Demonstration of the feasibility of a direct solid-phase split-pool Biginelli synthesis of 3,4-dihydropyrimidinones.
[reaction: see text] A direct, Lewis acid-catalyzed Biginelli synthesis of 3,4-dihydropyrimidinones has been performed on high-capacity polystyrene macrobeads with a polymer O-silyl-attached N-(3-hydroxypropyl)urea. Resin-urea was first reacted separately with either 4-bromo- or 4-chlorobenzaldehyde and LiOTf in MeCN at 80 degrees C. After washing, the beads were pooled and reacted with ethyl acetoacetate and LiOTf in MeCN at 80 degrees C. Formation of only one kind of Biginelli product per bead demonstrated the feasibility of a solid-phase non-Atwal two-step split-and-pool synthesis of 3,4-dihydropyrimidinones.
Lusch
Michael J
MJ
Harvard Institute of Chemistry and Cell Biology, Harvard Medical School, 250 Longwood Avenue, Boston, Massachusetts 02115, USA. michael.lusch@mnsu.edu
Tallarico
John A
JA
D002384:Catalysis; D007202:Indicators and Reagents; D015394:Molecular Structure; D011744:Pyrimidinones / Q000138:chemical synthesis*; D013696:Temperature; D014508:Urea / Q000031:analogs & derivatives / Q000737:chemistry
D007202:Indicators and Reagents; D011744:Pyrimidinones; D014508:Urea