Synthesis of 4-aryl-2,6,6-trimethyl-5-oxo-5,6-dihydro-4H-thieno[3,2-b]pyrroles

The method for the synthesis of 4-aryl-2,6,6-trimethyl-5-oxo-5,6-dihydro-4H-thieno[3,2-b]pyrroles from accessible 4-aminothiophene derivatives was developed.     

6H-indolo [3,2-b] naphthyridines.aza-analogues of ellipticine

The Friedlander quinoline synthesis is applied to prepare new potential DNA - intercalative compounds : The 6H-indolo [3,2-b] naphthyridines.     

Unexpected formation of a 11H-pyrido[2,1-b]quinazolin-11-one derivative from 5,11-dihydro-6H-pyrido[2,3-b]-1,4-benzodiazepin-6-one

The unexpected formation of 11H-pyrido[2,1-b]quinazolin-11-one derivative 6 from 5,11-dihydro-6H-pyrido[2,3-b]-1,4-benzodiazepin-6-one (2) has been observed. Its structure 6 was determined by X-ray crystallography. Detailed nmr study provided a complete set of proton and carbon-13 nmr parameters of compound 6 in solution.     

Novel synthesis of 5,11-dihydro-6H-pyrido[2,3-b]-[1,4]benzodiazepin-6-ones and related studies

5,11-Dihydro-6H-pyrido[2,3-6][1,4]benzodiazepin-6-one (1), a basic intermediate in the preparation of 11-α-aminoacetyl derivatives with important biological activities, has been obtained by a three-step synthesis starting from easily available isatoic anhydride and anhydro ornithine. Some model cyclisation reactions leading to 5-member ring derivatives 10 and 12 instead of 7-member ring analogues of 1 , are reported. Easy transformations of the tetrahydro congener of 1 , i.e., compound 4 into 19 , which actually represents a tetrahedral intermediate in the transformation of 5 into 4 , is noticed. Further rearrangement of 19 into spiro compound 20 , and return of the latter into 5 is described.     

Synthesis of 5-hydroxymethyl-11-methyl-6H-pyrido[4,3-b]carbazole and 5-formyl-11-methyl-6H-pyrido[4,3-b]carbazole (17-oxoellipticine)

A synthesis of 5-hydroxymethy1-ll-methy1-6H-pyrido[4,3-b]carbazole and the corresponding 5-formyl derivative, 17-oxoe66ipticine,³ is described, the key feature of which is the use of the Krohnke¹ aldehyde synthesis to effect the debenzylation of a p-nitrobenzyl-pyridinium salt under mild conditions.     

A convenient synthesis of 3,4-dihydro-2-methyl-3-oxo-2H-1,4-benzoxazine-2-carboxylic acids and 3,4-dihydro-2-methyl-3-oxo-2H-pyrido[3,2-b]-1, 4-oxazine-2-carboxylic acid

A convenient one pot synthesis of ethyl 3,4-dihydro-2-methyl-3-oxo-2H-1,4-benzoxazine-2-carboxylates and 3,4-dihydro-2-methyl-3-oxo-2H-pyrido[3,2-b]-1,4-oxazine-2-carboxylates and their conversion into the respective carboxylic acids are described.     

New synthesis of 11-acyl-5,11-dihydro-6H-pyrido[2,3-b][1,4]-benzodiazepin-6-ones and related studies

New synthesis of 11-acyl-5,11-dihydro-6H-pyrido[2,3-b][1,4]benzodiazepin-6-ones ( 42-44 ) is reported. The crucial steps (Scheme VI) represented N-oxydation of 1 ( 1A ) to 35 ( 35A ), facilitated ring-closure of 36 into 37 , its subsequent N-α-chloroacetylation to 38 , aminolysis to 39-41 (involving N-O anchimeric assistance as depicted in 38A ) and deoxygenation to 42-44 (Scheme VII). The central intermediate 37 is also obtained on oxygenation of 2 , a new synthesis of which was reported in the previous paper of this series [3]. Other attempts of cyclisation “from the top” or “from the bottom” (Scheme I) are described. Thus, interaction of 1 with acetamide afforded 3 and 4 instead of the expected 2A . Compound 5 cyclised into 3-pyridoquinazolone 6 while its 2-(4′-methylpiperazin-1′-yl analogue 9 was observed to be unstable for the attempted ring-opening and reclosure to 42 . “From the bottom” cyclisations of 10A-10C , via intermediary amines 11A-11C failed and pyridoquinazolinone 13 was isolated (Scheme V). The attempted oxidative cyclisation of the compounds 15 and 18 into 2 and 42 , respectively, 13 afforded imidazolo[5,4-b]pyridine derivative (18–19), while 15 remained unchanged. 3-Acylamino-2-arylaminopyridines ( 21-24 ), cyclised into imidazolopyridines 29-30 . Model compounds 45-50 were prepared to study selective aminolysis of the chlorine atoms in 2-chloro-3-(2′-chlorobenzoyl)aminopyridine 1 , and its N-oxide 35 .     

