title: Solution phase synthesis of a library of tetrasubstituted pyrrole amides.
abstract: 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.
authors.affiliation: NiKem Research, via Zambeletti 25, 20021 Baranzate, Milan, Italy.
authors.forename: Ivana
authors.initials: I
authors.lastname: Bianchi
authors.forename: Roberto
authors.initials: R
authors.lastname: Forlani
authors.forename: Giacomo
authors.initials: G
authors.lastname: Minetto
authors.forename: Ilaria
authors.initials: I
authors.lastname: Peretto
authors.forename: Nickolas
authors.initials: N
authors.lastname: Regalia
authors.forename: Maurizio
authors.initials: M
authors.lastname: Taddei
authors.forename: Luca F
authors.initials: LF
authors.lastname: Raveglia
mesh_terms: 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*
chemical_list: D000577:Amides; D004364:Pharmaceutical Preparations; D011758:Pyrroles