On the Synthesis of Pyrrolobenzo[<Emphasis Type="Italic">b</Emphasis>]thieno[1,4]diazepines

Summary. 2-Amino-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carbonitrile was converted into the corresponding 2-(pyrrol-1-yl) derivative, followed by reduction of the latter compound into the corresponding amine. This amine and its acyl, aroyl, and arylidene derivatives were used as synthons in the synthesis of several title compounds.     

Reactions of 1-Substituted Benzo[4,5]imidazo[1,2-a]pyridines

Bromination of 1-oxo(imino, amino)benzo[4,5]imidazo[1,2-a]pyridines gave the corresponding 2-bromo derivatives. Acylation using the Vilsmeier complex in acetic anhydride gave the N-formyl and N-acetyl derivatives. The reaction of the amine with the Vilsmeier complex, acetyl acetone, ethyl acetoacetate, and 2,5-dimethoxytetrahydrofuran occurs at the amino group.     

2-Chloro-3-quinolinecarboxaldehyde in the Synthesis of Condensed Quinoline Systems. 1. Synthesis of Derivatives of 3,4-Dihydro-2H-[1,3]thiazino[6,5-b]quinolines

A method for the synthesis of derivatives of previously unknown heterocyclic systems - 3,4-dihydro-2H-[1,3]thiazino[6,5-b]quinolines - has been developed based on 7,8-dimethyl-2-chloro-3-quinolinecarboxaldehyde via the consecutive steps of conversion into its Schiff's base with a primary amine, reduction to the corresponding aminomethyl derivative, conversion to the thiourea with isothiocyanates, and heterocyclization by intramolecular substitution of the chlorine atom.     

Synthesis of nitrogen-containing heterocycles. 5. A new route to 5-amino-[1,2,4]triazolo[1,5-a][1,3,5]triazine derivatives

Treatment of certain diaminomethylenehydrazones 1 of aromatic carbonyl compounds with ethyl N-cyanoimidate ( 2 ) in acetonitrile in the presence of a tertiary amine at room temperature gives the corresponding amino(N-cyanoiminomethyl)aminomethylenehydrazones 3 in high yields. The intermediate 3 can readily be cyclized to the corresponding 5-amino-2,3-dihydro[1,2,4]triazolo[1,5-a][1,3,5]triazines 4 in moderate to good yields by brief heating in acetonitrile. When the reaction of diaminomethylenehydrazones 1 with ethyl N-cyanoimidate ( 2 ) is performed at reflux temperature in the presence of a tertiary amine, 5-amino-2,3-dihydro[1,2,4]triazolo[1,5-a]1,3,5]triazines 4 can be directly obtained in moderate yields. The yields of triazolotriazine produced by the one-step synthesis are generally comparable or even higher than the overall yields from the two-step procedure.     

Synthesis of Pyrido[2′,3′: 3,4]pyrazolo[1,5‐a]pyrimidine,Pyrido[2′,3′:3,4]pyrazolo[5,1‐c][1,2,4]triazine,and Pyrazolyl Oxadiazolylthieno[2,3‐b]pyridine Derivatives

6‐(2‐Thienyl)‐4‐(trifluoromethyl)‐1H‐pyrazolo[3,4‐b]pyridine‐3‐amine reacted with different active methylene compounds to afford pyridopyrazolopyrimidine derivatives. On the other hand, it reacted with some halo compounds to give the imidazo[1′,2′:1,5]pyrazolo[3,4‐b]pyridine derivatives. Also, it diazotized to give the corresponding diazonium chloride that is coupled with several active methylene compounds to give the corresponding triazine derivatives. Furthermore, compound 3‐amino‐6‐(2(thienyl)‐4‐(trifluoromethyl)thieno[2,3‐b]pyridine‐2‐carbohydrazide reacted with some β‐dicarbonyl compounds and some sulfur‐containing compounds to afford the corresponding pyrazolyl oxadiazolylthieno[2,3‐b]pyridine derivatives.     

