TY - JOUR
T1 - Synthesis of polyheterocyclic pyrrolo[3,4-b]pyridin-5-ones via a one-pot (Ugi-3CR/aza diels-alder/N-acylation/aromatization/SN2) process. A suitable alternative towards novel Aza-analogues of falipamil
AU - Zamudio-Medina, Angel
AU - García-González, Ailyn N.
AU - Herrera-Carrillo, Genesis K.
AU - Zárate-Zárate, Daniel
AU - Benavides-Macías, Adriana
AU - Tamariz, Joaquín
AU - Ibarra, Ilich A.
AU - Islas-Jácome, Alejandro
AU - González-Zamora, Eduardo
N1 - Publisher Copyright:
© 2018 by the authors.
PY - 2018
Y1 - 2018
N2 - We describe the one-pot synthesis of twenty polyheterocyclic pyrrolo[3,4-b]pyridin-5-ones via a cascade process (Ugi-3CR/aza Diels-Alder/N-acylation/aromatization) in 20 to 95% overall yields, as well as four pharmacologically promising analogues via an improved cascade process (Ugi-3CR/aza Diels-Alder/N-acylation/aromatization/SN2): two piperazine-linked pyrrolo[3,4b]pyridin-5-ones in 33 and 34%, and a couple of Falipamil aza-analogues in 30 and 35% overall yields. It is worth highlighting the good substrate scope found, because final products are furnished with alkyl, aryl, and heterocyclic substituents. The use of chain-ring tautomerizable isocyanides (as key reagents for the Ugi-type three component reaction) allowed for a rapid and efficient assembly of the polysubstituted oxindoles, which were used in situ toward the complex products, conferring features like robustness, sustainability, and the one-pot approach to this synthetic methodology.
AB - We describe the one-pot synthesis of twenty polyheterocyclic pyrrolo[3,4-b]pyridin-5-ones via a cascade process (Ugi-3CR/aza Diels-Alder/N-acylation/aromatization) in 20 to 95% overall yields, as well as four pharmacologically promising analogues via an improved cascade process (Ugi-3CR/aza Diels-Alder/N-acylation/aromatization/SN2): two piperazine-linked pyrrolo[3,4b]pyridin-5-ones in 33 and 34%, and a couple of Falipamil aza-analogues in 30 and 35% overall yields. It is worth highlighting the good substrate scope found, because final products are furnished with alkyl, aryl, and heterocyclic substituents. The use of chain-ring tautomerizable isocyanides (as key reagents for the Ugi-type three component reaction) allowed for a rapid and efficient assembly of the polysubstituted oxindoles, which were used in situ toward the complex products, conferring features like robustness, sustainability, and the one-pot approach to this synthetic methodology.
KW - Aza Diels-Alder Cycloadditions
KW - Cascade processes
KW - Falipamil
KW - Microwave assisted synthesis
KW - Multicomponent reactions
KW - One-pot procedures
KW - Piperazine-linker
KW - Pyrrolo[3,4-b]pyridin-5-ones
KW - Ugi-3CR
UR - http://www.scopus.com/inward/record.url?scp=85044733474&partnerID=8YFLogxK
U2 - 10.3390/molecules23040763
DO - 10.3390/molecules23040763
M3 - Artículo
C2 - 29584639
AN - SCOPUS:85044733474
SN - 1420-3049
VL - 23
JO - Molecules
JF - Molecules
IS - 4
M1 - 763
ER -