DHPM library

With this set of five optimized reaction conditions in hand (Fig. 5.6), the production of a small DHPM library was performed. As a set of structurally diverse representative building blocks, 17 individual CH-acidic carbonyl compounds, 25 aldehydes, and 8 ureas/thioureas were chosen. Combination of all these building blocks would lead to a library of 3400 individual DHPMs. To demonstrate the practicability of the presented concept, a representative subset library of 48 DHPM analogues involving all of the aforementioned building blocks was generated [2],... 

All building blocks used for the construction of the DHPM library should be commercially available covering a reasonable diversity range. 

Fig. 9. Structural representation of a 48-member DHPM library. Given are the reaction parameters in the format conditions/temperature (°)/reaction time (min)/yield (%). Conditions refers to the solvent/catalyst systems A-E specified in Fig. 8.

Since the experimental conditions for the traditional Biginelli reaction are quite straightforward, small libraries of DHPMs are readily accessible by parallel synthesis. Along these lines the generation of a 140-member single compound DHPM library by combination of 25 aldehydes, 6 ureas/thioureas, and 7 acetoacetates or acetoamides under standard reaction conditions has been reported [123, 124]. More rapid approaches make use of microwave-enhanced solution-phase protocols [88, 89, 125]. Apart from these conventional solution-phase methods, it is also possible to employ polymer-supported reagents to aid in the purification and workup protocol. Polymer-assisted solution-phase chemistry using polymer-supported... 

The Biginelli reaction has also been extended to solid phase and combinatorial synthesis. In a recent combinatorial approach Kappe and coworkers used 4-chloroacetoacetate as a building block to create a library of diverse DHPMs under... 

To construct a small library of DHPMs via microwave-enhanced Bigi-nelli condensation, we felt that several criteria should be met. 

Kappe et al. reported a microwave-assisted automated screening of conditions for the BigineUi reaction which was then used to synthesize a library of dihydropyrimidines (DHPMs Scheme... 

Regioselective N-1 alkylation of DHPM derivatives using the highly reactive TMAD-TBP combination and readily available primary alcohols furnished a small library of N-1 alkylated DHPM derivatives 18 (X = O), in good yields (Scheme 7) (02SL1901). 

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