New heterocyclic systems based on 1-hydrazino-5,6,7,8-tetrahydro[2,7]naphthyridine: 7,8,9,10-tetra-hydro[1,2,4]triazolo[3,4-a]- and 7,8,9,10-tetra-hydro[1,2,4]triazolo[5,1-a][2,7]naphthyridines

Methods have been developed for the synthesis of new substituted 7,8,9,10-tetrahydro[1,2,4]triazolo-[3,4-a][2,7]naphthyridines from 3-chloro-1-hydrazino-7-methyl-5,6,7,8-tetrahydro-[2,7]naphthyridine-4-carbonitrile. It was shown that on heating in an amine (ethanolamine, pyrrolidine, 2-hydroxy-propylamine), they undergo a Dimroth rearrangement at the triazole fragment, being converted into 7,8,9,10-tetrahydro[1,2,4]triazolo[5,1-a][2,7]naphthyridine derivatives.     

Benzomorphan related compounds. XIII. Syntheses of 2,6-methanopyrrolo[1,2-d] [1,4]diazocines

Two alternative syntheses of 2,6-methanopyrrolo[1,2-d][1,4]diazocines (I) based in the acidic cyclization of 2-(1-pyrrolylmethyl)tetrahydropyridines are described. In the first synthetic route, lithium aluminum hydride reduction of 2-cyano-1,4-dimethyl-1,2,3,6-tetrahydropyridine (IIa) followed by reaction of the resulting primary amine with 2,5-diethoxytetrahydrofuran affords the requisite tetrahydropyridine IVa. An analogous sequence from 2-cyano-4,6-di-methylpyridine (V) leads to the corresponding 2-(1-pyrrolylmethyl)pyridine VII which by quaternization and borohydride reduction yields a mixture of isomeric tetrahydropyridines, precursors of the pyrrolodiazocine systems Ib and Ic. Structural and stereochemical assignment of the synthesized compounds are discussed.     

A new synthesis of naphtho[2,3-C]pyrroles. Conversion of naphtho[2,3-C]thiophene-4,9-diones to naphtho[2,3-C]pyrrole-4,9-diones

A series of 2-substituted-4,9-dihydronaphtho[2,3-c]pyrrole-4,9-diones was prepared by the reaction of 4,9-dihydronaphtho[2,3-c]thiophene-4,9-diones with primary amines under mild conditions. The presence of halogen in the naphtho[2,3-c]thiophene-4,9-dione and the presence of hydroxyl, ether, or tertiary amine functions in the amine reagent do not interfere with the course of the reaction.     

5,5,6-Trimethylbicyclo[2.2.1]heptan-2-one in the Synthesis of Carbocyclic Analogs of Prostaglandin Endoperoxides

1,3-Dipolar cycloaddition of nitrile oxides to 5,5,6-trimethyl-exo-2-ethynylbicyclo[2.2.1]heptan-endo-2-ol yields the corresponding 2-(isoxazol-5-yl) derivatives. Opening of the isoxazole ring in the latter gives rise to prostanoid precursors with partially built up or completed side chain. 5,5,6-Trimethyl-3-methylenebicyclo[2.2.1]heptan-2-one reacts with nitromethane in the presence of tetramethylguanidine to afford 5,5,6-trimethyl-exo-3-(2-nitroethyl)bicyclo[2.2.1]heptan-2-one which can be converted into the corresponding nitrile oxide by the action of phenyl isocyanate in benzene in the presence of triethylamine as catalyst. 1,3-Dipolar cycloaddition of the nitrile oxide to ethyl 4-pentynoate yields 3-exo-[5-(2-ethoxycarbonylethyl)isoxazol-3-ylmethyl]-5,5,6-trimethylbicyclo[2.2.1]heptan-2-one. Treatment of the latter with hydroxyl amine leads to formation of the corresponding Z-oxime whose reaction with n-hexyl bromide results in transalkylation of the ester group to afford 3-exo-[5-(2-hexyloxycarbonylethyl)isoxazol-3-ylmethyl]-5,5,6-trimethylbicyclo[2.2.1]heptan-2-one oxime.     

Synthesis of 2- and 3-substituted-1,2,3,4-tetrahydrodibenzo[f,h]isoquinolines

Some 2- and 3-substituted-1,2,3,4-tetrahydrodibenzo[f,h]isoquinolines were prepared by a synthetic scheme involving a selective Borch reduction of an amide to the corresponding amine and a Friedel-Crafts cyclization to obtain the dibenzo[f,h]isoquinoline system. The title compounds, which have a similarity to the cell growth inhibitory alkaloid cryptopleurine, failed to exhibit significant protein synthesis inhibitory activity.     

