Site-selective Pd(II) catalyzed cross-coupling reactions have been developed on 2-substituted-4H-pyrido[e][1,3]oxazin-4-ones. C 4-and C 5-alkynylated pyridooxazinones have been thus obtained via Sonogashira reaction while the efficient incorporation at C 5 position of (hetero)aryl, ethenyl substituents have been achieved via Stille reaction. Finally one example of a one pot sequential multiple Sonogashira reaction with different alkynes has been realized. The strategy developed herein provides a rapid access to polyfunctionnalized precursors with extended π-conjugation for further application as fluorescent material.