Efficient Three-Step One-Pot Synthesis of a Novel 2,3,5-Substituted Pyrazine Library

Abstract

The partnership between rational synthesis design and mass-triggered preparative LCMS is a powerful one, capable of furnishing very large libraries in a selective manner in a very short space of time. Herein, we communicate one example of possibly a perfect marriage between the synthetic chemistry and the subsequent purification method employed, affording a ∼1000-member library supplying 50 mg on average of final compound in less than a month.

Right-First-Time Isocratic Preparative Liquid Chromatography-Mass Spectrometry Purification

“…Formula proved to be efficient regardless of the chemical diversity of our compounds, covering a large range of lipophilicity. Some examples of such chemical structures are given in Figure . − As described by Degorce et al, the closely related compounds 5 , 6 , and 7 were nicely separated in one shot from one single reaction mixture …”

Late Stage CH Activation of a Privileged Scaffold; Synthesis of a Library of Benzodiazepines

“…Products were separated initially using am ass-triggered LC-MS protocol [14] but we found that ar eversed-phase LC-MSm ethod was equally useful and we were also able to recover traces of unreacteds tarting material. Moreover, diarylated productsw ere often observedi nt he crude reactionm ixtures and, in some cases,w ere isolated (Scheme 3, for example, 5c' ', 5d' ').T he yields of 5d and 5d' ' were rather low,e ven when using ahigher temperature.…”

Synthesis of 2,4,5‐triaryl‐5H‐chromeno[4,3‐b]pyridines under microwave radiation

“…Products were separated initially using a mass‐triggered LC‐MS protocol14 but we found that a reversed‐phase LC‐MS method was equally useful and we were also able to recover traces of unreacted starting material. Moreover, diarylated products were often observed in the crude reaction mixtures and, in some cases, were isolated (Scheme , for example, 5c′ , 5d′) .…”