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By Willi Bannwarth, Eduard Felder, Raimund Mannhold, Hugo Kubinyi, Hendrik Timmerman

As we input the hot millennium, combinatorial chemistry is delivering major impetus to new recommendations in artificial chemistry. Combinatorial chemistry has speedily turn into the emerging famous person between study tools, permitting scientists to successfully try out the feasibility of a large number of recent compounds. The pursuit of recent medications is yet one not easy box within which those combinatorial tools are really valuable, aiding researchers meet the modern day calls for of a hugely aggressive atmosphere. This e-book emphasises that smooth combinatorial synthesis is feasible not just within the strong part, but additionally in ideas. additionally, it discusses computer-assisted equipment in addition to the gear and instrumentation required for the combinatorial procedure. profitable and skilled researchers within the prime pharmaceutical businesses and most famous learn institutes supply a fantastic perception and standpoint into this different box. A 'must' for each scientist within the zone of pharmaceutical learn.

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The authors evaluated nine ion-exchange resins and three solvents, and obtained the best results using the weakly basic AmberlitemIRA-68 in combination with ethyl acetate. Using this method they obtained the desired products 30 in high yields (84-99 %) and purities (>95 %), but unfortunately only data of a nine-member library were given. Using this strategy, more than 4500 compounds were synthesized [23], starting from a series of substituted pyrimidine and benzene acid chlorides. Scheme 9 To purify a library of amines generated by reductive amination, the use of strong cationexchange adsorbents, based on silica gel was described [24].

The products were analyzed by HPLC-MS. Purities were assessed from peak areas recorded with the UV-detector set a t 280 nm. This reaction has been evaluated extensively for the preparation of the corresponding compound libraries [ 151. R2 R2 R'COOR + OH H~N-N R4 15 Scheme 9 In such a library, the aminimide 16 was identified as a HIV protease inhibitor. 4 Biginelli More Component Reaction A P-ketoester, an aryl aldehyde and a urea derivative, when refluxed in a protic solvent with catalytic amounts of acid, will result in 4-aryl-dihydropyrimidin-2-ones 17 (Scheme 10) [16].

Tetrahedron Lett. 38,61634166 (1997). 1, the benefits of solution-phase synthesis over solid-phase synthesis are the following. A great many more solution-phase reactions have been optimized and documented in the literature compared with currently available solid-phase reactions. A large number of protecting group reagents is available commercially, whereas the number of solid-phase synthesis resins, often used as solid-phase protecting reagents, is limited. Furthermore, in solution-phase chemistry the range of organic reactions is, in principle, very large, whereas on solid phase there are limitations, if one of the reagents or solvents used is not compatible with the support material.

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