2,4-DIMETHOXYBENZYL: AN AMIDE PROTECTING GROUP FOR 2-ACETAMIDO GLYCOSYL DONORS[1]

2,4-Dimethoxybenzyl (Dmob) was used as an amide protecting group for 2-acetamido glycosyl donors. The N-Dmob group was introduced by imine formation between 2,4-dimethoxybenzaldehyde and d-glucosamine, followed by per-O-acylation, reduction to form the amine, and finally N-acetylation to give 1,3,4,6-tetra-O-acetyl-2-deoxy-2-(2,4-dimethoxybenzylacetamido)-β-D-glucopyranose. Selective 1-O-deacetylation and treatment with trichloroacetonitrile gave the corresponding trichloroacetimidate glycosyl donor. Lewis acid-promoted glycosylations of the model substrate 3-nitrobenzyl alcohol gave exclusively the β-glycoside product, either with or without the Dmob protecting group remaining depending on the reagent and conditions employed. The N-Dmob protected 1-O-acetate glucosyl donor gave higher glycosylation yields than the corresponding 2-acetamido glucosyl donor without Dmob protection.     

Synthesis of Novel Disubstituted Pyrazolo[1,5‐a]pyrimidines,Imidazo[1,2‐a]pyrimidines,and Pyrimido[1,2‐a]benzimidazoles Containing Thioether and Aryl Moieties

A series of novel 6‐[(1,3,4‐thiadiazol‐2‐yl)sulfanyl]‐7‐phenylpyrazolo[1,5‐a]pyrimidines, 5‐phenyl‐6‐[(1,3,4‐thiadiazol‐2‐yl)sulfanyl]imidazo[1,2‐a]pyrimidines, and 2‐phenyl‐3‐[(1,3,4‐thiadiazol‐2‐yl)sulfanyl]pyrimido[1,2‐a]benzimidazoles have been synthesized in four steps starting with 2‐hydroxyacetophenone. The intermediate 3‐[(1,3,4‐thiadiazol‐2‐yl)sulfanyl]‐4H‐1‐benzopyran‐4‐ones reacted with pyrazol‐3‐amines, 5‐methylpyrazol‐3‐amine, and 1H‐imidazol‐2‐amine, 1H‐benzimidazol‐2‐amine via a cyclocondensation to give the title compounds in the presence of MeONa as base, respectively. The approach affords the target compounds in acceptable‐to‐good yields. The new compounds were characterized by their IR, NMR, and HR mass spectra.     

Alkylation of 2,3,6,11-tetrahydroanthra[2,1-d]isothiazole-3,6,11-trione and its S-oxide

The reactions of 2,3,6,11-tetrahydroanthra[2,1-d]isothiazole-3,6,11-trione with dimethyl sulfate, benzyl chloride, and allyl bromide afforded the corresponding 2-alkyl-2,3,6,11-tetrahydroanthra[2,1-d]isothiazole-3,6,11-triones and 3-(alkoxy)-6,11-dihydroanthra[2,1-d]isothiazole-6,11-diones. The reactions of 2,3,6,11-tetrahydroanthra[2,1-d]isothiazole-3,6,11-trione and its S-oxide with a formaldehyde—secondary amine system yielded 2-[(alkylamino)methyl]-2,3,6,11-tetrahydroanthra[2,1-d]isothiazole-3,6,11-triones and 2-[(alkylamino)methyl]-3,6,11-trioxo-2,3,6,11-tetrahydroanthra[2,1-d]isothiazole 1-oxides, respectively.     

Pyrazoles and Pyrazolo[4,3- e]pyrrolo[1,2- a]pyrazines, I. Synthesis and Antimicrobial Activity

The synthesis of the title compounds was achieved using 1-phenyl-5-(pyrrol-1-yl)-1H-pyrazole-3-carboxylic acid azide as starting material. The latter compound was allowed to react with alcohols and amines to afford the corresponding carbamates and urea derivatives. Alkaline hydrolysis of the carbamates gave the corresponding amine, which was acylated and/or aroylated to give amide derivatives. These and the urea derivatives were subjected to cyclodehydration to give the title compounds. Antibacterial and antifungal activities were observed for several derivatives.     

