bluuebunny/crossref_metadata_2025 huggingface dataset:
Synthesis of large‐ring lactams by a carbene‐anion bond forming reaction
Authors: Williams Eric L.
Published: March 2009

Treatment of large‐ring lactams 1 with potassium t‐butoxide results in the formation of bicyclic structures 2. Evidence was obtained to support the formation of 2 through a carbene‐anion coupling. The structures of a series of bicyclic lactams 2 have been rigorously defined.
Synthesis of substituted 1,4‐diazepino[5,6,7‐kl]acridines and imidazo[4,5,1‐de][1,4]diazepino[5,6,7‐mn]acridines
Authors: Cholody Wieslaw M. , Konopa Jerzy , Martelli Sante
Published: March 2009

The synthesis of some substituted ll‐methoxy‐7‐nitro‐4H,8H‐2,3‐dihydro‐1,4‐diazepino[5,6,7‐kl]acridines 4 with more diversified chains at position 4 is described. A convenient method for transformation of these compounds into the corresponding 4‐substituted 12‐methoxy‐4H‐2,3‐dihydroimidazo[4,5,1‐de][1,4]diazepino‐[5,6,7‐mn]acridine (5) is reported.
Thermolysis of pentasubstituted 3‐hydroxy‐1,2‐dioxolanes
Authors: Baumstark A. L. , Vasquez Pedro C.
Published: March 2009

A series of pentasubstituted 3‐hydroxy‐1,2‐dioxolanes, la‐e, was synthesized by oxygen trapping of β‐keto radicals formed during α‐azo hydroperoxide decomposition. Thermolysis of the pentasubstituted 3‐hydroxy‐1,2‐dioxolanes (hemiperketals) in benzene proceeded cleanly and yielded pairs of ketones and carboxylic acids. Two of the hemiperketals yielded only one pair of products while the others produced two sets of products. One of each pair of fragmentation products had undergone skeletal rearrangement. Only methyl migrations were observed when in competition with phenyl groups from the same position. The activation parameter data for ld [ΔH‡ = 24.3 kcal/mol, ΔS‡ = ‐8.4 eu, ΔG‡ = 27.1 kcal/mol, k60°. = 3.1 × 10−5 s−1] were consistent with 0.0 bond scission as the rate‐determining‐step. A likely mechanism for this thermolysis is initial peroxy bond homolysis to the 1,5‐oxygen diradical followed by β‐scissions with rearrangements.
On the synthesis and reactivity of 4,10‐dihydrobenzo‐[b]thieno[2,3‐e]thiepin‐10‐acetic acid and 5,10‐dihydrobenzo[e]thieno[3,2‐b]thiepin‐10‐acetic acid
Authors: Daich A. , Decroix B.
Published: March 2009

A simple method to synthesize 4,10‐dihydrobenzo[b]thieno[2,3‐e]thiepin‐10‐acetic acid(8a)and 5,10‐dihydrobenzo[e]thieno[3,2‐b]thiepin‐10‐acetic acid(8b)starting from ketonesla,bis described. The reactivity of the acid8ahas been investigated and some derivatives are reported.
Synthesis, structural, conformational and biochemical study of some 3β‐acyloxytropan‐3α‐carboxylic acid hydrochlorides
Authors: Burgos C. , Gálvez E. , Izquierdo M. L. , Arias M. S. , Sanz‐Aparicio J. , Fonseca I. , López P.
Published: March 2009

A series of 3β‐acyloxytropan‐3α‐carboxylic acid hydrochlorides have been synthesized and studied by 1H and 13C nmr spectroscopy, and the crystal structure of 3β‐(3,4,5‐trimethoxybenzoyloxy)tropan‐3α‐carboxylic acid hydrochloride 4c has been determined by X‐ray diffraction. The compounds studied display in methanol‐d4 the same preferred conformation. The pyrrolidine and piperidine rings adopt a flattened N8 envelope and distorted chair conformation; puckered at N8 and flattened at C3 respectively with the N‐substituent in equatorial position with respect to the piperidine ring. In all cases, there is only one mode (axial) of proton uptake at the piperidine nitrogen atom. These results are in close agreement with that found for compound 4c in the crystalline state. The inhibitory ability of the title compounds upon 3H‐GABA binding to sinaptosomal brain membranes is also reported.
Photochemistry of tetramethyl‐4‐pyrone in alcohol solvents
Authors: Pavlik James W. , Keil Elinor B. , Sullivan Eileen L.
Published: March 2009

Irradiation of tetramethyl‐4‐pyrone in alcohol solvents leads to the formation of tetramethyl‐2‐pyrone and to a variety of cyclopent‐2‐enone and cyclopent‐3‐enone solvent adducts. The structure and mode of product formation is consistent with photochemical generation of a short‐lived 2,6‐bridged oxabicyclohexenyl zwitterion which undergoes sigmatropic rearrangement to a longer‐lived epoxycyclopentenone. Although the zwitterion is efficiently trapped by methanol solvent, in less nucleophilic alcohol solvents it rearranges to the epoxycyclopentenone which isomerizes to the 2‐pyrone or reacts with the alcohol solvent to form the observed solvent adducts.
Synthesis and properties of methylene‐bis‐(nitraminofurazans)
Authors: Willer Rodney L. , Day Robert S. , Gilardi Richard , George Clifford
Published: March 2009

Methylene‐bis‐(3‐aminofurazans) and methylene‐bis‐3‐(nitraminofurazans) with methyl and nitro substituents at the 4‐ and 4′‐positions have been synthesized. The thermal properties and crystal structures of the compounds have been determined. As expected, the methyl‐substituted nitramino compound has better thermal stability than the nitro‐substituted compound. The densities predicted for the compounds by the Holden method and those determined by X‐ray crystallography are in close agreement.
Synthesis of 3,3‐dinitroazetidine from 1‐t‐butyl‐3,3‐dinitroazetidine
Authors: Hiskey Michael A. , Coburn Michael D. , Mitchell Michael A. , Benicewicz Brian C.
Published: March 2009

Treatment of 1‐t‐butyl‐3,3‐dinitroazetidine (1) with benzyl chloroformate resulted in a novel elimination of isobutylene to yield equimolar amounts of 1‐(benzyloxycarbonyl)‐3,3‐dinitroazetidine (3) and 1‐t‐butyl‐3,3‐dinitroazetidine hydrochloride. The carbamate 3 was effectively cleaved by trifluoromethanesulfonic acid to yield 3,3‐dinitroazetidinium trifluoromethanesulfonate (4). Free 3,3‐dinitroazetidine (5) has also been isolated.
Syntheses of substituted‐1,2,4‐triazoles
Authors: Shafiee A. , Naghashian F. , Reghabi N.
Published: March 2009

Starting from the readily available 3‐phenylpropionitrile, 3‐(or 5‐)(2‐phenethyl)‐1,2,4‐triazole3was prepared. Reaction of compounds3with diazomethane afforded 1‐methyl‐3‐(2‐phenethyl)‐1,2,4‐triazole(4)and 1‐methyl‐5‐(2‐phenethyl)‐1,2,4‐triazole(5). Reaction of compound3with methanesulfonyl chloride, benzenesulfonyl chloride orp‐toluenesulfonyl chloride afforded only one of the expected isomer; namely compounds6, 7 and8respectively.
Synthesis of [1,2,4]triazoloquinazoline and [1,2,4]‐triazolo‐1,4‐benzodiazepine derivatives
Authors: Gatta Franco , Del Giudice Maria Rosaria , Borioni Anna
Published: March 2009

