Arylaminoheterocyclic Compounds. I. Synthetic Method

Banks, C. K.

doi:10.1021/ja01235a022

Cited by 77 publications

(25 citation statements)

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“…[20] Furthermore, protonation of a nitrogen atom of a heteroaromatic ring can enhance the rate of a S N Ar reaction. [10][11][12][13] However, addition of an acid may deactivate the nucleophilic component of the reaction. The aniline needs to be in its non-protonated form, and thus increasing the amount of TFA will augment the population of unreactive protonated aniline.…”

Section: Mechanisms Of S N Ar Reactions Facilitated By Tfa-tfementioning

confidence: 99%

Trifluoroacetic Acid in 2,2,2‐Trifluoroethanol Facilitates S_NAr Reactions of Heterocycles with Arylamines

Carbain

Coxon

Lebraud

et al. 2014

Chemistry A European J

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Small-molecule drug discovery requires reliable synthetic methods for attaching amino compounds to heterocyclic scaffolds. Trifluoroacetic acid-2,2,2-trifluoroethanol (TFA-TFE) is as an effective combination for achieving SN Ar reactions between anilines and heterocycles (e.g., purines and pyrimidines) substituted with a leaving group (fluoro-, chloro-, bromo- or alkylsulfonyl). This method provides a variety of compounds containing a "kinase-privileged fragment" associated with potent inhibition of kinases. TFE is an advantageous solvent because of its low nucleophilicity, ease of removal and ability to solubilise polar substrates. Furthermore, TFE may assist the breakdown of the Meisenheimer-Jackson intermediate by solvating the leaving group. TFA is a necessary and effective acidic catalyst, which activates the heterocycle by N-protonation without deactivating the aniline by conversion into an anilinium species. The TFA-TFE methodology is compatible with a variety of functional groups and complements organometallic alternatives, which are often disadvantageous because of the expense of reagents, the frequent need to explore diverse sets of reaction conditions, and problems with product purification. In contrast, product isolation from TFA-TFE reactions is straightforward: evaporation of the reaction mixture, basification and chromatography affords analytically pure material. A total of 45 examples are described with seven discrete heterocyclic scaffolds and 2-, 3- and 4-substituted anilines giving product yields that are normally in the range 50-90 %. Reactions can be performed with either conventional heating or microwave irradiation, with the latter often giving improved yields.

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Section: Mechanisms Of S N Ar Reactions Facilitated By Tfa-tfementioning

confidence: 99%

Trifluoroacetic Acid in 2,2,2‐Trifluoroethanol Facilitates S_NAr Reactions of Heterocycles with Arylamines

Carbain

Coxon

Lebraud

et al. 2014

Chemistry A European J

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“…The 4-amido (6, 7) and 4-sulfamido (8) derivatives were prepared by classical acylation. The 4-amino substituted phenylarsonic derivatives (9)(10)(11)(12) were obtained by refluxing the corresponding chloride with 2 in 0.25 N HCl for 1 h [9]. The formation of the dithiarsolane ring with concomitant reduction of As V to As III was performed by stirring 1 equiv.…”

Section: Synthesismentioning

confidence: 99%

(2-Phenyl-[1,3,2]dithiarsolan-4-yl)-methanol derivatives show in vitro antileukemic activity

Gibaud¹,

Alfonsi²,

Mutzenhardt

et al. 2006

Journal of Organometallic Chemistry

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“…8,16 Acid catalysis, as measured (Table 1) by a significant change in yield (taken in this study as >10% increase in yield), was observed with some, but not all of the chloropyrimidines (discussed below). With the exception of 2,4,6-trichloropyrimidine (4), only one substitution product was obtained in each case.…”

Section: Introductionmentioning

confidence: 72%

Reaction of 3-aminopyrrole with chloropyrimidines to give pyrroloaminopyrimidines

Rosa¹,

Arnold²,

Wright³

et al. 2015

Arkivoc

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Reaction of 3-aminopyrrole with chloropyrimidines occured only at the 3-amino group. The activating group(s) (Cl, NO 2 or CF 3 ), their relative positions (C4/C6, C2, or C5), and the effect of added base (DIPEA) or acetic acid on the course of the reaction, was studied. When chloro groups were present on both C4/C6 and C2, the only or major product was from the displacement of the C4/C6 chloro group. Only in the reaction of 2,4,6-trichloropyrimidine was substitution at C2 competitive with reaction at C6. Both chloro groups of 2,4-dichloro-3-nitropyrimidine were displaced to give a novel compound with three-linked heterocyclic rings. Reactions of less reactive chloropyrimidines appeared to be favored by acid catalysis.

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Arylaminoheterocyclic Compounds. I. Synthetic Method

Cited by 77 publications

References 0 publications

Trifluoroacetic Acid in 2,2,2‐Trifluoroethanol Facilitates S_NAr Reactions of Heterocycles with Arylamines

Trifluoroacetic Acid in 2,2,2‐Trifluoroethanol Facilitates S_NAr Reactions of Heterocycles with Arylamines

(2-Phenyl-[1,3,2]dithiarsolan-4-yl)-methanol derivatives show in vitro antileukemic activity

Reaction of 3-aminopyrrole with chloropyrimidines to give pyrroloaminopyrimidines

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Arylaminoheterocyclic Compounds. I. Synthetic Method

Cited by 77 publications

References 0 publications

Trifluoroacetic Acid in 2,2,2‐Trifluoroethanol Facilitates SNAr Reactions of Heterocycles with Arylamines

Trifluoroacetic Acid in 2,2,2‐Trifluoroethanol Facilitates SNAr Reactions of Heterocycles with Arylamines

(2-Phenyl-[1,3,2]dithiarsolan-4-yl)-methanol derivatives show in vitro antileukemic activity

Reaction of 3-aminopyrrole with chloropyrimidines to give pyrroloaminopyrimidines

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Trifluoroacetic Acid in 2,2,2‐Trifluoroethanol Facilitates S_NAr Reactions of Heterocycles with Arylamines

Trifluoroacetic Acid in 2,2,2‐Trifluoroethanol Facilitates S_NAr Reactions of Heterocycles with Arylamines