Synthesis of 6-oxo-6,7,8,9-tetrahydro-10H-pyrimido-[5,4-b][1,4]benzoxazines and 6-oxo-6,7,8,9-tetrahydropyrimido[4,5-b][1,4]benzodioxanes

Reaction of 5-hydroxy-6-aminopyrimidines with 2-bromohydroresorcinol and bromodimedone in DMF in the presence of sodium hydride gave 6,7,8,9-tetrahydro-10H-pyrimido[5,4-b][1,4]benzoxazines. When 4-chloro-5-hydroxy-6-aminopyrimidine was treated with bromodimedone the principal products were 6,7,8,9-tetrahydropyrimido[4,5-b][1,4]benzodioxanes. The nucleophilic substitution of the chlorine atom in position 4 of the tetrahydropyrimidobenzoxazines by amines, sodium alkanoates, and thiourea has been studied and the corresponding amines and alkoxy- and thio derivatives of this tricyclic system obtained. Center for the Chemistry of Medicinal Substances, All Russian Chemico-Pharmaceutical Science Research Institute, Moscow 119815. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 10, pp. 1411–1417, October, 1998.     

Reactions of 4,4,9-trimethyl-4,9-dihydro-4-silanaphtho[3,2-b]thiophen-9-one with nucleophilic and electrophilic reagents

We have studied the reaction of 4,4,9-trimethyl-4,9-dihydro-4-silanaphtho[3,2-b]-thiophen-9-one with organometallic compounds, lithium aluminum hydride, sodium borohydride, aniline, and acetyl nitrate. We have obtained secondary and tertiary dihydrosilanaphtho[3,2-b]thiophen-9-ols and 9-phenyliminodihydrosilanaphtho[3,2-b]thiophene. We have established that nitration of dihydrosilanaphthothiophen-9-one occurs at the position of the thiophene moiety.Russian University of International Friendship, Moscow 117923. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 5, pp. 621–625, May, 1998.     

Synthesis of 1,4-dihydro-4-oxopyrrolo[1,2-b]pyridazine-3-carboxylic acids and 1,4-dihydro-4-oxoimidazo[1,5-b]pyridazine-3-carboxylic acids as potential antibacterial agents

To check the antibacterial potential of two families of aza analogues of the quinolones, 1,4-dihydro-4-oxopyrrolo[1,2-b]pyridazine-3-carboxylic acids and 1,4-dihydro-4-oxoimidazo[1,5-b]pyridazine-3-carboxylic acids, we have prepared a few derivatives in theses families using N-aminopyrrole and N-aminoimidazole derivatives as starting building blocks and the classical pathways of the quinolone series. The compounds showed no interesting antibacterial activity.     

Unambiguously confirmed structure of 2-phenacylidene-1,2-dihydro-4H-pyrido[2,3-b]pyrazin-3-one and 3-phenacylidene-3,4-dihydro-1H-pyrido[2,3-b]pyrazin-2-one

To determine the structures of two isomeric products, 2-phenacylidene-1,2-dihydro-4H-pyrido[2,3-b]pyrazin-3-one (2) and 3-phenacylidene-3,4-dihydro-1H-pyrido[2,3-b]pyrazin-2-one (3) obtained by condensation of 2,3-diaminopyridine (1) with ethyl benzoylpyruvate [1–3], these compounds were hydrolyzed to give 2-methyl-4H-pyrido[2,3-b]pyrazin-3-one (4) and 3-methyl-1H-pyrido[2,3-b]pyrazin-2-one (5) , respectively [4,5]. Both hydrolysates 4 and 5 were hydrogenated to afford 2-methyl-1,2-dihydro-4H-pyrido[2,3-b]pyrazin-3-one (6) and 3-methyl-3,4-dihydro-1H-pyrido[2,3-b]pyrazin-2-one (7) . The latter compound was identical with an unequivocally synthesized compound providing proof for the structures of all these compounds.     

