Optimized methods for utilizing and analyzing dialkylamine tags in encoded combinatorial chemistry are reported. A previously described LC/fluorescence method has been shortened from over 1 h to 6 min. A novel ion exchange LC/MS method for decoding has been developed which is both fast and rugged. The use of quantitative encoding schemes is described. These new techniques have allowed a simplified, automated sample preparation scheme, and over 300 encoded bead samples can be read in a day.

A novel approach using solid-phase chemistry for scale-up was developed. The method makes use of commercially available high-load Merrifield resin. Three representative solid-phase chemistries leading to a diketopiperazine, a tetramic acid, and a β-lactam were scaled-up effectively and resulted in products with good yields and high crude purities. Affording close to 1 g of product per 1 g of Merrifield resin, the high-load resins showed high-volume productivity. The advantages of the work-ups, consisting simply of resin washes, are discussed. The need for low reactant and reagent equivalents results from higher reactant concentration, and it is shown that these stoichiometries can be reduced to affordable amounts.

is weakly coupled to five vicinal hydrogens and would be expected to appear as a broad, ill-resolved band. In confirmation of the postulate that the resonance from the hydrogen at C-3 is shifted upfield and appears at 1.48 ppm, irradiation of this part of the spectrum in a double resonance experiment42 resulted in the transformation of the triplet centered at 2.26 ppm to a doublet centered at that point. Thus, the nmr spectrum appears to be more readily accommodated to structure 15 than to structures 12 or 13.

The preparation of novel N-Boc-alpha-amino-5-acyl Meldrum's acids is described. The synthetic inaccessibility and instability of several of these products have led to the development of a protocol that allows the synthesis of their corresponding 4-(dimethylamino)pyridine (DMAP) salts (5-AMA-DMAP's), which exhibit superior stability compared to that of the free 5-AMA. A simple and expedient ion-exchange method was developed for the quantitative removal of DMAP to liberate the synthetically useful DMAP-free form when needed.

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