By Willi Bannwarth, Eduard Felder, Raimund Mannhold, Hugo Kubinyi, Hendrik Timmerman
As we input the hot millennium, combinatorial chemistry is supplying major impetus to new concepts in man made chemistry. Combinatorial chemistry has quickly develop into the emerging megastar between study tools, permitting scientists to successfully attempt the feasibility of a mess of latest compounds. The pursuit of latest medications is yet one not easy box during which those combinatorial equipment are relatively beneficial, supporting researchers meet the modern day calls for of a hugely aggressive setting. This publication emphasises that smooth combinatorial synthesis is feasible not just within the reliable section, but in addition in strategies. in addition, it discusses computer-assisted equipment in addition to the gear and instrumentation required for the combinatorial procedure. winning and skilled researchers within the top pharmaceutical businesses and most famous examine institutes provide a superior perception and point of view into this varied box. A 'must' for each scientist within the region of pharmaceutical study.
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Additional resources for Combinatorial Chemistry: A Practical Approach (Methods and Principles in Medicinal Chemistry)
9 Mannich Reaction The Mannich reaction is another valuable more component reaction. Reaction of a secondary amine, an aldehyde, and a CH-acidic compound leads to an aminoalkylation of the latter compound. In solution chemistry this reaction has not gained importance in combinatorial approaches, but it has been applied successfully in solid-phase chemistry [27,28]. The reaction on solid support can be carried out in various ways, as any participant of this threecomponent reaction can be immobilized on the resin, providing at the same time three different routes for the generation of diverse compound libraries.
25 equiv. of 4-methoxyphenylisocyanate 36 to form a crude reaction mixture of product urea 37 plus excess isocyanate. Subsequently, the isocyanate impurity was removed by quenching either with N,Ndimethylaminoethylamine followed by cation exchange, or by quenching with 1-(2-hydroxypheny1)piperazine followed by anion exchange. Ion-exchange sorbents can also be used as activators or even reagents for chemical transformations, and in the area of combinatorial chemistry this principle has been applied first for the synthesis of combinatorial libraries of aryl and heteroaryl ethers .
The reaction proceeds with high efficiency to yield 3-amino-imidazo [1,2-a] pyri(mi)dines of the general type 14. R’CHO T N ] o R 2 + R3NC H+ MeOH 13 H NHR3 14 b Scheme 8 The reaction proceeded well in methanol and was not sensitive to moisture or oxygen. With respect to the reactivity of aldehydes there was virtually no limitation. , adenine) did not react. With regard to the reaction mechanism, the authors assumed a nonconcerted [4+1]-cycloaddition, as outlined in Scheme 8. About 30 000 compounds of type 14 were synthesized by this route, either by parallel synthesis as individual compounds or as mixtures.