Some [1,2,4]triazolo[1,5‐c]quinazolin‐5(6H)‐ones 7, the corresponding isomers [1,2,4]triazolo[4,3‐c]quinazo‐lin‐5(6H)‐ones and the 5‐amino derivatives 8, 9 and 11 have been synthesized starting from the acylamidrazones 5. The preparation of 5H‐[1,2,4]triazolo[1,5‐d]‐1,4‐benzodiazepin‐6(7H)‐ones 15 and of 5‐cyclicaminomethyl‐[1,2,4]triazolo[1,5‐c]quinazolines 16 and 17 is also reported.
Improved synthesis of quinaldines by the skraup reaction
Authors: Song Zhiguo , Mertzman Michael , Hughes David L.
Published: March 2009

A series of substituted quinaldines was synthesized with much improved yields from the reaction of croton‐aldehyde and the corresponding anilines using either p‐chloranil or 2,3‐dichloro‐1,4‐naphthoquinone as the oxidant.
Synthesis of Some amino‐4,5‐dihydropyrazolo[3,4‐a]acridines as potential cholinesterase inhibitors
Authors: Shutske Gregory M. , Tomer John D.
Published: March 2009

A synthesis of the 4,5‐dihydro derivatives of the previously known pyrazolo[3,4‐a]acridine ring system is described. The reaction of a 3,4‐dihydroacridin‐1(2H)‐one withN,N‐dimethylformamide dimethyl acetal gave a reactive enamino ketone, which yielded the desired heterocycle upon reaction with hydrazine. Using this chemistry, 11‐amino‐4,5‐dihydro‐2H‐pyrazolo[3,4‐a)acridine (3) and a number of its 2‐substituted derivatives4a‐kwere synthesized and evaluated as acetylcholinesterase inhibitors, based on their relationship to 1,2,3,4‐tetrahydro‐9‐acridinamine (THA). 1‐Amino‐4,5‐dihydro‐1H‐pyrazolo[3,4‐a]acridine (11a) and 2‐amino‐4,5‐dihydro‐1H‐pyrazolo[3,4‐a]acridine (11b) were also synthesized and investigated as potential cholinesterase inhibitors.
Synthesis, proton NMR stereochemical study and diels‐alder reaction of (E)‐7‐arylidene‐2H,6H‐naphtho[1,8‐bc]furan‐2,6‐diones
Authors: Bouaziz Zouhair , Fillion Houda , Pinatel Henri
Published: March 2009

7‐Arylidene‐2H,6H‐naphtho[1,8‐bc]furan‐2,6‐diones 3 were prepared by a retro‐Diels‐Alder reaction of the corresponding dihydro 1,3‐oxazines 2 or in a one pot synthesis from 6‐hydroxy‐2H‐naphtho[1,8‐bc]furan‐2‐one 1. Their E configuration was established from the chemical shift's values of the vinylic proton and by 1H nmr NOE difference spectroscopy. Cycloadditions of 3b upon styrene or stilbene were catalyzed by boron trifluoride etherate. The cycloadducts were obtained with the relative trans configuration.
Synthesis of tetrahydropyridazino[1,2‐a][1,2,4] benzotriazin‐6‐one derivatives. A novel heterocyclic system
Authors: Ray Partha S. , Buote Joan , Webster Charles A. , Manning Michael J.
Published: March 2009

Synthesis of pyridazino[1,2‐a][1,2,4]benzotriazin‐6‐one derivatives involving reaction of either 1,2,3,6‐tetra‐hydropyridazine (9) or hexahydropyridazine 14 with 2‐fluoro‐5‐nitrophenylisocyanate (5) to give, via intramolecular cyclization, 3a and 16 respectively is described. Compound 3a was converted to 18 via methylation and hydroxylation to give 20 followed by conversion to the acetonide derivative 18. Both 16 and 18 were reduced to the amino derivatives 17 and 19 respectively.
Novel perfluoroalkyl‐substituted pyrazoles. 1. Hydroxypyrazoles
Authors: Gaede Bruce J. , Mcdermott Lisa L.
Published: March 2009

Addition of methylhydrazine to a variety of haloalkyl‐substituted α,β‐unsaturated esters gives 1,5‐disubstituted 3‐hydroxypyrazoles, in contrast to the more common synthesis from β‐ketoesters, which gives 1,3‐disubstituted 5‐hydroxypyrazoles. This reaction is used to prepare several novel pyrazoles bearing haloalkyl substituents. Criteria for assignment of structures have been developed based on physical and spectroscopic properties of the isomers. The regiochemical preference in this addition is considered on the basis of steric, electronic, and mechanistic factors.
Synthesis of 4‐Amino‐substituted‐6‐hydroxy and 11‐hydroxynaphtho[2,3‐g]quinoline‐5,12‐diones, and the unexpected formation of disubstituted imidazo[4,5,l‐i,j]naphtho[2,3‐g]quinolin‐7‐ones
Authors: Croisy‐Delcey Martine , Bisagni Emile , Huel Christiane
Published: March 2009

4‐Chloroquinoline‐5,8‐dione (8a) and 6‐bromo‐4‐chloroquinoline‐5,8‐dione (8b) were reacted with homophthalic anhydride to give tetracyclic compounds 10 and 11 respectively. The 6,11‐dihydroxy derivative 12 was prepared in low yield by photochemical addition of benzocyclobutenedione to 4‐chloroquinoline‐5,8‐dione (8a) and in better yield through a Friedel‐Crafts reaction of phthalic anhydride with 4‐chloro‐5,8‐dimethoxyquinoline (7a). Whereas 4‐chloro‐6‐hydroxynaphtho[2,3‐g]quinoline‐5,12‐dione (11) was substituted by amines in the usual way to the corresponding 4‐amino‐substituted derivatives, 4‐chloro‐11‐hydroxynaph‐tho[2,3‐g]quinoline‐5,12‐dione (10) led to a mixture of 4‐amino derivatives and the unexpected 2,6‐disubstituted‐imidazo[4,5,l‐I‐j]naphtho[2,3‐g]quinolin‐7‐ones, 13a‐b.
Synthesis of C‐24 β‐lactams of bile acids
Authors: Siddiqui Abdul U. , Siddiqui A. H. , Sundara Ramaiah T.
Published: March 2009

Methyl 3α‐hydroxy‐5β‐cholan‐24‐oate III and methyl 3α,12α‐dihydroxy‐5β‐cholan‐24‐oate IV were converted into the respective hydrazides V and VI by reaction with hydrazine. These hydrazides were reacted with aryl aldehyde VII to give the corresponding 24‐arylidene‐hydrazides VIII and IX. The reaction of Schiff bases VIII and IX with monochloroacetyl chloride in the presence of triethylamine afforded β‐lactams X‐XI.
The synthesis and chemistry of 2‐hydroxy‐4,6‐bis(trifluoromethyl)pyridine‐5‐carboxylates
Authors: Goure William F.
Published: March 2009

