Synthesis of Fluorine-Containing Pyrido[4,3-d]pyrimidines

Significance

The synthesis of a series of fluorine-containing pyrido[4,3-d]pyrimidines is described. In two classical reactions, treatment of malononitrile 1 with carbon disulfide followed by condensation of the resulting product 2 with acetylacetone afforded the 4-aminopyridines 3. Pyridines 3 were easily converted into the form­amidates 4 on treatment with triethyl orthoformate using acetic acid as catalyst. Regioselective cyclization followed on addition of a primary amine to give the desired pyrido[4,3-d]pyrimidines in moderate to good overall yield.