclo- condensation of compound 2 with pentane-2,4-dione gave 4-[2-(3,5- dimethyl-1H-pyrazol-1-yl)-2-oxoethyl]-7-hydroxy-2H-chromen-2-one (11), while with carbon disulfide it afforded 7-hydroxy-4-[(5-mercapto-1,3,4-oxadiazol-2-yl)methyl]-2H- chromen-2-one (12) and with potassium isothiocyanate it gave 7-hydroxy-4-[(5- mercapto-4H-1,2,4-triazol-3-yl)methyl]-2H-chromen-2-one (14). Compound 7 was cyclized to afford 2-(7-hydroxy-2-oxo-2H-chromen-4-yl)-N -(4-oxo-2-phenylimino- thiazolidin-3-yl) acetamide (15).     

A practical synthesis of 4-[(4-methylpiperazin-1-yl)methyl]benzoic acid—the key precursor toward imatinib

A simple and efficient in situ synthesis of 4-[(4-methylpiperazin-1-yl)methyl]benzoic acid through direct reductive alkylation of 1-methylpiperazine in the presence of triacetoxy sodium borohydride in 95-99% yields is elaborated. The process is easy to scale-up for the large-scale synthesis of 4-[(4-methylpiperazin-1-yl)methyl]benzoic acid as the key synthetic intermediate of imatinib. This method was used for the synthesis of benzyl derivatives of heterocyclic amines in 87-90% yields.     

Novel synthesis of the pyrrolo[2,1-c][1,4]benzodiazocine ring system via a Dieckmann condensation

A novel four-step synthesis to the pyrrolo[2,1-c][1,4]benzodiazocine ring system is described. 1H-Pyrrole-2-carbaldehyde was alkylated with ethyl or methyl bromoacetate and the resulting ethyl or methyl (2-formyl-1H-pyrrol-1-yl)acetates oxidised with potassium permanganate to the corresponding 1-[(2-ethoxy or methoxy)-2-oxoethyl]-1H-pyrrole-2-carboxylic acids. The latter was converted into their acid chlorides by reaction with thionyl chloride and without isolation transformed into the respective methyl 2-({[1-(2-ethoxy or methoxy-2-oxoethyl)-1H-pyrrol-2-yl]carbonyl}amino)benzoates by reaction with methyl anthranilate. Dieckmann condensation of methyl 2-({[1-(2-methoxy-2-oxoethyl)-1H-pyrrol-2-yl]carbonyl}amino)benzoate provided the pyrrolo[2,1-c][1,4]benzodiazocine.     

Stepwise unidirectional synthesis of oligo phenylene vinylenes with a series of monomers. Use in plastic solar cells

Four new monomers for directional stepwise synthesis of oligophenylenevinylenes (OPVs) (4-{2-[4-(5,5-dimethyl[1,3]dioxan-2-yl)-2,5-dipropoxyphenyl]vinyl}benzyl)phosphonic acid diethyl ester, (5-{2-[4-(5,5-dimethyl[1,3]dioxan-2-yl)-2,5-dipropylphenyl]vinyl}thiophene-2-ylmethyl)phosphonic acid diethyl ester, (5-{2-[4-(5,5-dimethyl[1,3]dioxan-2-yl)-2,5-dipropoxyphenyl]vinyl}thiophene-2-ylmethyl)phosphonic acid diethyl ester, and (7-{2-[4-(5,5-dimethyl[1,3]dioxan-2-yl)-2,5-dipropylphenyl]vinyl}benzo[1,2,5]thiadiazol-4-ylmethyl)phosphonic acid diethyl ester have been prepared. Trimeric OPVs were then synthesized and tested as active materials in photovoltaic cells. Conversion efficiencies in the range of 0.5-1% were obtained in blends with the soluble C(60) derivative PCBM. A terpyridine end-functionalized trimer and a heterotrimer with a mixed composition of monomers were also prepared.     