The facile two step, one pot synthesis of heretofore unknown 2‐hydroxy‐4,6‐bis(trifluoromethyl)‐pyridine‐5‐carboxylates by condensation of 3‐amino‐4,4,4‐trifluoro‐2‐butenoate with 4,4,4‐trifluoroacetoacetyl chloride and subsequent intramolecular cyclization of the resultant enamineamide is described. Methodology for the introduction of electrophiles at the 3‐position and elaboration of substituents at the 2‐ and 5‐positions is also discussed.
Synthesis and catalytic activity of a new class of cyclophosphazenic polypodands
Authors: Bullitta Maria Paola , Maccioni Elias , Corda Luciana , Podda Gianni
Published: March 2009

A new class of solid‐liquid phase‐transfer catalysts (SL‐PTC) has been prepared by the reaction of octachlo‐rocyclotetraphosphazatetraene and polyethylene glycol monoalkyl ether. These polypodands are found to be powerful metal cation complexing agents and very efficient catalysts in anion promoted reactions (e.g. nucleophilic substitution and reduction reactions).
Synthesis of p‐aminobenzamides of several aminopyrazolidines: Potential antiarrhythmic agents related to procainamide
Authors: Kornet Milton J. , Abdul‐Nabi All K. , Steinberg Mitchell I.
Published: March 2009

Four heterocyclic amines including 1,2‐diethyl‐3‐aminomethylpyrazolidine (3), 1‐(2‐aminoethyl)‐2‐methyl‐pyrazolidine (5), 1,2‐dimethyl‐4‐aminomethylpyrazolidine (7), and 1,2‐diethyl‐4‐aminopyrazolidine (9) have been synthesized. Each was acylated with p‐nitrobenzoyl chloride and afforded the corresponding p‐nitro‐benzamides 10, 12, 14, and 16. Catalytic reduction of these nitro intermediates gave the corresponding p‐aminobenzamides 11,13,15, and 17. The latter compounds are analogs of procainamide and two of them, 15 and 17, were evaluated in the isolated cardiac Purkinje fiber preparation by measuring their effects on the action potential upstroke velocity.
A study of 2‐aminofurans
Authors: Lythgoe David J. , Mcclenaghan Ian , Ramsden Christopher A.
Published: March 2009

Catalytic reduction of 2‐nitrofurans 2 gives low yields of 2‐aminofurans 1 which are not isolated but are trapped using ethyl ethoxymethylenecyanoacetate (6) or ethoxymethylenemalononitrile (7). In these reactions 2‐aminofuran (1a) behaves like a dieneamine with substitution occurring at position 5 of the ring. When the 5‐position is substituted reaction takes place at position 3 and thermal cyclisation of the product gives furo‐[2,3‐b]pyridine derivatives 16. An AM1 calculation of the properties of 2‐aminofuran (1a) is reported and the results are consistent with observed properties.
β‐Ribo‐ and α‐arabinonucleosides containing the 1,2‐benzisoxazole and 1,2‐benzisothiazole rings
Authors: Yoshii Kiyotaka , Ohba Yoshihiro , Nishiwaki Tarozaemon
Published: March 2009

The reaction of the silylated base of 1,2‐benzisoxazol‐3(2H)‐one (1) and its 7‐methyl derivative5and 5‐methyl‐1,2‐benzisothiazol‐3(2H)‐one (9), respectively, with 1‐O‐acetyl‐2,3,5‐tri‐O‐benzoyl‐β‐D‐ribofuranose followed by basic deprotection gave the corresponding β‐D‐ribonucleosides, and the silylated base of1, when treated with 1‐O‐acetyl‐2,3,5‐tri‐O‐benzoyl‐α‐D‐arabinofuranose in the presence of stannic chloride, afforded the corresponding α‐arabinonucleoside. Structural proofs of these nucleosides are provided from elemental analyses and1H and13C nmr spectra.
The synthesis of novel polycyclic heterocyclic ring systems via photocyclization. 9. Phenanthro[9′,10′:4,5]thieno[2,3‐c]quinoline, benzo[f]phenanthro[9′,10′:4,5]thieno[2,3‐c]quinoline, and benzo[h]‐phenanthro[9′,10′:4,5]thieno[2,3‐c]quinoline
Authors: Camoutsis Charalampos , Castle Raymond N.
Published: March 2009

The synthesis of three novel polycyclic heterocyclic ring systems are reported via photocyclization. The specific final products in these ring systems are: phenanthro[9′,10′:4,5]thieno[2,3‐c]quinoline (13), benzo[h]‐phenanthro[9′,10′:4,5]thieno[2,3‐c]quinoline (14), and benzo[f]phenanthro[9′,10′:4,5]thieno[2,3‐c]quinoline (15).
First synthesis of the benzo[f]pyrido[2′,3′:3,4]‐pyrrolo[2,1‐a][2,7]naphthyridine ring system
Authors: Bracher Franz
Published: March 2009

The lithiated pyridine 7 on reaction with methyl 4‐methylquinoline‐3‐carboxylate (8) gave the ketone 9, which could be converted to the biaryl 11 via an effective two step anellation procedure. Treatment of 11 with dilute sulfuric acid resulted in an unexpected ring closure to give the title ring system.
Synthesis of 1,2,4‐triazolo[1,5‐a]pyrimidine‐2‐sulfonamides
Authors: Shankar Ravi B. , Pews R. Garth
Published: March 2009

The 1,2,4‐triazolo[1,5‐a]pyrimidine‐2‐sulfonamides are a new class of highly active herbicides. A novel cyclization method for the synthesis of these compounds is discussed.
The structure of the CT complex between 5,7,12,14‐tetramethoxydibenzo[b,i]thianthrene with TCNQ
Authors: Matsuoka Masaru , Iwamoto Akihiro , Ouchi Takeshi , Yoshioka Hiroshi , Nakatsu Kazumi
Published: March 2009

The structure of 1,4‐dithiines obtained from orthodihalogeno heterocycles with thiocarbonyl compounds was determined by X‐ray structure analysis of the intermolecular charge‐transfer complex between 5,7,12,14‐tetramethoxydibenzo[b,i]thianthrene and TCNQ. The formation of the thiazole ring has already been reported but the products were confirmed to be 1,4‐dithiines by X‐ray structure analysis and the previously reported results.
PolycyclicN‐heterocyclic compounds.XLI. Synthesis of 4‐substituted 6,7‐dihydro‐5H‐pyrimido[5,4‐d][1]benzazepines, 1,2,5,6‐tetrahydro‐4H‐imidazo[1′,2′:1,6]pyrimido[5,4‐d][1]benzazepines and their related compounds as a series of potential blood platelet aggregation inhibitors
Authors: Nagamatsu Tomohisa , Hantani Yoshiji , Yamada Minoru , Sasaki Kenji , Ohtomo Hiromi , Nakayama Taiji , Hirota Takashi
Published: March 2009

