bluuebunny/crossref_metadata_2025 huggingface dataset:
Synthesis of (R)‐1,2,11‐trihydroxy‐, (R)‐2,11‐, and (R)‐2,10‐dihydroxyaporphines — non naturally occurring aporphine alkaloids from pukateine and thebaine
Authors: Ram Vishnu J. , Neumeyer John L.
Published: March 2009

The synthesis of (R)‐2,10‐dihydroxyaporphine (3a), (R)‐2,10‐dihydroxy‐N‐n‐propylnoraporphine (3b) from thebaine and (R)‐2,11‐dihydroxyaporphine (7), and 1,2,11‐trihydroxyaporphine (9), from pukateine is reported. The rearrangement of thebaine and northebaine with methanesulfonic acid to 1a and 1b with subsequent N‐propylation gave 1b. Tetrazolyation of 1a, 1b and hydrogenolysis of 2a and 2b on Pd/C in acetic acid with subsequent O‐demethylation with hydrobromic acid (48%) led to 3a and 3b. R(‐)‐2,11‐Dihydroxyaporphine (7) was prepared by lithium/ammonia reduction of pukateine. (R)‐1,2,11‐Trihydroxyaporphine (9) was synthesized by reaction of pukateine with boron tribromide in dichloromethane.
Synthesis and properties of thiolactam analogs of pyrromethenones
Authors: Xie Meiqiang , Lightner David A.
Published: March 2009

Thiolactam analogs of kryptopyrromethenone and xanthobilirubic acid methyl ester were prepared from the parent pyrromethenone using Lawesson's reagent and are shown to form dimeric association complexes through intermolecular hydrogen bonding.
Deprotonations of 5‐nitroindole and 5‐nitroindole‐2‐carboxylate ion in zwitterionic surfactants
Authors: Cipiciani Antonio , Primieri Stefania
Published: March 2009

Deprotonations of 5‐nitroindole (1) and its 2‐carboxylate ion 2 at high pH have been examined in solutions of N,N‐dimethyl‐N‐tetradecylglycine (DTG) and N,N‐dimethyl‐N‐hexadecylglycine (DHG). We have compared the surfactant effects with those of single‐ and twin‐tailed ionic surfactants.
Synthesis of 6‐(4‐methyl‐1‐piperazinyl)‐7H‐indeno[2,1‐c]‐quinoline derivatives as potential 5‐HT receptor ligands
Authors: Anzini M. , Cappelli A. , Vomero S.
Published: March 2009

Two synthetic pathways for the achievement of the title compounds are reported. The key intermediate, namely 3‐carboxy‐4‐phenyl‐2(1H)‐quinolinone 9, was directly cyclized into the corresponding 6‐chloro‐7H‐indeno[2,1‐c]quinolin‐7‐one 10 or alternatively it was esterified, reduced to the alcohol, chlorinated and cyclized into the 6‐chloro‐7H‐indeno[2,1‐c]quinoline 8. Further reaction of the chloroindenoquinoline derivatives with N‐methylpiperazine afforded the piperazinyl derivatives 4a‐c.
Directed metalation of pyridinesulphonamides. Synthesis of pyridine‐fused isothiazoles and 1,2‐oxathioles
Authors: Alo Babajide I. , Familoni Oluwole B. , Marsais Francis , Queguiner Guy
Published: March 2009

4‐Lithio‐N‐t‐butylpyridine‐3‐sulphonamide reacted with benzophenone and carbon dioxide respectively to give the corresponding intermediates which on appropriate treatment gave isothiazolo[5,4‐c]pyridin‐3‐one 1,1‐dioxides. Metalation of 2‐ and 4‐(N,N‐dialkylaminosulphonyl)pyridines with lithium diisopropylamide (LDA) gave anions which reacted with benzophenone to give carbinols which thermally cyclised to 1,2‐oxathiolo[3,4‐b]pyridine and 1,2‐oxathiolo[4,3‐c]pyridine respectively.
Synthesis of selenobispyridines
Authors: Dunne Simon J. , Summers Lindsay A. , Von Nagy‐Felsobuki Ellak I.
Published: March 2009

2,3′‐Selenobispyridine, 2,4′‐selenobispyridine, 3,3′‐selenobispyridine and 3,4′‐selenobispyridine have been synthesised.
Photochemical cyclization of some aldehyde thiosemicarbazones
Authors: Gruttadauria Michelangelo , Buccheri Francesco , Buscemi Silvestre , Cusmano Giuseppe , Noto Renato , Werber Giuseppe
Published: March 2009

