STUDIES ON QUINAZOLINONES .2. SYNTHESIS OF 2-(4-BENZYLPIPERAZIN-1-YLMETHYL)-2,3-DIHYDRO-5H-OXAZOLO[2,3-B]QUINAZOLIN-5-ONE AND -2,3-DIHYDRO-5H-THIAZOLO[2,3-B]QUINAZOLIN-5-ONE

To search for novel antihypertensive heterocycles in the condensed quinazoline series, two representative compounds were synthesized via a suitable reaction sequences. Treating anthranilonitrile with allyl isocyanate gave 2‐(allylureido)benzonitrile (10) in a quantitative yield. Compound 10 was cyclized to 3‐allylquinazoline‐2(1H, 4(3H)‐dione (11). Bromination of 11 in carbon tetrachloride converted it into the corresponding 3‐(2,3‐dibromopropyl) derivative (12) in 92% yield. Ring closure of 12 was effected by the action of alkali to afford 2‐bromomethyl‐2,3‐dihydro‐5H‐oxazolo[2,3‐b]quinazolin‐5‐one (13). The title compound, 2‐(4‐benzylpiperazin‐1‐ylmethyl)‐2,3‐dihydro‐5H‐oxazolo[2,3‐b]quinazolin‐5‐one (7) could be obtained by a reaction of either 12 or 13 with 1‐benzylpiperazine respectively. Starting from the readily available 3‐allyl‐2H‐thioxoquinazolin‐4(3H)‐one (16) via the analogous reactions gave the 2‐bromomethyl‐2,3‐dihydro‐5H‐thiazolo[2,3‐b]‐quinazolin‐5‐one (19) in good yield. However, the reaction of 19 with 1‐benzylpiperazine provided another target compound, 2‐(4‐benzylpiperazin‐1‐ylmethyl)‐2,3‐dihydro‐5H‐thiazolo[2,3‐b]quinazolin‐5‐one (8) only in poor yield (8%). As major product, the dehydrobrominated compound, 2‐methylene‐2,3‐dihydro‐5H‐thiazolo[2,3‐b]quinazolin‐5‐one (22) was isolated. A preliminary pharmacological evaluation revealed that both compounds 7 and 8 are devoid of the antihypertensive activity. Copyright © 1990 Journal of Heterocyclic Chemistry