As a series of polyheterocyclic compounds for exploitation as anti‐platelet agents, tricyclic heterocyclic compounds, 4‐substituted 6,7‐dihydro‐5H‐pyrimido[5,4‐d][1]benzazepines3–6, 9, 12–14, and16–26, having nitrogen, oxygen, or sulfur containing functional groups at the 4‐position, were prepared. In addition, tetra‐cyclic heterocyclic compounds, 3‐methyl‐1,2,5,6‐tetrahydro‐4H‐imidazo[1′,2′:1,6]pyrimido[5,4‐d][1]benzaze‐pinium chloride (7), 1,2,5,6‐tetrahydro‐4H‐imidazo[1′,2′:1,6]pyrimido[5,4‐d][1]benzazepines10a‐e, 2,3,6,7‐tetrahydro‐1H5H‐pyrimido[1′,2′:1,6]pyrimido[5,4‐d][1]benzazepine (11), and 1,2,5,6‐tetrahydro‐4H‐thiazolo‐[3′,2′:1,6]pyrimido[5,4‐d][1]benzazepinium chloride (15)viaring closure of 4‐(hydroxyalkylamino)‐6, 9a‐e, and3c, and 4‐(2‐hydroxyethylthio)‐6,7‐dihydro‐5H‐pyrimido[5,4‐d][1]benzazepine (14) with phosphoryl chloride or thionyl chloride, respectively, were also prepared. Their inhibitory activities against collagen‐induced aggregation of rabbit blood plateletsin vitrowere investigated. Among them, compound5having a morpholino group at the 4‐position on the tricyclic nucleus, which enhanced the activity more than 14‐fold as compared with aspirin, was found to have the most satisfactory in inhibitory activity.
Synthesis and properties of 1,4,8,11,15,18,22,25‐octaalkoxy‐2,3,9,10,16,17,23,24‐octakis(phenylthio)phthalocyaninato copper(II)
Authors: Azuma Natsuhiro , Kitahara Kiyoshi , Motoi Takashi , Tokita Sumio , Nishi Hisao
Published: March 2009

1,4,8,11,15,18,22,25‐Octaalkoxy‐2,3,9,10,16,17,23,24‐octakis(phenylthio)phthalocyaninato copper(II) was synthesized. They were easily soluble in organic solvents and their Q‐bands showed bathochromic shifts about 100 nm compared with unsubstituted phthalocyaninato copper(II). Their properties were examined.
PolycyclicN‐hetero compounds.XLIII.Syntheses and properties of 2‐substituted 1‐acetoxy‐6‐acetyl‐5,6‐dihydro‐4H‐imidazo[1′,2′:1,6]‐pyrimido[5,4‐d][1]benzazepinesviaN‐(6,7‐dihydro‐5H‐pyrimido[5,4‐d]‐[1]benzazepin‐4‐yl)amino acids and their analogous mesoionic compounds, and their related compounds as a series of potential blood platelet aggregation inhibitors
Authors: Nagamatsu Tomohisa , Hantani Yoshiji , Sasaki Kenji , Ohtomo Hiromi , Nakayama Taiji , Hirota Takashi
Published: March 2009

A study of the cyclization method by heating ofN‐(6,7‐dihydro‐5H‐pyrimido[5,4‐d][1]benzazepin‐4‐yl)amino acids3a‐h, 6, and9a,bwith excess acetic anhydride for the preparation of 2‐substituted 1‐acetoxy‐6‐acetyl‐5,6‐dihydro‐4H‐imidazo[1,2′:1,6]pyrirnido[5,4‐d][1]benzazepines4a‐hand tetra‐ and penta‐cyclic mesoionic compounds7and10a,bhas been made. In addition, a tetracyclic mesoionic compound having a sulfur atom on the skeleton, 5,6‐dihydro‐4H‐thiazolo[3′,2′:1,6]pyrimido[5,4‐d][1]benzazepiniurn‐1‐one (12) was similarly prepared by treatment of 2‐(6,7‐dihydro‐5H‐pyrimido[5,4‐d][1]benzazepm‐4‐ylthio)acetic acid (11) with excess acetic anhydride. Their inhibitory activities against collagen‐induced aggregation of rabbit blood plateletsin vitrowere also investigated, and some heterocycles exhibited from a two‐ to a four‐fold more potent activity as compared with aspirin.
A convenient synthesis of tricyclic purine derivatives
Authors: Shimada Junichi , Kuroda Takeshi , Suzuki Fumio
Published: March 2009

A convenient synthesis of new heterocycles such as 7,8‐dihydro‐1H‐imidazo[2,1‐i]purin‐5(4H)‐ones (2, n = 0) and 5,6‐dihydro‐1H‐imidazo[2,1‐b]purin‐9(8H)‐ones (3) was described. The syntheses of 2 and 3 were accomplished by treatment of 6‐methylthio‐7H‐purin‐2(3‐H)‐ones 7 or 2‐benzylthio‐1‐methyl‐9‐triphenylmethyl‐9H‐purin‐6(1H)‐one (15) with appropriate aminoalcohol followed by dehydrative cyclization using thionyl chloride. Compound 15 was efficiently prepared by benzylation of 6‐hydroxy‐2‐mercaptopurine (12) followed by tritylation and N‐methylation.
Convenient synthesis of 4‐amino‐7‐(dialkylamino)pyrido[2,3‐d]pyrimidines from polysubstituted pyridines
Authors: Cocco Maria Teresa , Congiu Cenzo , Maccioni Antonio , Onnis Valentina
Published: March 2009

A convenient synthesis of 4‐amino‐7‐(dialkylamino)pyrido[2,3‐d]pyrimidines via cyclization of functionalized pyridines is reported. The preparation of the starting pyridines from 3‐amino‐3‐(dialkylaraino)propene‐nitriles and ethoxymethylenemalononitrile is described.
Synthesis of 4,6‐disubstituted 2‐methylpyridines and their 3‐carboxamides
Authors: Shibata Katsuyoshi , Katsuyama Isamu , Izoe Hideaki , Matsui Masaki , Muramatsu Hiroshige
Published: March 2009

A new one‐pot synthesis of title compounds by the reactions of α,β‐unsaturated carbonyl compounds with β‐aminocrotononitrile in the presence of sodium hydroxide is described.
Synthesis of 6,7,8,9‐tetrahydro‐5H‐pyrimido‐[4,5‐b][1,4]diazepine‐6,8‐diones
Authors: Phillips Oludotun A. , Knaus Edward E.
Published: March 2009

The sodium ethoxide catalyzed condensation of 4,5‐diaminopyrimidine (3) with diethyl malonate afforded 6,7,8,9‐tetrahydro‐5H‐pyrimido[4,5‐b][1,4]diazepine‐6,8‐dione (4). Methylation of 6,7,8,9‐tetrahydro‐5H‐pyrimido[4,5‐b][1,4]diazepine‐6,8‐dione (4) using sodium hydride and two equivalents of iodomethane gave 5,9‐dimethyl‐6,7,8,9‐tetrahydro‐5H‐pyrimido[4,5‐b][1,4]diazepine‐6,8‐dione (5) which on further methylation using sodium hydride and one equivalent iodomethane yielded 6,7,8,9‐tetrahydro‐5,7,9‐trimethyl‐5H‐pyrimido[4,5‐b][1,4]diazepine‐6,8‐dione (6). Reaction of 6,7,8,9‐tetrahydro‐5H‐pyrirnido[4,5‐b][1,4]diazepine‐6,8‐dione (4) with 4.2 equivalents of sodium hydride and 4.1 equivalents of iodomethane afforded 6,7,8,9‐tetrahydro‐5,7,7, 9‐tetramethyl‐5H‐pyrimido[4,5‐b][1,4]diazepine‐6,8‐dione (7). 6,7,8,9‐Tetrahydro‐5,7,7,9‐tetramethyl‐5H‐pyrimido[4,5‐b][1,4]diazepine‐6,8‐dione (7) exhibited weak anticonvulsant activities in the subcutaneous pentylenetetrazole and maximal electroshock anticonvulsant screens indicating it is a partial bioisostere of the anticonvulsant drug clobazam (2).
The reaction of 2‐nitrosopyridine with nitrile oxides: First synthesis of 1,2,4‐triazolo[1,5‐a]pyridine 1,3‐Di‐N‐oxides
Authors: Gallos John K. , Lioumi Maria I. , Lekka Anastasia N.
Published: March 2009

