Journal of Combinatorial Chemistry · 2003 · 11 citations · 10 references
PharmacyChemistryMedicinal ChemistryCombinatorial ChemistryDrug DiscoveryOrganic ChemistryChemical Library DesignCombinatorial SynthesisDiversity-oriented SynthesisHigh-throughput SynthesisLibrary ScreeningLigand-based DesignChemical Library SynthesisLibrary Screening StrategiesMedicinal Chemistry ApplicationsMorpholine ChemistryReagent ScreeningReagent-based Library SynthesisSolution PreparationTemplate-based Library Design
Efficient and general procedures have been developed for the solution-phase preparation of substituted morpholine derivatives, and a library has been produced around generic structure 1. This library was designed with proprietary modeling software for use as a general screening library. The 30 R1 reagents were phenols, and the 275 R2 reagents were taken from five different reagent classes, giving a variety of product classes in the final library of 8250 potential products. All of the library members were generated from a common intermediate, mesylate (5), which was synthesized efficiently, in bulk, in three steps from N-benzylethanolamine (2). High-throughput chemistry using robotics was carried out to produce the 7907 library members, which were individually characterized by reversed-phase LC/MS analysis.
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