Solution-phase synthesis of discrete compounds

Selway et al. [13] have employed a selection of other chemistries in addition to acylation, notably sulphonylation, alkylation and aryl coupling, using boronic acid in the generation of solution-phase arrays in lead optimisation work. 

Purify by acid/base Purify by acid/base 

Among other chemistries being developed, the synthesis of heterocychc molecules has proved a popular option both from chemical and biological perspectives. Two approaches employed are the modification of existing heterocyclic systems and the construction of the heterocycle dining the reaction ofinterest. Whitten et al. [14] have exemplified the former in sequential halide displacement reactions of dichlorotriazines with amines. 

The latter approach has been exemplified in a number of published cases. An indication of the development requirements of well-known reactions for successful employment in array synthesis is provided by the work ofWatson and co-workers [15] to prepare thiazole derivatives. Adaptation of the Hantzch synthesis of 2-aminothiazoles (Fig. 2) from a-haloketones and thioureas was used in the one-step preparation of discrete samples. Inclusion in the array of a compound of known biological activity provided a valuable internal control. 

Hanessian and Yang [16] have reported a high yielding general method for the preparation of5-alkoxyhydantoins (Fig. 3) both in solution and on solid support using a four-step procedure in a strategy allowing access to three points of diversity. It was used to produce two libraries of 25 distinct hydantoins in which each compound was fully characterised. 

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