Synthesis of new 4-aryl-isoxazolo[5,4-d]pyrimidin-6-one(thione) and 4-aryl-pyrazolo[3,4-d]-pyrimidin-6-one derivatives of potential antihypertensive activity

摘要

Some aromatic aldehydes are subjected to react with urea (or thiourea) and acetyl acetone in a one-pot Biginelli-type cyclocondensation reaction to give 5-acetyl-4-aryl-6-methyl-1,2,3,4-tetrahydro-pyrimidines 2a-j. Aldehydes with ortho-hydroxy substituent namely salicylaldehyde and 2-hydroxy-3-methoxybenzaldehyde undergo Michael-type addition of the hydroxyl-proton to the C_5-C_6 double bond of the pyrimidine ring to form the tricyclic derivatives 3a-d while 2-hydroxy-3-nitrobenzaldehyde reacted normally to give 2j. Compounds from the type 2 react with basic hydroxylamine to give the respective isoxazolopyrimidine derivatives 4a-g through an intramolecular addition of the oxim-hydroxyl proton to the C_5-C_6 double bond of the pyrimidine ring. The oxime derivatives from the tricyclic compounds 3a,c undergo rupture of the oxacyclic ring followed by addition of the oxim-proton to the C_5-C_6 double bond of the pyrimidine ring giving rise to the corresponding isoxazolophenols 5a,b. Furthermore, when hydrazine hydrate reacts with the acetyl derivatives 2a, 2f and 2h afford the corresponding 4-aryl-5-(1-hydrazono-ethyl)-6-methyl-3,4-dihydro-1H-pyrimidin-2-one 6a-c, while the compounds 2d and 3c react under the same reaction conditions to give the pyrazolopyrimidine derivatives 7 and 8, respectively.