Behavior of 2-halo- and 2-trifluoromethyl-1,4-benzoquinones in the Nenitzescu indole synthesis

Littell, Ruddy; Allen, George R.

doi:10.1021/jo01269a076

Cited by 25 publications

(18 citation statements)

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“…2-Chlor0467. 489. It is known that electron-donor substituents at C-2 in thep-benzoquinone ring activate the C-5 and C-6 positions of the ring to nucleophilic attacking agents while electron-withdrawing substituents at C-2 favor such attack at C- 3.491 Although amines are known to react with p-benzoquinone to give structures of the type 62PB2 (Eq.…”

Section: E the Nenitzescu Indole Synthesismentioning

confidence: 99%

Synthesis of the Indole Nucleus

Brown

1971

Chemistry of Heterocyclic Compounds: A Series of Monographs

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Section: E the Nenitzescu Indole Synthesismentioning

confidence: 99%

Synthesis of the Indole Nucleus

Brown

1971

Chemistry of Heterocyclic Compounds: A Series of Monographs

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“…7 As part of an ongoing synthetic study towards the bisindole natural product sciodole (4), we required a supply of the 'lower half' of this alkaloid, specifically 5-methoxy-2,4-dimethylindole (1). Although 5-methoxy-2,4-dimethylindole (1) has been synthesized previously, 8 this route starts with a trifluoromethylbenzoquinone that is not readily attainable. Here, we report a synthesis of 1 via an ortho-quinone methide (o-QM) that has enabled access to grams of the natural product.…”

Section: Introductionmentioning

confidence: 99%

Synthesis of three Tricholoma-derived indoles via an ortho-quinone methide

Homer¹,

Sperry²

2018

Arkivoc

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“…6-Bromoindoles 4b,c were hydrogenated with hydrogen on 10% Pd/C to form indoles unsubstituted at position 6 (compounds 5a, b); reaction of 6-bromoindole 4a with copper (I) cyanide in N-methylpyrrolidone (NMP) produced the corresponding 6-cyanoindole compound 6, while use of 6-bromoindoles 4a -g in the Suzuki reaction with pyridylboronic acids in the presence of dichloro-bis(triphenylphosphine)palladium (II) led to conversion to the corresponding 2-aminomethyl-5-hydroxy-6-pyridin-3(or 4)-yl-1H-indoles (compounds 7a -i). Reagents The ethyl ester of 2-dimethylaminomethyl-5-hydroxy-1-methyl-6-fluoro-1H-indole-3-carboxylic acid (compound 11) was prepared (Scheme 2) using a method analogous to that for 6-bromo derivative 4a from the corresponding 1,2-dimethyl-6-fluoro-1H-indole compound 7, whose synthesis was described in [6]. The ethyl ester of 6-acetylamino-2-dimethylamiomethyl-5-hydroxy-1-methyl-1H-indole-3-carboxylic acid (compound 16) was prepared using a five-stage synthesis (Scheme 3) from the ethyl ester of 5-acetoxy-1,2-dimethyl-1H-indole-3-carboxylic acid (compound 2a).…”

mentioning

confidence: 99%

Synthesis and Antiviral Activity of Substituted Ethyl-2-Aminomethyl-5-Hydroxy-1H-Indole-3-Carboxylic Acids and Their Derivatives

et al. 2015

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Novel substituted 5-hydroxy-2-aminomethyl-1H-indole-3-carboxylic acids and their derivatives were synthesized. The antiviral properties of these compounds were investigated in relation to bovine viral diarrhea virus (BVDV), hepatitis C virus (HCV), and influenza A/Aichi/2/69 (H3N2) virus. Of the compounds synthesized here, only the 5-hydroxy-2-(dimethylaminomethyl)-1-methyl-6-pyridin-3-yl-and 5-hydroxy-2-(dimethylaminomethyl)-1-methyl-6-fluoro-1H-indole-3-carboxylic acid ethyl ester hydrochlorides had significant activity against these viruses, these agents not only suppressing the replication of influenza A/Aichi/2/69 (H3N2) virus in cell cultures at micromolar concentrations, but also demonstrating high efficacy, greater than that of Arbidol, in a model of influenza pneumonia in mice infected with influenza A/Aichi/2/69 (H3N2) virus, when given at a dose of 25 mg/kg/day.Keywords: 2-aminomethyl-5-hydroxy-1H-indole-3-carboxylic acids, antiviral activity, antiinfluenza activity, influenza A/Aichi/2/69 (H3N2), BVDV, HCV.Substituted 2-and 4-aminomethyl-5-hydroxyl-1H-indole-3-carboxylic acids are known to have some degree of antiviral activity [1 -3]. In particular, 1-benzyl-2-dimethylaminomethyl-3-carbethoxy-5-acetoxy-6-bromoindole hydrochloride demonstrated antiinfluenza activity in studies using a mouse model of influenza pneumonia [3]. We have previously described the synthesis and antiviral activity of a series of 2-aminomethyl-5-hydroxy-1H-indole-3-carboxylic acids and have shown them to have limited activity against influenza A/New Caledonia/20/99 (H1N1) virus, bovine viral diarrhea virus (BVDV), and HCV [4].We describe here the synthesis and antiviral activities of novel derivatives of 2-aminomethyl-5-hydroxy-1H-indole-3-carboxylic acids (compounds 4 -7, 11, 16 -20, 24). Substituted ethyl esters of 2-aminomethyl-5-hydroxy-1H-indole-3-carboxylic acids 4 -7 were prepared (scheme 1) from 1-substituted ethyl esters of 5-hydroxy-2-methyl-1H-indole-3-carboxylic acids 1a -e, which, by analogy [5] with 1,2-dimethylindole (compound 1a), were sequentially converted to 5-acetyloxy-(compounds 2a -e) and 5-acetyloxy-6-bromoindoles (compounds 3a -e). Interaction of these latter compounds with dimethylamine, pyrrolidine, and morpholine gave the corresponding 2-aminomethyl-6-bromoindoles (4a -g). 6-Bromoindoles 4b,c were hydrogenated with hydrogen on 10% Pd/C to form indoles unsubstituted at position 6 (compounds 5a, b); reaction of 6-bromoindole 4a with copper (I) cyanide in N-methylpyrrolidone (NMP) produced the corresponding 6-cyanoindole compound 6, while use of

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Behavior of 2-halo- and 2-trifluoromethyl-1,4-benzoquinones in the Nenitzescu indole synthesis

Cited by 25 publications

References 0 publications

Synthesis of the Indole Nucleus

Synthesis of the Indole Nucleus

Synthesis of three Tricholoma-derived indoles via an ortho-quinone methide

Synthesis and Antiviral Activity of Substituted Ethyl-2-Aminomethyl-5-Hydroxy-1H-Indole-3-Carboxylic Acids and Their Derivatives

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