A practical and scaleable synthesis of A-224817.0, a novel nonsteroidal ligand for the glucocorticoid receptor.
A practical and scaleable synthesis of a novel nonsteroidal ligand for the glucocorticoid receptor A-224817.0 1A is described. The synthesis proceeds in seven steps starting from 1,3-dimethoxybenzene. The biaryl intermediate 5 was prepared by an optimized high-yielding and high-throughput Negishi protocol. The quinoline core 8 was constructed by using a modified Skraup reaction. The final product was obtained by a direct allylation reaction of lactol 10 with allyltrimethylsilane. The process was accomplished efficiently to produce 1A in 25% overall yield and >99% purity with simple and practical isolation and purification procedures.
Ku
Yi-Yin
YY
D-R450, Process Chemistry, Global Pharmaceutical, Research and Development, Abbott Laboratories, North Chicago, IL 60064-4000, USA. yiyin.ku@abbott.com
Grieme
Tim
T
Raje
Prasad
P
Sharma
Padam
P
Morton
Howard E
HE
Rozema
Mike
M
King
Steve A
SA
D002384:Catalysis; D020650:Combinatorial Chemistry Techniques; D006574:Heterocyclic Compounds, 2-Ring / Q000032:analysis / Q000138:chemical synthesis*; D007202:Indicators and Reagents; D008024:Ligands; D015394:Molecular Structure; D011804:Quinolines / Q000032:analysis / Q000138:chemical synthesis*; D011965:Receptors, Glucocorticoid / Q000378:metabolism*; D013237:Stereoisomerism
C478923:A224817.0; D006574:Heterocyclic Compounds, 2-Ring; D007202:Indicators and Reagents; D008024:Ligands; D011804:Quinolines; D011965:Receptors, Glucocorticoid