Discovery of dual orexin receptor antagonists with rat sleep efficacy enabled by expansion of the acetonitrile-assisted/diphosgene-mediated 2,4-dichloropyrimidine synthesis

Expansion of the acetonitrile-assisted, diphosgene-mediated synthesis of bicyclic pyrimidines (compound B) expeditiously afforded dual orexin receptor antagonists (DORAs) with excellent potency and rat sleep efficacy. In vitro bioactivation studies on key compounds are also described.