Preparation,structural characterization,and acid-catalyzed isomerization of 3-, 7-, and 9-benzyl-6-benzylthiopurines

Benzylation of 6-benzylthiopurine was examined. Structural assignments of the products were determined by 1-D and 2-D nmr spectroscopy (HMQC, HMBC, and nOe). In the presence of base, the isomeric N3-, N7-, and N9-benzylated products 4, 3 , and 2 were isolated; however, only 9-benzyl-6-benzylthio-purine ( 2 ) was obtained in the absence of base. In the latter case, the initially formed N3- and N7-isomers were, in the presence of acid, converted to 9-benzyl-6-benzylthiopurine ( 2 ) via a 6-benzylthiopurine intermediate as evidenced by analysis of the reaction over time using reversed-phase hplc.     

Dmap-Catalyzed Synthesis of Novel Pyrrolo[2,3-D]Pyrimidine Derivatives Bearing an Aromatic Sulfonamide Moiety

4-(N,N-Dimethylamino)pyridine (DMAP), with a dual role as a basic nucleophilic catalyst, was shown to be a highly efficient catalyst for the synthesis of some new N-(2-aryl-7-benzyl-5,6-diphenyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)benzenesulfonamides through the reaction of 2-aryl-7-benzyl-5,6-diphenyl-7H-pyrrolo[2,3-d]pyrimidin-4-amines (7-deazaadenines) with benzenesulfonyl chlorides. It was also found that the use of DMAP under solvent-free conditions is much more effective than other catalytic systems such as pyridine as both the catalyst and solvent, t-BuOK in t-BuOH, Et₃N in ethanol (EtOH), and even DMAP in dimethylformamide (DMF). The influences of the reaction parameters, temperature, and the catalyst amount, on the catalytic performance have been studied. All synthetic compounds were characterized on the basis of their full spectral data.     

Ring expansion of functionalized octahydroindoles to enantiopure cis-decahydroquinolines

A new synthetic entry to enantiopure cis-decahydroquinolines is reported. Endo and exo derivatives of cis-1-benzyl-2-(hydroxymethyl)octahydroindol-6-one ethylene acetal undergo ring enlargement upon treatment with TFAA and then Et3N (thermodynamic conditions) to give enantiopure 1-benzyl-3-hydroxydecahydroquinolin-7-one derivatives in 77 and 82% yield, respectively. For 2-(1-hydroxyethyl) analogues, the best synthetic result is obtained from the (2S,1'R) endo isomer, which under kinetic reaction conditions (MsCl, THF, -20 degrees C, then AgOAc at rt ) gives the expanded product in 54% yield.     

Lactams—I The synthesis and acid hydrolysis of 4- and 5-substituted 1-benzyl-2-piperidone derivatives

In order to explain the difficulty in hydrolysing the lactam linkage of 1-benzyl-2-oxo-5-ethyl-4-piperidineacetic acid (XIV) under acid conditions, several model compounds such as 1-benzyl-2-piperidone (X), 1-benzyl-5-ethyl-2-piperidone (XI), 1-benzyl-4-ethyl-2-piperidone (XII) and 1-benzyl-2-oxo-4-piperidineacetic add (XIII) were prepared and their hydrolysis in boiling 6N HCl was studied. For each of the lactams, the hydrolysis was found to proceed to an equilibrium as shown in Table 1. Substituents at the 4- and 5-positions of the piperidone ring seemed to favour the ring form in the equilibrium between piperidones (X-XIV) and ω-amino acid hydrochlorides (type XV).     

Approaches to the Synthesis of Cytochalasans. Part 2. Pyrrolinone derivatives as basic units

Several attempts to prepare 3-acetyl-5-benzyl-3-pyrrolin-2-one ( 7 ) from phenylalanine are described. This goal was only reached formally, because compound 7 exists in the tautomeric form of (Z)-5-benzyl-3-(1′-hydroxyethylidene)-4-pyrrolin-2-one ( 17 ) according to the spectral data. The problem of tautomerism in pyrrolinone systems is discussed.     

