Solution phase synthesis of a library of tetrasubstituted pyrrole amides.
An efficient strategy for the solution-phase parallel synthesis of a library of pyrrole-amides is described. Key reactions include functional homologation of beta-ketoesters with a set of aldehydes followed by oxidation to produce a series of differently substituted 1,4-dicarbonyl compounds. Rapid cyclization using a microwave-assisted Paal-Knorr reaction provided a set of 24 pyrrole esters that were further functionalized through a trimethylaluminum-mediated aminolysis to obtain a larger library of 288 diverse pyrrole-3-amides. The tetrasubstitution allows a good exploration of the chemical space around the central pyrrole core. The last step was entirely automated with a Bohdan Myriad personal synthesizer.
Bianchi
Ivana
I
NiKem Research, via Zambeletti 25, 20021 Baranzate, Milan, Italy.
Forlani
Roberto
R
Minetto
Giacomo
G
Peretto
Ilaria
I
Regalia
Nickolas
N
Taddei
Maurizio
M
Raveglia
Luca F
LF
D000577:Amides / Q000138:chemical synthesis*; D001331:Automation; D020650:Combinatorial Chemistry Techniques; D003500:Cyclization; D008872:Microwaves; D008956:Models, Chemical; D015394:Molecular Structure; D004364:Pharmaceutical Preparations / Q000138:chemical synthesis*; D011758:Pyrroles / Q000138:chemical synthesis*
D000577:Amides; D004364:Pharmaceutical Preparations; D011758:Pyrroles