A novel pentacyclic pyridine dilactone. 7-methyl[1]benzopyrano[4,3-d][1]benzoxacino[4,3-b]pyridine-6,16-dione

When equimolar quantities of salicylaldehyde 2 and ethyl 3-amino-2-butenoate 3 or its constituents (ethyl 3-oxobutanoate and ammonia) were refluxed on a steam-bath for 6 hours with a trace of acetic acid, two products, a pentacyclic pyridine dilactone 4 and 3-acetyl coumarin 5 , resulted in 15% and 45% yields, respectively. The structure of 4 was elucidated as 7-methyl[1]benzopyrano[4,3-d][1]benzoxacino[4,3-b]-pyridine-6,16-dione on the basis of its spectral data. The mechanism of its formation has been discussed. The reaction has been extended to three more substituted salicylaldehydes.     

Synthesis of [1]benzopyrano[3,4-b] [1,4]oxazines as potential antidepressants

Stereospecific syntheses, from Δ-3-chromene, of cis and trans-4-aminochroman-3-ols, 5 and 8 , and their conversion into cis and trans-1,2,3,4a,5,10b-hexahydro[1]benzopyrano[3,4-b][1,4]-oxazines, 15 and 16 , are described.     

Synthesis of 6,7,8,9-tetrahydro-5H-pyrimido-[4,5-b][1,4]diazepine-6,8-diones

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 ).     

Part 1: Synthesis of Polyfused Heterocyclic Systems Derived From 3-Phenyl-5,6,7,8-tetrahydro[1,2,4]triazolo[3,4- b ][1,3,4]thiadiazepine-6,8-dione

3-Phenyl-5,6,7,8-tetrahydro[1,2,4]triazolo[3,4- b ][1,3,4]thiadiazepine-6,8-dione ( 1 ) was condensed with o -aminothiophenol, 2-amino-ethanol or cystamine to afford compounds 2-4 respectively. Treatment of compound 1 with dimethylthiomethylenemalononitrile yielded the corresponding pyrano[3,2- f ][1,2,4]triazolo[3,4- b ]-[1,3,4]thiadiazepine derivative 5 . 7-[5-Amino-1,3-dithiolan-2-ylidene]-3-phenyl-5,6,7,8-tetrahydro[1,2,4]triazolo[3,4- b ][1,3,4]thiadiazepine-6,8-dione ( 6 ) was obtained by treating compound 1 with CS 2 and chloroacetonitrile. Thiation of compound 1 gave the corresponding thioanalog 7 , which in turn was condensed with malononitrile to give 3-phenyl-5,6,7,8-tetrahydro[1,2,4]triazolo[3,4- b ][1,3,4]thiadiazepine-6-one-8-ylidenemalononitrile ( 8 ). On treating compound 8 with benzaldehyde or p -nitrobenzaldehyde, pyrano[1,2,4]triazolo[1,3,4]thiadiazepin derivatives 9a , b , respectively, were obtained. Compound 8 was treated with CS 2 and methyl iodid to give the corresponding dithiomethylmethylene derivative 10 which was subjected to react with aniline to give pyrido[1,2,4]triazolo[1,3,4]thiadiazepine derivative 11 . Compound 8 was treated with 3-aminopyridine, o -aminothiophenol, or o -phenylenediamene to yield compounds 12 and 13a , b respectively. Finally, tertiary amines or activated phenols were condensed with compound 8 to yield compounds 14 and 15a , b respectively.     

Synthesis of tricyclic 4-chloro-pyrimido[4,5-b][1,4]benzodiazepines

[reaction: see text] A novel methodology was developed for the efficient synthesis of 4-chloro-pyrimido[4,5-b][1,4]benzodiazepines. The key is the intramolecular Friedel-Crafts cyclization of 5-amino-4-(N-substituted)anilino-6-chloropyrimidine with either a carboxylic acid or its derivatives to construct the 4-chloro-pyrimido[4,5-b][1,4]benzodiazepine core. Subsequent nucleophilic substitution allows the introduction of one more diversity point in the target molecules. This strategy provides an efficient method to access a library of compounds based on privileged substructures that are of great interest in drug discovery.     

