Reinvestigation by a Design of Experiments Approach

The yields for the optimized microwave-assisted Biginelli condensations are in general comparable to or higher than those obtained using the standard reflux conditions. More importantly, however, reaction times have been brought down from several hours (4—12 h) under reflux conditions to 10-20 min employing microwave 

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], 

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