NEW HETEROCYCLIC SYSTEM SYNTHESIS IV.4a, 5,6, 12-TETRAHYDRO-1H-1,3-OXAZ1NO [3,2-d][1,5]-BENZOTHIAZEPINE-1-ONE

Addition of a-carbonylketenes, generated from 2-diazo-1, 3-diaryl-1, 3-propandione or 2-diazo-1-phenyl-1,3-butandione by heating, to 2,4-diaryl-2,3-dihydro-[1,5]-benzothiazepines gave 2,3-disubstituted-4a, 6-diaryl-4a,5,6,12-telrahydro-1H-1, 3-oxazino[3,2d][1,5]-benzothiazepine-l-ones, a new ring system.     

NEW HETEROCYCLIC SYSTEM SYNTHESIS H THE REACTION OF 2,3-DIHYDRO-1,5-BENZOTHIAZEPINES WITH DICHLOROCARBENE

The reaction of two series of 2,3-dihydro-1,5-henzothiazepines Ⅰ with dichloro-carbene,gave azirino[2,1-d][1,5]benzothiazepines Ⅷ,azirino[2,1-e][1,6]benzothiazocines Ⅸ,pyrrolo[2,1-b][1,3]benzothiazoles Ⅹ,substituted-cyclopropanes Ⅺ and 2H-1,4-benzothiazin-2-onesⅫ.The structures of these products were confirmed by the analytical and spectral data.CompoundⅧ and Ⅸ are two new ring systems.     

Cycloaddition of benzoheteroazepine II Reactions and conformations of cycloadducts on1,5-benzothiazepines and 1,5-benzodiazepines with nitrile imine and nitrile oxides

Benzodiazepine and benzothiazepine derivatives have been well known as therapeutically important compounds. Four new tricyclic heterocyclic compounds, 3a,4,5,11-tetrahydro-3H-1,2,4-triazolo[4,3-d] [1, 5]benzothiazepines (3), 3a,4,5,11-tetrahydro-3H,6H-1,2,4-triazolo[4,3-d][1,5]benzodiazepine (4), 3a, 4,5,11-tetrahydro-1,2,4-oxadiazolo[4,5-d] [1,5]benzothiazepines (5, 6) and 3a,4,5,11-tetrahydro-6H-1, 2,4-oxadiazolo[4, 5-d] [ 1, 5 ] benzodiazepines (7,8), have been synthesized by 1,3-dipolar cycloaddition reactions of 2, 3-dihydro-1, 5-benzothiazepines and 2, 3-dihydro-1H-1, 5-benzodiazepine with benzonitrile N-phenylimine and benzonitrile oxides, respectively. The conformations of some cycloadducts and cycloaddition mechanism are described.     

Differentiation of Constitutional Isomer of 2,2a,3,4-Tetrahydro- 4-methyl-2a-phenyl-2- （thiophen-2-yl）- 1H-azeto [-2,1-d] [- 1,51benzothiazepin-1-one-5-oxide and Fragmentations of 2,3-Dihydro-2,4-diphenyl-1,5-benzothiazepine-l-oxide／- 1,1-d

Mass spectrometric behaviour of 2,2a, 3,4-tetrahydro-4-methyl-2a-phenyl-2- (thiophen-2-yl)- 1H-azeto [-2,1-d-J1-1,5-]benzothiazepin-l-one-5-oxide and 2,3-dihydro-2,4-diphenyl-1,5-benzothiazepine-l-oxide/-1,1-dioxide have been studied with the aid of mass-analyzed ion kinetic energy spectrometry and accurate mass measurements under electron impact ionization. The monooxide derivatives showed a tendency to eliminate an alkene or an oxygen atom. 1H-Azeto[-2,1-d][1,5]benzothiazepin-1-one-5-oxide could also eliminate the thiophen- 2-ylketene molecule via a reverse [-2 q- 2 ~ cycloaddition. 2,3-Dihydro-2,4-diphenyl- 1,5-benzothiazepine-1-oxide/-1, 1-dioxide could eliminate SO2 or SO, respectively. The structure of 2,2a, 3, 4-tetrahydro-4-methyl-2a-phenyl-2- (thiophen-2-yl)-1H-azeto 1-2,1-d-] [1,5 -] benzothiazepin-1-one-5-oxide was identified on the basis of its fragmentation. The identification was supported by the fragmentations of model compound, 2,3-dihydro-2,4-diphenyl-1,5-benzothiazepine-1-oxide/-1,1-dioxide.     

