bluuebunny/crossref_metadata_2025_split huggingface dataset:
Aerial oxidation kinetics of a phenolic porphyrin in acid solution
Authors: Milgrom Lionel R. , Hill Jonathan P. 
Published: March 2009

AbstractThe rate of aerial oxidation of the title porphyrin (1) in dichloromethane (DCM), acidified with trifluoro‐acetic acid (TFA), was found to be first‐order in 1 and second‐order in TFA at low TFA concentrations, and second‐order in both 1 and TFA at higher TFA concentrations. At the lower TFA concentrations, aerial oxidation gives the two‐electron oxidised product 2, while at the higher TFA concentrations, a porphyrin pication radical 3 is formed. These results are rationalised by a kinetic scheme requiring, (i), preequilibrium involving transient formation of a porphyrin tetracation 4, (ii), two‐electron oxidation of 4 to a diprotonated oxidised porphyrin 5, (iii) reaction of 5 with solvent water and (iv), conproportionation of 5 with 1 to generate 3.
Synthesis of (r)‐ and (s)‐1‐formyl‐6,7,8,9‐tetrahydro‐ N,N‐(dipropyl)‐3H‐benz[e]indol‐8‐amines: Potent and orally active 5‐ht1a receptor agonists
Authors: Lin Chiu‐Hong , Ennis Michael D. , Hoffman Robert L. , Phillips Gillian , Haadsma‐Svensson Susanne R. , Ghazal Nabil B. , Chidester Connie G. 
Published: March 2009

AbstractAn efficient synthesis of the potent and orally active 5‐HT1A agonists, (R)‐(+)‐ and (S)‐(‐)‐1‐formyl‐6,7,8,9‐tetrahydro‐N,N‐dipropyl‐3H‐benz[e]indol‐8‐amines 1a and 1b, is described. This synthesis was accomplished in twelve steps from commercially available 1,5,6,7‐tetrahydro‐4H‐indol‐4‐one (5). The key step involved a regio‐controlled Friedel‐Crafts acylation of 1‐(p‐toluenesulfonyl)indol‐4‐acetyl chloride with ethylene to yield a versatile synthon, 3‐(p‐toluenesulfonyl)‐6,7,8,9‐tetrahydro‐3H‐benz[e]indol‐8‐one (10). Subsequent coupling of this ketone with chiral α‐methylbenzylamine under reductive amination conditions yielded a mixture of diastereomers. These diastereomers were efficiently separated by either chromatography or fractional recrystallization of the derived hydrochloride salts. Debenzylation of the pure diastereomers was followed by alkylation and formylation to yield (R)‐(+)‐ and (S)‐(‐)‐enantiomers 1a and 1b with >99% purity.
Chemistry of thienopyridines. XLII. Three novel compounds derived from thienopyridine N‐oxides
Authors: Klemm L. H. , Muchiri Daniel R. , Anderson Mark , Salbador William , Ford John 
Published: March 2009

AbstractExtension of the Reissert‐Henze reaction to treatment of thieno[2,3‐b]pyridine 7‐oxide with potassium thiocyanate and benzoyl chloride in water‐methylene chloride gives a 2% yield of bis(6‐thieno[2,3‐b]pyridyl) disulfide. Peroxidation of 5‐ethylthieno[2,3‐b]pyridine (4) forms the 7‐oxide 5 (53%), converted to a monopicrate 5a. Picrate 5a undergoes N‐deoxygenation to 4‐picrate on drying at 78° in vacuo, but shows the expected additive mass spectrum of 5 (thermally stable) and picric acid. Nucleophilic displacement of chloride ion from 7‐chlorothieno[3,2‐b]pyridine (derived, in turn, from thieno[3,2‐b]pyridine 4‐oxide) by the anion from ethyl cyanoacetate gives 7‐(1‐cyano‐1‐ethoxycarbonyl)methylene‐4,7‐dihydrothieno[3,2‐b]pyridine (82%), stable in this iminodienic tautomeric form.
Studies on isocyanides and related compounds. A convenient synthesis of 2,3‐disubstituted spiroimidazolones
Authors: Bossio Ricardo , Marcaccini Stefano , Papaleo Sandro , Pepino Roberto 
Published: March 2009