The photochemical behaviour of some substituted aldehyde thiosemicarbazones 1a‐k has been investigated in methanol at 254 nm. Thiosemicarbazones of glyoxil methyl ester 1a‐f cyclized to furnish the 3‐thioxo‐ 1,2,4‐triazin‐5‐one 2 ring system. The remaining thiosemicarbazones 1g‐j gave 1,2,4‐triazoline 4 derivatives.
1‐Methylimidazolium chlorochromate: A new Cr(VI) oxidant and use of anhydrous acetic acid as the catalyst for the oxidation of primary and secondary alcohols
Authors: Agarwal Seema , Tiwari H. P. , Sharma J. P.
Published: March 2009

The synthetic potential of a new Cr(VI) reagent, viz., 1‐methylimidazolium chlorochromate, analogous to Corey's reagent‐PCC, has been examined. Anhydrous acetic acid has been found to catalyze the oxidation reaction.
Carbon‐nitrogen bond formation in cyclisation by deoxygenation, thermolysis or photolysis of phenylimidazo[1,2‐a][1,8]naphthyridines
Authors: Gueiffier A. , Blache Y. , Viols H. , Chapat J. P. , Chavignon O. , Teulade J. C. , Dauphin G. , Debouzy J. C. , Chabard J. L.
Published: March 2009

Triethyl phosphite deoxygenation of 2‐(2‐nitrophenyl)imidazo[1,2‐a][1,8]naphthyridine (3) led to the C‐insertion to give the indoloimidazonaphthyridine 5. Our attempt to promote the N‐insertion by blocking the C‐3 position failed. Triethyl phosphite deoxygenation of 1‐nitroso‐2‐(4‐fluorophenyl)imidazo[1,2‐a][1,8]‐naphthyridine (12) led to the corresponding amine structure (15). Thermolysis and photolysis of 6,8‐dimethyl‐2‐(2‐azidophenyl)imidazo[1,2‐a][1,8]naphthyridine (17) are also reported.
The crystal structure of 1,5‐bis(3,5‐dimethyl‐2‐hydroxybenzyl)‐1,5‐diazocan‐2,6‐dione
Authors: Aversaw M. C. , Bonaccorsi P. , Giannetto P. , Beagley B. , Leigh D. A. , Pritchard R. , Truscello A. M.
Published: March 2009

The study of the molecular geometry of 1,5‐bis(3,5‐dimethyl‐2‐hydroxybenzyl)‐1,5‐diazocan‐2,6‐dione (2) as determined by X‐ray analysis is reported and compared with that of cyclodi‐β‐alanyl (3). Interestingly there are 1.5 molecules of 2 in the asymmetric unit, showing the two conformations (1 twist‐boat‐ and 0.5 chair‐type) with two parallel aromatic rings (from alternate twist‐boat conformers) sandwiching the eight‐membered ring of the centrosymmetric chair‐type conformation. The twist‐boat is shown by pmr spectroscopy to be the only significantly populated conformer at low temperature in deuteriodichloromethane solution.
Synthesis of 5,7‐disubstituted‐4‐β‐D‐ribofuranosylpyrazolo[4,3‐d]‐pyrimidines and 2,4‐disubstituted‐1‐β‐D‐ribofuranosylpyrrolo[3,2‐d]‐pyrimidines as congeners of uridine and cytidine
Authors: Sudhakar Rao T. , Revankar Ganapathi R. , Vinayak Ravi S. , Robins Roland K.
Published: March 2009

