Synthesis of N-alkyl-octahydroisoquinolin-1-one-8-carboxamide libraries using a tandem Diels-Alder/acylation sequence.
A synthetic sequence was developed in which a diene containing an attached secondary amine was reacted with maleic anhydride to afford the title structures in one step. The reaction involves a Diels-Alder reaction combined with a transacylation reaction of the imide group. A series of six scaffolds was constructed using this methodology. Each scaffold was subsequently reacted with 12 amines to afford a library containing 72 compounds.
Frankowski
Kevin J
KJ
KU Chemical Methodology and Library Development Center, University of Kansas, lawrence, Kansas 66046, USA.
Hirt
Erin E
EE
Zeng
Yibin
Y
Neuenswander
Ben
B
Fowler
Drew
D
Schoenen
Frank
F
Aubé
Jeffrey
J
D000215:Acylation; D000466:Alkadienes / Q000737:chemistry; D000473:Alkanes / Q000138:chemical synthesis*; D000588:Amines / Q000737:chemistry*; D020650:Combinatorial Chemistry Techniques; D003500:Cyclization; D007546:Isoquinolines / Q000138:chemical synthesis*; D008299:Maleic Anhydrides / Q000737:chemistry*; D008956:Models, Chemical; D013237:Stereoisomerism
D000466:Alkadienes; D000473:Alkanes; D000588:Amines; D007546:Isoquinolines; D008299:Maleic Anhydrides