Reactions of 2‐nitrosopyridine with nitrile oxides afford either the novel title compounds or the corresponding 1,2,4‐triazolo[1,5‐a]pyridine 3‐oxides.
A simple stereoselective one‐pot synthesis of C‐nucleosides by 1,3‐dipolar cycloaddition of chiral azomethine imines prepared in situ
Authors: Žličar Marko , Stanovnik Branko , Tišler Miha
Published: March 2009

The NH,NH‐dihydrocycloadduct 1 (6‐chloro‐9,9‐dimethyl‐7,8‐dihydro‐9H‐pyrazolo[4,3‐d]tetrazolo[1,5‐b]‐pyridazine) obtained by the cycloaddition of 2‐diazopropane to 6‐chlorotetrazolo[1,5‐b]pyridazine, is transformed with protected or unprotected carbohydrates 2, 5, 7,9, 11, 13 and 15 in the presence of methyl acrylate (3) into the corresponding C‐nucleosides 4,6,8,10,12,14 and 16. In this one‐pot synthesis two new chiral centers are formed stereoselectively, dependent on the chirality at C‐atom next to aldehydo group in the carbohydrate.
Synthesis and biological evaluation of nucleosides containing 8‐amino‐imidazo[1,2‐α]pyrazine as an isosteric replacement for adenine
Authors: Maccoss M. , Meurer L. C. , Hoogsteen K. , Springer J. P. , Koo G. , Peterson L. B. , Tolman R. L. , Emini E.
Published: March 2009

A number of novelC‐nucleosides related to purine derivatives are described in which the purine moiety has been replaced by the isosteric heterocycle, 8‐aminoimidazo[1,2‐α]pyrazine. The nucleosides prepared include the ribo, 3′‐deoxy, 2′,3′‐dideoxy, and 2′,3′‐unsaturated derivatives. TheseC‐nucleosides represent derivatives containing acid stable glycosyl bonds and they can be considered as analogs of adenine‐ or 3‐deazaade‐nine‐containing nucleosides. Preparation of the parent ribonucleoside was accomplished by reaction of the C‐l functionalized sugar, (2ξ)‐1‐amino‐3,6‐anhydro‐l‐deoxy‐4,5‐O‐isopropylidene‐7‐O‐trityl‐D‐allo‐heptitol with 2,3‐dichloropyrazine, followed by ring closure to the 8‐chloroimidazo[1,2‐α]pyrazine nucleoside, conversion to the 8‐amino derivative and deblocking. A single crystal X‐ray structure of the parent 8‐amino‐3‐(β‐D‐ribofuranosyl)imidazo[1,2‐α]pyrazine is described and the conformation compared to that of formycin. The sugar‐modified analogs were prepared by subsequent functional group manipulations on the sugar moiety. Biological evaluation againstHIVinH9T‐lymphoid cell culture showed the nucleosides to be devoid of significant antiviral activity compared to DDA. The 3‐deazaadenosine analog also demonstrated weak suppression of mouse splenic NK activity toward YAC cells (mouse lymphoma cell targets). The imidazo[1,2‐α]pyrazine analog of 3‐deazaadenosine showed antiinflammatory activityin vivoin the rat pleurisy carrageenan model in the same range with 3‐deazaadenosine.
Heterocyclic amino acids as synthons. Reactions with dicarbonyl compounds
Authors: Kolar Patrik , Tišler Miha
Published: March 2009

From some alkyl heteroarylglycinates and dicarbonyl compounds various heterocyclic systems are easily accessible. Transformations are described which lead to imidazo[1,5‐α]pyridines, heteroaryl‐substituted pyrroles, pyrido[1,2‐α]pyrazines, pyrido[1,2‐α]pyrimidines or quinolizin‐4‐ones.
β‐lithiations of carboxamides. Synthesis of β‐substituted‐α,β‐unsaturated amides
Authors: Katritzky Alan R. , Szajda Maria , Lam Jamshed N.
Published: March 2009

N‐Methyl‐2‐methyl‐3‐(benzotriazol‐l‐yl)propanamide, on treatment with butyllithium forms a dianion which on treatment with alkyl and benzyl halides, aldehydes and ketones affords monosubstituted products; with ethylp‐toluate, a lactam is formed. The alkylated derivatives eliminate benzotriazole in the presence of base to afford trisubstituted α,β‐unsaturated amides.
Synthesis and reactions of tetrazolo[1,5‐α]pyrimidines
Authors: Kappe Thomas , Roschger Peter , Färber Gerald
Published: March 2009

The reaction of “magic malonates” (bis‐2,4,6‐trichlorophenyl malonates, 1) with 5‐aminotetrazole (2) in the presence of triethylamine yields the ammonium salts 3. Upon treatment of 3 with strong acids compounds 4a‐d were obtained as a mixture of isomeric tetrazolopyrimidines (A) and 2‐azidopyrimidines (B). Reaction of 4d with bromine or sulfuryl chloride leads by ring opening and decarboxylation to the halogenated tetrazole derivatives 5 or 7, respectively. The action of acetic anhydride in pyridine on 3d yields the zwitterionic tetra‐mic acid derivative 10.
Pyridine‐substituted hydroxythiophenes. II. Alkylation of o‐(2‐, 3‐ and 4‐pyridyl)‐3‐hydroxythiophenes: Regiospecific formation of o‐pyridyl‐3‐alkoxythiophenes
Authors: Zhang Yihua , Hörnfeldt Anna‐Britta , Gronowitz Salo
Published: March 2009

The alkylation of o‐(2‐, 3‐ and 4‐pyridyl)‐3‐hydroxythiophenes has been investigated. In the case of 4‐(2‐, 3‐ and 4‐pyridyl)‐3‐hydroxythiophene systems, the soft alkylating reagent, methyl iodide, using sodium hydride as the base and dimethylimidazolidinone as the solvent, gave rise to a mixture of O‐alkylated and O,C‐dialkylated products in the proportions of 4.6–6.5 to 1. However, in the case of 2‐(2‐, 3‐ and 4‐pyridyl)‐3‐hydroxythiophene systems, the same reaction conditions brought about exclusively O‐alkylated compounds in yields of 45–53%. In both cases, the hard alkylating reagent, methyl p‐toluenesulfonate, with the same base and solvent, only give O‐alkylated compounds in yields of 51–77%. These latter conditions resulted in a good preparative route for the regiospecific formation of o‐pyridyl‐3‐alkoxythiophenes by using ethyl 2‐bromopro‐pionate as well as methyl p‐toluenesulfonate as alkylating reagents. The hydrolysis of the esters, derived from alkylation with ethyl 2‐bromopropionate, has also been investigated.
Photoinduced β‐elimination of the triazole group in the 1‐(N,N‐bisacyl)amino‐1,2,3‐triazoles
Authors: Kalambokis E. A. , Maroulis A. J. , Alexandrou N. E.
Published: March 2009