Synthesis and Biological Activity of Compounds Obtained by Reacting Methyl Aroylpyruvates with Sulfadimidine

The reaction of methyl aroylpyruvates and 2-(4-aminobenzenesulfamido)-4,6-dimethylpyrimidine in glacial acetic acid in the presence of anhydrous sodium acetate afforded (2Z)-4-aryl-2-hydroxy-N-{4-[(4,6-dimethylpyrimidin-2-yl)sulfamoyl]phenyl}-4-oxobut-2-enamides. Reaction of the above reagents in a mixture of acetic acid and ethanol (1: 1) in the absence of anhydrous sodium acetate gave methyl (2Z)-4-aryl-2-{4-[(4,6-dimethylpyrimidin-2-yl)sulfamoyl]phenylamino}-4-oxobut-2-enoates. Analgesic and anti-inflammatory activities of the synthesized compounds was studied.     

Rhenium tricarbonyl core complexes of thymidine and uridine derivatives

Thymidine and uridine were modified at the C2' and C5' ribose positions to form amine analogues of the nucleosides (1 and 4). Direct amination with NaBH(OAc)3 in DCE with the appropriate aldehydes yielded 1-{5-[(bis(pyridin-2-ylmethyl)amino)methyl]-4-hydroxytetrahydrofuran-2-yl}-5-methyl-1H-pyrimidine-2,4-dione (L1), 1-{5-[(bis(quinolin-2-ylmethyl)amino)methyl]-4-hydroxytetrahydrofuran-2-yl}-5-methyl-1H-pyrimidine-2,4-dione (L2), and 1-[3-(bis(pyridin-2-ylmethyl)amino)-4-hydroxy-5-(hydroxymethyl)tetrahydrofuran-2-yl]-1H-pyrimidine-2,4-dione (L5), while standard coupling procedures of 1 and 4 with 5-(bis(pyridin-2-ylmethyl)amino)pentanoic acid (2) and 5-(bis(quinolin-2-ylmethyl)amino)pentanoic acid (3) in the presence of HOBT-EDCI in DMF provided a second novel series of bifunctional chelators: 5-(bis(pyridin-2-ylmethyl)amino)pentanoic acid [(3-hydroxy-5-(5-methyl-4-oxo-3,4-dihydro-2H-pyrimidin-1-yl)tetrahydrofuran-2-yl)methyl] amide (L3), 5-(bis(quinolin-2-ylmethyl)amino)pentanoic acid [(3-hydroxy-5-(5-methyl-4-oxo-3,4-dihydro-2H-pyrimidin-1-yl)tetrahydrofuran-2-yl)methyl] amide (L4), 5-(bis(pyridin-2-ylmethyl)amino)pentanoic acid [2-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-hydroxy-5-(hydroxymethyl)tetrahydrofuran-3-yl] amide (L6), and 5-(bis(quinolin-2-ylmethyl)amino)pentanoic acid [2-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-4-hydroxy-5-(hydroxymethyl)tetrahydrofuran-3-yl] amide (L7). The rhenium tricarbonyl complexes of L1-L4, L6, and L7, [Re(CO)3(LX)]Br (X=1-4, 6, 7: compounds 5-10, respectively), have been prepared by reacting the appropriate ligand with [NEt4][Re(CO)3Br3] in methanol. The ligands and their rhenium complexes were obtained in good yields and characterized by common spectroscopic techniques including 1D and 2D NMR, HRMS, IR, cyclic voltammetry, UV, and luminescence spectroscopy and X-ray crystallography. The crystal structure of complex 6.0.5NaPF6 displays a facial geometry of the carbonyl ligands. The nitrogen donors of the tridentate ligand complete the distorted octahedral spheres of the complex. Crystal data: monoclinic, C2, a = 24.618(3) A, b = 11.4787(11) A, c = 15.5902(15) A, beta = 112.422(4) degrees , Z = 4, D(calc) = 1.562 g/cm3.     

