Solid-Supported Solution-Phase Synthesis of 4-Amino-1,2,4,5-tetrahydro-2-benzazepine-3-ones
Autor: | Dirk Tourwé, Karolien Van Rompaey, and Francesco Lazzaro, Isabelle Van den Eynde |
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Přispěvatelé: | Organic Chemistry, Vrije Universiteit Brussel |
Rok vydání: | 2004 |
Předmět: |
Sulfonyl
chemistry.chemical_classification Aldehydes Molecular Structure Extraction (chemistry) chemistry.chemical_element General Chemistry Benzazepines Hydroxylation Amides Reductive amination Nitrogen Benzazepine Solutions Benzaldehyde chemistry.chemical_compound chemistry Reagent Organic chemistry Amine gas treating Sulfur Amination |
Zdroj: | Journal of Combinatorial Chemistry. 6:468-473 |
ISSN: | 1520-4774 1520-4766 |
DOI: | 10.1021/cc049940w |
Popis: | Starting from Boc-o-aminomethylphenylalanine, a solution-phase parallel synthesis of 2,4-substituted 4-amino-1,2,4,5-tetrahydro-2-benzazepine-3-ones is described. This heterocycle has two nitrogen functions, which are differentiated and can be selectively substituted. The sources of diversity are aldehydes for the R(1) position and carboxylic acids, sulfonyl chlorides, or isocyanates for the R(2) position. High-throughput synthesis and purification of this multistep synthetic sequence was accomplished using polymer-bound reagents and scavengers and liquid-liquid extraction protocols, and a small library of compounds was prepared. Polymer-bound cyanoborohydride was found to work well for the reductive amination. Scavenging of excess of amine was performed by polymer-bound benzaldehyde, and cyclization was performed in the presence of polymer-bound coupling reagent 1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide (EDC). After Boc-deprotection, the second nitrogen can be acylated using carboxylic acids, sulfonylated or converted to a urea. The acylation is again performed by polymer-bound EDC. Excellent yields and purities were obtained. |
Databáze: | OpenAIRE |
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