bluuebunny/crossref_metadata_2025_split huggingface dataset:
Synthesis, structural and conformational study of some amides derived from 3,7‐dimethyl‐9‐amino‐3,7‐diazabicyclo[3.3.1]nonane‐9‐carboxamide
Authors: Fernandez M. J. , Toledano M. S. , Gálvez E. , Matesanz E. , Martínez‐Ripoll M. 
Published: March 2009

AbstractA 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 1H 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 fatty acids having an o‐heterocycle in their terminal positions. IV. (2‐Methyl‐2H‐chromen‐2‐yl)acetic acids
Authors: Yamaguchi Seiji , Takahashi Koichi , Kawase Yoshiyuki 
Published: March 2009

Abstract(2‐Methyl‐2H‐chromen‐2‐yl)acetic acid 2a was prepared by condensations of salicylaldehyde with diethyl isopropylidenemalonate followed by hydrolyses. Similarly three methoxy derivatives 2c, 2d, and 2e were also prepared from the corresponding salicylaldehyde.
The synthesis of novel polycyclic heterocyclic ring systems via photocyclization. 7. [1]Benzothieno[2,3‐c]naphtho[2,1‐h]quinoline and [1]benzothieno[2,3‐c]naphtho[2,1‐h][1,2,4]triazolo[4,3‐a]quinoline
Authors: Sasaki Kenji , Castle Raymond N. 
Published: March 2009

AbstractThe synthesis of two novel polycyclic heterocyclic ring systems via photocyclization is described. These are [1]benzothieno[2,3‐c]naphtho[2,1‐h]quinoline and [1]benzothieno[2,3‐c]naphtho[2,1‐h][1,2,4]triazolo[4,3‐α]‐quinoline. In the 1H nmr spectrum the proton at position 6 is strongly deshielded in the first ring system while the proton at position 6 in the second ring system is shifted considerably upfield while the proton at position 8 in the second ring system is the most deshielded proton in that ring system. The bay regions in both ring systems are severely congested.
Reaction of 2‐(5‐aminopyrazol‐1‐yl)quinoxaline 4‐oxides with dimethyl acetylenedicarboxylate
Authors: Kurasawa Yoshihisa , Katoh Ritsuko , Mori Fumiko , Fukuchi Minori , Okamoto Megumi , Takada Atsushi , Kim Ho Sik , Okamoto Yoshihisa 
Published: March 2009

AbstractThe reaction of 6‐chloro‐2‐hydrazinoquinoxaline 4‐oxide 6 with ethyl 2‐(ethoxymethylene)‐2‐cyanoacetate or (1‐ethoxyethylidene)malononitrile gave 2‐(5‐amino‐4‐ethoxycarbonylpyrazol‐1‐yl)‐6‐chloroquinoxaline 4‐oxide 7a or 2‐(5‐amino‐4‐cyano‐3‐methylpyrazol‐1‐yl)‐6‐chloroquinoxaline 4‐oxide 7b, respectively. The reaction of compound 7a or 7b with dimethyl acetylenedicarboxylate resulted in the 1,3‐dipolar cycloaddition reaction and then ring transformation to afford 4‐(5‐amino‐4‐ethoxycarbonylpyrazol‐1‐yl)‐8‐chloro‐1,2,3‐trismethoxycarbonylpyrrolo[1,2‐α]quinoxaline 8a or 4‐(5‐amino‐4‐cyano‐3‐methylpyrazol‐1‐yl)‐8‐chloro‐1,2,3‐trismethoxycarbonylpyrrolo[1,2‐α]quinoxaline 8b, respectively.
Preparation of novel 1,2,4‐thiadiazoles by cyclization with 4‐methylbenzenesulfonyl cyanide (tosyl cyanide)
Authors: Unangst Paul C. , Shrum Gary P. , Connor David T. 
Published: March 2009

AbstractThe preparation of 1,2,4‐thiadiazoles with a di‐tert‐butylphenol substituent at the thiadiazole 3‐position is described. A thermally generated nitrile sulfide was reacted with tosyl cyanide in a 1,3‐dipolar cyclization reaction to provide a thiadiazole intermediate containing a labile 5‐tosyl substituent.
Synthesis of 5‐aroylamino‐3H‐1,3,4‐thiadiazole‐2‐thiones and their tautomerism
Authors: Cho Nam Sook , Kim Goo Ni , Párkányi Cyril 
Published: March 2009

