Studies on quinazolinones. <b>2</b>. Synthesis of 2‐(4‐benzylpiperazin‐1‐ylmethyl)‐2,3‐dihydro‐5<i>H</i>‐oxazolo[2,3–6]quinazolin‐5‐one and ‐2,3‐dihydro‐5<i>H</i>‐thiazolo[2,3‐<i>b</i>]quinazolin‐5‐one

Abstract

Abstract 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(1 H , 4(3 H )‐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‐5 H ‐oxazolo[2,3‐ b ]quinazolin‐5‐one ( 13 ). The title compound, 2‐(4‐benzylpiperazin‐1‐ylmethyl)‐2,3‐dihydro‐5 H ‐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‐2 H ‐thioxoquinazolin‐4(3 H )‐one ( 16 ) via the analogous reactions gave the 2‐bromomethyl‐2,3‐dihydro‐5 H ‐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‐5 H ‐thiazolo[2,3‐ b ]quinazolin‐5‐one ( 8 ) only in poor yield (8%). As major product, the dehydrobrominated compound, 2‐methylene‐2,3‐dihydro‐5 H ‐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.