AbstractThe four‐component condensation between cycloketones 1, ammonium formate, and isocyanides 2 afforded formamides 3, which were dehydrated to the corresponding isocyanides 4. Upon treatment with n‐butyllithium, compounds 4 cyclized to spiroimidazolones 6, via the carbanions 5. A series of 2,3‐disubstituted spiroimidazolones 8 was obtained by reacting 5 with aldehydes 7.
On the bromination of thieno[c]‐fused 1,5‐naphthyridines and their isomeric N‐oxides using dibromoisocyanuric acid in fuming sulfuric acid
Authors: Malm Johan , Hörnfeldt Anna‐Britta , Gronowitz Salo 
Published: March 2009

AbstractThieno[2,3‐c]‐1,5‐naphthyridine (3), thieno[2,3‐c]1,5‐naphthyridine 5‐oxide (7), thieno[3,2‐c]‐1,5‐naphthyridine (5) and thieno[3,2‐c]‐1,5‐naphthyridine 5‐oxide (9) could conveniently be brominated at room temperature using dibromoisocyanuric acid in fuming sulfuric acid. Bromination occurred in good to moderate yields at the β position in the thiophene ring. Thieno[2,3‐c]‐1,5‐naphthyridine 9‐oxide (12) and thieno[3,2‐c]‐1,5‐naphthyridine 9‐oxide (13) also gave substitution in the thiophene ring at 95°. It was also found that 12 was deoxygenated under these reaction conditions. Direct oxidation of the brominated thieno[c]naphthyridines with m‐chloroperbenzoic acid gave the 5‐oxides in high yield.
Praziquantel analogs. Synthesis of substituted 4‐(2‐,3‐ and 4‐R)‐carboxyphenyl‐1,4‐pyrazin‐2‐ones
Authors: Martínez Roberto , Rubio Manuel F. , Toscano Ruben A. , Villalobos Xochitl , Brito Marco A. 
Published: March 2009

AbstractThe title compounds have been synthesized in a one step reaction by condensation between 2‐piperazinone with substituted benzoic acids.
Reactions of 2,3‐dihydro‐1H‐cyclohepta[b]pyrazines with acyl halides
Authors: Kawamata Yuuki , Imafuku Kimiaki , Li Dong‐Hao , Jin Zhong‐Tian , Li Zhi‐Hong , Xiao Yan‐Wen 
Published: March 2009

Abstract2 When3‐dihydro‐1H‐cyclohepta[b]pyrazine (3) was treated with acetyl chloride under the Friedel‐Crafts conditions, its pyrazine ring opened to afford 2‐[N'‐acetyl‐(2‐aminoethyl)amino]tropone. Reactions with propionyl and butyryl chloride also gave similarly ring‐opened products. On the other hand, aromatic benzoyl chlorides reacted with compound 3 to afford N‐benzoyl‐substituted 2,3‐dihydro‐1H‐cyclohepta[b]pyrazines, in addition to ring‐opened compounds.
Synthesis and Properties of a selenium‐bridged bisquinolone
Authors: Löwe Werner , Schmidt Robert 
Published: March 2009

AbstractThe preparation of the selenium‐bridged bisquinolone 5 has been investigated. Compound 5 was methylated giving the N‐methyl derivative 6. Compound 5 and phosphorus oxychloride yielded 4‐chloroquinoline 8 which was converted to novel selenium heterocycles 7, 11 and 12 and the 4‐phenoxy product 9.
Ring opening reaction of the pyridinium salt of 4‐nitro‐3‐isoxazolin‐5‐one: A preparation of trifunctionalized methane derivatives
Authors: Nishiwaki Nagatoshi , Takada Yuji , Inoue Yoji , Tohda Yasuo , Ariga Masahiro 
Published: March 2009

AbstractThe ring cleavage of the pyridinium salt of 4‐nitro‐3‐isoxazolin‐5‐one 1 was found to proceed under mild basic conditions and to give cyano‐aci‐nitroacetates 2 in quantitative yields. The ring opened products 2 have three different functional groups at the same carbon atom, and are worth applying as a useful building block to syntheses of polyfunctionalized compounds.
A study of some isopropenyl‐substituted dihydrofuro[1]benzopyranones
Authors: Yamaguchi Seiji , Saitoh Akihito , Kawase Yoshiyuki 
Published: March 2009

