A practical and scaleable synthesis of A-224817.0, a novel nonsteroidal ligand for the glucocorticoid receptor |
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Authors: | Ku Yi-Yin Grieme Tim Raje Prasad Sharma Padam Morton Howard E Rozema Mike King Steve A |
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Institution: | D-R450, Process Chemistry, Global Pharmaceutical, Research and Development, Abbott Laboratories, North Chicago, IL 60064-4000, USA. yiyin.ku@abbott.com |
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Abstract: | 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. |
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