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A solid phase organic synthesis method has been developed for the preparation of substituted methylene malonamic acids and malonic ester mono acids 5. Two substituents are introduced into the core molecule 5 by preparation of unsymmetrical malonic acid derivatives 2, followed by Knoevenagel condensation with aromatic or aliphatic aldehydes, giving resin-bound 4. Evaluation of the scope of these reactions led to the preparation of a 96-member library from a set of eight amines/alcohols (seven amines and one alcohol) and 11 aldehydes leading to 88 substituted methylene malonamic/malonate mono acids 5 and eight unsymmetrical malonamic/malonate mono acids 3. Structural validation and quantitation for every member of the library was obtained by evaluation of ¹H NMR and HPLC, respectively. The ¹H NMR data were obtained using automated delivery of DMSO solutions of every library member from a 96-deep well microtiter plate to a flow probe-equipped NMR spectrometer. HPLC data were used for determination of the extent of conversion of malonamic/malonate esters 2 to the products 5 by an external standard method. Summary information from the ¹H NMR and HPLC data is viewed as plate diagrams for analysis of the final library.