ISHC2015 has ended

For Campus Prearrival Information <click here>
For a PDF of the 2015 Program Materials <click here>
For ALL Abstracts [1-220] in sequential order <click here>
For ALL Authors of the Lecture and Poster Presentations <click here>

Back To Schedule
Tuesday, August 25 • 4:00pm - 4:20pm
[0218] An Efficient Synthesis of Tetrahydroimidazo[1,2-a]pyrazines via Tandem Multicomponent Reaction

Sign up or log in to save this to your schedule, view media, leave feedback and see who's attending!

Limited Capacity seats available

Isocyanide based multicomponent reactions (IMCRs) followed by cyclization have become a valuable tools of drug discovery oriented synthetic heterocyclic chemistry since they allow synthesizing diverse nature-like heterocyclic small molecules in simple one-pot procedures. Recently we have developed IMCR of various primary diamines and carbonyl compounds that leads to a wide variety of heterocyclic scaffolds with pyrazine, quinaxoline, hetarenopyrazine, 1,4-diazepine, 1,4-benzodiazepine, and other pharmaceutically relevant cores [1].

Here we report post-condensation modification of the discovered IMCR by involving of dimethyl isocyanoacetal as a bifunctional isocyanide component. This enables further cyclization of intermediate pyrazine-2-amines 4 into target imidazopyrazines 5 under acidic conditions. Since no purification is required for intermediates 4, the entire synthesis can be performed in one-pot mode. 

Notably, imidazopyrazine core of general formula 5 is a key structural feature of orexin receptor antagonists (2012), kappa receptor agonists, mGluR5 modulators, and TrkA inhibitors.

Scope of the developed tandem reaction including its expansion for the synthesis of spiro-imidazopyrazines and tetrahydroimidazo[1,2-a][1,4]diazepines as well as its application for small molecule libraries synthesis will be discussed.

[1] Kysil, V. et al. Eur. J. Org. Chem. 2010, 1525–1543.

ST Lecturers
avatar for Volodymyr Kysil

Volodymyr Kysil

Director of Chemistry, ChemDiv, Inc.
MS/BS 1980, Kyiv National Taras Shevchenko University, Ukraine Ph.D. 1989, Kyiv National Taras Shevchenko University, Ukraine Previous work: 1980 – 2002, Sr. Research Scientist, Kyiv National Taras Shevchenko University, Ukraine My research interests focus on medicinal chemistry... Read More →

Tuesday August 25, 2015 4:00pm - 4:20pm PDT
UCEN Harbor