Synthesis of N(3-dimethylaminopropyl)-6-substituted naphtho[2,1-b]thiophene-4-carboxamides

A series of N-(3-dimethylaminopropyl)-6-substituted naphtho[2,1-b]thiophenes-4-carboxamides have been synthesized. 6-Substituted naphtho[2,1-b]thiophene-4-carboxylic acids were obtained upon oxidative-photo-cyclization of α-(2-thienyl)-β-arylacrylic acids. The naphtho[2,1-b]thiophene carboxylic acids were converted to the corresponding amides through their acid chlorides or, in one case, by use of 1,1-carbonyldiimidazole coupling of the amine and the acid.     

2,4-Disubstituted Pyrrolo[2,3-d]pyrimidine α-D- and β-D-Ribofuranosides Related to 7-Deazaguanosine

Nucleobase-anion glycosylation (KOH, tris[2-(2-methoxyethoxy)ethyl]amine (TDA-1), MeCN) of the pyrrolo[2,3-d]pyrimidines 4a – d with 5-O-[(1,1-dimethylethyl)dimethylsilyl]-2,3-O-(1-methylethylidene)-α-D -ribo-furanosyl chloride ( 5 ) gave the protected β-D -nucleosides 6a – d stereoselectively (Scheme 1). Contrary, the β-D -halogenose 8 yielded the corresponding α-D -nucleosides ( 9a and 9b ) apart from minor amounts of the β-D -anomers. The deprotected nucleosides 10a and 11a were converted into 4-substituted 2-aminopyrrolo[2,3-d]-pyrimidine β-D -ribofuranosides 1 . 10c , 12 , 14 , and 16 and into their α-D -anomers, respectively (Scheme 2). From the reaction of 4b with 5 , the glycosylation product 7 was isolated, containing two nucleobase moieties.     

Carbon-nitrogen bond formation in cyclisation by deoxygenation,thermolysis or photolysis of phenylimidazo[1,2-a][1,8]naphthyridines

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.     

杯芳烃多齿水杨醛亚胺衍生物的合成

以对叔丁基杯[n]芳烃1a～1b (n＝6, 8)为原料, 经过三步反应, 以较高产率合成了一系列含多个水杨醛亚胺端基的西佛碱衍生物5a～5f. 对叔丁基杯[n]芳烃用溴乙酸乙酯进行烃基化反应, 生成杯芳烃氧代乙酸乙酯2a～2b, 后者与过量脂肪族二胺NH₂(CH₂)_mNH₂ (m＝2, 4, 6)反应, 生成含有游离氨基的杯芳烃酰胺衍生物4a～4f, 再与水杨醛在乙醇中反应生成目标产物席夫碱衍生物.     

Some transformations of 3-amino-4-alkoxycarbonyl-6-hydroxy-2H-1-benzopyran-2-ones. The synthesis of [1] benzopyrano[3,4-d]-[1,3]oxazine and [1] benzopyrano[3,4-d]pyrimidine derivatives

Acylation of 4-alkoxycarbonyl-3-amino-6-hydroxy-2H-1-benzopyran-2-one derivatives 3 and 4 gave under mild conditions the O-substituted derivatives 5–10, N,O -disubstituted derivative 11 and N,N-disubstituted derivative 12 . The compound 4 was transformed with benzoyl chloride under more drastic conditions into 13 , a derivative of a new heterocyclic system 2-benzopyrano[3,4-d][1,3]oxazine. The derivatives of 1-benzopyrano-[3,4-d]pyrimidine 19 and 20 were prepared either from 3 and 4 through the corresponding N-heteroarylformamidines 14 and 15 and N-heteroarylformamide oximes 17 and 18 or by cyclization of thiourea derivative 20 .     

Novel syntheses of thiazolo[3,2-b]-s-triazoles

The reaction of 2-amino-and 2-acylaminothiazoles with O-mesitylenesulfonylhydroxylamine resulted in the ready formation in the corresponding 3-aminium salts, which were converted into thiazolo[3,2-b]-s-triazoles in high yields.