Abstract5‐Aroylamino‐3H‐1,3,4‐thiadiazole‐2‐thiones 2 have been synthesized by acylation of 5‐amino‐3H‐1,3,4‐thiadiazole‐2‐thione 1. 5‐Aroylamino‐3H‐1,3,4‐thiadiazole‐2‐thiones can exist in two tautomeric forms — a thiol form and a thione form. On the basis of the 13C nmr spectra and additional experimental information, it has been established that the thione form is the stable form in which these compounds exist.
Synthesis of tellurobispyridines
Authors: Dunne Simon J. , Summers Lindsay A. , Von Nagy‐Felsobuki Ellak I. 
Published: March 2009

AbstractAll six isomers of tellurobispyridine, namely 2,2′‐tellurobispyridine, 2,3′‐tellurobispyridine, 2,4′‐tellurobis‐pyridine, 3,3′‐tellurobispyridine, 3,4′‐tellurobispyridine and 4,4′‐tellurobispyridine have been synthesised.
Synthesis and structure of theN‐alkyl‐2,6‐dimethyl‐4‐oxopyridine‐3‐carboxylic acids
Authors: Dobbin Paul S. , Hider Robert C. , Venkatramani Lalitha , Siripitayananon Jintana , van der Hel Dick 
Published: March 2009

AbstractA range ofN‐alkyl‐2,6‐dimethyl‐4‐oxopyridine‐3‐carboxylic acidsXVhave been preparedviareactions of primary alkyl amines with differing 2,6‐dimethyl‐4‐oxopyran‐3‐carboxylate estersIX. The quantity of desired product formed and the character of by‐products formed are determined by the natures of the amine and esterIXrespectively. X‐ray crystallography data for theN‐ethyl analogue ofXVindicates very strong intramolecular hydrogen bonding to be present, with the heterocyclic ring exhibiting considerable aromaticity.
Oxidative cyclization of some aldehyde semicarbazones induced by metallic salts
Authors: Gruttadauria Michelangelo , Buccheri Francesco , Cusmano Giuseppe , Lo Meo Paolo , Noto Renato , Werber Giuseppe 
Published: March 2009

AbstractThe oxidative cyclization of some aldehyde semicarbazones 10 with four different oxidizing agents has been effected. The structure of the semicarbazones and the nature of cyclizing agent affected the rate and yield of cyclization but they did not show any influence on the regiochemistry of reaction. In fact, 1,2,4‐triazoline 20 was the only heterocyclic ring obtained by the cyclization reaction.
5,6‐Dihydro‐4H‐pyrrolo[1,2‐a][1,4]benzodiazepine‐4,4‐diacetic acid diethyl ester, an useful synthon for the synthesis of new polycyclic nitrogen systems of pharmacological interest
Authors: Massa Silvio , Mai Antonello , Santo Roberto Di , Artico Marino 
Published: March 2009

