The amide is a ubiquitous functional group in the pharmaceutical, agrochemical and polymer industries. There are many methods to access amides but an efficient, yet sometimes underutilized, approach is the direct reaction of esters with amine nucleophiles. 1,5,7-triazabicyclo[4.4.0]dec-5-ene (TBD) is a reagent that has been reported to by highly effective at promoting direct ester amidations. We have leveraged the unique reactivity of TBD to develop a mild, single vessel lactamization method for the expedited synthesis of pyridopyrazine-1,6-diones - a unique class of lactams critical to the development of gamma secretase modulators as potential treatments for Alzheimer's Disease. The development method has a broad substrate scope and has been applied to the synthesis of milligram to hundred gram quantities of pyridopyrazine-1,6-diones without the use of specialized equipment.

Rethinking amidation chemistry: Development of a mild and direct lactamization protocol for the synthesis of pyridopyrazine-1,6-diones

255th National Meeting (2018)

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