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Synlett 2005(8): 1322-1324  
DOI: 10.1055/s-2005-868476
LETTER
© Georg Thieme Verlag Stuttgart · New York

Solid-Phase Synthesis of Disubstituted 1,3-Dihydro-2H-imidazol-2-ones

M. Patek*, A. S. Weichsel, B. Drake, M. Smrcina
Sanofi-Aventis Center for Combinatorial Technologies, 1580 E. Hanley Blvd., Tucson, Arizona 85737, USA
Fax: +1(520)5758283; e-Mail: Marcel.Patek@sanofi-aventis.com;
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Publication History

Received 23 February 2005
Publication Date:
21 April 2005 (online)

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Abstract

An efficient and straightforward solid-phase synthesis of sulfonylimidazolones 2a-g is described. Our design was directed toward obtaining molecules for a general library development and incorporates functionalities that fulfill lead-like criteria. The synthesis was realized with the use of SPOS in fair to good yields and purity. Monitoring and quantitation of intermediates and final products were performed by the use of LCMS and NMR spectroscopy.

Key words

imidazolones - solid-phase synthesis - acyliminium ion - nucleophiles - combinatorial chemistry

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Formation of Polymer-Supported Urea ( 4).
A solution of the corresponding isocyanate (0.6 mmol) in anhyd DMF (2 mL) was added to resin 3 (0.06 mmol). The suspension was shaken for 5-16 h at r.t, filtered off and washed five times with DMF (3 mL) followed by five washes with CH2Cl2 (3 mL). The resin was dried under vacuum to afford the solid-phase bound urea 4. General Procedure for the Solid-Phase Synthesis of Target Molecules ( 9).
To a suspension of resin 4 (0.06 mmol) in AcOH (2 mL), 40 wt% aqueous solution of glyoxal (1.2 mmol) was added followed by addition of arylsulfinic acid sodium salt (0.6 mmol). The suspension was shaken for 16 h at r.t. or for 30 min at 80 °C. The resin was then washed ten times with CH2Cl2 (3 mL) and the product was cleaved by treatment with 80% TFA/CH2Cl2 and 4% triisopropylsilane for 16 h at r.t. The TFA solution was concentrated to afford crude product 9 that was further purified by preparative LCMS.