The synthesis of the congeners of uridine and cytidine in the pyrazolo[4,3‐d]pyrimidine and pyrrolo[3,2‐d]‐pyrimidine ring system is described. Glycosylation of the trimethylsilyl (TMS) derivative of pyrazolo[4,3‐d)pyrimidine‐5,7(1H,4H,6H)‐dione (4) with either 1‐bromo‐ or 1‐O‐acetyl‐2,3,5‐tri‐O‐benzoyl‐D‐ribofuranose 5 and 6, respectively in the presence of a Lewis acid catalyst gave the protected nucleoside 7, which on debenzoylation afforded the uridine analogue 4‐β‐D‐ribofuranosylpyrazolo[4,3‐d]pyrimidine‐5,7(1H,6H)‐dione (8). Thiation of 7 gave 13, which on deprotection yielded 4‐β‐D‐ribofuranosyl‐5‐oxopyrazolo[4,3‐d]pyrimidine‐7(1H,‐6H)‐thione (14). Ammonolysis of 13 gave a low yield of the cytidine analogue 15. A chlorination of 7, followed by amination furnished an alternative route to 15. A similar glycosylation of TMS‐4 with 2,3,5‐tri‐O‐benzyl‐α‐D‐arabinofuranosyl chloride (16) gave mainly the N4 glycosylated product 17, which on debenzylation furnished 4‐β‐D‐arabinofuranosylpyrazolo[4,3‐d]pyrimidine‐5,7(1H,6H)‐dione (18). 7‐Amino‐4‐β‐D‐arabinofuranosylpyrazolo[4,3‐d]pyrimidin‐5(1H)‐one (23) was prepared from 17 via the pyridinium chloride intermediate 21. Condensation of the TMS derivative of pyrrolo[3,2‐d]pyrimidine‐2,4(1H,3H,5H)‐dione (24) with 6, followed by deprotection of the reaction product gave 1‐β‐D‐ribofuranosylpyrrolo[3,2‐d]pyrimidine‐2,4(3H,5H)‐dione (26). Similarly, TMS‐24 was reacted with 16 to give a mixture of the blocked nucleosides 31 and 32, which on debenzylation afforded a mixture of two isomeric compounds 34 and 35. 1‐β‐D‐Arabinofuranosylpyrrolo[3,2‐d]pyrimidine‐2,4(3H,5H)‐dione (34) was converted to the ara‐C analogue 38 via the 3‐nitrotriazolyl intermediate 36. The structure of 38 was confirmed by single crystal X‐ray diffraction studies.
Nucleocyclitols. Synthesis of substituted purinyl‐muco‐inositol derivatives
Authors: Aguilar Guillermo J. , Gelpi María E. , Cadenas Raúl A.
Published: March 2009

Several carbocyclic nucleoside analogs possessing a 6‐substituted purine linked to a mesylated muco‐inositol were synthesized. The coupling of triethylamine‐activated 6‐chloropurine with 2,3‐anhydro‐l,5,6‐tri‐O‐(methanesulfonyl)‐epi‐inositol gave a 6‐chloro purinyl muco‐inositol amenable to further synthetic transformations in the heterocyclic moiety by substitution of the chlorine atom by nitrogen nucleophiles such as methylamino, diethylamino, benzylamino, hydrazino, morpholino, hydroxylamino, piperidino, and glycyl groups.
Furan derivatives. Part 13. Synthesis of thiopyrano[4,3,2‐cd]benzofuran
Authors: Horaguchi Takaaki , Hasegawa Kohei , Hasegawa Eietsu , Shimizu Takahachi , Tanemura Kiyoshi , Suzuki Tsuneo
Published: March 2009

Thiopyrano[4,3,2‐cd]benzofuran 9 possessing benzofuran and methylenethiopyran structures in the molecule was synthesized starting from 1‐chloro‐4‐methoxy‐2‐nitrobenzene 11. Some reactions (formylation, protonation and catalytic hydrogenation) on 9 were examined. The 2‐position of 9 was highly reactive toward electrophilic reagents and the furan ring was readily reduced by catalytic hydrogenation with palladium‐charcoal. Thiopyrano[4,3,2‐cd]benzofuran 9 has both properties of methylenethiopyran and benzofuran.
Conjugated macrocycles related to the porphyrins. Part 3. Acid catalyzed condensations of thiophenecarboxaldehydes with a dipyrrylmethane
Authors: Armiger Yoek Lin See‐Tow , Lash Timothy D.
Published: March 2009

MacDonald condensation of a dipyrrylmethanedicarboxylic acid 3b with 2,2′‐dithienylmethane‐5,5′‐dicarboxaldehyde (2b) failed to give the expected dithiophene porphyrin analog 1b. However, oxidation of the reaction mixtures with DDQ gave trace amounts of porphyrin‐like materials. Model studies indicate that these fractions are meso‐dithienylporphyrins. The synthesis of three related α,γ‐disubstituted porphyrins is described.
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

A 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

(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

The 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

The 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

The 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

5‐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

All 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.
Convenient synthesis of porphine
Authors: Neya Saburo , Yodo Hiromi , Funasaki Noriaki
Published: March 2009