AbstractA pyrone‐ring formation using N,N‐dimethylacetamide dimethyl acetal in refluxing xylene converted some o‐hydroxyacetophenone derivatives 1a‐e to the corresponding dihydrofuro[1]benzopyranones 2a‐e.
Synthesis of 1,4‐benzodiazepine‐1‐carbothioamides, bicyclic analogues of the TIBO‐type anti‐HIV agents
Authors: Liu Jie , Dodd Robert H. 
Published: March 2009

AbstractA series of N'‐substituted 1,4‐benzodiazepine‐1‐carbothioamides 2a‐j were prepared by reacting the precursor 1,4‐benzodiazepine 11 with the corresponding N‐substituted isothiocyanates 2a‐i or with sodium thiocyanate‐trifluoroacetic acid (2j). Despite the structural ressemblance of these molecules with the potent TIBO‐type anti‐HIV compound R82150, 2a‐j displayed no anti‐HIV activity in vitro.
Comparative reactivity of 3‐methyl‐5‐phenylisoxazole and 3‐methyl‐5‐phenylisothiazole against electrophilic compounds
Authors: Alberola Angel , Calvo Luis , Rodríguez Rodríguez Ma Teresa , Sañudo Ma Carmen 
Published: March 2009

AbstractA comparative study of reactions of 3‐methyl‐5‐phenylisoxazole and 3‐methyl‐5‐phenylisothiazole with electrophilic compounds in the presence of n‐BuLi, LICA or LICA‐TMEDA is reported. By using LICA‐TMEDA, regioselective reactions of the heterocyclic compounds at the C‐3 methyl group are obtained. With n‐BuLi or LICA and the isoxazole derivative a product mixture at the C‐4 position and the C‐3 methyl group is found. In the case of isothiazole compound, only with methyl iodide and n‐BuLi, the dialkylated product at both positions is formed.
Substituent effects on the tautomer ratios between the enamine and methylene imine forms in side‐chained quinoxalines
Authors: Kurasawa Yoshihisa , Miyashita Ryuichiro , Takada Atsushi , Kim Ho Sik , Okamoto Yoshihisa 
Published: March 2009

AbstractThe p‐ and m‐substituted 3‐arylcarbamoylmethylene‐2‐oxo‐1,2,3,4‐tetrahydroquinoxalines 3a‐o showed the tautomeric equilibria between the enamine C and methylene imine D forms in dimethyl sulfoxide or dimethyl sulfoxide/trifluoroacetic acid media. The linear correlation of the Hammett σp and σm values with the log KT values was observed in the dimethyl sulfoxide/trifluoroacetic acid (2:1) media of compounds 3a‐o, wherein KT meaned the tautomeric equilibrium constants ([D]/[C]).
Syntheses of various 5‐(bromoaryl)‐substituted uracils
Authors: Wellmar Ulf , Hörnfeldt Anna‐Britta , Gronowitz Salo 
Published: March 2009

AbstractThe Suzuki Pd(0)‐catalyzed coupling between arylboronic acids and aryl bromides or iodides in weakly alkaline medium, previously further developed by us, has been used for regioselective preparation of 5‐(2′‐bromo‐5′‐furyl)‐, 5‐(2′‐bromo‐4′‐furyl)‐, 5‐(2′‐bromo‐5′‐thienyl)‐, 5‐(2′‐bromo‐4′‐thienyl)‐, 5‐(4′‐bromo‐2′‐thiazolyl)‐, 5‐(3′‐bromophenyl)‐, 5‐(6′‐bromo‐2′‐pyridyl)‐ and 5‐(4′‐bromo‐2′‐pyrimidyl)‐substituted 2,4‐di‐t‐butoxypyrimidines. In the coupling between 2,4‐di‐t‐butoxy‐5‐pyrimidineboronic acid and the nine different aryl dibromides that were tried as coupling partners, only the 2,4‐ and 2,5‐dibromothiazoles did not give satisfactory yields, 15% and 0%, respectively. The other seven aryl dibromides gave the desired 5‐(bromoaryl)‐2,4‐di‐t‐butoxypyrimidines in 58‐89% yield. Attempts to synthesise 2,4‐di‐t‐butoxy‐5‐(2′‐bromo‐4′‐thienyl)pyrimidine from 2‐bromo‐4‐iodothiophene failed. Dealkylation of the 5‐(bromoaryl)‐2,4‐di‐t‐butoxypyrimidines in 2.5 M hydrochloric acid gave the corresponding 5‐(bromoaryl)uracils in almost quantitative yields.
Rearrangements of substituted 3‐azidoazetidines: Unexpected formation of a substituted oxazole
Authors: Marchand Alan P. , Rajagopal D. , Bott Simon G. 
Published: March 2009

