A practical synthesis to Glucokinase activator (1) as a potential drug for treating type-2 diabetes will be described. The key intermediate, chiral alpha-arylpropionic acid (2), was synthesized in high diastereomeric excess through the diasteromeric resolution without the need for a chiral resolving agent. The counterpart 2-aminopyrazine derivative (3) was synthesized using a palladium-catalyzed C−N coupling reaction. This new synthetic process enabled a robust and chromatography-free synthesis. The first pilot-scale manufacturing yielded 19.0 kg of (1) for the first GMP lot.

Development of a practical and scalable synthesis of a Glucokinase activator

255th National Meeting (2018)

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