AbstractThis report describes the synthesis of derivatives of two nitrogen tetracyclic ring systems, respectively 9H,11H‐pyrimido[4,3‐c]pyrrolo[1,2‐a][1,4]benzodiazepine and spiro[piperidine‐4,4′‐[4H]pyrrolo[1,2‐a][1,4]‐benzodiazepine], by the use of the diethyl ester of 5,6‐dihydro‐4H‐pyrrolo[1,2‐a][1,4]benzodiazepine‐4,4‐diacetic acid as a synthon. This compound was obtained by condensation of 1‐(2‐aminomethylphenyl)‐1H‐pyrrole with diethyl 1,3‐acetonedicarboxylate in acid medium. Pyrimidopyrrolobenzodiazepine derivatives were obtained by treating either the pyrrolobenzodiazepine 4,4‐diacetate or the related 4‐methyl‐4‐acetate with phenylisocyanate in boiling diethyl ether in the presence of sodium metal. The structure of 12,13‐dihydro‐11,13‐dioxo‐12‐phenyl‐9H,11H‐pyrimido[4,3‐c]pyrrolo[1,2‐a][1,4]benzodiazepine, a product formed by loss of an acetate unit when 5,6‐dihydro‐4H‐pyrrolo[1,2‐a][1,4]benzodiazepine‐4,4‐diacetate, sodium metal and phenyl‐isocyanate reacted in boiling xylene, was proved by catalytic reduction to 11,13‐dioxo‐12‐phenyl‐12,13,14,14a‐tetrahydro‐9H,11H‐pyrimido[4,3‐c]pyrrolo[1,2‐a][1,4]benzodiazepine, which was synthesized by unambiguous pathway via 5,6‐dihydro‐4H‐pyrrolo[1,2‐a][1,4]benzodiazepine‐4‐acetate. The 2,6‐dioxospiro[piperidine‐4,4′‐[4H]pyrrolo[1,2‐a][1,4]benzodiazepine] derivatives were synthesized from the N‐BOC derivative of 5,6‐dihydro‐4H‐pyrrolo[1,2‐a][1,4]benzodiazepine‐4,4‐diacetic acid diethyl ester, by hydrolysis followed by treatment with 2 equivalents of 1,1′‐carbonyldiimidazole (CDI) and then with aniline or benzylamine. Removal of BOC from the N‐phenyl‐2,6‐dioxopiperidine derivative was obtained by heating the related spiroderivative in toluene in the presence of p‐toluenesulphonic acid. Similar reaction failed when the N‐benzyl‐2,6‐dioxopiperidine analog was used as substrate.
Acridine derivatives. V. Synthesis and P388 antitumor activity of the novel 9‐anilino‐2,3‐ethylenedioxyacridines
Authors: Kimura Michio , Okabayashi Ichizo , Kato Akira 
Published: March 2009

AbstractA new class of deoxyribonucleic acid (DNA)‐intercalating antitumor agents, novel 9‐anilino‐2,3‐ethylenedioxyacridines (five compounds) have been synthesized and evaluated for activity against P388 leukemia in vivo. A few of them possessed the same potency of antitumor activity as amsacrine (m‐AMSA) which is an important antitumor agent in clinical use.
Synthesis of detomidine and medetomidine metabolites: 1,2,3‐trisubstituted arenes with 4′(5′)‐imidazolylmethyl groups
Authors: Stoilov Ivan , Watt David S. , Goodman Jack P. , Pyrek Jan S. T. 
Published: March 2009

AbstractTwo synthetic strategies permitted the synthesis of various metabolites of detomidine (1) and medetomidine (4), potent α‐2 adrenoceptor agonists that undergo rapid oxidative metabolism at the aromatic methyl group distal to the imidazole ring. In the detomidine series, the addition of a Grignard reagent prepared from 2‐((3′,4′‐dimethoxyphenyl)methoxy)methyl)‐6‐bromotoluene (13) to imidazole‐4(5)‐carboxaldehyde (7) provided 2‐(((3′,4′‐dimethoxyphenyl)methoxy)methyl)‐6‐(1′‐hydroxy‐1′‐(5′‐imidazolyl)methyl)tolulene (14). In a subsequent reduction, it was possible to differentiate between the secondary benzylic hydroxyl group and the primary benzylic hydroxyl group protected as a 3,4‐dimethoxybenzyl ether. Removal of the protecting group provided 3‐(hydroxymethyl)detomidine (3‐HD)(2) and an oxidation furnished 3‐carboxydetomidine (3‐CD)(3). However, in the medetomidine series, a similar hydrogenolysis of 2‐(((3′,4′‐dimethoxyphenyl)methoxy)methyl)‐6‐(1′‐hydroxy‐1′‐methyl‐1′‐(5′‐imidazolyl)methyl)toluene (17) failed, and an alternate, longer route involving dehydration and reduction was necessary to secure 3‐(hydroxymethyl)medetomidine (3‐HM) (5) and following an oxidation, 3‐carboxymedetomidine (3‐CM) (6). Finally, an expeditious route to 3‐CM (6) involved the addition of the Grignard reagent prepared from 2‐(3‐bromo‐2‐methylphenyl)‐4,4‐dimethyl‐2‐oxazoline (22) to 4‐acetyl‐1H‐imidazole and the hydrogenolysis and hydrolysis of 2‐(1‐(4,4‐dimethyl‐2‐oxazolyl))‐6‐(1′‐oxo‐1′‐(5′‐imidazolyl)methyl)toluene (23).
Tautomeric structure of 1‐methyldihydropyridazino‐[3,4‐b]quinoxalines in solution
Authors: Kurasawa Yoshihisa , Takada Atsushi , Kim Ho Sik , Okamoto Yoshihisa 
Published: March 2009

