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Scaffold Preparation and Parallel Synthesis of Arrays of 5,6,7,8‐Tetrahydropyrrolo‐azepinones in the Solution Phase
Author(s) -
Piras Leonarda,
Genesio Eva,
Ghiron Chiara,
Taddei Maurizio
Publication year - 2008
Publication title -
european journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 1434-193X
DOI - 10.1002/ejoc.200701024
Subject(s) - chemistry , azepine , beckmann rearrangement , oxime , alkylation , combinatorial chemistry , scaffold , stereochemistry , substrate (aquarium) , organic chemistry , catalysis , oceanography , geology , medicine , biomedical engineering
An efficient synthesis of a pyrrolo‐azepine scaffold for the parallel preparation of an array of (oxo‐pyrrolo‐azepinyl)acetamides is described. The Stetter cyclisation of 1,3‐cyclohexanedione with ethyl bromopyruvate was the key reaction in the assembly of a tetrahydrobenzofuran substrate which was submitted to a rapid transformation into a tetrahydroindole by microwave‐assisted cyclocondensation in the presence of glycine. The carbonyl group was then stereoselectively transformed into the corresponding ( Z )‐oxime which gave the pyrrolo‐azepinone by Beckmann rearrangement in the presence of polyphosphoric acid. Trimethylaluminium‐mediated amidation gave the corresponding amides which were finally N ‐alkylated at the 5‐position to give 52 diverse (pyrrolo‐azepinyl)acetamides, showing an appreciable exploration of the chemical space around the central heterocyclic core. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008)