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Regioselective alkylation at the N4 positionof a 3-oxo-1,4-benzodiazepine on solid support

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Abstract

An efficient solid phase regioselective alkylation at the N4 positionof a 3-oxo-1,4-benzodiazepine template exemplified by 4-H-2,3,4,5-tetrahydro-7-iodo-3-oxo-1H-1,4-benzodiazepine-2-acetate-polymerester is described. Further chemical elaboration atposition 7, utilizing a modified Heck reaction, allows the incorporationof amides from primary or secondary amines. The two diversity points atpositions 4 and 7 were utilized tosynthesize a 28-membered, combinatorial array on Sasrin® resin in moderate yields and >80% purity. Having validated the chemistry on solid support, acombine and splitapproach to prepare a bead-bound combinatorial library is achievableutilizing similar experimental practices and procedures as in thearray synthesis.

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Authors and Affiliations

  1. Department of Medicinal Chemistry, Research and Development Division,SmithKline Beecham Pharmaceuticals, 709 Swedeland Road, P.O. Box 1539, King of Prussia, PA, 19406-0939, U.S.A.

    Fadia E. Ali, Catherine C.K. Yuan, Stephen T. Ross & Leon B. Hall

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  1. Fadia E. Ali
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  2. Catherine C.K. Yuan
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  3. Stephen T. Ross
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  4. Leon B. Hall
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Correspondence to Fadia E. Ali.

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Ali, F.E., Yuan, C.C., Ross, S.T. et al. Regioselective alkylation at the N4 positionof a 3-oxo-1,4-benzodiazepine on solid support. Mol Divers 5, 1–5 (2000). https://doi.org/10.1023/A:1011377008730

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