AbstractThe reaction of 6‐chloro‐2‐(1‐methylhydrazino)quinoxaline 4‐oxide 1 with ethyl 2‐ethoxymethylene‐2‐cyano‐acetate or ethoxymethylenemalononitrile gave 6‐chloro‐2‐[2‐(2‐cyano‐2‐ethoxycarbonylvinyl)‐1‐methylhy‐drazino]quinoxaline 4‐oxide 3a or 6‐chloro‐2‐[2‐(2,2‐dicyanovinyl)‐1‐methylhydrazino]quinoxaline 3b, respectively. The reaction of 3a with a base afforded 7‐chloro‐1‐methyl‐1,5‐dihydropyridazino[3,4‐b]quinoxaline 4. From the NOE spectral data, the 1‐methyldihydropyridazino[3,4‐b]quinoxalines 2a, 2b and 4 were found to exist as the 1,5‐dihydro form in a dimethyl sulfoxide or trifluoroacetic acid/dimethyl sulfoxide solution.
Synthesis of isocoumarin, 1‐isoquinolone and 4(1H)‐quinolone derivatives via seleno‐intermediates
Authors: Izumi Taeko , Morishita Nobuya 
Published: March 2009

AbstractThe reaction of 2‐styrylbenzoic acids 2 with N‐phenylselenosuccinimide (N‐PSS) affords 3‐phenyl‐iso‐coumarin derivatives 3 and 3,4‐dihydro‐3‐phenyl‐4‐(phenylseleno)isocoumarins 4 via selenolactonization. The reaction of 2‐styrylbenzamides 5 and 1‐(2‐aminophenyl)‐3‐phenyl‐2‐peropen‐1‐one derivatives 11 with N‐PSS also resulted in the formation of 1‐isoquinolone 6 and 4(1H)‐quinolone derivatives 12, respectively.
Heterocyclizations in the pyrido[2,3‐b]pyrazine series
Authors: Blache Y. , Gueiffier A. , Chavignon O. , Teulade J. C. , Milhavet J. C. , Viols H. , Chapat J. P. , Dauphin G. 
Published: March 2009

AbstractIn this paper, we report the results of heterocyclizations in the pyrido[2,3‐b]pyrazine series to give the pyrido[2,3‐e] or [3,2‐e]pyrrolo[1,2‐a]pyrazine. The Clauson‐Kaas reaction on 2,3‐diaminopyridine is investigated; regioselectivity on the 3‐amino group is shown by 1H‐ and 13C‐nmr. Synthesis and reactivity of the original pyrazino[2,3‐g]indolizine series is also reported.
Polycondensed nitrogen heterocycles. Part 25. Aminopyrrolo[1,2‐f]‐phenanthridines by decomposition of 2‐(3‐azidophenyl)‐1‐arylpyrroles
Authors: Almerico Anna Maria , Cirrincione Girolamo , Dattolo Gaetano , Aiello Enrico , Mingoia Francesco 
Published: March 2009

AbstractAcid catalyzed decomposition of the azido derivatives 4a‐c gave rise to amino‐hydroxy‐phenylpyrroles of type 7 and 8 upon hydrolysis of the intermediate aryl nitrenium ions, together with the hydrogen abstraction compounds of type 3. The aminopyrrolo[1,2‐f]phenanthridines 10, 11, and 12 were obtained by treatment with TFMSA of the azide 4d in which the ring being attacked was made more nucleophilic by the introduction of the methoxy group.
Synthesis of 4‐ and 5‐disubstituted 1‐benzylimidazoles, important precursors of purine analogs
Authors: Alves M. José , Proença M. Fernanda J. R. P. , Booth Brian L. 
Published: March 2009

