bluuebunny/crossref_metadata_2025_split huggingface dataset:
Synthesis of 4,7,8a,9‐tetrahydro‐3H‐diimidazo‐[1,5‐a:4′,5′‐d]pyridine derivatives
Authors: Braña Miguel F. , Guisado Cristina , Pérez‐Castells Javier , Pérez‐Serrano Leticia 
Published: March 2009

AbstractThe synthesis and evaluation of new ligands for the H3receptor of histamine is described. These new compounds are diimidazopyridine derivatives readily prepared by a condensation reaction of spinacine and isocyanates.
Novel five‐membered ring formation by oxidative photocyclization of 4‐(2‐arylvinyl)benzo[a]quinolizinium salts
Authors: Arai Sadao , Yoda Hiroe , Sato Kiyoshi , Yamagishi Takamichi 
Published: March 2009

AbstractOxidative photocyclization of 4‐(2‐arylvinyl)benzo[a]quinolizinium salts (6) gave five‐ or six‐mem‐bered rings depending on the aryl substituent. The olefins 6a and 6b with a phenyl or naphthyl substituent resulted in a normal six‐membered ring formation to afford 6a‐azoniapicene and 6a‐azoniabenzo[b]picene salts (7 and 8), respectively. In contrast, the photo‐reaction of pyridyl substituted derivative 6c resulted in novel five‐membered ring formation to yield 3b‐azonia‐5‐(2‐pyridyl)acephenanthrylene salt (10).
Synthesis and cytotoxic activity of certain new arylazothiazole containing compounds
Authors: El‐Meligie Salwa , El‐Awady Raafat A. 
Published: March 2009

Abstract2‐Amino‐5‐arylazo‐4‐(2‐chlorophenyl)thiazoles (2a‐e) were prepared by the coupling of aryldiazonium chlorides with 2‐amino‐4‐(2‐chlorophenyl) thiazole (1). The thioureas 3a‐e were obtained by condensing the arylazothiazoles 2a‐c with the appropriate isothiocyanates. Reaction of 2d with aromatic aldehydes afforded the chalcone analogues 4a‐c. The pyridone derivatives 5a,b were synthesized by reacting the ketone 2d with different aromatic aldehydes, ethyl cyanoacetate and ammonium acetate. On the other hand, 5b was also prepared by cyclizing 4c with ethyl cyanoacetate and ammonium acetate. Furthermore, 6‐chloroimidazo[2,l‐b]‐thiazole 7 was obtained from the acid derivative 6b by treatment with POC13. While, the imidazo[2,l‐b]‐thiazolones 9a‐d were produced by the cyclization of the chloroacetyl derivatives 8a‐d with DMAP/pyri‐dine. Representative examples of the prepared compounds were tested for in vitro antitumor activity against two human tumor cell lines. Some compounds showed activity against brain tumor cell lines.
New domino‐reaction for the synthesis of N4‐(5‐aryl‐1,3‐oxathiol‐2‐yliden)‐2‐phenylquinazolin‐4‐amines and 4‐[4‐aryl‐5‐(2‐phenylquinazolin‐4‐yl)‐1,3‐thiazol‐2‐yl]morpholine
Authors: Fathalla Walid , Pazdera Pavel , Marek Jaromír 
Published: March 2009

AbstractThe model morpholine‐1‐carbothioic acid (2‐phenyl‐3H‐quinazolin‐4‐ylidene) amide (1) reacts with phenacyl bromides to afford N4‐(5‐aryl‐1,3‐oxathiol‐2‐yliden)‐2‐phenylquinazolin‐4‐amines (4) or N4‐(4,5‐diphenyl‐1,3‐oxathiol‐2‐yliden)‐2‐phenyl‐4‐aminoquinazoline (5) by a thermodynamically controlled reversible reaction favoring the enolate intermediate, while the 4‐[4‐aryl‐5‐(2‐phenylquinazolin‐4‐yl)‐1,3‐thiazol‐2‐yl]morpholine (8) was produced by a kinetically controlled reaction favoring the C‐anion intermediate. 1H nmr, 13C nmr, ir, mass spectroscopy and x‐ray identified compounds (4), (5) and (8).
Reactivity study on morpholine‐1‐carbothioic acid (2‐phenyl‐3H‐quinazolin‐4‐ylidene) amide
Authors: Fathalla Walid , Pazdera Pavel , Čajan Michal , Marek Jaromír 
Published: March 2009