Synthesis of Fluoroalkylated Heterocycles via the Reaction of 3-（1-Hydropolyfluoroalkenyl）-l-oxo-2,4,1-benzoxazines with Dinucleophilic Reagents

The reaction of 3-（1-hydropolyfluoroalkenyl）-1-oxo-2,4,1-benzoxazines 1 with some dinucleophiles was investigated. 7-Fluoroalkyl-2,3-dihydro- 1,4-diazepine[ 1,2-d]quinazolin- 11-ones 2, 2-fluoroalkylisoxazolo[3,2-b]quinazolin-9-ones 3 and 2-fluoroalkylbenzoimidazoles 4 were obtained from the reaction of 1 with 1,2-diaminoethane, hydroxylamine hydrochloride and 1,2-diaminobenzene respectively.     

7-Deazapurines:Synthesis of new pyrrolo[2,3d]pyrimidin-4-onescatalyzed by a Brφnsted-acidic ionic liquid as a green and reusable catalyst

<正>Some new 2-aryl-3,7-dihydro-4H-pyrrolo[2,3-d]pyrimidin-4-ones have been prepared through cyclocondensation of 2-amino 1H-pyrrole-3-carboxamides with aromatic aldehydes followed by air oxidation in the presence of 3-methyl-1-(4-sulfonic acid)butylimidazolium hydrogen sulfate[(CH_2)_4SO_3HMIM][HSO_4],a Br(?)nsted-acidic ionic liquid,as a green and reusable catalyst in solvent-free conditions.     

Synthesis of 3,7—Disubstituted 1,4—Benzodiazepin—2—one

A series of 3-methoxycarbonylpropoxy-7-(imidazol-4-ylpropinamide)-1,3-dihydrogen-1-methyl-5-phenyl-2H-1,4-benzodiazepin-2-ones,as farnesyltransferase(Ftase) inhibitors,were synthesized. The preparation of the key intermediate,7-amino-3-methoxycabonylpropoxy-1-methyl-5-phenyl-2H-1,4-benzodiazepin-2-one,was improved.     

Synthesis of novel benzo[b]pyrimido[4',5':5,4]thieno[2,3-e][1,6]naphthyridine-8-ones via Pictet–Spengler cyclization

An efficient method for the synthesis of novel benzo[b]pyrimido[4',5':5,4]thieno[2,3e]-[1,6]naphthyridine-8-one derivatives via Pictet–Spengler cyclization is reported. The reaction of 4-(3-aminopyrimido[4,5-d]thieno-2-yl)quinoline-2-ones, which could be obtained from Thorpe–Ziegler isomerization of 4-bromomethylquinoline-2-ones and 5-cyano-1,6-dihydro-4-methyl-2-phenyl-6-thioxopyrimidine,with aromatic aldehydes in the presence of BF_3·OEt_2 gives pyrimidothieno[1,6]naphthyridines in good yields.     

Mass Spectrometry of 2a, 4-Disubstituted 5-Benzoyl-2a, 3,4,5-tetrahydro-2-phenoxy-azeto [ 1,2-a ] [1,5 ] benzodiazepin - 1 （2H）-ones Under Electron Impact Ionization Conditions

The mass spectrometric fragmentation of 2a, 4-disubstituted 5-benzoyl-2a, 3,4, 5-tetrahydro-2-phenoxy-azeto[1,2-α] [ 1,5 ] benzodiazepin-I (2H)-ones has been investigated by means of mass-analyzed ion kinetic energy spectrometry under electron impact ionization conditions. All compounds tend to lose different moieties, such as phenoxy, phenoxy and H, and phenoxyketene. Both [ M^ - PhO ] and [ M^ - PhOH ] ions could further lose CO, and the [ M^ - PhOCH = C = O] ions could lose propene or styrene, PhCON, PhCOHN, and other fragments.     

A Selective Synthesis of 2-Alkylamino-5, 6, 7, 8-tetrahydrobenzothieno[2, 3-d]pyrimidin-4（3H）-ones

2-Alkylamino-5, 6, 7, 8-tetrahydrobenzothieno [2,3-d] pyrimidin-4(3H)-ones 7 were synthesized by a new selective synthetic method, which includes aza-Wittig reaction of iminophosphorane 4 with aromatic isocynate to give carbodiimide 5 and subsequent reaction of 5 with various aliphatic primary amine in the presence of EtO^-Na^ .     

