ORGN 10 |
| A library of 77 alkyl- and alkylidene-oxepanecarboxamides was synthesized. The key transformation in the preparation of an oxepene intermediate is the rhodium(I)-catalyzed ene-allene carbocyclization reaction. This pivotal intermediate afforded two functionally unique scaffolds by using different hydrogenation conditions. Each scaffold contained a methyl á, á, á-trifluoromethyl-carboxylate-ether functionality and either a lipophilic or polar group. The carboxylate-ethers were hydrolyzed to the carboxylic acids which were coupled with 10 different primary amines to provide the corresponding carboxamides. In order to facilitate the library synthesis, a microwave assisted protocol using polymer bound DCC was employed. In addition, library purification was achieved by automated parallel chromatography. The final library members were obtained in quantities ranging from 5 mg to 58 mg each with an average purity of 99% by LC/MS/ELSD. The design and synthesis of this library will be discussed. |
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Combinatorial, Parallel, and Process Chemistry
8:00 AM-11:40 AM, Sunday, August 19, 2007 BCEC -- 253 A/B/C, Oral
Division of Organic Chemistry |