Darstellung von 1,5‐Benzothiazepin‐2,4(3<i>H</i>,5<i>H</i>)‐dionen

Ried, Walter; Sell, G.

doi:10.1002/cber.19801130625

Cited by 11 publications

(1 citation statement)

References 6 publications

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“…These can formally be subdivided into three classes, A , B , and C , based on the retrosynthetic disconnection of the basic skeleton 3 . In strategy A (by far the most frequently employed), 3 was derived from nucleophilic attack of substituted 2-aminothiophenols, 4 , or 2-nitrothiophenols, 5 , on aliphatic electrophiles, 6 , such as β-halo-propionic acids, α,β-unsaturated carboxylic acids, β-propiolactones, malonic acids, or phenylglycidic esters . In the converse scenario B , a β-mercapto acid (typically a cysteine derivative), 8 , was allowed to react with substituted 2-fluoronitroarenes, 7 , followed by nitro group reduction and cyclization …”

Section: Introductionmentioning

confidence: 99%

Solid-Phase Synthesis of 3,5-Disubstituted 2,3-Dihydro-1,5-benzothiazepin-4(5H)-ones

1999

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A solid-phase route affording novel 3,5-disubstituted 1,5-benzothiazepin-4(5H)-ones in optically pure form has been enabled. SNAr reaction of polymer-bound 4-fluoro-3-nitrobenzoic acid, 12, with l-Fmoc-cysteine, l-13, under basic conditions, followed by tin(II) chloride mediated nitro group reduction, furnished the primary aniline 15. Reductive alkylation of 15 to the corresponding secondary anilines 17 was shown to be feasible for a wide range of aldehydes, using an optimized solvent system composed of CH(OMe)3, DMF, MeOH, and HOAc, with NaCNBH3 as the reducing agent. In cases of enolizable aldehydes, benzotriazole was found to be a beneficial additive for the suppression of side-products due to imine−enamine tautomerization. Subsequent cyclization of the secondary anilines 17 using DIC in apolar solvents furnished the corresponding N(5)-alkylated 1,5-benzothiazepin-4-ones 19. Following Fmoc removal from 19, the primary amino group was finally reacted with carboxylic acids, isocyanates, sulfonyl chlorides, or aldehydes to afford the respective amides 32, ureas 33, sulfonamides 34, or secondary amines 35. Performing the synthesis with the d-form of Fmoc-cysteine, d-13, resulted in the corresponding antipodal products, with no detectable scrambling at C(3). The solid-phase assembly of 1,5-benzothiazepin-4-ones was also shown to be compatible with chemical encoding based on dialkylamine tags, enabling the construction of large combinatorial libraries of the title compounds.

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