The photoelimination of the 1,2,3‐triazole group from the title compounds proceeds, depending upon the reaction conditions, via an intra‐ or intermolecular hydrogen abstraction or electron‐transfer mechanism, followed by homolytic cleavage of the N,N bond. It can also proceed via π−‐assisted β‐cleavage of the same weak bond, when light of shorter wavelength is used. The composition of the products suggests that in all cases most probably a α‐type 1,2,3‐triazolyl radical 10 is eliminated which is further quenched by hydrogen or chlorine abstraction.
2′‐O,5‐dimethyluridine: A total synthesis and single crystal X‐ray diffraction study
Authors: Lewis Arthur F. , Revankar Ganapathi R. , Hogan Michael E.
Published: March 2009

A new method for the synthesis of 2′‐O,5‐dimethyluridine (5) has provided the title compound in a higher yield. Application of a one‐pot ribosylation methodology resulted in an efficient, high yield synthesis of 5‐methyluridine (ribothymine, 3b). An X‐ray diffraction analysis of 5 disclosed the conformation of the sugar moiety of this nucleoside as anti, N(3′‐endo), g+.
On Triazoles. XXXII. The reaction of 5‐amino‐1 H‐1,2,4‐triazolylcarbothiohydrazides with β‐ and γ‐oxo‐esters
Authors: Reiter József , Barkóczy József , Pallagi István
Published: March 2009

5‐Amino‐lH‐1,2,4‐triazolylcarbothiohydrazides gave β and γ‐oxo‐esters in boiling ethanol [1,2,4]triazolo‐ [1,5‐d][1,2,4,6]tetrazepine‐5‐thiones 3. Analogously ethyl 2‐oxocyclohexanecarboxylate provided a mixture of two diastereomeric spiro derivatives 5 and 6. At 130°, 2‐acetonyl‐5‐methyl‐4,5‐dihydro‐1,3,4‐oxadiazole‐5‐thione (8) was formed. Ring closure of 3e (R1 = CH3, R2 = CH2CH2COOEt, Q = morpholino) lead to the isomeric pyrrolo[2,1‐g][1,2,4]triazolo[1,5‐d][1,2,4,6]tetrazepin‐8(11H)‐one (12) and pyrrolo[1,2‐f][1,2,4]triazolo‐[1,5‐d][1,2,4,6]tetrazepin‐10(7H)‐one (13) derivatives representing two new ring systems.
Synthesis of certain N‐ and C‐alkyl purine analogs
Authors: Bhattacharya Birendra K. , Rao T. Sudhakar , Lewis Arthur F. , Revankar Ganapathi R. , Sanghvi Yogesh S. , Robins Roland K.
Published: March 2009

A number of N‐ and C‐alkyl derivatives of selected guanine analogs have been synthesized as potential antiviral agents. n‐Pentyl, n‐hexyl and 6‐hydroxyhexyl derivatives in the imidazo[1,2‐α]‐s‐triazine, 9–11, imid‐azo[1,2‐α]pyrimidine, 13–17, and thiazolo[4,5‐d]pyrimidine, 19–21, ring system have been prepared by the direct alkylation of the sodium salt of the appropriate aglycon with the respective alkylbromides. Dehydra‐tive coupling of 3‐amino‐6‐hydrazino‐1,2,4‐triazin‐5(4H)‐one (22) with either hexanoic acid or heptanoic acid, and further ring closure of the reaction products 24a and 24b provided the n‐pentyl and n‐hexyl derivatives of 6‐amino‐1,2,4‐triazolo[3,4‐f][1,2,4]triazin‐8(7H)‐one 25a and 25b, respectively. A similar condensation of 3‐amino‐6‐aminomethyl‐1,2,4‐triazin‐5(4H)‐one (23) with heptanoic acid, followed by ring annulation, readily gave 2‐amino‐7‐n‐hexylimidazo[5,1‐f][1,2,4]triazin‐4(3H)‐one (25c). Bromination of 25c with N‐bromosuccini‐mide afforded the corresponding 5‐bromo derivative 26. Alkylation of the in situ generated sodium salt of 4‐methoxycarbonylmethyl‐5‐methoxycarbonyl‐2‐oxo‐1H,3H‐imidazole (27) with 1‐bromohexane gave the N‐1 alkylated product 31. Manipulation of the functional groups in 31 and further hydrazine mediated ring annulation furnished 5,6‐diamino‐1‐n‐hexyl‐3‐methylimidazo[4,5‐c]pyridine‐2,4‐dione (39). Catalytic hydrogena‐tion of 39 gave 7‐methyl‐8‐oxo‐9‐hexyl‐3‐deazaguanine (40), a congener of the immunostimulator 7‐methyl‐8‐oxoguanosine.
New azomycin acyclonucleoside. Synthesis and biodistribution of radiohalogenated analogues in tumor‐bearing mice
Authors: Hasan Ahmad , Knapp Furn F. , Kilbourn Michael R. , Buchsbaum Donald J.
Published: March 2009

The design, synthesis and biological activities of several acyclonucleoside analogues related to misoni‐dazole are described. The hydroxy‐5, bromo‐6, iodo‐7, and fluoro‐8 derivatives of ethoxymethylazomycin and iodopropenyloxymethylazomycin (12) have been prepared. Alkylation of silylated azomycin with haloethoxy‐methylene chloride gave the corresponding acyclonucleosides. Similarly, propargyloxymethylene chloride gave propargyloxymethylazomycin (10), which after hydrostannylation and subsequent iododestannylation yielded iodopropenyloxymethylazomycin (12). The radiolabeled [125I] or [18F] compounds were prepared from the corresponding substrates. Biodistribution results of the radiolabeled analogues in mice showed that compound 7 had good tumor uptake (2.0% injected dose/g at 1 hour). The high radioactive levels in blood and stomach, however, were perhaps due to in vivo deiodination or metabolism. Compound [125I]‐12 showed the highest tumor uptake (4.8 and 3.6% injected dose/g at 1 and 4 hours respectively) of all of the compounds tested. Relatively low thyroid uptake of radioactivity in mice dosed with compound [125I]‐12 indicates significantly reduced in vivo deiodination in comparison to compound [125I]‐7.
Aza‐analogues of cage compounds: Potential precursors to azacubanes and 1‐azahomocubanes
Authors: Gilardi Richard , George Clifford , Karle Jerome , Eaton Philip E. , Fisher Allison M.
Published: March 2009

Exploration of the reactions of the 9‐azahomocubane system led to derivatives of two small‐ring systems containing aza‐bridging atoms, 5‐azatetracyclo[4.2.0.03,8.04,7]octane and 9‐azatetracyclo[4.3.0.02,5.04,7]nonane. The structures were characterized by X‐ray diffraction analyses. There are no prior X‐ray structural reports on these systems.
Synthesis of novel C‐2 substituted pyrimidine nucleoside analogs
Authors: Dunkel Martin , Dan Cook P. , Acevedo Oscar L.
Published: March 2009

A series of 2‐(2‐oxoalkylidene)‐4(1H)‐pyrimidinone nucleoside analogs were synthesized by the addition of the lithium enolates of methylketones to 2,5′‐ and 2,2′‐anhydrouridines and to 2,5′‐anhydrothymidines. Alternatively, 2‐thiouridine was alkylated with bromomethyl ketones to yield 2‐(2‐oxoalkyl)thio‐4(1H)‐pyrimidinone ribofuranosides in good yields. These intermediates were subsequently transformed into the title compounds via an Eschenmoser sulfur extrusion reaction. The 2‐(2‐oxoalkylidene)‐4‐(1H)‐pyrimidinone nucleoside analogs exhibit enol proton signals in their 1H nmr spectra indicative of hydrogen bonding between N‐3 and keto oxygen. These structures offer functional groups with potential for Watson‐Crick hydrogen bonding.
Synthesis of saulatine
Authors: Kim Dong Chin , Yoon Won Hyung , Choi Hoon , Kim Dong H.
Published: March 2009