Porphine formation from pyrrole and formaldehyde was examined in detail. Under optimized conditions, 9 mg of crystalline porphine was obtained per 1 ml of pyrrole.
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

A 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

The 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

This 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

A 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

Two 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

The 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

The 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

In 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

Acid 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

(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

A 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

Biogenic 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

Transformation 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

Several 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

The 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

Derivatives 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

This 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

A 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

1‐[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

Phthalic 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.
Metalation of diazines. XI. Directed ortho‐lithiation of fluoropyrimidines and application to synthesis of an azacarboline
Authors: Plé N. , Turck A. , Heynderickx A. , Quéguiner G.
Published: March 2009

For the first time fluoropyrimidines were successfully lithiated. The resulting lithio derivatives were reacted with various electrophiles for the synthesis of new pyrimidines. The synthesis of an azacarboline derivative is reported.
Pyrimidine derivatives XII. A convenient preparation of 6‐formylpyrimidinedione and 2‐ and 3‐formylpyridine derivatives from corresponding nitrooxymethyl derivatives
Authors: Kinoshita Toshio , Ohishi Hiroshi
Published: March 2009

The convenient preparation of 6‐fomylpyrimidinedione derivatives and 2‐ and 3‐formylpyridine are described. Thus, 5‐bromo‐1,3‐dimethyl‐ (1a), 5‐bromo‐3‐methyl‐1‐(2‐nitrooxyethyl)‐ (1b), and 5‐bromo‐3‐methyl‐1‐(3‐nitrooxypropyl)‐2,4(1H,3H)‐pyrimidine‐dione (1c) were converted to the corresponding 6‐formyl compounds2a, 2b, and2c, respectively, in excellent yields by the reaction with triethylamine and 1,4‐diazabicyclo[2.2.2]octane. These 6‐formylpyrimidinedione derivatives are key intermediates for the preparation of 6‐carbon‐carbon substituted compounds, which are expected to be potential antitumor and antiviral agents. Similarly, 2‐(and 3‐)formylpyridine (9a(and9b)) were obtained by the reaction of 2‐(and 3)nitrooxymethylpyridine (8a(and8b)) with 1,4‐diazabicyclo[2.2.2]octane.
Reaction of azole condensed quinoxaline N‐oxides with acetic anhydride
Authors: Kurasawa Yoshihisa , Hosaka Tomoyoshi , Matsumoto Yuko , Ishikura Aiko , Ikeda Kazue , Takada Atsushi , Kim Ho Sik , Okamoto Yoshihisa
Published: March 2009

The reaction of 7‐chlorotetrazolo[1,5‐α]quinoxaline 5‐oxide 6a with acetic anhydride gave 7‐chloro‐5‐(7‐chlorotetrazolo[1,5‐α]quinoxalin‐4‐yl)‐4,5‐dihydro‐4‐oxotetrazolo[1,5‐α]quinoxaline 7a, while the reaction of 7‐chloro‐1,2,4‐triazolo[4,3‐α]quinoxaline 5‐oxide 6b with acetic anhydride afforded 7‐chloro‐5‐(7‐chloro‐1,2,4‐triazolo[4,3‐α]quinoxalin‐4‐yl)‐4,5‐dihydro‐4‐oxo‐1,2,4‐triazolo[4,3‐α]quinoxaline 7b and 7‐chloro‐4,5‐dihydro‐4‐oxo‐1,2,4‐triazolo[4,3‐α]quinoxaline 8b. The reaction of compound 6a or 6b with acetic anhydride/acetic acid provided 7‐chloro‐4,5‐dihydro‐4‐oxo‐tetrazolo[1,5‐α]quinoxaline 8a or compound 8b, respectively.
Formation of isoindoline derivatives from o‐bromoacetylbenzophenones
Authors: Nan'Ya Seiko , Ishida Hirofumi , Butsugan Yasuo
Published: March 2009

o‐Dibromoacetylbenzophenone, 2 or o‐bromoacetylbenzophenone 3 reacted with aqueous ammonia to produce 3‐phenylisoindolin‐1‐one 5. The reaction of 3 with methylamine afforded 3‐hydroxy‐2‐methyl‐3‐phenyl‐isoindolin‐1‐one 4 and 2‐methyl‐3‐phenylisoindolin‐1‐one 5. Whereas from 2 with methylamine only 5 was obtained.
Syntheses and properties of selenium‐bridged bischromones
Authors: Löwe Wernexsr , Rütjes Thomas
Published: March 2009

