Regioselective synthesis of 1-alkyl-5-(indol-3-yl- and -2-yl)pyrrolidin-2-ones from available reagents

The reaction under mild conditions of 1-alkyl-5-hydroxypyrrolidin-2-ones with different indoles having a free 3 position leads exclusively to 1-alkyl-5-(indol-3-yl)pyrrolidin-2-ones but if position 3 is occupied to 1-alkyl-5-(indol-2-yl)pyrrolidin-2-ones.     

Synthesis of 3-amino-5H-pyrimido[5,4-b]indol-4-one derivatives

Starting with ethyl 3-aminoindole-2-carboxylate, the synthesis of 3-amino-5H-pyrimido[5,4-b]indole-2,4-dione 5 , 3-amino-5H-pyrimido[5,4-b]indol-4-one 10 and some related compounds is described. Preliminary results about the inhibition of platelet aggregation by these compounds is reported.     

Cyclic allylamine/enamine systems-6: Some reactions of 4-(indol-2-ylcarbonyl)-, 4-(indol-3-ylcarbonyl and 4-(indol- 3-ylmethyl)-1,2,5,6-tetrahydro-1 -methylpyridines

Indol-3-yl 1-methyl-1,2,5,6-tetrahydropyridin-4-yl ketone (1d) can be isomerised to indol-3-yl l-methyl-l,2,3,4-tetrahydropyridin-4-yl- ketone but the protonated form of this enamine could not be cyclised to the indole α-position. Both indol-2-yl l-methyl-l,2,5,6-tetrahydropyridin-4-yl ketone (1c) and its isomer (1d) were cyclised to 5-membered ketones by mineral acid catalysed Michael-type addition of indole β- and α-positions respectively onto the unsaturated ketone systems. Ketone (1d)was transformed to l-acetylindol-3-yl 3-acetyl-l,4,5,6-tetrahydropyridin-4-yl ketone by hot acetic anhydride. Strong base treatment of indol-3-yl(l,2,5,6-tetrahydropyridin-4-yl) methane caused isomerisation of the double bond into conjugation with the indole rather than into the endocyclic enamine position.     

Synthesis of 3-amino-5H-1,2,3-triazino[5,4-b]indol-4-one. New compounds with blood platelet antiaggregation activity

Starting with 3-aminoindole-2-carbohydrazide 1 a series of arylidene hydrazones 2 was obtained with good yields (79–85%). Upon treating 2 with nitrous acid a series of 3-arylidineamino-5H-1,2,3-triazino[5,4-b]indol-4-ones 3 was obtained (80–86%). The reaction of 4-methoxybenzylidene derivative 3e with hydrazine hydrate, in ethanol, gave 3-amino-5H-1,2,3-triazino[5,4-b]indol-4-one 4 (64%). However, by treating 3e in boiling hydrate, 3-aminoindole-2-carbaldehyde azine 5 was obtained (44%). By boiling 1 in N,N-dimethylformamide, 3-amino-5H-pyrimido[5,4-b]indol-4-one, 6 was obtained (52%).     

Synthesis of benzothiopyrano[2,3-b]indol-11-one and benzopyrano[2,3-b]indol-11-one

The fused heterocycles benzothiopyrano[2,3-b]indol-11-one and benzopyrano[2,3-b]indol-11-one, have been prepared from methyl 3-indole carboxylate in two steps.     

Synthesis of 6,7-dihydrobenzo[4,5]cyclohept-[1,2-b]indol-12(5H)-one and related compounds

The synthetic routes of 6,7-dihydrobenzo[4,5]cyclohept[1,2-b]indol-12(5H)-one 5 from either 1-methyl or 1-sulfonylindole-2-carboxaldehyde 1 or ethyl 1,2-dimethylindole-3-carboxylate 6 are reported. The structure of the ketone 5a was confirmed by X-ray crystallography. Several indole derivatives have been prepared with potential antitumor activity.     

Synthesis of indol-3-yl aryl ketones through visible-light-mediated carbonylation

A visible-light-catalyzed synthesis of indol-3-yl aryl ketones from aryldiazonium salts, CO and indoles at room temperature was developed. This process provides a useful method for the preparation of diverse indol-3-yl aryl ketones from readily accessible reactants under base-free, acid-free and transition-metalfree conditions.     

