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Synthesis 1997; 1997(7): 778-782
DOI: 10.1055/s-1997-1415
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Generation of Secondary Alkyl Amines on Solid Support by Borane Reduction: Application to the Parallel Synthesis of PPAR Ligands

Peter J. Brown, Kevin P. Hurley, L. William Stuart, Timothy M. Willson*
  • *Department of Medicinal Chemistry, Glaxo Wellcome Research and Development, NTH-M2134, Five Moore Drive, Research Triangle Park, North Carolina 27709, USA, Fax +1(919)3155668; E-mail:willson~tm@glaxo.com
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Publication Date:
31 December 2000 (online)

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A solid phase parallel synthesis of fibrate PPAR ligands 1 has been developed. The key reaction is a novel borane reduction of resin bound amides that generates secondary amines not accessible by reductive alkylation of primary amines. The FMOC-protected aminofibrate 2 was loaded onto Sasrin resin via the carboxylic acid. The amine was elaborated by amide bond formation followed by reduction with borane. The resulting secondary amines reacted with aryl isocyanates to generate the fibrates 1 in high yield and purity following cleavage from the solid support.

parallel synthesis - solid-phase synthesis - reduction - amide - amine