AbstractRegioselective reactions of morpholine‐1‐carbothioic acid (2‐phenyl‐3H‐quinazolin‐4‐ylidene) amide (1) with electrophiles and nucleophiles were studied. The compound (1) reacts with alkyl halides in basic medium to afford S‐substituted isothiourea derivatives, with amines to give 1,1‐disubstituted‐3‐(2‐phenyl‐3H‐quinazolin‐4‐ylidene) thioureas and l‐substituted‐3‐(2‐phenyl‐quinazolin‐4‐yl) thioureas via transami‐nation reaction. The reaction of (1) with amines in the presence of H2O2 provided N4‐disubstituted‐N'4‐(2‐phenylquinazolin‐4‐yl)morpholin‐4‐carboximidamide via oxidative desulfurization. Estimation of reactivity sites on (1) was supported using the ab initio (HF/6‐31G**) quantum chemistry calculations. The ir, 1H nmr, 13C nmr, mass spectroscopy and x‐ray identified the isolated products.
Synthesis of novel fused tricyclic quinolones: 4a,5‐Dihydro‐1H‐[1;2,4]triazino[1,6‐a]quinoline‐2,4,6(3H)‐triones
Authors: Edmont Dolorès , Marot Christophe , Chenault Jacques 
Published: March 2009

AbstractA versatile methodology to build the 1H‐[1,2,4]triazino[1,6‐a]quinoline‐2,4,6(3H)‐trione structure from methyl 6‐fluoro4‐oxo‐1,4‐dihydro‐2‐quinolinecarboxylate was developed. The method involves an N‐ami‐nation followed by condensation of an aroyl isocyanate to form an alpha semicarbazidocarboxylate that readily cyclizes to the fused [1,2,4]triazino ring under ammonia/ethanol condition. Also, the reactivity of the [1,2,4]triazino ring thus obtained was studied.
Preparation of 3‐aminoalkylbenzo[b]thiophenes
Authors: Burkamp Frank , Fletcher Stephen R. 
Published: March 2009

AbstractWe report an efficient entry into substituted 3‐(ω‐aminoalkyl)‐benzo[b]thiophenes that allows rapid generation of structural diversity. Alkylation of α,ω‐dihaloketones with thiophenols followed by acid‐catalysed cyclisation led to an efficient synthesis of 3‐(ω‐aminoalkyl)benzo[b]thiophenes. 2‐Carboethoxy derivatives were prepared using a directed ortho‐metallation approach. These derivatives were readily converted into the corresponding amines.
Synthesis of 7‐aza‐5,8,10‐trideazafolic acid and its 4‐amino‐derivative as potential antifolates
Authors: Wollein Günther , Troschütz Reinhard 
Published: March 2009

Abstracto‐Aminoamide 8, an intermediate in our multistep synthesisof the title compounds was prepared from 1,3‐diketone 3. The following condensation of 8 with chloroformamidine‐HCl (9) gave pyrido[3,4‐d]pyrimidine 10. Dehydratisation of amide 8 led to o‐aminonitrile 15, which was cyclocondensated with guanidine (16) to yield pyrido[3,4‐d]pyrimidine‐2,4‐diamine 17. Coupling of the acids 11 and 18 with diethyl L‐glutamate (12) and following saponification provided 7‐aza‐5,8,10‐trideazafolic acid 14 and its 4‐amino‐derivative 20.
Carbocyclic galanthamin analogs: 4a,5,9,10,11,12‐hexahydro‐6H‐benzo[b]cyclohepta[cd]benzofurans
Authors: Treu Matthias , Hametner Christian , Frohlich Johannes , Jordis Ulrich , Mereiter Kurt 
Published: March 2009