Synthesis and reactions of 1-benzyl-3-haloalkyl-5-chloropyrazoles

Synthesized 1-benzyl-3-chloroalkyl-5-chloropyrazoles reacted with indole and pyrrole in DMSO in the presence of alkali to give 3-(heter-1-yl)alkyl-substituted 1-benzyl-5-chloropyrazoles. 1-[(1-Benzyl-5-chloropyrazol-3-yl)methyl]indole reacted regiospecifically with chloroal trifluoromethylsulfonyl- and 4-chlorophenylsulfonylimines providing the products of C-amidotrichloroethylation into the position 3 of the indole ring. {1-[(1-Benzyl-5-chloropyrazol-3-yl)methyl]indol-3-yl}sulfanylacetic acid was obtained by the reaction of 1-[(1-benzyl-5-chloropyrazol-3-yl)methyl]-indole with iodine, thiourea, and chloroacetic acid.     

Asymmetric synthesis of N-3 substituted phenoxypropyl piperidine benzimidazol-2-one derivatives, potent and selective NOP agonists

The asymmetric synthesis of the potent selective NOP agonist 2-(3-{1-[3-(5-methoxy-2-methyl-phenoxy)-4-methyl-pentyl]-piperidin-4-yl}-2-oxo-2,3-dihydro-benzimidazol-1-yl)-N-methyl-acetamide and analogues was developed. The key step, chiral reduction of methyl isobutyryl acetate, was achieved using a mild Noyori-type asymmetric hydrogenation.     

Condensation of Propan-2-one with Formaldehyde and Propane-2-thiol

Three-component condensation of propan-2-one with formaldehyde and propane-2-thiol in the presence of sodium hydroxide afforded 3-{[(propan-2-yl)sulfanyl)]methyl}but-3-en-2-one or 4-[(propan-2-yl)sulfanyl]-3-{[(propan-2-yl)sulfanyl]methyl}butan-2-one, depending on the amount of the base. The formation of 4-[(propan-2-yl)sulfanyl]-3-{[(propan-2-yl)sulfanyl]methyl}butan-2-one from 4-[(propan-2-yl)sulfanyl]butan-2-one involved aldol condensation of the latter with formaldehyde and subsequent nucleophilic addition of propane-2-thiol to the C=C double bond of intermediate 3-{[(propan-2-yl)sulfanyl]methyl}but-3-en-2-one in the presence of sodium hydroxide.     

Synthesis and characterization of novel bis-triazolyl quinazolinones

Russian Journal of General Chemistry - A series of 2-methyl-1-[(1-phenyl-1H-1,2,3-triazol-4-yl)methyl]-2-(4-{[(1-phenyl-1H-1,2,3-triazol-4-yl)methyl}amino]phenyl)-2,3-dihydroquinazolin-4(1H)-ones...     

Synthesis and some transformations of methyl [4-(oxoacetyl)phenyl]carbamate

The oxidation of methyl (4-acetylphenyl)carbamate with selenium dioxide in dioxane–water (30: 1) gave methyl [4-(oxoacetyl)phenyl]carbamate whose condensation with ethyl acetoacetate or diethyl malonate and hydrazine hydrate afforded ethyl 3-methyl-6-[4-(methoxycarbonylamino)phenyl]pyridazine-4-carboxylate and methyl {4-[5-(hydrazinecarbonyl)-6-oxo-1,6-dihydropyridazin-3-yl]phenyl}carbamate, respectively. The reaction of methyl [4-(oxoacetyl)phenyl]carbamate with o-phenylenediamine in dimethylformamide–ethanol on heating led to the formation of methyl [4-(quinoxalin-2-yl)phenyl]carbamate. Methyl {4-(5,7-dioxo- 4,4a,5,6,7,8-hexahydropyrimido[4,5-c]pyridazin-3-yl)phenyl}carbamate and methyl {4-(5-oxo-7-sulfanylidene- 4,4a,5,6,7,8-hexahydropyrimido[4,5-c]pyridazin-3-yl)phenyl}carbamate were synthesized by reactions of methyl [4-(oxoacetyl)phenyl]carbamate with barbituric and thiobarbituric acids, respectively, and hydrazine hydrate in the presence of zirconyl chloride octahydrate at room temperature.     