AbstractThermolysis of neat N‐carboethoxy‐3‐azido‐3‐ethylazetidine (3) at 200° under argon produced the corresponding cyclic imine 4 (68% yield). Prolonged refluxing of a mixture of N‐triflylazetidin‐3‐one (7), sodium azide, and titanium tetrachloride in acetonitrile solvent afforded recovered 7 (25% yield) along with a colorless microcrystalline solid, 8, mp 104–105° (20% yield), whose structure was established unequivocally via application of X‐ray crystallographic methods.
Synthesis and in vitro anti‐human cytomegalovirus (hcmv) activity of certain alkenyl substituted cytosines and 5‐halocytosines
Authors: Lewis Arthur F. , Revankar Ganapathi R. , Rando Robert F. 
Published: March 2009

AbstractThe 1‐[(Z)‐2‐penten‐1‐yl] and 1‐(3‐methyl‐2‐buten‐1‐yl) derivatives of cytosine, 5‐bromocytosine, 5‐fluorocytosine, and 5‐iodocytosine were prepared by a reaction of the sodium salt of the requisite cytosine with (Z)‐1‐bromo‐2‐pentene and 4‐bromo‐2‐methyl‐2‐butene, respectively. The eight alkenylcytosines 5a‐5h were evaluated in cell culture for their anti‐HCMV activity. Only the derivatives of 5‐bromocytosine, 5c and 5d, showed slight activity in this assay.
Preparation of fused 1,3‐oxazine‐2,4‐diones as potential antitumor agents
Authors: Player Mark R. , Walter Sowell J. 
Published: March 2009

AbstractA series of indole, thiophene and pyrrole‐fused 1,3‐oxazine‐2,4‐diones, 2‐methyl‐1,3‐oxazin‐4‐ones and 2‐dimethylamino‐1,3‐oxazin‐4‐ones were synthesized and evaluated as antitumor agents.
Synthesis and spectroscopic characterizations of both 1‐ethyl‐4,8‐dihydro‐10‐methoxy‐3‐methyl‐8‐r1‐6‐r2‐dipyrazolo[3,4‐b:4′,3′‐f]‐[1,5]diazocin‐5(1H)‐ones and 1‐ethyl‐1,4,8,9‐tetrahydro‐3,9‐dimethyl‐8‐r1‐6‐r2‐dipyrazolo[3,4‐b:4′,3′‐f][1,5]diazocine‐5,10‐diones of pharmaceutical interest
Authors: Migliara Onofrio , Lamartina Liliana , Rainieri Rosina 
Published: March 2009

AbstractThe non‐selective methylation of compounds 3a‐d using ethereal diazomethane, allowed the synthesis of isomers 4 and 5 which were useful intermediates for the preparation, by a simple approach, of the title compounds 7 and 9. A complete assignment of the chemical shifts to the carbon atoms of the compounds 7 and 9 was performed by different nmr experiments, such as DEPT and XHDEPT for onebond CH correlations and COLOC experiments for long‐range C‐H correlations.
Temperature dependence of 13c nmr spectra of 9‐methylaminoacridinium and 4‐methylaminopyridinium perchlorate
Authors: Kalatzis Evangelos 
Published: March 2009

AbstractThe double bond character of the exocyclic carbonnitrogen bond of 9‐methylaminoacridinium ion is less than that of 4‐methylaminopyridinium ion since the energy barrier of rotation around this bond is lower by 8 kJ mol−1 in the case of the 9‐methylaminoacridinium ion.
Application of the ortho‐lithiation‐cyclization strategy to N‐benzyl‐and N‐phenethylamine derivatives
Authors: Lete Esther , Collado M. Isabel , Sotomayor Nuria , Vicente Teresa , Villa MarÍA‐JesÚS 
Published: March 2009