Synthesis, characterization, and application of indolo[3,2-b]carbazole semiconductors

The synthesis, characterization, and field-effect transistor (FET) properties of new indolo[3,2-b]carbazoles are described. In particular, an extensive characterization of their crystal structures has revealed the importance of the nature of the side chains (alkyl, phenyl, thienyl substituents) on their solid-state organization. These organic materials have exhibited p-type FET behavior with hole mobilities as high as 0.2 cm2 V(-1) s(-1) with an on/off current ratio higher than 10(6). Best results were obtained with phenyl-substituted indolo[3,2-b]carbazoles since the presence of phenyl substituents seems to allow efficient overlap between the oligomeric molecules. More importantly, FET properties were kept constant during several months in air.     

Facile rearrangement of 2-amino-3-carbethoxy-4-ethylfuro[3,2-b]pyridinium cation to 2-oxo-3-cyano-4-ethyl-4H-furo[3,2-b]pyridine

The rearrangement of 2-amino-3-carbethoxy-4-ethylfuro[3,2-b]pyridinium iodide in basic solution was studied. The reaction product is 2-oxo-3-cyano-4-ethyl-4H-furo[3,2-b]pyridine which was obtained also by alkylation with ethyl iodide and sodium hydride in dimethylformamide of 2-oxo-3-cyano-3H-furo[3,2-b]-pyridine or of p-nitrophenyl-3-acetoxypyridine-2-cyanacetate.     

Nitrogen-, oxygen-, and sulfur-containing heterocycles. 43. Synthesis and properties of 6-oxo-5H-pyrido[2,3-b][1,4]thiazines

It has previously been observed that the carbamide residue in 2-phenacyl-3-ureido- and 2-cyanomethylpyridine is readily cleaved on cyclization to pyridothiazines [1–4]. It was of interest to establish whether a similar process occurs when the carbonyl component is an -halo- or unsaturated acid. If this were the case, this reaction could be used to obtain 6-oxopyrido[2,3-b][1,4]thiazines.For communication 42, see [6].Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 2, pp. 214–218, February, 1985.     

The synthesis of 5,10-dihydro- and 2,3,5,10-tetrahydrothiazolo-[3,2-b] [2,4]benzodiazepines, 1,2,3,4,7,12-hexahydrobenzothiazolo-[3,2-b] [2,4] benzodiazepine,and 9,14-dihydro-6H-[1]benzothiopyrano-[4′,3′:4,5]thiazolo[3,2-b] [2,4] benzodiazepine via 1,2,4,5-Tetrahydro-3H-2,4-benzodiazepine-3-thione

Catalytic reductive scission of phthalazine (II) utilizing a two-stage palladium-Raney nickel procedure afforded o-xylene-α,α′-diamine (III) in 97% yield. Treatment of III with carbon disulfide gave [o-(aminomethyl)benzyl]dithiocarbamic acid (IV), which upon thermal cyclization furnished 1,2,4,5-tetrahydro-3H-2,4-benzodiazepine-3-thione (V). Reaction of V with 1,2-dibromoethane, chloro-2-propanone, ethyl 2-chloroacetoacetate, ethyl chloroacetate, and ethyl 2-bromohexanoate gave 2,3,5,10-tetrahydrothiazolo[3,2-b][2,4]benzodiazepine (VII) and substituted 5,10-dihydrothiazolo[3,2-b][2,4]benzodiazepines (Villa and b, IX, and X), respectively. Condensation of V with 2-chlorocyclohexanone and 3-bromothiochroman-4-one afforded 1,2,3,4,7,12-hexahydrobenzothiazolo[3,2-b][2,4]benzodiazepine (XII) and 9,14-dihydro-6H-[1]benzothiopyrano[4′,3′:4,5]thiazolo[3,2-b][2,4]benzodiazepine(XIll). None of the compounds possessed appreciable biological activity.     

Attempts at new synthesis of 5,11 -Dihydro-6H-pyrido[2,3-b][1,4]benzodiazepin-6-one

Attempting some new approaches to 5,11-dihyro-6H-pyrido[2,3-b][1,4]benzodiazepin-6-one ( 6 ), compounds 8, 10 and 11 were prepared. Ring enlargement of 4 into 6 failed, as well as condensation of 10 and 11 into ID, which is the potential precursor of pirenzepin (11-[2′-(4″-methylpiperazin-1″-yl)]acetyl derivative of 6 ) via an envisaged intramolecular Diels-Alder reaction. Model compounds 5 and 13 were prepared and their behaviour in analogous reactions explained the failures of the intended transformations of 4 , as well as of condensation of 10 and 11 .