Polymer-assisted solution phase synthesis preparation

The Use of Polymer-Assisted Solution-Phase Synthesis and Automation for the High-Throughput Preparation of Biologically Active Compounds... 

A small library of 4,5-dihydro-l,4-benzoxazepin-3(2/f)-ones was prepared by polymer assisted solution phase synthesis based on saheyhe aldehydes, a-bromoaeetie acid esters and primary amines <05MI643>. As noted previously, pyrimido[4,5-fe][l,4]-benzoxazepines (and diazepines, and thiazepines) can be accessed via a neat variation of the Pictet-Spengler cyclisation. The compounds are of interest as inhibitors of particular receptor tyrosine kinases <05JOC9629>. Liu et al. have also reported a synthesis of 5,6-dihydro-pyrimido[4,5-Z)][l,4]benzoxazepines 173, 174 based on a cyclocondensation of the imines 172 <05TL7523>. The advantage of the approach was the incorporation of poorly reactive pyrimidyl amines 170,171. 

The practicability of catalyst 2 has been demonstrated in the synthesis of peptide aldehydes libraries targeting caspases 1 and 3 [12], The peptide aldehydes were prepared using a succession of solid phase, and polymer-assisted solution phase synthesis, and were obtained in excellent purity. 

The Horner-Wadsworth-Emmons reaction can also be performed in the PASS (polymer-assisted, solution-phase synthesis) flow system. In this case, polymer-bound hydroxide ions in the flow reactor allow the preparation of alkenes in very high yield with minimal purification (Scheme 5.12) [26]. 

One of the major innovations in combinatorial and medicinal chemistry in recent years aiming at efficient diversity-oriented synthesis has been the implementation of polymer reagents in polymer-assisted solution phase (PASP) synthesis. This contribution will present—following an introduction to the field—a concept of advanced polymer reagents based on reactive intermediates and active reactants that should extend the scope PASP synthesis significantly. Experimental procedures describing preparation and use of the novel polymer reagents are included. 

Under certain condition, however, reactions are still preferably conducted in solution. This is the case e.g., for heterogeneous reactions and for conversions, which deliver complex product mixtures. In the latter case, further conversion of this mixture on the solid support is not desirable. In these instances, the combination of solution chemistry with polymer-assisted conversions can be an advantageous solution. Polymer-assisted synthesis in solution employs the polymer matrix either as a scavenger or for polymeric reagents. In both cases the virtues of solution phase and solid supported chemistry are ideally combined allowing for the preparation of pure products by filtration of the reactive resin. If several reactive polymers are used sequentially, multi-step syntheses can be conducted in a polymer-supported manner in solution as well. As a further advantage, many reactive polymers can be recycled for multiple use. 

Abstract Recent developments in the microwave-assisted synthesis of heterocycles are surveyed with the focus on diversity-oriented multi-component and multi-step one-pot procedures. Both solution- and solid-phase as well as polymer-supported methodologies for the preparation of libraries of heterocycles are reviewed. Advantages of microwave dielectric heating are highlighted by comparison with conventional thermal conditions. 

Many laboratories have investigated alternative solution-phase strategies for preparing combinatorial libraries to overcome these limitations of solid-phase organic synthesis.This chapter reviews advances that have been made over the last two years in polymer-assisted syntheses. This... 

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