AbstractThe ortho‐lithiation‐cyclization of iodinated N,N‐diacylphenethylamines provides a convenient method for the preparation of 2‐(2‐acetoamidoethyl)acetophenones and 2‐(2‐benzamidoethyl)benzophenones, which could be easily transformed into dihydroisoquinolines. By contrast, the N‐ethylamino, N‐acetylamino, and N‐trimethylsilylamino moieties studied as ortho‐directing groups provide poor assistance to the metalation of N‐benzyl‐ and N‐phenemylamines and the corresponding isoindolone or isoquinolone derivatives are obtained in low yields.
Heteroannulation of naphthoquinones. Studies on the reaction of 2‐bromo‐2,3‐dihydronaphthoquinone derivatives with 1,2‐binucleophiles.
Authors: Couladouros Elias A. , Plyta Zoi F. , Iliadis Theodoros , Roussis Vassilios , Papageorgiou Vassilios P. 
Published: March 2009

AbstractHeterocyclic derivatives of naphthoquinones were synthesized via their 2‐bromo‐2,3‐dehydro‐intermediates. This new route may lead to the formation of benzo[a]phenothiazin‐5‐ones, benzo[f]quinoxalin‐6‐ones as well as their 1,4 (or 7,10) dihydroxy‐derivatives in high yields. The possible mechanisms involved in the formation of these compounds are discussed.
New pyrazole‐annulated azathioxanthenes as potential intercalators: Synthesis and structure elucidation
Authors: Varvaresou A. , Tsotinis A. , Siatra‐Papastaikoudi Th. , Calogeropoulou T. 
Published: March 2009

AbstractAs part of our program aiming at developing efficacious intercalating agents, a new series of pyrazole‐annulated azathioxanthenes 15a‐e has been synthesized. Structure elucidation of 15a‐e was based on their spectral data and especially the NOESY nmr spectrum of analog 15a.
A quantitative study of substituent effects on oxidative cyclization of some 2‐methylsubstituted aldehydes. Thiosemicarbazones induced by ferric chloride
Authors: Noto Renato , Meo Paolo Lo , Gruttadauria Michelangelo , Werber Giuseppe 
Published: March 2009

AbstractIn order to gain further mechanistical information about the cyclization of thiosemicarbazones and thiosemicarbazone‐type substrates induced by metallic salts as oxidizing agents, we performed the synthesis of substrates 1a‐s and a kinetic study of the oxidative cyclization of 1 to 5‐imino‐Δ2‐1,3,4‐thiadiazole 2 and 1,2,4‐triazoline‐5‐thione 3 derivatives induced by methanolic ferric chloride solutions. The results of cyclization were compared to those of corresponding semicarbazones. The kinetic data were analyzed by means of the Hammett's equation and ρ values discussed.
Fluorescence studies of some 1,2,3‐triazolo[1,5‐a]pyridine and imidazo[1,2‐a]pyridine esters and their vinylogues
Authors: Latham Elliot J. , Stanforth Stephen P. 
Published: March 2009

AbstractThe relative fluorescence intensity of a number of 1,2,3‐triazolo[1,5‐a]pyridine esters 6 and 7 and imidazo‐[1,2‐a]pyridine esters 10 and 11 were determined and compared with methyl imidazo[1,2‐a]pyridine‐5‐carboxylate 2 and 4‐methylumbelliferone 3.
Studies on pyrrolidinones. Catalyst induced selectivity during heterocyclizations of organosilicon compounds into 1,3,4‐oxadiazoles or 1,2,4‐triazines
Authors: Cauliez Pascal , Rigo BenoǏT , Fasseur D. , Couturier D. 
Published: March 2009

AbstractHeterocyclizations of trisilylated diacylhydrazines derived from pyroglutamic acid occurs selectively and yields, depending on the conditions, either to 1,3,4‐oxadiazoles (basic catalyst: fluoride anion) or to fused 1,2,4‐triazines (acidic catalyst: triflic acid).
Preparation and structure determination of 1‐benzyl‐, 1‐methyl‐ and 1H‐5‐[(2‐nitro‐2‐phenyl)ethenyl]imidazoles
Authors: Aulaskari Paula , Ahlgrén Markku , Rouvinen Juha , Vainiotalo Pirjo , Pohjala Esko , Vepsäläinen Jouko 
Published: March 2009

