Synthesis of highly substituted 5-(trifluoromethyl)ketoimidazoles using a mixed-solid/solution phase motif.
Using a combination of solid phase synthesis for the preparation of N-substituted-N-acylglycines 7 followed by solution-phase ring transformation of trifluoromethylacyl munchnone intermediate 8, a library of 200 trisubstituted-5-trifluoromethylketo (TFMK) imidazoles 9 was prepared. In a sublibrary, bromoacetate resin 4 was treated with 5 amines in parallel to give N-substituted glycines 5 followed by acylation with 12 acid chlorides to provide, upon cleavage from the resin, 60 individual N-substituted-N-acylglycines 7. The glycines 7 were converted to munchnones 8 by treatment with trifluoroacetic anhydride followed by reaction with benzamidine to give trisubstituted-5-TFMK-imidazoles 9. The structural content of the library was analyzed using PlateView of the LCMS results, and individual members were isolated by automated preparative LCMS.
Hamper
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BC
Monsanto Company, AG Sector, 800 N. Lindbergh Boulevard, St. Louis, Missouri 63167, USA. c.hamper@monsanto.com
Jerome
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KD
Yalamanchili
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G
Walker
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DM
Chott
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Mischke
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D019992:Databases as Topic; D005998:Glycine / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000737:chemistry; D007093:Imidazoles / Q000138:chemical synthesis* / Q000737:chemistry; D007202:Indicators and Reagents; D007659:Ketones / Q000138:chemical synthesis / Q000737:chemistry; D008958:Models, Molecular; D012116:Resins, Plant
D007093:Imidazoles; D007202:Indicators and Reagents; D007659:Ketones; D012116:Resins, Plant; D005998:Glycine