Bisindoles. 18. Some electrophilic substitution reactions in the 1,2-di(indol-5-yl)ethane series

A quantum-chemical calculation has been made and the laws of the electron-density distribution in the molecule of 1,2-di(indol-5-yl)ethane have been determined. The electrophilic substitution reactions most characteristic for it have been studied.For communications 15–17, see [1–3].Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 1, pp. 73–77, January, 1984.     

New 3,4-bis(indol-1-yl)maleimides as protein kinase inhibitors

Chemistry of Heterocyclic Compounds - Several previously unknown derivatives of 3,4-bis(indol-1-yl)maleimide, as well as 3-(2,3-dihydroindol-1-yl)-4-(indol-1-yl)maleimide were synthesized as...     

A new and versatile one-pot synthesis of indol-2-ones by a novel Ugi-four-component-Heck reaction

A novel one-pot-synthesis of highly substituted indol-2-ones using a combination of Ugi and Heck reaction (U-4CR-Heck) is described. The synthesized indol-2-ones represent an interesting pharmacological scaffold with four potential points of diversity. Thus, this novel reaction-type is amenable to combinatorial high-throughput screening.     

Isoindolo[2,1-a]indol-6-one--a new pyrolytic synthesis and some unexpected chemical properties

Isoindolo[2,1-a]indol-6-one 1 is formed by a sigmatropic shift-elimination-cyclisation cascade by flash vacuum pyrolysis (FVP) of methyl 2-(indol-1-yl)benzoate 7 at 950 degrees C. The dihydro compound 16 is easily obtained by catalytic reduction of 1, but the reaction is very sensitive to steric effects at the 11-position. Attempted ring-opening of 1 in basic methanol provides an equilibrium of isoindolo[2,1-a]indol-6-one 1 and the ester 19. Lithium aluminium hydride reduction of 1 provides the alcohol 22 which can be dehydrated to a mixture of 23 and 24 by FVP at 800-950 degrees C.     

The chemistry of indoles. CIII. Simple syntheses of serotonin, N-methylserotonin, bufotenine, 5-methoxy-N-methyltryptamine, bufobutanoic acid, N-(indol-3-yl)methyl-5-methoxy-N-methyltryptamine, and lespedamine based on 1-hydroxyindole chemistry

Application of regioselective nucleophilic substitution reactions of 1-hydroxytryptamines to novel and simple syntheses of serotonin (1a), N-methylserotonin (1b), bufotenine (1c), 5-methoxy-N-methyltryptamine (2a), bufobutanoic acid (3a), N-(indol-3-yl)methyl-5-methoxy-N-methyltryptamine (4), and lespedamine (5) are described. Effective syntheses of 5-benzyloxytryptamine and 1-methoxy-2-oxindoles are also reported.     

Synthesis of 1-(β-D-ribofuranosyl)indol-3-acetic acid

By condensation of ethyl indolin-3-acetate ( 4 ) and 2,3,5-tri-O-benzoylribofuranosyl-1-acetate ( 5 ), ethyl 1-(2,3,5-tri-O-benzoyl-β-D-ribofuranosyl)indolin-3-acetate ( 6 ) was obtained in good yield. The indoline nucleoside 6 was aromatized to ethyl 1-(2,3,5-tri-O-benzoyl-β-D-ribofuranosyl)indol-3-acetate ( 7 ) with DDQ. The treatment of the indole nucleoside with barium hydroxide and methanol gave the methyl ester 8 , which was further treated in water to give the desired 1-(β-D-ribofuranosyl)indol-3-acetic acid ( 9 ).     

Synthesis of (indol-2-yl)furazans

The Bischler reaction and some its modifications were used for the synthesis of derivatives of (indol-2-yl)furazans starting from 3-bromoacetyl-4-methylfurazan and substituted annilines. Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 2, pp. 400–401, February, 1999.     

Photochromic fluorescent indol-3-yl-substituted maleimides

New hetarylethenes, 3-(indol-3-yl)-4-thienyl(but-1-en-1-yl)-substituted pyrrole-2,5-diones containing coumarin or fluorene substituents on the pyrrole nitrogen atom, were synthesized by reactions of furan-2,5-diones with 9H-fluoren-2-amine and 6-amino-2H-chromen-2-one. Acyclic maleimide isomers showed fluorescence with quantum yields of 0.002 to 0.072. Their irradiation with UV light generates non-fluorescing cyclic isomer. The reverse ring opening occurs in the excited state.     