AbstractThe synthesis of a novel unnatural carbocyclic analog of the acetylcholine esterase inhibitor galanthamine with a K3[Fe(CN)6] promoted oxidative tandem cyclization as the key step is reported.
Synthesis of some [1,2,4]triazino[5,6‐b]quinoline derivatives
Authors: Stýskala Jakub , Slouka Jan , Lycka Antonín 
Published: March 2009

AbstractBy coupling of diazonium salts with ethyl N‐(4‐oxo‐1,4‐dihydroquinolin‐2‐yl)carbamate 4, the corresponding 3‐arylazocompounds 5 were obtained. These ones were cyclized thermally or in alkaline medium to the corresponding 2‐aryl‐2,3,5,10‐tetrahydro‐[1,2,4]triazino[5,6‐b]quinolin‐3,10‐diones 6. Compounds 6 were transformed by alkaline hydrolytic splitting to the corresponding 2‐amino‐3‐arylazo‐1,4‐dihydroquino‐lin‐4‐ones 7. Starting carbamate 4 was prepared by a two‐step synthesis from 2‐amino‐1,4‐dihydroquinolin‐4‐one 1.
Synthesis of 3‐thiocyanato‐1H,3H‐quinoline‐2,4‐diones
Authors: Klásek Antonín , Polis Jirí , Mrkvička Vladimír , Košmrlj Janez 
Published: March 2009

Abstract4‐Hydroxy‐1H‐quinolin‐2‐ones (1) react with thiocyanogen in acetic acid to the corresponding 3‐thiocyanato‐1H,3H‐quinoline‐2,4‐diones (2) in good yields. In some cases, 3‐bromo‐1H,3H‐quinoline‐2,4‐diones (4) were isolated as minor reaction products. Compounds 2 are very reactive towards nucleophiles and easily hydrolyze to the corresponding 4‐hydroxy‐1H‐quinoline‐2‐ones (1).
New azabenzoquinones by ring‐expansion reactions
Authors: Poschenrieder H. , Stachel H.‐D. , Wiesend B. , Polborn K. 
Published: March 2009

AbstractOzonolysis of the pyrrolidinediones 4 afforded the pyrrolidinetriones 5, which in the presence of Lewis acids were converted into maleimide 6. Analogously, ozonolysis of the pyrrolidinones 7 gave the pyrrolidinediones 8, which were converted into the pyridinetriones 11a, b via Lewis acid catalyzed isomerization to yield the trihydroxypyridones 10 and ensuing air oxidation. In solution two tautomeric forms of the pyridinetriones 11 may exist both of which represent hydroxy‐azabenzoquinones. In two steps compounds 11 were transformed into the azaquinone derivatives 19. Representatives of another type of azaquinones are compounds 28a, b. These were generated in two steps from the pyridones 25. The azaquinone 28a reacted easily with acidic compounds yielding the adducts 26, 27 and 29 or with 2‐butenal forming the cycloadduct 30.
New heterocycles from 8‐hydroxyquinoline via dipolar 1,3‐cycloadditions: Synthesis & biological evaluation
Authors: Bahloul Abdelmejid , Sebban Abdelfatah , Dardari Zainaba , Boudouma Mohammed , Kitane Said , Belghiti Touria , Joly Jean‐Pierre 
Published: March 2009

AbstractDiarylnitrilimine and arylnitriloxide dipoles react with two 8‐hydroxyquinoline substrates to give respectively pyrazolinic and isoxazolinic derivatives. The structure of these new heterocycles was established on the basis of their spectroscopic data and by chemical methods. The inhibition activity of one of these heterocycles was evaluated in vitro against 8 pathogenic μ‐organisms.
Synthesis and bioactivity of xyridin A and B, metabolites fromxyris indica
Authors: Saeed Aamer 
Published: March 2009