Abstract(Z)‐N‐(2‐amino‐1,2‐dicyanovinyl)‐N'‐benzylformamidine 6 has been prepared both from the reaction of benzylisonitrile with the hydrochloride salt of diaminomaleonitrile and from reaction of ethyl (Z)‐N‐(2‐amino‐1,2‐dicyanovinyl)formimidate with benzylamine. Based‐catalyzed cyclization of amidine 6 led to imidazoles 7 and 8 depending on the reaction conditions. Compound 7 reacts with acetone and butane‐2,3‐dione to give the 2,2‐disubstituted‐6‐carbamoyl‐1,2‐dihydropurines 9a and 9b respectively. 2‐Methyl‐6‐carbamoylpurine 12 was obtained from the reaction of imidazole 7 with pentane‐2,4‐dione. The same compound was observed in the 1H nmr spectrum of a solution of 1,2‐dihydropurine 9b in deuteriochloro‐form. Benzylimidazole 7 can be acetylated with acetic anhydride leading to compound 14. This, in solution, undergoes an acyl migration reaction to give imidazoles 15 and 17. Imidazole 15 cyclizes in the presence of base to the corresponding 6‐cyanopurine 16. A solution of 14 in methanol is slowly converted into the 6‐methoxypurine 18, possibly via a methoxymidoyl intermediate. A similar intermediate 13 has been isolated from 7 in methanol.
Electrophilic substitution and cyclization of 2,2′‐bis(N‐methylindolyl): A simple access to potential protein kinase C inhibitor
Authors: Pindur U. , Kim Y.‐S. , Schollmeyer D. 
Published: March 2009

AbstractA strategy is described for the synthesis of functionalized and cyclized 2,2′‐bisindolyl derivatives related to several basic systems of natural products. The starting 2,2′‐bis(N‐methylindolyl) (8) reacts with a variety of electrophiles and electrophilic dienophiles to furnish the novel, functionalized and cyclized bisindolyl derivatives 9–16. In addition, some reactivity and structural aspects are discussed; an X‐ray crystallographic analysis of the 2,2′‐bisindolyl 8 provided valuable information for the conformational analyses.
The pictet‐spengler reaction and biogenic tryptamines: Formation of tetrahydro‐β‐carbolines at physiological pH
Authors: Callaway James C. , Gyntber Jukka , Poso Antti , Airaksinen Mauno M. , Vepsäläinen Jouko 
Published: March 2009

AbstractBiogenic tryptamines 1a‐c were reacted with aldehydes 2a & b and α‐keto acids 2c & d to form 1,2,3,4‐tetrahydro‐β‐carbolines (THBCs) 4d‐1, and other products, in a buffered solution at 37° and pH 7.4. These reactions were followed over time by 1H nmr through integral changes in discrete signals in the spectra. Reactions between tryptamines and acetaldchyde (2b) gave the expected 1‐methyl‐THBCs 4d‐f, while those with sodium glyoxylate (2c) resulted in THBC‐1‐carboxylic acids 4g‐1. Surprisingly, reactions with sodium pyruvate (2d) or formaldehyde (2a) did not form the expected products 4a‐c or 4j‐1, respectively under these conditions. In successful reactions, 5‐methoxytryptamine (1c) was found to be more reactive than tryptamine (1a) or serotonin (1b). MOPAC calculations were employed to investigate reaction intermediates. These results are applicable in research related to aberrant tryptamine metabolism; e.g. depression and alcoholism.
Chlorination of 3,4‐quinolinediyl bis‐sulfides and 3‐thiosubstituted 4‐quinolinethiones with phosphoryl chloride
Authors: Pluta Krystian , Maślankiewicz Andrzej , Zieba Andrzej 
Published: March 2009

AbstractTransformation of some 4‐quinolinyl sulfides 3 and 4‐quinolinethiones 4 into 4‐chloroquinolines 5 was performed in the reaction with phosphoryl chloride (alone or in N, N‐dimethylformamide and ethanol). 3‐Quinolinyl sulfides were stable in the reaction conditions.
Syntheses of reactive fluorescent stains derived from 5(2)‐aryl‐2(5)‐(4‐pyridyl)oxazoles and bifunctionally reactive linkers
Authors: Litak Peter T. , Kauffman Joel M. 
Published: March 2009

AbstractSeveral bifunctionally reactive linkers containing halide or sulfonate ester groups were prepared. The linkers were used to quaternize 5‐(4‐methoxyphenyl)‐2‐(4‐pyridyl)oxazole and 2‐(6‐chromanyl)‐5‐(4‐pyridyl)oxazole to produce fluorescent stains that contained a reactive group such as an isothiocyanate, an N‐hydroxysuccinimidyl ester, a maleimide, or an oxirane. The stains were derivatized with either 1‐propylamine, 1‐propanethiol, or piperidine, as appropriate, to help in characterization. The stains may serve as more photostable alternatives to fluoresceins or coumarins.
Synthesis of 4(pyrazol‐3‐yl)[1,2,4]triazolo[4,3‐a]quinoxalines and tetrazolo analog
Authors: Atta Kamal F. , El‐Massry Abdel Moneim , Hamid Hamida Abdel , El Ashry El Sayed H. , Amer Adel 
Published: March 2009