Synthesis of 5H-[1]benzopyrano[4,3-b]pyridin-5-ones containing an azacannabinoidal structure

Starting from 7-alkoxy-4-aminocoumarins 5,6,8,12 , and 13 as key intermediates, this paper describes two different methods for the preparation of azacannabinoidal 5H[1]benzopyrano[4,3-b]pyridin-5-ones 24–27, 38 , and 39 containing typical structural requirements for ZNS activity. First, Michael addition of 6 and 8 to the double bonds of alkyl vinyl ketones 14 and 15 resulted in a mixture of tetrahydropyridines 24–27 and fused pyridines 20–23 the latter of which were reduced by sodium cyanoborohydride to give the target compounds 24–27 . The second, pyridine ring closure was accomplished by a combination of Vilsmeier acetylation and formylation resulting in fused 4-chloropyridines 31–33 followed by reduction.     

6,6-Heptamethylenetetrahydropyran-2,4-dione in the Synthesis of Benzo[f]pyrano[3,4-b]quinolines and Pyrano[4,3-b][4,7]phenanthrolines

Three-component condensation of 6,6-heptamethylenetetrahydropyran-2,4-dione with 2-amino-naphthalene or 6-aminoquinoline and aromatic aldehydes in an aliphatic alcohol afforded 12-aryl-9,9-hepta-methylene-8,9,10,12-tetrahydro-7H-benzo[f]pyrano[3,4-b]quinolin-11-ones and 12-aryl-9,9-heptamethylene-8,9,10,12-tetrahydro-7H-pyrano[4,3-b][4,7]phenanthrolin-11-ones, new N,O-heterocycles which include azaor diazaphenanthrene system fused to -pyrone ring and aromatic and spiro substituents.     

Convenient Synthesis of [1,2,4]Triazolo[4,3-a][1,3,5]triazin-5-amines, [1,2,4]Triazolo[4,3-c][1,3,5]thiadiazine-5-thiones,and [1,2,4]Triazolo[4,3-c][1,3,5]thiadiazin-5-imines from N-(4H-1,2,4-Triazol-3-yl) Carboximidates

Russian Journal of Organic Chemistry - The condensation of 4H-1,2,4-triazol-3-amine with ortho esters derived from acetic, propionic, and benzoic acids gave the corresponding...     

Synthesis of New Fused Derivatives of 4-(Fur-2-yl)pyrano[4,3-b]pyridines

Russian Journal of General Chemistry - A method for the synthesis of new fused derivatives of 4-(fur-2-yl)pyrano[4,3-b]pyridines was developed by hydrolysis of...     

Solution-phase synthesis of a combinatorial library of 3-[4-(coumarin-3-yl)-1,3-thiazol-2-ylcarbamoyl]propanoic acid amides

The parallel solution-phase synthesis of a new combinatorial library of 3-[4-(R1-coumarin-3-yl)-1,3-thiazol-2-ylcarbamoyl]propanoic acid amides 9 has been developed. The synthesis involves two steps: 1) the synthesis of core building blocks - 3- [4-(coumarin-3-yl)-1,3-thiazol-2-ylcarbamoyl]propanoic acids, 6 - by the reaction of 3-(omega-bromacetyl)coumarins 1 with 3-amino(thioxo)methylcarbamoylpropanoic acid (5); 2) the synthesis of the corresponding 3-[4-(coumarin-3-yl)-1,3-thiazol-2-yl- carbamoyl]propanoic acids amides 9 using 1,1'-carbonyldimidazole as a coupling reagent. The advantages of the method compared to existing ones are discussed.     

Synthesis and study of some properties of 1-aryl-2-oxo-1,2,3,6-tetrahydro[1,4]diazepino[6,5-b]indole 4-oxides

A number of 1-aryl-2-oxo-1,2,3,6-tetrahydro[1,4]diazepino[6,5-b]indole 4-oxides were synthesized based on 3-[N-aryl-N-(chloroacetyl)amino]-2-formylindoles. The nature of the substituent in the 1-aryl fragment has a pronounced influence on the course of reactions throughout the whole sequence of transformations during the synthesis of diazepinoindoles. The reduction of 4-oxides by formamidinosulfinic acid, hydrogen in the presence of Pd/C, and sodium bisulfite was studied. The structures of the reaction products were confirmed using IR and ¹H NMR spectroscopy and mass spectrometry.