746677-53-2Relevant articles and documents
Tandem Michael-addition/cyclization synthesis and EGFR kinase inhibition activity of pyrido[2,3-d]pyrimidin-7(8H)-ones
Boros, Eric E.,Wood, Edgar R.,McDonald, O. Bradley,Spitzer, Timothy D.,Sefler, Andrea M.,Reep, Bryan R.,Thompson, James B.
, p. 355 - 358 (2004)
5-Methoxy and 5-anilinopyrido[2,3-d]pyrimidin-7(8H)-ones 2a-2f were obtained by a tandem Michael addition-cyclization reaction of methanol and anilines with pyrimidinylpropynoate 5. Methoxy derivative 2a was obtained in 62% yield by treatment of 5 with methanol and potassium carbonate. Anilino derivatives 2b-2f were prepared in 31-71% yields by reacting 5 with the corresponding anilines in refluxing methanol. This methodology accomplishes Michael-addition and pyridopyrimidinone ring formation in one-pot and affords the desired products in reasonable yield without chromatography. Propynoate 5 did not react with 4-cyanoaniline under these conditions. Reaction of 5 with 2-aminopyridine gave the unexpected arylpyrido[2,3-d]pyrimidinone 8 in 58% yield and reaction of 5 with imidazole afforded Michael-adduct 9 in 69% yield. Compounds 2a and 5 were submicromolar inhibitors of epidermal growth factor receptor (EGFR) tyrosine kinase.