A study directed toward the synthesis of saulatine (5,8,9,14a‐tetrahydro‐3,4,11,12‐tetramethoxy‐isoquino[1,2‐b]benzazepine‐6,14‐dione) is described. The successful synthetic route consists of three steps starting with 3,4‐dimethoxyphenethylamine and 2‐bromo‐(3,4‐dimethoxy‐2‐ethoxycarbomethylphenyl)‐acetate. It was found that the methoxy moieties present on the aromatic rings prohibit the use of the intramolecular Friedel‐Crafts reaction with a Lewis acid catalyst for ring construction because of their demethylation tendency under the reaction conditions.
Synthesis of 4‐[(1,3‐diaminopyrrolo[3′,4′:4,5]pyrido[2,3‐d]‐pyrimidin‐8‐yl)benzoyl]‐L‐glutamic acid as a potential antifolate
Authors: Su Tsann‐Long , Yang Yu‐Kun , Huang Jai‐Tung , Ren Wu‐Yun , Watanabe Kyoichi A. , Chou Ting‐Chao
Published: March 2009

This paper is dedicated to the memory of Professor Roland K. Robins

The synthesis of 4‐[(1,3‐diaminopyrrolo[3′,4′:4,5]pyrido[2,3‐d]pyrimidin‐8‐yl)benzoyl]‐L‐glutamic acid (18), a potential antifolate and anticancer agent, has been achieved starting from 1,4‐dibromobutan‐2‐ol with alkyl p‐aminobenzoic acids. Condensation of these two agents gave 1‐(4‐alkoxycarbonylphenyl)pyrrolidin‐3‐ols 7a,b, which were oxidized to the corresponding pyrrolidin‐3‐one derivatives 8a,b. Compounds 8a,b were converted into 1,3‐diamino‐8‐(4‐alkoxycarbonylphenyl)‐7,8‐dihydro‐9H‐pyrrolo[3′,4′:4,5]pyrido[2,3‐d]pyrimidines 12a,b in 4 steps. Saponification of 12b the benzoate ester and coupling with di‐tert‐butyl glutamate afforded a mixture of 7,8‐dihydro product 16 and its aromatized derivative 17. Finally hydrolysis of esters 16 or 17 gave only the title compound 18. The 7,8‐dihydro tricyclic derivatives were easily air‐oxidized to form their fully aromatized compounds. The title compound 18 was one tenth less active than MTX against HL‐60 cells in culture.
Reactions of ring‐expanded xanthines containing the imidazo[4,5‐e][1,4]diazepine ring system
Authors: Bhan Anila , Hosmane Ramachandra S.
Published: March 2009

4,5,7,8‐Tetrahydro‐6H‐imidazo[4,5‐e][1,4]diazepine‐5,8‐dione underwent bromination at the 2‐position with or without substituents at the 3‐, 4‐ or 7‐position, using bromine, N‐bromosuccinimide, or acetyl hypobro‐mite. The activation of position 6 with an ester functionality, as in 7, did not alter the site of bromination. The base‐catalyzed bromination of the ring‐open precursor, diethyl 2‐[N‐(1‐benzyl‐5‐nitroimidazolyl‐4‐carbon‐yl)amino]malonate (5), resulted either in introduction of an alkoxy functionality in the above aminomalonate side‐chain, yielding 17 when the reaction was quenched with an alcohol, or in degradation of the side‐chain, yielding 1‐benzyl‐5‐nitroimidazole‐4‐carboxamide (19) when the reaction was quenched with water. Both 17 and 19 are formed by oxidative bromination of 5 via the bromo intermediate 15. An indirect evidence for the latter was obtained by base‐catalyzed methylation of 5 which gave diethyl 2‐methyl‐2‐[N‐(1‐benzyl‐5‐nitroimid‐azolyl‐4‐carbonyl)amino]malonate (21). The base‐catalyzed bromination of 5 with N‐bromosuccinimide gave rise to two products, the dimer 24a and the monomer 24b that contained the substituted 2,2‐diaminomalon‐ate side‐chain. The structure of 24b was confirmed by single‐crystal X‐ray diffraction analyses. Reduction of the 5‐nitro group of 17 to the corresponding amino derivative 25, followed by ring‐closure with sodium meth‐oxide/methanol, yielded three products, a 5:6‐fused system 26 and two 5:7 fused systems 27 and 28. The structures of 26 and 27 were confirmed by single‐crystal X‐ray diffraction analyses. A tentative reaction pathway for the formation of all three products has been proposed. Hydrolysis of 27 with aqueous hydrochloric acid resulted in ring‐opening to form 5‐amino‐1‐benzylimidazole‐4‐carboxamide (40). A mechanism for the hydrolysis reaction has been proposed. Catalytic hydrogenation of 5 in acetic acid yielded the aminoimidazo‐lone derivative 11 which upon ring‐closure with sodium methoxide in methanol produced imidazo[4,5‐e][1,4]‐diazepine‐2,5,8‐trione (12).
Regioselective synthesis of 5‐unsubstituted benzyl pyrrole‐2‐carboxylates from benzyl isocyanoacetate
Authors: Ono Noboru , Katayama Hiromi , Nisyiyama Siho , Ogawa Takuji
Published: March 2009

A general synthesis of 5‐unsubstituted benzyl pyrrole‐2‐carboxylates was developed based on the reaction of β‐nitroacetates with benzyl isocyanoacetate. The advantage of this route over other pyrrole syntheses was the regiochemical control of the substitution pattern on the pyrrole ring.
Synthesis and spectral properties of 6H‐2,7,7‐trimethyl‐4‐(o,p‐R‐phenylamino)‐7,8‐dihydrofuro[3,2‐c]azepines
Authors: Cortés Eduardo Cortés , Romero Eduardo Cortés , Taylor Alicia Domínguez
Published: March 2009

The preparation of nine novel 6H‐2,7,7‐trimethyl‐4(o‐,p‐R‐phenylamino)‐7,8‐dihydrofuro[3,2‐c]‐azepines with possible pharmacological activity is described. The structure of all products was corroborated by ir, 1H‐nmr and ms.
Synthesis of benzothiopyrano[4,3,2‐de]quinoline
Authors: Okabayashi Ichizo , Fujiwara Hidetoshi
Published: March 2009

[1]Benzothiopyrano[4,3,2‐de]quinoline (13), a novel tetracyclic compound without substituents on the ring has been synthesized from 1‐amino‐9H‐thioxanthen‐9‐one (4) via 1‐ethoxycarbonylacetamido)‐9H‐thioxanthen‐9‐one (7) in six steps.
Synthesis of novel derivatives of 1H‐imidazo[1,2‐b]pyrazole as potential CNS‐agents
Authors: Vanotti E. , Fiorentini F. , Villa M.
Published: March 2009

