Synthesis of new 4-aryl-isoxazolo[5,4-<i style="">d</i>]pyrimidin-6-one(thione) and 4-aryl-pyrazolo[3,4-<i style="">d</i>]-pyrimidin-6-one derivatives of potential antihypertensive activity

Abstract

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 <b style="">2a-j</b>. Aldehydes<i style=""> </i>with<i style=""> ortho</i>-hydroxy substituent namely salicylaldehyde and 2-hydroxy-3-methoxybenzaldehyde undergo Michael-type addition of the hydroxyl-proton to the C₅-C₆ double bond of the pyrimidine ring to form the tricyclic derivatives <b style="">3a-d</b> while 2-hydroxy-3-nitrobenzaldehyde reacted normally to give <b style="">2j</b>. Compounds from the type <b style="">2</b> react with basic hydroxylamine to give the respective isoxazolopyrimidine derivatives <b style="">4a-g</b> through an intramolecular addition of the oxim-hydroxyl proton to the C₅-C₆ double bond of the pyrimidine ring. The oxime derivatives from the tricyclic compounds <b style="">3a,c</b> undergo rupture of the oxacyclic ring followed by addition of the oxim-proton to the C₅-C₆ double bond of the pyrimidine ring giving rise to the corresponding isoxazolophenols <b style="">5a</b>,<b style="">b</b>. Furthermore, when hydrazine hydrate reacts with the acetyl derivatives <b style="">2a</b>, <b style="">2f</b> and 2h afford the corresponding 4-aryl-5-(1-hydrazono-ethyl)-6-methyl-3,4-dihydro-1<i style="">H</i>-pyrimidin-2-one <b style="">6a-c</b>, while the compounds <b style="">2d</b> and <b style="">3c</b> react under the same reaction conditions to give the pyrazolopyrimidine derivatives <b style="">7</b> and <b style="">8</b>, respectively.