The preparation of the new selenium‐bridged chromones 5a‐e is described. Compound 5c reacts with m‐CPBA under various conditions to give the corresponding selenoxide 7 and the Pummerer products 8 and 9. The selenides 5a‐c react with excess m‐CPBA to form the diselenides 13a‐c. Oxidation of 13c with hydrogen peroxide afforded the chromone‐3‐seleninic acid 22.
Preparation of 1,3‐disubstituted isoquinoline derivatives from N‐boc‐3‐substituted‐1,2‐dihydroisoquinolines
Authors: Clark Robin D. , Jahangir
Published: March 2009

3‐Substituted N‐Boc‐1,2‐dihydroisoquinolines 2 can be functionalized at the 1‐position via lithiation and subsequent electrophilic trapping. The resulting products 3 can be deprotected and oxidized to afford the corresponding 1,3‐disubstituted isoquinolines 5. Deprotection of dihydroisoquinoline 3k followed by sodium borohydride reduction affords the cis‐1,3‐disubstituted tetrahydroisoquinoline 11. The 1,3‐disubstituted N‐Boc‐1,2‐dihydroisoquinoline 3g is efficiently alkylated at the 1‐position to give 1,1,3‐trisubstituted analogs 12.
A direct synthesis of α‐keto five‐ and six‐membered cyclic ethers
Authors: Enholm Eric J. , Schreier Jeffrey A.
Published: March 2009

A simple synthesis of tetrahydro‐2H‐pyran‐2‐yl and tetrahydrofuran‐2‐yl ketones from their corresponding carboxylic acids was studied. A comparison was made of organolithium and Grignard alkylating reagents as a means of reducing the formation of byproducts and improving the yields.
Synthesis and properties of bilirubin analogs with one propionic acid group
Authors: Holmes Darren L. , Lightner David A.
Published: March 2009

Unsymmetric bile pigment analogs of mesobilirubin‐XIIIα and mesobilirubin‐IVα were synthesized following oxidative coupling of dipyrrinones: methyl xanthobilirubinate with kryptopyrromethenone; methyl ψ‐xanthobilirubinate with kryptopyrromethenone.
Highly diastereoselective synthesis and NMR characterization of natural indolizidine alkaloids
Authors: Fleurant Anne , Saliou Chantal , Célérier Jean Pierre , Moc Thuy Vu , Lhommet Gérard , Platzer Nicole
Published: March 2009

A diastereoselective, general and versatile access to disubstituted indolizidines is described. The nmr conformational analysis permits us to establish preferred conformations.
1,3‐Dipolar cycloaddition reactions of cyclooctyne with azomethine ylides
Authors: Matsumoto Kiyoshi , Ohta Ryuji , Uchida Takane , Nishioka Hiroyasu , Yoshida Maki , Kakehi Akikazu
Published: March 2009

Cyclooctyne smoothly underwent 1,3‐dipolar cycloaddition with aziridines and pyridinium ylides to afford the corresponding pyrroles and indolizines in moderate to good yields.
The synthesis of benzofuroquinolines. IX. A benzofuroisoquinolinone and a benzofuroisocoumarin
Authors: Yamaguchi Seiji , Uchiuzoh Yasuto , Sanada Kunio
Published: March 2009

Some procedures for a benzofuroisoquinolinone 1 were studied. Its O‐analogous benzofuroisocoumarin 2 was synthesized from methyl salicylate with diethyl α‐bromohomophthalate (9). And, the benzofuroisoquinolinone 1 was obtained by treating 2 with ammonia gas in a sealed tube.
Palladium(0)‐catalyzed phenylation of imidazo[4,5‐b]pyridines
Authors: Grivas Spiros , Lindström Stefan
Published: March 2009

The tetrakis(triphenylphosphine)palladium(O)‐catalyzed coupling of benzeneboronic acid with 2‐chloro, 6‐bromo and 6‐bromo‐2‐chloro derivatives of 1‐ and 3‐methylimidazo[4,5‐b]pyridines to novel 2‐phenyl‐, 6‐phenyl‐ and 2,6‐diphenylimidazo[4,5‐b]pyridines is described. The phenylation of imidazo[4,5‐b]‐pyridines containing labile hydrogens was not successful.
Ring‐opening reactions of halogenated N‐aryl‐1,2,3,4‐tetrahydroisoquinoline and 2,3,4,5‐tetrahydro‐1H‐2‐benzazepine derivatives
Authors: Stanley Alan L. , Stanforth Stephen P.
Published: March 2009

