TAK-733 (1) is an investigational, novel MEK kinase inhibitor that bears a 6- fluoropyridopyrimidone core. Process research of 1 was conducted, and an efficient, scalable route was developed. The key intermediate, a multisubstituted fluoropyridone, was formed in one pot via a three-step cascade reaction: condensation between α- fluoromalonate and malononitrile, methyl amide formation, and intramolecular cyclization. ...