Studies towards the synthesis of the fluorescent bases of phenylalanine transfer ribonucleic acids: synthesis of 7-methylwye isolated from extremely thermophilic archaebacteria

Acid- or base-catalyzed acylation of 1-benzylwye (7) provided the 7-substituted derivatives 9, 10, and 11 in poor yields. Although the reactions of lithiated 7 with electrophiles gave the 2-substituted derivatives 14, 15, 17, 20, 21, and 22, lithiation of 1-benzyl-7-bromo-2-chlorowye (23) followed by treatment with Me2CHCH2CHO (13) successfully introduced a side chain at the 7-position to afford 1-benzyl-2-chloro-7-(1-hydroxy-3-methylbutyl)wye (24). Cyclization of 1-benzyl-3-methylguanine (5) with 3-bromo-2-butanone followed by catalytic hydrogenolysis afforded 7-methylwye (2b), the hypermodified base isolated from archaebacterial transfer ribonucleic acids. A more efficient route for the synthesis of 2b has been developed via a series of reactions: the Vilsmeier-Haack reaction of 7, reduction with NaBH4, and catalytic hydrogenolysis over Pd-C.     

Synthetic access of new 6-purineselenyl and 8-(1,3,4-thiadiazolyl)-7-benzyl-1, 3-dimethyl-1H-purine-2,6-(3H,7H)-dione derivatives

Abstract

New 6-purineselenyl, 1, 3, 4-thiadiazols bearing 7-benzyl-1,3-dimethyl-1H-purine-2,6-(3H,7H)-diones and (8-[2-(3-phenyl-5-substituted-1,3,4-thiadiazol-2(3H)-ylidene) hydrazinyl)-7-benzyl-1,3-dimethyl-1H-purine-2,6-(3H,7H)-diones derivatives were synthesized. The structures of the newly synthesized compounds were elucidated by spectroscopic methods (1H-NMR, 13C-NMR, and MS spectrometry) and elemental analysis.     

Five-membered 2,3-dioxoheterocycles: XC. Reaction of 4,5-bis(methoxycarbonyl)-1H-pyrrole-2,3-diones with enaminoesters. crystal and molecular structure of 4-methyl 9-ethyl 7-benzyl-3-hydroxy-8-methyl-1-(4-methoxyphenyl)-2,6-dioxo-1,7-diazaspiro[4.4]nona-3,8-diene-4,9-dicarboxylate

1-Aryl-4,5-bis(methoxycarbonyl)-1H-pyrrole-2,3-diones react with ethyl 3-(benzylamino)but-2-enoate and ethyl 3-(benzylamino)-3-phenylacrylate giving 4-methyl 9-ethyl 1-aryl-7-benzyl-3-hydroxy-8-methyl- and 4-methyl 9-ethyl 1-aryl-7-benzyl-3-hydroxy-8-phenyl-2,6-dioxo-1,7-diazaspiro[4.4]nona-3,8-diene-4,9-dicarboxylates.     

Synthesis and Crystal Structure of 3-Benzyl-6-trichloromethyl-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazole

The title compound 3-benzyl-6-trichloromethyl-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazole I （C11HTC13N4S, Mr = 333.62） has been synthesized, and its structure was determined by elemental analyses, IR, ^1H NMR, ^13C NMR, and X-ray diffractions. The crystal is of triclinic, space group P1^-, with a = 5.898（3）, b = 10.510（4）, c = 11.580（5） A, α = 74.936（7）, β= 75.476（7）, γ = 79.647（7）°, V= 665.9（5）/A^3, F（000） = 336, Z= 2, Dc = 1.664 g/cm^3, 2 = 0.71073A, p = 0.834 mm^-1, the final R = 0.0605 and wR = 0.0900. The secondary bonding interactions （SBIs） S…N and π-π stacking interactions are found in the crystal structure and they link the molecules into a three-dimensional network.     

Synthesis of N6-substituted adenines from 3-methylxanthine

A series of 6-arylalkyl(hetarylalkyl, cycloalkyl, carboxyalkyl)amino-7-benzyl-2-chloropurines have been synthesized from 3-methylxanthine via the reaction of the intermediate 7-benzyl-2,6-dichloropurine with amines and aminoacids. N⁶-benzyladenine, N⁶-(-furfuryl)adenine (kinetin), and N-(purinyl)glycine have been obtained via the catalytic hydrogenation of 7-benzyl-6-benzyl(furfuryl, carboxymethyl)amino-2-chloropurines.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 4, 529–532, April, 2000.     

Azaindoles. 69. Some reactions of 5-cyano-6-chloro-7-azaindoles and lactam-lactim tautomerism in 5-cyano-6-hydroxy-7-azaindolines

Electrophilic substitution in the 3-position of 1-benzyl-4-methyl-5-cyano-6-chloro-7-azaindole requires more severe conditions than in 7-azaindoles without the 5-cyano-substituent. Increased ease of nucleophilic replacement of the chlorine atom by the methoxy group has been observed in 1-benzyl- (and 1-butyl)-4-methyl-5-cyano-6-chloro-7-azaindoles, and the cyano-group in these compounds has been found to be resistant to hydrolysis and alcoholysis. The introduction into 1-benzyl- (and 1-butyl)-4-methyl-6-hydroxy-7-azaindoles of a 5-cyano-substituent results in a shift of the lactam-lactim tautomeric equilibrium towards the lactim forms.For communication 68, see [1].Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 1, pp. 100–106, January, 1987.     