AbstractA facile synthesis of the title isocoumarins isolated from.Xyris indicawas accomplished. Condensation of butanoyl chloride and 2‐oxo‐butanoyl chloride with 3,4‐methylenedioxyhomophthalic acid afforded xyridin A and xyridin B respectively. Xyridin A was saponified to the corresponding keto acid which on reduction furnished the (±)‐3,4‐dihydro‐6,7‐methylenedioxy‐3‐propylisocoumarin. All of the synthesized compounds were examinedin vitrofor antibacterial and antifungal activities.
Synthesis of lariat ethers with pendent amine, amide, O‐benzylhydroxamate, and urethane groups
Authors: Elshani Sadik , Hwang Hong‐Sik , Pugia Michael J. , Krzykawski Jan , Bartsch Richard A. 
Published: March 2009

AbstractSynthetic routes to twenty‐six new crown ether compounds with pendent amine, amide, O‐benzylhydrox‐amate, and urethane groups are reported. The new lariat ether compounds are based on sym‐dibenzo‐16‐crown‐5, sym‐dicyclohexano‐16‐crown‐5, and 14‐crown‐4 scaffolds.
Oximes as intermediates or final products in reactions of nitroheteroarenes with nucleophiles in the presence of sodium methoxide‐methanol system
Authors: Suwińaski J. , Świerczek K. , Wagner P. , Kubicki M. , Borowiak T. , Stowikowska J. 
Published: March 2009

AbstractIt has been shown that reactions of 4‐nitroimidazoles and some other nitroaromatic systems with phenyl‐acetonitrile in the presence of sodium methoxide in methanol lead to the reduction of the nitro to nitroso group and to the nucleophilic displacement of hydrogen atom at the ring by the respective carbanion followed by tautomerization of the nitroso compound to an oxime. Similar reactions of 4‐nitroimidazoles with such nucleophiles as anions generated from 4‐amino‐1,2,4‐triazole occur with the ring transformation of imidazole into 1,2,4‐oxadiazole derivatives sometimes undergoing further processes in the reaction medium. Structures of some products have been confirmed by X‐ray diffraction analysis.
Novel Synthesis of 3‐Amino‐4‐oxo‐(2H)‐pyrazolo[3′,4′:4,5]pyrimido‐[2,1‐b]benzothiazole and its 2‐ and 3‐Substituted Derivatives
Authors: Baheti K. G. , Kuberkar S. V. 
Published: March 2009

AbstractReaction of 4H‐pyrimido[2,1‐b]benzothiazole‐2‐thiomethyl‐3‐cyano‐4‐one (1) with hydrazine hydrate/aryl hydrazine/heteryl hydrazine in the presence of anhydrous potassium carbonate and dimethyl formamide afforded 3‐amino‐4‐oxo‐(2H)/aryl/heteryl pyrazolo[3′,4′:4,5]pyrimido[2,1‐b]benzothiazoles in good yield. These pyrazole derivatives on diazotization followed by replacement with hydroxy, chloro, bromo, iodo and on reduction gave the corresponding 3‐substituted derivatives.
Photochemistry of trifluromethyl substituted 1‐methylpyrazoles
Authors: Pavlik James W. , Na Ayudhaya Theppawut Israsena , Pandit Chennagiri R. , Tantayanon Supawan 
Published: March 2009

AbstractTrifluromethyl substitution on the pyrazole ring was found to enhance photoreactivity via the P4 pathway which involves interchange of the N2‐C3 ring atoms. Thus, 1‐methyl‐3‐(trifluromethyl)pyrazole (1) and 1‐methyl‐5‐(trifluromethyl)pyrazole (3) transposed with a P4/P6 or P4/P6+P7 ratio of 2.1:1. 1‐methyl‐4‐(trifluromethyl)pyrazole (2) transposed regiospecifically by the P4 transposition pathway. Compounds 2 and 3 were also observed to undergo photocleavage to yield enaminonitrile and enaminoisocyanide products.
New trends in the chemistry of condensed heteromacrocycles part B: Macrocyclic formazans
Authors: Ibrahim Yehia A. , Abbas Ashraf A. , Elwahy Ahmed H. M. 
Published: March 2009