Midrange affinity fluorescent Zn(II) sensors of the Zinpyr family: syntheses, characterization, and biological imaging applications

The syntheses and photophysical characterization of ZP9, 2-{2-chloro-6-hydroxy-3-oxo-5-[(2-{[pyridin-2-ylmethyl-(1H-pyrrol-2-ylmethyl)amino]methyl}phenylamino)methyl]-3H-xanthen-9-yl}benzoic acid, and ZP10, 2-{2-chloro-6-hydroxy-5-[(2-{[(1-methyl-1H-pyrrol-2-ylmethyl)pyridin-2-ylmethylamino]methyl}phenylamino)methyl]-3-oxo-3H-xanthen-9-yl}benzoic acid, two asymmetrically derivatized fluorescein-based dyes, are described. These sensors each contain an aniline-based ligand moiety functionalized with a pyridyl-amine-pyrrole group and have dissociation constants for Zn(II) in the sub-micromolar (ZP9) and low-micromolar (ZP10) range, which we define as "midrange". They give approximately 12- (ZP9) and approximately 7-fold (ZP10) fluorescence turn-on immediately following Zn(II) addition at neutral pH and exhibit improved selectivity for Zn(II) compared to the di-(2-picolyl)amine-based Zinpyr (ZP) sensors. Confocal microscopy studies indicate that such asymmetrical fluorescein-based probes are cell permeable and Zn(II) responsive in vivo.     

A concise synthesis of a novel antiangiogenic tyrosine kinase inhibitor

An efficient synthesis of the potent KDR inhibitor 3-[5-[[4-(methylsulfonyl)-1-piperazinyl]methyl]-1H-indole-2-yl]quinolin-2(1H)-one (1) is described. The process features a noncryogenic indole boronation and a dicyclohexylamine-mediated Suzuki coupling.     

Asymmetric synthesis of the carbon-14-labeled selective glucocorticoid receptor modulator using cinchona alkaloid catalyzed addition of 6-bromoindole to ethyl trifluoropyruvate

We describe in this study the asymmetric synthesis of radioisotope (RI)-labeled selective glucocorticoid receptor modulator. This synthesis is based on optimization of the cinchona alkaloid catalyzed addition of 6-bromoindole to ethyl trifluoropyruvate and Negishi coupling of zinc cyanide to the 6-bromoindole moiety. [1?C] Labeled (-)-{4-[(1-{2-[6-cyano-1-(cyclohexylmethyl)-1H-indol-3-yl]-3,3,3-trifluoro-2-hydroxypropyl}piperidin-4-yl)oxy]-3-methoxyphenyl}acetic acid (-)-1 was synthesized successfully with high enantioselectivity (>99% ee) and sufficient radiochemical purity.     

Synthesis of ferrocenyl-containing heterocyclic derivatives of 5-(4-aminophenyl)-10,15,20-triphenylporphyrin for sonodynamic therapy

The condensation of 1-(ferrocenylalkyl)pyrazole-3-carbaldehydes with 4′-aminotetraphenylporphyrin, followed by reduction with NaBH(OAc)₃ in 1,2-dichloroethane, provides a convenient method for the synthesis of 5-{4-[({1-[1-(ferrocen-1-yl)alkyl]-5-methyl-1H-pyrazol-3-yl}methyl)amino]phenyl}-10,15,20-triphenylporphyrins which exhibit pronounced cytotoxicity against Staphylococcus aureus under ultrasonic irradiation.     

Design and the synthesis of 1-heteroaryl-1,2,3-triazoles connected to coumarins via ether linker

In this paper, we report an efficient and versatile methodology for the synthesis of a series of novel heteroaryl-1,2,3-triazoles connected to 4-methylcoumarin (4-methyl-2H-chromen-2-one) via oxymethylene linker. The desired molecules were accessed by both two-step synthesis and the one-pot copper catalyzed cycloaddition reaction of heteroaromatic azides with coumarin containing acetylenes. The developed protocol was found to be facile and effective for preparing a series of novel heteroaryl-1,2,3-triazole-coumarin conjugates in excellent yields. Practical utility of one-pot protocol has been confirmed by the successful gram-scale synthesis of 1,3-Dimethyl-6-(4-[([4-methyl-2-oxo-2H-chromen-7-yl]oxy)methyl]-1H-1,2,3-triazol-1-yl)pyrimidine-2,4(1H,3H)-dione.     