Manganese(III)–Arsenic(III) Reaction Catalyzed by Some Antidotic Oxime Iodides

Manganese(III)–arsenic(III) reaction in the presence of sulfuric acid is proposed in this work as an indicator reaction for the kinetic determination of some antidotic oxime iodides. As 2-hydroxyiminomethyl-1-benzyl-3-methylimidazolium iodide, 2-hydroxyiminomethyl-3-benzyl-1-[3-(2-hydroxyiminomethyl-3-benzyl-1-imidazolio)-2-oxapropyl]-imidazolium diiodide, and 2-[(hydroxyimino)methyl]-1-methylpyridinium iodide catalyze the proposed reaction, a kinetic method for their determination in the range from 1.0 × 10⁻⁸to 8.0 × 10⁻⁸mol dm⁻³was developed. The effect of some other antidotic oximes on the accuracy of these determinations was investigated.     

2-Phenylphthalimidine derivatives. A probable formation mechanism of adducts from 3-benzylidenephthalide and aniline

3-Benzyl-3-hydroxy-2-phenylphthalimidine ( 1 ) and 3-anilino-3-benzyl-2-phenylphthalimidine ( 2 ), the unusual adduct, are obtained from the title compounds. 3-Alkoxy-3-benzyl-2-phenylphthalimidines 3 are synthesized. The behaviour of 1 , 3-benzylidene-2-phenylphthalimidines ( 4 and 5 ), 3-(α-bromobenzylidene)-2-phenylphthalimidines ( 6 and 7 ) with respect to bases and the preparation of the open tautomer 13 of 1 and its hydrochloride are described. A hypothetical mechanism about the formation of 1 and 2 is suggested.     

Reactions of 6-benzyl-5-methyl-2-(methylsulfanyl)pyrimidin-4(3H)-one with aliphatic and aliphatic-aromatic amines

Russian Journal of Organic Chemistry - The rules were investigated of the regioselective synthesis of N2-substituted derivatives of 2-amino-6-benzyl-5-methylpyrimidin-4(3H)-one from...     

Synthesis and molecular structure of 6-amino-3-benzylmercapto-1,2,4-triazolo[3,4-f][1,2,4]triazin-8(7H)-one

The title compound 6-amino-3-benzylmercapto-1,2,4-triazolo[3,4-f][1,2,4]-triazin-8(7H)-one (4), molecular formula C(11)H(10)N(6)OS, was obtained by the reaction of 3-amino-2-benzyl-6-hydrazino-1,2,4-triazin-5(2H)-one (3) with carbon disulfide in a water/pyridine mixture. Compound 4 can also be synthesized by reacting 6-amino-3(2H)mercapto-1,2,4-triazolo[3,4-f][1,2,4]triazin-8(7H)-one (7) with benzyl bromide in methanolic ammonia water. The compound crystallizes in the monoclinic space group P2(1)/c with a = 7.2926(15), b = 14.456(2), c = 11.436(2) A, beta = 105.30(2) degrees , V= 1162.9(4) A(3) and Z = 4, resulting in a density Dcalc of 1.567 g/cm(3). Molecules of 4 are linked by extensive intermolecular N-H...N and N-H...O hydrogen bonding [graph set R(2)(2 )(9)]. The structure is further stabilized by pi-pi stacking interactions.     

Synthesis, and antitumor activity of some N1-(coumarin-7-yl) amidrazones and related congeners

A series of new N1-(coumarin-7-yl)amidrazones incorporating N-piperazines and related congeners were synthesized by reacting the hydrazonoyl chloride derived from 7-amino-4-methylcoumarin with the appropriate piperazines. The chemical structures of the newly prepared compounds were supported by elemental analyses, 1H-NMR, 13C-NMR, and ESI-HRMS spectral data. The antitumor activity of the newly synthesized compounds was evaluated. Among all the compounds tested, 7-{2-[1-(4-(1-benzyl-2-ethyl-4-nitro-1H-imidazol-5-yl)piperazin-1-yl)-2-oxopropylidene]hydrazinyl}-4-methyl-2H-chromen-2-one (3n) was the most potent against MCF-7 and K562 cells, with IC?? values of 20.2 and 9.3 μM, respectively.     