AbstractThis review article, covering the literature from 1979 to 2002, deals with the main strategies for the synthesis of macrocyclic crown formazans as well as their specific syntheses. Reactivities and applications of these compounds are also in focus.
A new biginelli reaction procedure using potassium hydrogen sulfate as the promoter for an efficient synthesis of 3,4‐dihydropyrimidin‐2(1H)‐one
Authors: Tu Shujiang , Fang Fang , Zhu Songlei , Li Tuanjie , Zhang Xiaojing , Zhuang Qiya 
Published: March 2009

AbstractSimple and improved conditions have been found to carry out the Biginelli reaction for the synthesis of 3,4‐dihydropyrimidin‐2(1H)‐one derivatives. This synthesis was performed using potassium hydrogen sulfate as the promoter in ethylene glycol solution. Compared with the classical Biginelli reaction conditions, this new method has the advantage of excellent yields (85–95%) and short reaction time (0.5–2 h).
Synthesis of substituted 3‐(5‐amino‐[1,3,4]thiadiazol‐2‐yl)‐2H‐pyrano[2,3‐c]pyridin‐2‐ones
Authors: Zhuravel' Irina O. , Kovalenko Sergiy M. , Ivachtchenko Alexandre V. , Chernykh Valentin P. , Shinkarenko Pavlo E. 
Published: March 2009

AbstractAn efficient two‐step synthesis of novel 3‐(5‐amino‐[1,3,4]thiadiazol‐2‐yl)‐2H‐pyrano[2,3‐c]pyridine‐2‐ones was developed. In the first step, a new 2H‐pyrano[2,3‐c]pyridine‐3‐carboxamide 5 was prepared by Knoevenagel condensation of pyridoxal hydrochloride with cyanoacetamide. In the second step, the reaction of carboxamide 5 with a series of N4‐substituted thiosemicarbazides yielded a library of 35 dis crete compounds 8{1–35} in high yields. The intermolecular recyclization mechanism leading to these products is discussed.
Synthesis of lipophilic lariat ethers with pendant N‐(X)sulfonyl carboxamide groups
Authors: Hu Hui , Bartsch Richard A. 
Published: March 2009

AbstractSynthetic routes to sixteen lipophilic lariat ether N‐(X)sulfonyl carboxamides with X = trifluoromethyl, methyl, phenyl, and p‐nitrophenyl are described. For this new family of proton‐ionizable lariat ethers in which the acidity can be ‘tuned’ by X group variation, the ring size is systematically varied from 12‐crown‐4 to 14‐crown‐4 to 15‐crown‐5 to 18‐crown‐6.
Diastereoselective synthesis of substituted 2,3,4,5‐tetrahydro‐1H‐1‐benzazepine‐5‐carboxylic esters by a tandem reduction‐reductive animation reaction
Authors: Bunce Richard A. , Johnson Lara B. , Holt Elizabeth M. 
Published: March 2009

AbstractAn efficient, diastereoselective synthesis of substituted and unsubstituted 2,3,4,5‐tetrahydro‐1H‐1‐benzazepine‐5‐carboxylic esters has been developed based on the tandem reduction‐reductive amination reac tion. Catalytic hydrogenation of a series of 2‐(2‐nitrophenyl)‐5‐oxoalkanoic esters initiates a reaction sequence involving (1) reduction of the aromatic nitro group, (2) condensation of the N‐hydroxylamino (or amino) nitrogen with the side chain carbonyl, and (3) reduction of the seven‐membered cyclic imine. Cyclizations that produce 2‐alkyl‐2,3,4,5‐tetrahydro‐1H‐1‐benzazepine‐5‐carboxylic esters are diastereose lective for the product having the C2 alkyl and the C5 ester groups cis. In these reactions, the transannular ester group exerts a strong stereodirecting effect on the reduction of the cyclic imine intermediate, though not as strong as that observed in previous closures of 2‐alkyl‐1,2,3,4‐tetrahydroquinoline‐4‐carboxylic esters. This decrease in diastereoselectivity is attributed to (1) the greater distance between the ester and the imine double bond and (2) the increased conformational mobility of the larger ring, both of which diminish the stereodirecting effect of the ester. Finally, formation of the seven‐membered ring is sufficiently slow that reaction with the side chain ester group competes with heterocycle formation in several of the reactions.
New N6‐substituted 8‐alkyl‐2‐phenylmethylsulfanyl‐adenines. II
Authors: Biagi Giuliana , Giorgi Irene , Livi Oreste , Pacchini Federica , Scartoni Valerio , Salerni Oreste Leroy 
Published: March 2009