Compounds 4a‐4d, 4f and 10 were prepared and their ring‐opening reactions with N‐bromosuccinimide (NBS) investigated. Compounds 4a and 4b gave a mixture of products which did not contain any significant quantity of the corresponding aldehydes 5a and 5b whereas compounds 4c, 4d and 4f gave exclusively the aldehydes 5c, 5d and 5f respectively. Compound 10 similarly gave the aldehyde 11 when treated with NBS.
Synthesis of 5′‐halo‐2′,3′‐lyxo‐epoxy and 2′,3′‐unsaturated thieno[3,2‐d]pyrimidine nucleosides
Authors: Fossey Christine , Ladurée Daniel , Robba Max
Published: March 2009

A series of thieno[3,2‐d]pyrimidine‐2,4‐dione nucleosides modified in the carbohydrate moiety has been synthesized. In the first part, synthetic routes are described for the replacement of 5′‐hydroxyl group in preformed 1‐(β‐D‐ribofuranosyl)thieno[3,2‐d]pyrimidine‐2,4‐dione I by fluoro, iodo or chloro atoms. Reduction of the 5′‐iodo substituent ofVIwas then carried out catalytically using palladium on carbon as catalyst to give the expected 5′‐deoxy derivativeVIII.Thelyxo‐epoxide derivativeXIIwas then synthesized by sequential treatment of the 5′‐deoxy‐5′‐chloro derivativeXwith methanesulfonyl chloride and with sodium hydroxide. In the second part, most of attention has been devoted to apply different methods reported in the literature that allow access to 2′,3′‐olefinic derivatives from the corresponding 2′,3′‐dihydroxy precursor. The 5′‐O‐silyl protected bisxanthateXIVeither on reduction with tri‐n‐butyltin hydride or by reductive elimination of the haloacetateXVIafforded the free 2′,3′‐olefin nucleoside after removal of the 5′‐protecting group. However none of the compounds in this series exhibited significant antiviral activity against HIV at the doses tested.
Synthesis of 1‐amino‐[1,2,3]oxadiazolo[4,3‐α]phthalazin‐4‐ium chloride and substituted dihydro derivatives. New annelated sydnonimines
Authors: Ruxer J. M. , Mauger J. , Bénard D. , Lachoux C.
Published: March 2009

The sydnonimine 5 has been prepared by an original one‐pot nitrosation and cyclisation procedure of the carbonyl chloride Reissert adduct 14 of phthalazine. This synthetic method could be extended to the preparation of dihydro derivatives 7a to 7f and represents a new access to annelated sydnonimines. The para anisoyl and ethoxycarbonyl derivatives of these sydnonimines were also prepared with analogy to molsidomine 1 or pirsidomine 2.
2,3,6,7,8,9‐hexahydro‐8,8‐dimethyl‐5‐phenyl‐1‐H1,4‐benzodiazepin‐6‐one
Authors: Egg Helmut , Knauseder Hubert , Mayr Sabine , Schöpf Daniela
Published: March 2009

Several approaches for the synthesis of the title compound 1 were investigated. Treatment of the ethane‐1,2‐diamine derivative 2 with phosphoryl chloride afforded 3‐chloro‐5,5‐dimethylcyclohex‐2‐enone (3) and 1‐(5,5‐dimethyl‐3‐oxocyclohex‐1‐enyl)‐4,5‐dihydro‐2‐phenylimidazole (4), The reaction of 2‐benzoyl‐dimedone (5) with an equimolar amount of ethane‐1,2‐diamine led to the 2:1 adduct 6, whereas with an excess of ethane‐1,2‐diamine, 4,5‐dihydro‐2‐phenylimidazole (7) and dimedone were obtained. The synthesis of the title compound 1 was achieved by reacting 2‐benzoyl‐3‐chloro‐5,5‐dimethylcyclohex‐2‐enone (8) with ethane‐1,2‐diamine.
Reaction of 4‐chloropyrimidines with alkylisothioureas
Authors: Hurst Derek T.
Published: March 2009