Synthesis of some 5H,12H-[1]benzoxepino[4,3-b]indol-6-ones. A new heterocyclic ring system

The synthesis of the title compounds 5H,12H-[1]benzoxepino[4,3-b]indol-6-ones 10 was effected by the Fischer indole cyclization of some 2,3-dihydro-4-phenylhydrazono[1]benzoxepin-5-ones 9 , obtained from the 3,4-dihydro-4-hydroxymethylene[1]benzoxepin-5(2H)-ones 7 by the Japp-Klingemann reaction. The structure of these new heterocyclic compounds was supported by ir, ¹H nmr and ms spectral data.     

Condensation of 1-Substituted 1,2,3,9a-Tetrahydro-9H-imidazo[1,2-a]indol-2-one Derivatives with Aromatic Aldehydes

Condensation of 1-alkyl-, 1-allyl-, and 1-benzyl-1,2,3,9a-tetrahydro-9H-imidazo[1,2-a]indol-2-ones with benzaldehydes in acetic acid and subsequent treatment of the reaction mixture with potassium hydroxide afforded 1-substituted 9a-(2-phenylethenyl)-1,2,3,9a-tetrahydro-9H-imidazo[1,2-a]indol-2-one derivatives. 1-Methyl- and 1-ethyl-9a-[2-(4-dimethylaminophenyl)ethenyl]-1,2,3,9a-tetrahydro-9H-imidazo[1,2-a]indol-2-ones were synthesized by alkylation of 9a-[2-(4-dimethylaminophenyl)ethenyl]-1,2,3,9a-tetrahydro-9H-imidazo[1,2-a]indol-2-one with methyl- and ethyl iodides in DMF in the presence of a strong base.     

Synthesis of the new ring system pyrrolizino[2,3-b]indol-4(5H)-one

Derivatives of the new ring system pyrrolizino[2,3-b]indol-4(5H)-one were prepared in four steps starting from substituted benzonitriles bearing a functionalized amino group in the adjacent position. The unsubstituted- and the dimethoxy-pyrrolizinoindolones 5a and 5b exhibited modest activity against the HL-60(TB) human leukemia cell line, whereas the N-methylated dimethoxy-pyrrolizinoindolone 6b showed to be selective against MOLT-4 leukemia, A549/ATCC, HOP-92, and NCI-H460 non-small cell lung cancer, and CAKI-1 renal cancer cell lines.     

Alkylation of 1,2,3,4,10,10a-hexahydropyrimido[1,2-a]indol-2-one

A mixture of N- and O-alkylation products is formed in the reaction of 1,2,3,4,10,-10a-hexahydropyrimido[1,2-a]indol-2-ones with ethyl iodide, allyl bromide, or benzyl chloride in DMFA (dimethylformamide) in the presence of potassium hydroxide. In the presence of aqueous solutions of acids with subsequent treatment with bases, the alkylation products are converted to 1-[2-(alkoxycarbonyl)-ethyl]-2-methylene-2,3-dehydro-1H-indoles. The reaction of 1,2,3,4,10,10a-hexahydropyrimido[1,2-a]indol-2-one with triethyloxonium fluoroborate gives 1-[2-(ethoxycarbonyl)ethyl]-2-methylene-2,3-dihydro-1H-indole.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 9, pp. 1224–1227, September, 1989.     

Synthesis and structures of benzo[<Emphasis Type="Italic">cd</Emphasis>]furo[2,3-<Emphasis Type="Italic">f</Emphasis>]indol-4(5<Emphasis Type="Italic">H</Emphasis>)-one derivatives

A procedure was developed for the synthesis of derivatives of the new heterocyclic system, benzo[cd]furo[2,3-f]indole, based on the cyclodehydration of 6-acylmethyloxy-1-alkyl-benzo[cd]indol-2(1H)-ones. Either 7- or 8-aryl derivatives of benzo[cd]furo[2,3-f]indol-4(5H)-ones can be prepared depending on the reaction conditions. The molecular and crystal structures of 7- and 8-phenylbenzo[cd]furo[2,3-f]indol-4(5H)-ones were established by X-ray diffraction.