As part of a preliminary study on novel 5‐HT3ligands, the synthesis of a series of 1H‐imidazo[1,2‐b]‐pyrazole derivatives is described. The bicyclic heteroaromatic nucleus was functionalized at positions 1, 6 and 7 to give the series of tropanyl derivatives4a‐g, 12a, 12d(Table 1). Different synthetic approaches were utilized to obtain the desired molecules: endo and exo 6‐amides4a, 12aand 6‐ester4brequired two independent schemes due to the opposite behavior of the intermediate imidazolide3towards tropine and tropanamine. The 7‐congeners, ester4c, its tropinium salt4e, the endo and exo amides4dand12dwere prepared from the known common precursor8[1], while derivatives4f‐g, originated by functionalizing position 1, were obtained from 1H‐imidazo[1,2‐b]pyrazole by directN‐acylation. Since the structural features of these molecules seemed to meet the main rules of the S.A.R. studies published so far [2‐5], they were evaluated “in vitro” for 5‐HT3receptor affinity (Table 2). The biochemical data show significant activity for derivatives4a‐e, 4g.These results are encouraging and justify further investigational work on this class of molecules.
Acetylation of a heterocyclic enaminonitrile: Unambiguous structural assignment using NMR methods
Authors: Dell Colin P. , Howe Trevor J. , Prowse Will G.
Published: March 2009

Using a combination of nmr techniques, the structure of the acetylation product of methyl 3‐[2‐amino‐3‐cyano‐9‐methoxy‐4H‐5,6‐dihydronaphtho[1,2‐b]pyran‐4‐yl] benzoate 2b has been shown to be the N‐acetyl derivative 5a, rather than the rearranged 2‐acetoxydihydropyridine 6a.
Chemistry of α‐(benzotriazol‐l‐yl)alkylpyridines. Unusual nucleophilic attack at c‐3a of the benzotriazolyl ring
Authors: Katritzky Alan R. , Yao Guowei , Rachwal Stanislaw
Published: March 2009

Lithiation of 2‐, 3‐ and 4‐[α‐(benzotriazol‐l‐yl)methyl]pyridines with butyllithium followed by reactions with electrophiles (alkyl halides, aldehydes, ethyl benzoate and diphenyl disulfide) gave the corresponding α‐sub‐stituted derivatives in good yields. Repetition of the reaction sequence allowed substitution of the second α‐proton by an electrophile. 2‐[α‐(Benzotriazol‐l‐yl)‐α‐(phenylthio)pentyl]pyridine thus obtained gave an unusual attack of the Grignard reagents at C‐3a of the benzotriazole system on treatment with arylmagnesium bromides.
General preparative synthesis of 2′‐O‐methylpyrimidine ribonucleosides
Authors: Ross B. S. , Springer R. H. , Vasquez G. , Andrews R. S. , Cook P. D. , Acevedo O. L.
Published: March 2009

A convergent and general approach to synthesizing 2′‐O‐Methylpyrimidine ribonucleosides 4a‐e, 6,7 on a multigram scale is described which begins with an improved procedure for making larger quantities of 2‐O‐methyl‐1,3,5‐tri‐O‐benzoyl‐α‐D‐ribose. The sugar was reacted with the desired silylated pyrimidines at room temperature under Vorbrüggen conditions. The crude products contained less than 10% of the α anomers and the desired β anomers were isolated by crystallization. The blocked nucleosides were then deprotected and isolated by standard methods.
The reaction of methyl 3‐amino‐4‐cyano‐5‐methylthiothiophene‐2‐carboxylate with dmad. A new synthesis of polyfunctionalized quinolines
Authors: Tominaga Yoshinori , Luo Jiann‐Kuan , Castle Raymond N.
Published: March 2009

The Reaction of Methyl 3‐Amino‐4‐cyano‐5‐methylthiothiophene‐2‐carboxylate (2), which was prepared by the reaction of bis(methylthio)methylenepropanedinitrile (1) with methyl thioglycolate followed by dimethyl acetylenedicarboxylate (DMAD) in the presence of potassium carbonate in dimethyl sulfoxide gave the polyfunctionalized quinoline, pentamethyl 4‐amino‐5‐mercaptoquinoline‐2,3,6,7,8‐pentacarbox‐ylate (3). The oxidation of 3 with iodine in DMSO provided the novel ring system in the form of the derivative, pentamethyl 2H‐isothiazolo[3,4,5‐de]quinoline‐3,4,6,7,8‐pentacarboxylate (4).
Synthesis of some dibenzodiazepinone derivatives as potent and m2‐selective antimuscarinic compounds
Authors: Cohen Victor I. , Jin Biyun , Gitler Miriam S. , De Cruz Rosanna A. La , Rzeszotarski Waclaw J. , Zeeberg Barry R. , Baumgold Jesse , Reba Richard C.
Published: March 2009

Two series of 5‐[[4‐[4‐(dialkylamino)butyl]‐l‐cyclohexyl]acetyl], and 5‐[(dialkylamino)acyl]‐10,11‐dihydro‐5H‐ dibenzo[b,e][1,4]diazepin‐11‐ones were synthesized as potential m2‐selective ligands1,2.Their affinity and selectivity for the muscarinic cholinergic receptorm‐AChR subtypes were determined. Replacing a nitrogen with CH in the piperidine ring of 5‐[[4‐[4‐(dialkylamino)butyl]‐l‐piperidinyl]acetyl]‐10,11‐dihydro‐5H‐dibenzo‐[b,e][1,4]diazepin‐11‐ones3significantly altered the affinity and selectivity to the muscarinic receptor subtypes.
6,6‐Disubstituted furo[3,4‐c]isoxazoles and 7,7‐disubstituted pyrano‐[3,4‐c]isoxazoles from intramolecular cycloaddition reactions
Authors: Schneider Raphaël , Gérardin Philippe , Loubinoux Bernard
Published: March 2009

The reaction of β‐nitroenones with unsaturated alkoxides anions, followed by intramolecular 1,3‐dipolar cycloaddition, afforded in good yields 6,6‐disubstituted furo[3,4‐c]isoxazoles and 7,7‐disubstituted pyrano[3,4‐c]isoxazoles.
Reissert compound studies. LXVII. The pyrido[3,4‐b]pyrazine reissert compound
Authors: Duarte Frederick F. , Popp Frank D.
Published: March 2009

The pyrido[3,4‐b]pyrazine systems investigated were found to form Reissert compounds in the presence of an acyl halide (or chloroformate) and trimethylsilyl cyanide. Only the mono Reissert compounds were isolated. In the case of 2,3‐diphenylpyrido[3,4‐b]pyrazine (7), its reaction with benzene sulfonyl chloride and trimethylsilyl cyanide gave 5‐cyano‐2,3‐diphenylpyrido[3,4‐b]pyrazine (16). Alkylation of the Reissert compound 11 and analog 12 either directly gave the alkylated hetercyclic base or the alkylated Reissert analog compound.
Saturated heterocycles. Part 209. Synthesis of 1‐cyclohexyl‐substituted isoquinoline derivatives
Authors: Kóbor Jenő , Lázár János , Fölöp Ferenc , Bernáth GÁBor
Published: March 2009

In contrast with earlier literature data [7], both acrylic esters and acrylonitrile underwent Michael addition to l‐methyl‐3,4‐dihydroisoquinolines 1‐4 to yield the diesters 5‐9 or the dinitrile 10, respectively. Compounds 5‐10 were converted by Claisen condensation to 1‐[(3′‐methoxycarbonyl‐ or 1‐[(3′‐ethoxycarbonyl‐4′‐oxo)‐l'‐cyclohexyl]‐3,4‐dihydroisoquinoline derivatives 11‐16. Several derivatives of 12 were prepared. The new compounds possess various pharmacological actions.