AbstractTitle compounds bearing substituents on C(2), C(6) and C(8) were prepared from a newly synthesized pyrimidine derivative 11. The new pyrimidine 11 was generated from compound 2 through two different synthetic schemes. In one pathway, compound 2 was nitrosated, reduced and alkylated to produce com pounds 9, 10 and 11 respectively (Scheme). In an alternate route using compound 2 as the starting material, a coupling reaction using the diazonium salt derived from p‐methylaniline afforded the azo derivative 7, which was subsequently alkylated and reductively cleaved to form compounds 8 and 11 respectively (See Scheme). Compound 11 was annulated to the corresponding hypoxanthine derivatives 12–14; compounds 12 and 13 were chlorinated with phosphorus oxychloride, then reacted with amines to yield compound 17 and 20 respectively. Compounds 21, 22 and 23 were obtained by oxidation of the corresponding sulfide as depicted in Scheme. Alkylation of the thiol function of 1 gave a mixture of 3 and 4. Compound 3 was chlo rinated to 5. Nitration of 5 resulted in electrophilic aromatic substitution of the aryl ring and concomitant oxidation of the sulfide to the sulfoxide, producing 6.
4‐hydroxy‐6‐methyl‐3‐(5‐phenyl‐2E,4E‐pentadien‐1‐oyl)‐2H‐pyran‐2‐one: Synthesis and reactivity with amines
Authors: Aït‐Baziz Nabila , Rachedi Yahia , Hamdi Maamer , Silva Artur M. S. , Balegroune F. , Thierry Roisnel , Sellier N. 
Published: March 2009

AbstractThe synthesis and reactivity studies of 4‐hydroxy‐6‐methyl‐3‐(5‐phenyl‐2E,4E‐pentadien‐1‐oyl)‐2H‐pyran‐2‐one 2 with nucleophiles are reported. Reactions of 2 with hydrazine derivatives gave new pyrazole‐type com pounds while the reaction with ortho‐phenylenediamines yielded 1,5‐benzodiazepines. The reaction of 2 with ethylamine implies the 2H‐pyran‐2‐one ring opening and the formation of a strong conjugated compound 3.
Synthesis of 5H‐1,2,3‐triazolo[4,3‐a][2]benzazepines from the baylis‐hillman adducts of 2‐alkynylbenzaldehydes
Authors: Ko Seung Ho , Lee Kee‐Jung 
Published: March 2009

AbstractThe facile synthesis of 5H‐1,2,3‐triazolo[4,3‐a][2]benzazepines 5a‐d by the intramolecular 1,3‐dipolar cycloaddition reaction of 2‐alkynylphenylallyl azides 4a‐d is described. The latter were readily obtained from 2‐alkynylbenzaldehydes 1a‐d through the Baylis‐Hillman adducts 2a‐d followed by acetylation to compounds 3a‐d and nucleophilic substitution by azide to compounds 4a‐d.
The cleavage of heterocyclic compounds in organic synthesis II Use of 5‐nitroisatine for synthesis of various nitrogenous heterocycles
Authors: Hlaváč Jan , Soural Miroslav , Hradil Pavel , Fryšová Iveta , Slouka Jan 
Published: March 2009

