A facile synthesis and heteroannulation of pyrido[2,3-d]pyrimidine and related heterocyclic systems

Abstract

7-Amino-1,2,3,4-tetrahydro-4-oxo-2-thioxo-5-(3,4,5-trimethoxyphenyl)pyrido[2,3- d]pyrimidine (1) was prepared and reacted with methyl iodide and ethyl chloroacetate to give the S-alkylated products 2 and 3, respectively. The reaction of 1 or 3 with hydrazine hydrate yielded the same 2-hydrazino derivative 4. Treatment of 4 with 2,4-pentanedione, 2-acetylcyclohexanone and ethyl acetoacetate afforded the corresponding pyrazolylpyrido[2,3- d]pyrimidine derivatives (5–7), while phthalic anhydride gave the phthalazinyl compound 8. Ethoxymethylenemalononitrile with the hydrazine 4 formed the fused 1,2,4-triazepine 9, while triazolopyrido[2,3- d]pyrimidines were obtained from the reaction of 4 with benzylidene malononitrile or benzaldehyde (forming 10), acetic acid/anhydride (giving 11), and ethyl chloroformate (giving 12).