AbstractThe transformation of 2‐chloro‐3‐[5‐(acetoxymethyl)‐1‐phenylpyrazol‐3‐yl]quinoxaline 3 to 1‐aryl‐4‐[5‐(hydroxymethyl‐1‐phenylpyrazol‐3‐yl][1,2,4]triazolo[4,3‐a]quinoxalines 4a‐c has been achieved upon treatment with aroylhydrazines in boiling butanol. Compounds 4a‐c were smoothly acetylated by acetic anhydride to give their acetyl derivatives 5a‐c in good yield. 4‐[5‐(Acetoxymethyl)‐1‐phenylpyrazol‐3‐yl]‐1‐methyl[1,2,4]triazolo[4,3‐a]quinoxaline was prepared by ring closure of 2‐hydrazino‐3‐[5‐(hydroxymethyl)‐1‐phenylpyrazol‐3‐yl]quinoxaline 6 by the action of acetic anhydride. The reaction of 6 with acetylacetone afforded 3‐[5‐(hydroxymethyl)‐1‐phenylpyrazol‐3‐yl]‐2‐(3,5‐dimethylpyrazol‐1‐yl)quinoxaline 8. In addition, the reaction of 3 with sodium azide in boiling N, N‐dimethylformamide yielded the fused tetrazolo[1,5‐a]quinoxaline 9.
Bridgehead nitrogen heterocycles derived from the potassium salt of 2,3,5,6,7,8‐hexahydro‐3‐amino‐2‐thioxo benzothieno[2,3‐d ]pyrimidin‐4‐(1H)‐one
Authors: Santagati Andrea , Modica Maria , Santagati Maria 
Published: March 2009

AbstractDerivatives of tetraheterocyclic linear system 2, 4 and 5 were prepared by reacting the potassium salt 1 with the appropriate alpha‐halocarbonyl compounds. Moreover, through reaction of methyl mercapto 6 with hydrazine the new heterocyclic system 1,4,7,8,9,10‐hexahydro‐6H‐[1]benzothieno[2′,3′:4,5]pyrimido[1,2‐b]‐[1,2,4,5]tetrazin‐6‐one (8) was also obtained.
Synthesis of 2,8‐disubstituted 1,2,4‐triazolo[5,1‐i]purines
Authors: Gatta Franco , Giudice Maria Rosaria Del , Borioni Anna , Mustazza Carlo , Fazio Cristina 
Published: March 2009

AbstractThis paper describes the preparation of 2‐aryl‐8‐fluorobenzyl‐1,2,4‐triazolo[5,1‐i]purines 2, starting from 2‐aryl‐7,8‐diamino‐1,2,4‐triazolo[1,5‐c]pyrimidines 9. Our synthetic procedure represents the first example of a feasible approach for the synthesis of 2,8‐disubstituted triazolo[5,1‐i]purines. New syntheses of 5‐amino‐3‐arylpyrimido[5,4‐e]1,2,4‐triazines 12 and 8‐fluorobenzyl‐6‐hydrazinopurines 15 are also reported.
Reactivity of 7‐(2‐dimethylaminovinyl)pyrazolo[1,5‐a]pyrimidines: Synthesis of pyrazolo[1,5‐a]pyrido[3,4‐e]pyrimidine derivatives as potential benzodiazepine receptor ligands. 1
Authors: Bruni Fabrizio , Selleri Silvia , Costanzo Annarella , Guerrini Gabriella , Casilli Maria Lucia 
Published: March 2009