4,6‐Dichloro‐5‐nitropyrmidine reacts with S‐methylisothiouronium sulfate to give 1‐(4‐chloro‐5‐nitropyrimidin‐6‐yl)‐S‐methylisothiourea by an unusual nucleophilic attack involving an isothiouronium nitrogen atom.
Enzymatic resolution of trans‐2,3‐dihydro‐3‐hydroxy‐2‐phenyl‐4H‐1‐benzopyran‐4‐one (trans‐flavanon‐3‐ol) by lipase
Authors: Izumi Taeko , Murakami Satoshi
Published: March 2009

trans‐2,3‐Dihydro‐3‐hydroxy‐2‐phenyl‐4H‐l‐benzopyran‐4‐one (trans‐flavanon‐3‐ol) was resolved to acetate of (2S,3S)‐(‐)‐trans‐flavanon‐3‐ol and (2R,3R)‐(‐)‐trans‐flavanon‐3‐ol by an enzymatic transesterification with vinyl acetate in the presence of Pseudomonas cepacia lipase.
Synthesis of 2‐(3‐tropolonyl)‐1‐benzopyrylium perchlorates and related compounds
Authors: Wang Dao‐Lin , Lu Du‐Ren , Jin Zhong‐Tian , Imafuku Kimiaki
Published: March 2009

3‐Acetyltropolone (1) reacted with 2‐hydroxybenzaldehyde (3a) in the presence of perchloric acid in ethyl orthoformate to afford 2‐(3‐tropolonyl)‐1‐benzopyrylium perchlorate (4a). The reactions with 2‐hydroxy‐5‐methylbenzaldehyde (3b), 5‐chloro‐2‐hydroxybenzaldehyde (3c), and 2‐hydroxy‐1‐naphthalde‐hyde (3d) gave respectively the corresponding products 4b‐d. The reactions of 2‐acetyl‐7‐methylamino‐tropone (2) with 3a‐d also gave the corresponding products 5a‐d, respectively.
Potential of alkyl orthoformates as alkylating agents of non‐electron rich nitrogen heterocycles
Authors: Guccione Salvatore , Russo Filippo , Raffaelli Andrea , Barretta Gloria Uccello , Pucci Sergio , Scolaro Luigi Monsu
Published: March 2009

Findings and suggestions about the potential of the alkyl orthoformates as alkylating agents of non electron rich nitrogen heterocycles and unambiguous instrumental and chemical characterization of the alkylated compounds are reported.
Diheterocyclic compounds from dithiocarbamates and derivatives thereof. VII. 1‐(2‐benzazolylaminophenylsulphonyl)‐4‐[4‐oxo‐2‐thioxo(oxo)‐1,2,3,4‐tetrahydro‐3‐quinazolinyl]benzenes
Authors: Franco Santiago , Meléndez Enrique , Merchán Francisco L.
Published: March 2009

Bisheterocycles 8 with two different heterocyclic rings attached to the central benzene nucleus are readily synthesized from dithiocarbamic acid derivatives 4 or 5, using compound 1 as the starting material.
Synthesis of pyrimidine analogs of 2,6‐Di‐tert‐butylphenol antiinflammatory agents
Authors: Unangst Paul C. , Connor David T. , Kostlan Catherine R. , Shrum Gary P. , Miller Steven R. , Kanter Gerald
Published: March 2009

The preparation of pyrimidine analogs of the 2,6‐di‐tert‐butylphenol antiinflammatory agents Prifelone (R‐830), Tebufelone (NE‐11740) and Ym‐13,162 is described. Grignard addition to the N‐methoxy‐N‐methylamide derived from 4,6‐bis(1,1‐dimethylethyl)‐5‐hydroxy‐2‐pyrimidinecarboxylic acid yielded a series of 2‐pyrimidinyl ketones. Further elaboration of an ethyl ketone and cyclization with sodium cyanate gave a pyrimidinylimidazole.
An unusual structure of the hydrated sodium chloride complex of cryptand [2.2.2]
Authors: Dalley N. Kent , Bradshaw Jerald S. , Kou Xiaolan , Izatt Reed M. , Krakowiak Krzysztof E.
Published: March 2009

The solid state structure of the Na[2.2.2]C1·3H2O complex has the sodium ion displaced towards one of the cryptand nitrogens and the chloride and water molecules associated by hydrogen bonds to form a pseudo cube with two chloride ions at opposite corners of the cube and water oxygens at the other six corners.