Library aminopyrimidines

As for the solid support, several polymer-supported amines were tested (Fig. 2). For either the pyrazole and isoxazole synthesis, the best results were given by aniline-functionalized cellulose, which has also the advantage of a relatively low cost. For the 2-aminopyrimidine library, polystyrene-based piperazine and piperidine gave products with a much higher purity compared with other secondary non-cyclic or primary amines, hi both cases, the resins could be reused for up to four times before degradation in their behavior was observed. This reusability could be further enhanced (up to 10 cycles for cellulose-based aniline) when the microwave-assisted protocols were used. 

Libraries of 3,4-dihydropyrimido[l,2- ]pyrimidines were formed by reacting 2-aminopyrimidines with an aldehyde and an olefin in a one-pot reaction in the presence of acid, for example, TFA <2002W0030934>. 

Aldehydes and the corresponding 2-aminopyridine, pyrazine, or pyrimidine are admixed in presence of a catalytic amount of clay (50 mg) to generate iminium intermediate. Isocyanides are subsequently added to the same container and the reactants are further exposed to MW to afford the corresponding imidazo[l,2-a]pyridines, imi-dazo[l,2-a]pyrazines and imidazo[l,2-a]pyrimidines (Scheme 6.48). The process is general for all the three components, e. g. aldehydes (aliphatic, aromatic and vinylic), isocyanides (aliphatic, aromatic and cyclic) and amines (2-aminopyridine, 2-amino-pyrazine and 2-aminopyrimidine). A library of imidazo[l,2-a]pyridines, imidazo[l,2-ajpyrazines and imidazo[l,2-a]pyrimidines can be readily obtained by varying the three components [151]. 

Scheme 8 Gram-scale generation of a 23-membered aminopyrimidine library...

Libraries of fused 3-aminopyrimidin-4-ones (such as TP 7) and other compounds... 

Another example of annelation was demonstrated by Hoffmann-La Roche at the thiazolo[4,5-d]pyrimidine scaffold synthesis and decoration. Under thionation with P2S5, the acylated 6-aminopyrimidine 195 gives the corresponding thioamide, which cyclised spontaneously into thiazolo[4,5-d]pyrimidine thione 196. Thione 196 was used further transformation for synthesis of key building block 197 applied for the preparation of the library 198 (Scheme 42) [185]. 

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