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Efficient Construction of Drug-like Bispirocyclic Scaffolds Via Organocatalytic Cycloadditions of α-Imino γ-Lactones and Alkylidene Pyrazolones
Published on: February 7, 2019
A highly efficient synthesis of potent and selective butyrolactam inhibitors of 11beta-HSD1
Vince S C Yeh1, Ravi Kurukulasuriya, Francis A Kerdesky
1Metabolic Disease Research, Target and Lead Discovery Research, and Process Chemistry Research, Abbott Laboratories, 100 Abbott Park Road, Dept R4MC, AP-10, Abbott Park, IL 60064-6113, USA. vince.yeh@abbott.com
Abstract:
A convergent synthesis of structurally novel butyrolactam 11beta-HSD1 inhibitors is described. The approach features an efficient Ireland-Claisen reaction to construct a highly substituted aldehyde building block which is converted to a lactam via a tandem reductive amination/cyclization sequence. The generality of the synthetic sequence is demonstrated during the preparation of two additional potent 11beta-HSD1 inhibitors.
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