Differentiation of Constitutional Isomer of 2,2a,3,4-Tetrahydro- 4-methyl-2a-phenyl-2-(thiophen-2-yl)-1H-azeto[2,1-d][1,5] benzothiazepin-1-one-5-oxide and Fragmentations of 2,3-Dihydro- 2,4-diphenyl-1,5-benzothiazepine-1-oxide/-1,1-dioxide

Introduction Mostimportantantibioticspossessarepresen- tativestructureofaβ-lactamfusedfive-orsix- memberedheterocyclicringcontainingnitrogenand sulfuratoms.Forinstance,theeffectiveantibi- otics,penicillin,penamandpenem,havefusedthi- azolidine-β-lactam,andtheeffectiveantibiotics, cephalosporinandcephem,arefuseddihydroth- iazine-β-lactams[1].Recently,someβ-lactam derivativeshavealsobeenrecognizedasthein- hibitorsofhumanleukocytaseelastase[2]andserine protease[3].Thesynthesisofbicyclicβ-lact…     

Mass Spectrometric Fragmentation of 2a,4-Disubstituted 2,2a,3,4-Tetrahydro-2-phenyl-1H-azeto[2,1-d]- [1,5]benzothiazepin-1-ones Under Electron Impact Ionization Conditions and Comparison with their 2-Heteroatom Substituted Analogues

The mass spectrometric behavior of seven 2a,4-disubstituted 2,2a,3,4-tetrahydro-2-phenyl-1H-azeto[2,1-d][1,5]benzothiazepin-1-ones has been studied with the aid of mass-analyzed ion kinetic energy spectrometry and accurate mass measurements under electron impact ionization. All compounds show a tendency to eliminate a phenylketene molecule, an ethyl or benzyl radical, or a phenylketene molecule plus an SH radical. The mass spectrometric behavior of the title compounds was compared to those of 2-heteroatom-substituted analogues.     

Unexpected Direction of Iodocyclization of 3-Allylthio-5-phenyl-4H-1,2,4-triazole

The reaction of 3-allylthio-5-phenyl-4H-1,2,4-triazole with iodine to give a mixture of 5,6-dihydro-5-iodomethyl-3-phenyl[1,3]thiazolo[2,3-c][1,2,4]triazole, 6,7-dihydro-6-iodo-3-phenyl-5H-[1,2,4]triazolo[3,4-b][1,3]thiazine, 5,6-dihydro-6-iodomethyl-2-phenyl[1,3]thiazolo[3,2-b][1,2,4]triazole, and 6,7-dihydro-6-iodo-2-phenyl-5H-[1,2,4]triazolo[5,1-b][1,3]thiazine has been studied. The structure of the products obtained was established using ¹H NMR spectroscopy of their dehydriodination products.     

Synthesis of 3-Substituted Pyrido[4′,3′:4,5]thieno[2,3-d]pyrimidines and Related Fused Thiazolo Derivatives

New ethyl 3-(substituted)-4-oxo-2-thioxo-1,2,3,4,5,6,7,8-octahydropyrido[4',3':4,5]thieno-[2,3-d]pyrimidine-7-carboxylates ( 3a , b ), ( 6 ),( 11-13 ), ethyl 3-methyl-5-oxo-2,3,6,9-tetrahydro 5 H -pyrido[4',3':4,5]thieno[2,3-d][1,3]thiazolo[3,2-a]pyrimidine-8(7H)-carboxylate ( 4 ), and ethyl 2-methyl-5-oxo-2,3,6,9-tetrahydro-5 H -pyrido[4',3':4,5]thieno[2,3-d][1,3]thiazolo[3,2-a]-pyrimidine-8(7H)-carboxylate ( 8 ) have been synthesized from diethyl 2-isothiocyanato-4,5,6,7-tetrahydrothieno[2,3-c]pyridine-3,6-dicarboxylate 1. The structure of these compounds as well as their intermediates have been established by their spectral data.     

A NOVEL SYNTHESIS OF 2-SUBSTITUTED-4H-THIENO [2,3-d][1,3] OXAZIN-4-ONE AND 2,3-DISUBSTITUTED THIENO [2,3-d]PYRIMIDIN-4(3H)-ONE DERIVATIVES