Synthesis of pyrido[3,4-<Emphasis Type="Italic">d</Emphasis>]pyrimidines by condensation of ethyl 1-benzyl-3-oxopiperidine-4-carboxylate with morpholine-4-carboxamidine

A method has been developed for the synthesis of 4-amino-substituted 7-benzyl-2-morpholin-4-yl-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidines by condensation of ethyl 1-benzyl-3-oxopiperidine-4-carboxylate with morpholine-4-carboxamidine and subsequent reaction of the 7-benzyl-2-morpholin-4-yl-5,6,7,8-tetrahydro-3H-pyrido[3,4-d]pyrimidin-4-one with trifluoromethanesulfonic anhydride and secondary amines. __________ Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 5, pp. 762–768, May, 2007.     

Synthesis of 2-pyridyl-substituted derivatives of 7-benzyl-5,6,7,8-tetra-hydropyrido[3,4-<Emphasis Type="Italic">d</Emphasis>]pyrimidine

A method has been developed for the synthesis of 2-pyridyl-substituted derivatives of 7-benzyl-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidine based on the condensation of ethyl 1-benzyl-3-oxopiperidine-4-carboxylate with pyridyl-2-, pyridyl-3-, and pyridyl-4-carboxamidines and subsequent reactions of 7-benzyl-2-pyridyl-5,6,7,8-tetrahydro-3H-pyrido[3,4-d]pyrimidin-4-ones with trifluoromethanesulfonic anhydride and secondary amines. __________ Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 10, 1556–1561, October, 2007.     

Synthesis and characterization of novel 2-(1-benzyl-3-[4-fluorophenyl]-1H-pyrazol-4-yl)-7-fluoro-4H-chromen-4-one derivatives

Novel 1-benzyl-3-(4-fluorophenyl)-1H-pyrazole-4-carbaldehydes 3a to 3e were synthesized via Vilsmeier-Haack reaction of the appropriate 1-benzyl-2-(1-(4-fluorophenyl)ethylidene)hydrazines, derived from 4-fluoroacetophenone 1 with substituted 2-benzylhydrazines 2a to 2e . The base catalyzed condensation of 1-benzyl-3-(4-fluorophenyl)-1H-pyrazole-4-carbaldehydes 3a to 3e with 1-(4-fluoro-2-hydroxyphenyl)ethanone 4 gave (E)-3-(1-benzyl-3-(4-fluorophenyl)-1H-pyrazol-4-yl)-1-(4-fluoro-2-hydroxyphenyl)prop-2-en-1-ones 5a to 5e . On cyclization with dimethyl sulfoxide (DMSO)/I₂, compounds 5a to 5e gave 2-(1-benzyl-3-(4-fluorophenyl)-1H-pyrazol-4-yl)-7-fluoro-4H-chromen-4-ones 6a to 6e . Structures of all novel compounds were confirmed by infrared (IR), proton nuclear magnetic resonance (¹H NMR), carbon nuclear magnetic resonance (¹³C NMR), and mass spectral data. All the synthesized compounds were screened for their antibacterial activities.     

Stereocontrolled transformation of nitrohexofuranoses into cyclopentylamines via 2-oxabicyclo[2.2.1]heptanes. Part 6: synthesis and incorporation into peptides of the first reported 2,3-dihydroxycyclopentanecarboxylic acid

Herein we report the intramolecular alkylation of nitronates of methyl-5-O-benzyl-3,6-deoxy-6-nitro-β-d-glucofuranoside and methyl-5-O-benzyl-3,6-deoxy-6-nitro-α-d-glucofuranoside into the corresponding 2-oxabicyclo[2.2.1]heptane derivatives. Similarly, methyl-3-O-benzyl-5-deoxy-5-nitromethyl-β-d-xylofuranoside and methyl-3-O-benzyl-5-deoxy-5-nitromethyl-α-d-xylofuranoside were cyclized to (1R,3R,4S,5R,7R)-7-benzyloxy-3-methoxy-5-nitro-2-oxabicyclo[2.2.1]heptane and (1R,3S,4S,5R,7R)-7-benzyloxy-3-methoxy-5-nitro-2-oxabicyclo[2.2.1]heptane, respectively. These 2-oxabicyclo[2.2.1]heptane derivatives were eventually transformed into enantiopure methyl (1S,2S,3R,4S,5R)-2-amino-2,3-dihydroxycyclopentanecarboxylate and this novel β-amino acid was incorporated into peptides.