Abstract1‐R‐5‐[(2‐Nitro‐2‐phenyl)ethenyl]imidazoles (R = Bn, Me, H) 6a,b,c were synthesized by the Knoevenagel reaction of the corresponding aldehydes 4a,b,c with phenylnitromethane 5. The E‐isomers 6a,b,c were precipitated from the reaction mixture as crystalline compounds in 89, 81 and 60% yields, respectively. Traces of the Z‐isomers 6a′b′,c′ were found in the reaction mixtures but could be obtained in a ratio of 4:3 from the E‐form with UV irradiation. The E‐forms were more stable and the Z‐isomers changed again to the E‐isomers in several weeks.
Reaction of 3‐hydroxy‐1,2,3,4‐tetrahydroquinoline‐2,4‐diones with ethyl(triphenylphosphoranylidene)acetate
Authors: Kafka Stanislav , Kovář Michal , Klásek Antonín , Kappe Thomas 
Published: March 2009

AbstractThe Wittig reaction of 3‐hydroxy‐1,2,3,4‐tetrahydroquinoline‐2,4‐diones 2 with ethyl (triphenyl‐phosphoranylidene)acetate 3 proceeds stereoselectively to give E‐4‐carbethoxymethylene‐1,2,3,4‐tetra‐hydro‐2‐quinolones 4, which were hydrolyzed to corresponding acids 6 Butenolides 5 were detected and, in some cases, isolated as a minor product of the Wittig reaction.
Syntheses of 2‐(2‐arylethyl)imidazoles
Authors: Shafiee A. , Rastkary N. , Foroumadi A. 
Published: March 2009

AbstractCondensation of 2‐methylimidazole with arylaldehyde 4 and subsequent reduction of the intermediate 5 with Raney‐nickel gave 2‐[2‐(2,4‐dichlorophenyl)ethyl]imidazole 2. Compound 11 was prepared from compound 10 similarly. Reaction of compound 2 with methylsulfonyl chloride gave 1‐methylsulfonyl‐2‐[2‐(2,4‐dichlorophenyl)ethyl]imidazole (7a) in moderate yield. Nitration of compound 11 (Ar = 3‐pyridyl) gave the desired nitro compounds 14 and 15.
Ring closure and rearrangement reactions of 4‐azido‐2‐oxoquinoline‐3‐carboxylates and 4‐azidocoumarin‐3‐carboxylates
Authors: Stadlbauer Wolfgang , Prattes Susanne , Fiala Werner 
Published: March 2009

Abstract4‐Azido‐2‐oxoquinoline‐3‐carboxylates and 4‐azidocoumarin‐3‐carboxylates 6, which were obtained from the corresponding 4‐hydroxy derivatives 1 via 4‐tosylates 2 or 4‐chloro compounds 4, cyclized upon thermolysis to 3‐alkoxyisoxazolo[4,3‐c]quinolin‐4(5H)‐ones or the corresponding coumarins 8, whereas at slightly higher temperatures a 3‐O, 4‐O‐rearrangement took place to give the 4‐alkoxy‐isoxazolo[4,3‐c]‐quinolin‐3‐ones and the corresponding coumarins 9. The necessary reaction conditions could be obtained easily with the help of differential scanning calorimetry.
Synthesis of 6,7‐dimethoxy‐1‐[(halophenoxy)‐methyl]‐1,2,3,4‐tetrahydroisoquinolines
Authors: Cho Su‐Dong , Kim Sung‐Kyu , Chung Hyun‐A , Kang Young‐Jin , Yoon Yong‐Jin 
Published: March 2009

AbstractSome 6,7‐dimethoxy‐1‐[(halophenoxy)methyl]‐1,2,3,4‐tetrahydroisoquinolines were synthesized from N‐[2‐(3,4‐dimethoxyphenyl)ethyl]‐2‐chloroacetamide via three steps in good yield.
Synthesis of chiral azamacrocycles using the bis(α‐chloroacetamide)s derived from chiral 1,2‐diphenylethylenediamine
Authors: Hu Kejiang , Bradshaw Jerald S. , Dalley N. Kent , Xue Guoping , Izatt Reed M. , Krakowiak Krzysztof E. 
Published: March 2009