Abstract

The synthesis of acetic 2-{[1-methyl-2-(4-oxo-5,6,7,8-tetrahydro-4H-benzo [4,5]-thieno [2,3-d] [1,3-oxazin-2-yl)ethylidene]amino}-4,5,6,7-tetrahydrohenzo[b]thiophene ?3-carboxylic acid anhydride 5 and 2-(oxopropyl)-5,6,7,8-tetrahydro-4H-benzo-[4,5] thieno[2,3-d][1,3]oxazin-4-one 7, has been achieved in three steps from ethyl 2-amino-4,5,6,7-tetrahydrobenzo(b]thiophene-3-carboxlate 1 via the reaction with ethyl acetoacetate followed by hydrolysis and acetic anhydride-induced cyclization. The 2-substituent in compound 5 has two functional groups i.e. active methylene and acid anhydride which are suitably located for intramolecular transformation. Thermal and/or base catalyzed intramolecular cyclization of 5 afforded 2-(4-acetoxy-(hydroxyl)-2-methyl-5,6,7,8-tetrahydrobenzo[4,5] thieno[2,3-b]pyridin-3-yl)-5,6,7,8- tetrahydro-4H-benzo[4,5]thieno[2,3-d] [1,3]oxazin-4-one 10 and 9 respectively. Treatment of 5 with hydrazine hydrate, aromatic and/or heterocyclic amines induced the same intramolecular cyclization with a concomitant oxazine-pyrimidine interconversion to give 3-amino(aryl or heteryl)-2-(4-hydroxy-5,6,7,8-tetrdhydrobenzo-[4,5]thieno[2,3-b]pyridin-3-yl)-3,4,5,6,7,8-hexahydrobenzo[4,5] thieno[2,3-d] pyrimid in-4-one 11–14 respectively.     

Reaction of 2-Aryl-5-R-5,6-dihydro-7H-[1,2,4]-triazolo[5,1-<Emphasis Type="Italic">b</Emphasis>][1,3]thiazin-7-ones with Aryl Bromomethyl Ketones and Benzyl Bromide

The products of the reaction of 2-aryl-5-R-5,6-dihydro-7H-[1,2,4]triazolo[5,1-b][1,3]thiazin-7-ones with aryl bromomethyl ketones are 2-aryl-7H-[1,2,4]triazolo[5,1-b][1,3]thiazin-7-ones and aryl methyl ketones or 2,5-diaryl[1,3]thiazolo[3,2-b][1,2,4]triazoles and 3-phenyl-2-propenoic acid, depending on the structure of R. The reaction of 2-aryl-5-R-5,6-dihydro-7H-[1,2,4]triazolo[5,1-b][1,3]thiazin-7-ones with benzyl bromide yields 5-aryl-3-benzylthio-4H-1,2,4-triazoles and 3-aryl-2-propenoyl bromide. __________ Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 6, pp. 905–909, June, 2005.     

Aminolysis of 2-Aryl-5-R-5,6-dihydro-7H-[1,2,4]triazolo[5,1-<Emphasis Type="Italic">b</Emphasis>]1,3]thiazin-7-ones

We have established that the products of aminolysis of 2-aryl-5-R-5,6-dihydro-7H-[1,2,4]triazolo-[5,1-b][1,3]thiazin-7-ones in boiling ethanol are 3-R-3-(5-aryl-4H-1,2,4-triazol-3-ylsulfanyl)-propanamides, and at 180°C–210°C (depending on the structure of the substituent R): 3-phenyl-4,5-dihydro-1H-1,2,4-triazoline-5-thione and 3-arylacrylamides or 3-(3-aryl-5-thioxo-4,5-dihydro-1H-1,2,4-triazol-1-yl)propanamides. __________ Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 10, pp. 1587–1592, October, 2005.     

Electron impact mass spectral fragmentation of 2a,4-disubstituted 2-chloro/2,2-dichloro-2,2a,3,4-tetrahydro-1H-azeto[2,1-d][1,5]benzothia zepin-1-ones

The mass spectrometric behaviour of nine 2a,4-disubstituted 2-chloro/2,2-dichloro-2,2a,3,4-tetrahydro-1H-azeto[2,1-d][1,5]b enzothiazepin-1-ones has been studied with the aid of mass-analysed ion kinetic energy spectrometry and accurate mass measurements under electron impact ionization. All compounds show a tendency to eliminate a neutral chlorine atom, or a chloroketene, or neutral propene, or styrene or substituted styrene molecule, plus Cl and/or H (or Cl) atom(s), to yield [M-Cl]+ ions, 2,3-dihydro-1,5-benzothiazepine derivative ions, 4,5-dihydro-5H-1,5-benzothiazepin-4-one ions which can further lose CO to give 1,4-benzothiazine ions. Both molecular ions and [M-Cl]+ ions show a tendency to eliminate an ethyl or benzyl/substituted benzyl radical to produce 2,2a-dihydro-1H-azeto[2,1-c][1,4]benzothiazin-1-one ions. The [M-Cl]+ ions could undergo rearrangement to yield 2,2a-dihydro-1H-azeto[2,1-d][1,5]benzothiazepin-1-one ions, 2,2a,3,4-tetrahydro-1H-azeto[1,2-a]quinoline ions or 1,1a,2,3-tetrahydro-azirino[2,1-d][1,5]benzothiazepine ions by loss of an ethane or a benzene/substituted benzene, a SH radical or a CO molecule. The molecular ions could also undergo rearrangement reactions to form other small fragment ions.