AbstractA series of 7‐methylpyrazolo[1,5‐a]pyrimidines were reacted with dimethylformamide dimethylacetal to give the corresponding dimethylaminovinyl derivatives. These were reacted with ammonium acetate affording, through a ring closure, a number of 6‐methylpyrazolo[1,5‐a]pyrido[3,4‐e]pyrimidines bearing various substituents on the pyrazole ring. The 6‐acetyl‐2‐hydroxy‐7‐methylpyrazolo[1,5‐a]pyrimidine was used as starting material for obtaining some O‐alkyl derivatives. Catalytic transfer hydrogenation of 2‐benzyloxy‐6‐methylpyrazolo[1,5‐a]pyrido[3,4‐e]pyrimidine led to the 2‐hydroxy derivative.
5‐Deaza‐7‐desmethylene analogues of 5,10‐methylene‐5,6,7,8‐tetrahydrofolic acid and related compounds: Synthesis andin vitrobiological activity
Authors: Rosowsky Andre , Bader Henry , Wright Joel E. , Moran Richard G. 
Published: March 2009

Abstract1‐[4‐(tert‐Butyloxycarbonyl)phenyl]‐3‐pyrrolidinone and 1‐[3‐(tert‐butyloxycarbonyl)phenyl]‐4‐piperidinone were condensed with ethyl cyanoacetate or malononitrile to form ylidene derivatives, which were then subjected sequentially to (i) catalytic or chemical reduction, (ii) condensation with guanidine, and (iii) gentle tri‐fluoroacetic acid treatment to obtain 3‐(2,4‐diamino‐6(5H)‐oxopyrimidin‐5‐yl)‐1‐(4‐carboxyphenyl)pyrrolidine (27), 4‐(2,4‐diamino‐6(5H)‐oxopyrimidin‐5‐yl)‐1‐(carboxyphenyl)piperidine (35), and 3‐(2,4,6‐triaminopyrimidin‐5‐yl)‐1‐(carboxyphenyl)pyrrolidine (40). Condensation of27, 35, and40with diethyl or di‐tert‐butyl L‐glutamate followed by removal of the ester groups yieldedN‐[4‐[3‐(2,4‐diamino‐6(5H)‐oxopyrimidin‐5‐yl)pyr‐rolidino]benzoyl]‐L‐glutamic acid (13),N‐[4‐[4‐(2,4‐diamino‐6‐(5H)‐oxopyrimidin‐5‐yl)piperidino]benzoyl]‐L‐glutamic acid (14), andN‐[4‐[3‐(2,4,6‐triaminopyrimidin‐5‐yl)pyrrolidino]benzoyl]‐L‐glutamic acid (15). Compounds13and14may be viewed as 5‐deaza‐7‐desmethylene analogues of 5,10‐methylene‐5,6,7,8‐tetrahydrofolic and 5,10‐ethylene‐5,6,7,8‐tetrahydrofolic acid, respectively. Compounds13and15were good substrates for mouse liver folylpolyglutamate synthetase, with Kmvalues of 20 and 18 μMand a relative first‐order rate constant Vmax/Kmof 2.2 (aminopterin = 1.0). In contrast,14was a very poor substrate, with a Kmof 490 μMand a relative Vmax/Kmof 0.052. As expected from its structure,15was a dihydrofolate reductase inhibitor. However its potency was unexceptional (IC50= 1.2 μM). Compounds13and14were inactive at concentrations of up to 100 μM, and likewise showed no activity against thymidylate synthase or glycinamide ribotide formyltransferase, two other key enzymes of folate‐mediated one‐carbon metabolism. Compound15was moderately active as an inhibitor of the growth of cultured tumor cells (SCC25 human squamous cell carcinoma), with an IC50of 0.37 μM(72 hour exposure). By comparison the IC50of aminopterin was 0.0069 μM. Thus, even though15is a good folylpolyglutamate synthetase substrate, the deep‐seated skeletal changes embodied in this structure are unfavorable for DHFR binding and may also be unfavorable for transport into cells.
A short‐step synthesis of naphtho[2,3‐b]furan‐4,9‐dione
Authors: Koyanagi Jyunichi , Yamamoto Katsumi , Nakayama Kouji , Tanaka Akira 
Published: March 2009

AbstractPhthalic anhydride in THF was added to 3‐lithiofuran 2 in THF to give 3,3‐di‐(3‐furyl)‐1,3‐dihy‐droisobenzofuran‐1‐one 4. On the other hand, 2 in THF was added to phthalic anhydride in THF to give 2‐(3‐furanoyl)benzoic acid 3 by the inverse addition method. Further, the parent naphtho[2,3‐b]furan‐4,9‐dione 1 was obtained from the reaction of 3 with two equimolar amounts of LDA.