AbstractOptically active diphenyl‐substituted tetraaza‐12‐crown‐4 diamide (10), tetraaza‐15‐crown‐5 diamide (12), tetraaza‐18‐crown‐6 diamide (11), and hexaaza‐18‐crown‐6 diamide (9) ligands were prepared by treating the appropriate secondary diamines with the (R,R)‐ and (S,S)‐ forms of 1,2‐bis(N‐methyl‐α‐chloracetamido)‐1,2‐diphenylethane (20). Macrocyclic diamides 9 and 10 were reduced to form the optically active diphenyl‐substituted hexaaza‐18‐crown‐6 (13) and tetraaza‐12‐crown‐4 (14), respectively. Reduction of macrocyclic diamide ligands 11 and 12 gave a complex mixture of products from which the desired tetraaza‐15‐crown‐5 and 18‐crown‐6 compounds could not be isolated. Dichloride 20 was prepared by treating the chiral forms of 1,2‐ diphenylethylenediamine with chloroacetic anhydride or chloroacetyl chloride. The crystal structures for the (R,R)‐form of dichloride 20 and the (S,S)‐forms of macrocycles 10 and 11 are reported.
Preparation of 2‐phenyl‐2‐hydroxymethyl‐4‐oxo‐1,2,3,4‐tetrahydroquinazoline and 2‐methyl‐4‐oxo‐3,4‐dihydroquinazoline derivatives formation
Authors: Hradil Pavel , Kvapil Lubomír , Hlaváč Jan , Weidlich TomáŠ , Lyčka Antonín , Lemr Karel 
Published: March 2009

AbstractThe cyclization of phenacyl anthranilate has been studied with the aim to develop the synthesis of 2‐(2′‐aminophenyl)‐4‐phenyloxazole. However, a different course of the reaction than expected was observed. 2‐Phenyl‐2‐hydroxymethyl‐4‐oxo‐1,2,3,4‐tetrahydroquinazoline (3a) was formed by the reaction of phenacyl anthranilate (2) with ammonium acetate under various conditions.3‐Hydroxy‐2‐phenyl‐4(1H)‐quinolinone (4) arose by heating compound 3a in acetic acid. The same compound was obtained by melting compound 3a, but the yield was lower.Different types of products resulted in the reaction of compound 3a with acetic anhydride. Under mild conditions acetylated products 2‐acetoxymethyl‐2‐phenyl‐4‐oxo‐1,2,3,4‐tetrahydroquinazoline (7a) and 2‐acetoxymethyl‐3‐acetyl‐2‐phenyl‐4‐oxo‐1,2,3,4‐tetrahydroquinazoline (8) were prepared. If the reaction was carried out under reflux of the reaction mixture, molecular rearrangement took place to give cis and trans 2‐methyl‐4‐oxo‐3‐(1‐phenyl‐2‐acetoxy)vinyl‐3,4‐dihydroquinazolines (9a and 9b). All prepared compounds have been characterised by their 1H, 13C and 15N NMR spectra, IR spectra and MS.
The synthesis of new 2,4‐diaminofuro[2,3‐d]pyrimidines with 5‐biphenyl, phenoxyphenyl and tricyclic substitutions as dihydrofolate reductase inhibitors
Authors: Gangjee Aleem , Dubash Nauzer P. , Queener Sherry F. 
Published: March 2009

AbstractNonclassical 2,4‐diamino‐5‐substituted furo[2,3‐d]pyrimidines 4a‐i, 5a‐b and 7a‐f were synthesized as extended aromatic ring appended analogs of previously reported antifolates 1a‐b. The extended aromatic system was designed to better interact with a phenylalanine residue (Phe69) of dihydrofolate reductase from the opportunistic pathogen Pneumocystis carinii to afford potent and selective inhibitors of Pneumocystis carinii dihydrofolate reductase. The target compounds were synthesized by nucleophilic displacement of 2,4‐diamino‐5‐(chloromethyl)furo[2,3‐d]pyrimidine 3 with the appropriate aromatic amine or thiol. The compounds were evaluated as inhibitors of dihydrofolate reductase from Pneumocystis carinii and Toxoplasma gondii, and their selectivity was determined using rat liver dihydrofolate reductase as the mammalian reference. In the C8‐N9 bridged series, compound 4e, with a 3‐(2‐methoxydibenzofuran)‐ side chain, exhibited greatest potency and was more than 3 times as selective for Pneumocystis carinii dihydrofolate reductase compared to rat liver dihydrofolate reductase. Compounds 4b and 4c also exhibited selectivity. Compounds in the C8‐S9 bridged series showed comparable potencies, and each showed higher selectivity for Pneumocystis carinii dihydrofolate reductase compared to rat liver dihydrofolate reductase.