AbstractThe reactions of 5‐nitroisatine were studied with nucleophiles like heterocyclic amines and alkaline hydroxide. With the use of alkaline hydroxide it was converted into 2‐amino‐5‐nitrophenylglyoxylic acid 2, with piperidine, morpholine and carbethoxypiperazine to its amides 4a‐4c or by oxidation to 5‐nitroanthranilic acid 7. This acid was used for synthesis of 3‐hydroxy‐6‐nitro‐2‐phenyl‐1H‐quinolin‐4‐one 10. Semicarbazone of 5‐nitroisatine 11 was converted to 5‐(2‐amino‐5‐nitrophenyl)‐2,3,4,5‐tetrahydro‐1,2,4‐triazine‐3,5‐dione 12. Cyclocondensation of this compound to afford 8‐nitro‐2,3‐dihydro‐5H‐[1,2,4]triazino‐[5,6‐b]indol‐3‐one 13 was unsuccessful.
Unexpected formation of 1,2‐dihydro‐2‐azolyl‐and azinylisoquinolines by the reduction of the corresponding isoquinolinium salts with sodium borohydride in methanol
Authors: Prauda Ibolya , Tóth‐Lauritz Mária , Reiter József 
Published: March 2009

AbstractThe reduction of different 2‐azolyl‐and azinylisoquinolinium salts with sodium borohydride in methanol was studied. Surprisingly, contrary to what is found in the literature 1,2‐dihydroisoquinoline derivatives were obtained. Their formation was attributed to the electron withdrawing character of the heterocyclic ring in position 2 of the isoquinolinium moiety. This was corroborated by synthesis and reduction of differently substituted 2‐phenyl‐ and 2‐methylisoquinolinium salts.
Synthesis of classical and nonclassical 2‐amino‐4‐oxo‐6‐benzylthieno‐[2,3‐d]pyrimidines as potential thymidylate synthase inhibitors
Authors: Gangjee Aleem , Qiu Yibin , Kisliuk Roy L. 
Published: March 2009

AbstractA series of seven nonclassical 2‐amino‐4‐oxo‐6‐substituted thieno[2,3‐d]pyrimidines 2‐8 and one classical N‐[4‐(2‐amino‐4‐oxo‐3,4‐dihydrothieno[2,3‐d]pyrimidin‐6‐ylmethyl)benzoyl]‐L‐glutamic acid 9 (Table I) were designed as the first in a series of 6‐substituted 6‐5 fused ring analogs as potential thymidylate synthase (TS) inhibitors and as antitumor agents. The target compounds were synthesized via a Heck coupling of appropriately substituted iodobenzenes and allyl alcohol followed by cyclization using cyanoacetate and sulfur powder to afford substituted thiophenes. The resulting thiophenes were then cyclocondensed with chloroformamidine hydrochloride to afford 2‐amino‐4‐oxo‐6‐substituted thieno[2,3‐d]pyrimidines 2‐8 and 26. Hydrolysis of 26 followed by coupling with diethyl L‐glutamate afforded 28. The classical analog 9 was obtained by hydrolysis of 28. None of the target compounds inhibited human recombinant thymidylate synthase at 23 μm except 9 for which the IC50 value was 100 μm.
Tetrahydro‐1,5‐benzoxazepines and tetrahydro‐1H‐1,5‐benzodiazepines by a tandem reduction‐reductive amination reaction
Authors: Bunce Richard A. , Smith Christopher L. , Lewis Jason R. 
Published: March 2009

AbstractA tandem reduction‐reductive amination reaction has been applied to the synthesis of (±)‐4‐alkyl‐2,3,4,5‐tetrahydro‐1,5‐benzoxazepines and (±)‐4‐alkyl‐1‐benzoyl‐2,3,4,5‐tetrahydro‐1H‐1,5‐benzodiazepines. The nitro aldehydes and ketones required for 1,5‐benzoxazepine ring closures were prepared by nucleophilic aromatic substitution of the alkoxides from several 3‐buten‐1‐ol derivatives with 2‐fluoro‐1‐nitrobenzene followed by ozonolysis. Precursors for the 1,5‐benzodiazepines were prepared by similar addition of N‐(3‐butenyl)benzamide anions to 2‐fluoro‐1‐nitrobenzene followed by ozonolysis. Catalytic hydrogenation of the nitro carbonyl compounds using 5% palladium‐on‐carbon in methanol then gave the target heterocycles by a tandem reduction‐reductive amination sequence. The 1,5‐benzoxazepines were isolated in high yield following chromatographic purification; the 1,5‐benzodiazepines were isolated as solids directly from the hydrogenation mixture and possessed differentiated functionality on the two nitrogen atoms.