Libraries generation

This transformation can also be carried out under solvent-free conditions in a domestic oven using acidic alumina and ammoniiun acetate, with or without a primary amine, to give 2,4,5-trisubstituted or 1,2,4,5-tetrasubstituted imidazoles, respectively (Scheme 15A) [69]. The automated microwave-assisted synthesis of a library of 2,4,5-triarylimidazoles from the corresponding keto-oxime has been carried out by irradiation at 200 ° C in acetic acid in the presence of ammonium acetate (Scheme 15B) [70]. Under these conditions, thermally induced in situ N - O reduction occurs upon microwave irradiation, to give a diverse set of trisubstituted imidazoles in moderate yield. Parallel synthesis of a 24-membered library of substituted 4(5)-sulfanyl-lff-imidazoles 40 has been achieved by adding an alkyl bromide and base to the reaction of a 2-oxo-thioacetamide, aldehyde and ammonium acetate (Scheme 15C) [71]. Under microwave-assisted conditions, library generation time was dramatically re-... 

The advantage of the self-assembly approach is its inherent possibility for combinatorial ligand library generation through mixing of two differ-... 

Figure 70 Guest-controlled assembly of PdII-linked cage-like receptors from a dynamic library generated from a Pd11 complex and two different tridentate ligands.

Reaction Optimization and Library Generation - A Case Study I 97... 

In order to make the Biginelli protocol amenable to an automated library generation format, utilizing the integrated robotic interface of the instrument, attempts were made to dissolve most of the building blocks used in solvents compatible with the reaction conditions. Since many of the published protocols employ either ethanol or acetic acid as solvents in Biginelli-type condensations, a 3 1 mixture of acetic acid... 

Scheme 7.26 Library generation on a cellulose membrane employing the SPOT technique.

The first solid-phase application of the Ugi four-component condensation, generating an 18-member acylamino amide library, was presented in 1999 by Nielsen and Hoel [53]. The authors described a library generation utilizing amino-functionalized PEG-polystyrene (Tentagel S RAM) as the solid support (Scheme 7.36). A set of three aldehydes, three carboxylic acids, and two isonitriles was used for the generation of the 18-member library. 

To demonstrate the feasibility of this method for library generation, the isocyanides produced were subjected to an Ugi three-component condensation with various primary amines and carboxybenzaldehyde. The resulting 2-isoindolinone derivatives were obtained in high to excellent yields. 

A remarkable series of CH functionalizations has been described whereby the regiochemical outcome of the reaction is determined by the catalyst employed. Directed and nondirected C-H functionalizations on 2-phenylimi-dazole were observed. This orthogonal approach is excellent for introducing diversity and may have applications in library generation in areas including medicinal chemistry (Scheme 18). 

Scavenger-Based Purification of Combinatorial Libraries Generated... 

Having defined the utility of a waveform library we go on to investigate the utilities of a few libraries. Specifically, we consider libraries generated from a fixed waveform 4>o, usually an unmodulated pulse of some fixed duration, by symplectic transformations. Such transformations form a group of unitary transformations on L2(R) and include linear frequency modulation as well as the Fractional Fourier transform (FrFT) in a sense that we shall make clear. 

Scheme 2.33 Urea library generation and purification using polymer-sup-ported systems.

Scheme 2.36 Combinatorial library generation using novel polyamine scavengers.

Scheme 2.52 Peptide library generation using supported reagents.

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