Synthesis of aromatic carbamates derivatives with a chromen-2-one fragment

Condensation of methyl N-(3-hydroxyphenyl)carbamate with ethyl trifluoromethylacetoacetate, 2-methoxyethyl acetoacetate in the presence of conc. sulfuric acid, and also with acetonedicarboxylic acid formed in situ from citric acid under the action of conc. sulfuric acid afforded chromene derivatives. The esterification of 2-{7-[(methoxycarbonyl)amino]-2-oxo-2H-chromen-4-yl}acetic acid with methanol in the presence of TsOH provided the corresponding ester. The oxidation of its α-methylene group with selenium dioxide led to the formation of methyl 2-{7-[(methoxycarbonyl)amino]-2-oxo-2H-chromen-4-yl}-2-oxo-acetate entering into a condensation with o-phenylenediamine resulting in a derivative with a dihydroquinoxaline fragment. The reaction of phenyl N-(4-formylphenyl)carbamate with 3-acetyl-2H-chromen-2-one in butanol in the presence of catalytic quantity of piperidine and acetic acid furnished 4-[(E)-3-oxo-2H-chromen-3-yl)-1-propenyl]phenyl N-phenylcarbamate.     

Low-valent vanadium complexes of a pyrrolide-based ligand. Electronic structure of a dimeric V(I) complex with a short and weak metal-metal bond

Deprotonation of the nitrogen atoms of the two pyrrole rings of 1,3-bis-{[(1'-pyrrol-2-yl)-1,1'-dimethyl]methyl}benzene with KH followed by further reaction with either VCl 3(THF) 3 or with VCl 2(TMEDA) 2 respectively gave the paramagnetic complexes [1,3-bis-{[(1'-pyrrol-2-yl)-1,1'-dimethyl]methyl}benzene]VCl(DME) ( 1) and [1,3-bis-{[(1'-pyrrol-2-yl)-1,1'-dimethyl]methyl}benzene]V(THF) 3 ( 2). Further reduction with the appropriate amount of KH afforded diamagnetic dinuclear [1,3-bis-{[(1'-pyrrol-2-yl)-1,1'-dimethyl]methyl}benzene]V} 2] ( 3). In complex 3, the bridging interaction between the two metal centers is realized via the ligand central benzene ring. Density functional theory calculations have elucidated the nature of the electronic interaction between the two metals with the bridging pi-system thus accounting for its visible structural distortion. Calculations also pointed out the presence of only a weak V-V bond in spite of the short V-V distance.     

Synthesis and characterization of novel 1-[(2-hydroxyethoxy)methyl]-6-(phenylthio)thymine (HEPT) and dihydro-alkylthio-benzyloxopyrimidine (S-DABO) analogs containing a benzo[<Emphasis Type="Italic">d</Emphasis>]thiazol moiety

A series of novel dihydro-alkylthio-benzyloxopyrimidine (S-DABO) and 1-[(2-hydroxyethoxy) methyl]-6-(phenylthio)thymine (HEPT) analogs bearing a (benzo[d]thiazol-2-yl)methyl moiety at the C⁶ position of the pyrimidine core have been synthesized. 5-Allyl-6-{(benzo[d]thiazol-2-yl)methyl}-2-thiouracil and 5-allyl-6-{(benzo-[d]thiazol-2-yl)methyl}uracil were alkylated to give, respectively, S²- and N¹- ethoxymethyl and -methylthiomethyl uracil derivatives. 5-Allyl-6-[(benzo[d]thiazol-2-yl)methyl]-2-thiouracil was also alkylated by S² with methyl bromoacetate and hydrolyzed to the corresponding acid.     

Bronsted acidic ionic liquid catalyzed an eco-friendly and efficient procedure for synthesis of 2,4,5-trisubstituted imidazole derivatives under ultrasound irradiation and optimal conditions

Research on Chemical Intermediates - 2-[(1H-imidazol-3-ium-3-yl)methyl]-4-{bis[3-((1H-imidazol-3-ium-3-yl) methyl-(4-hydroxyphenyl]methylene}cyclohexa-2,5-dienone trihydrogen sulfate...