New synthesis of 7‐bromo‐1, 3‐dihydro‐3‐hydroxy‐5‐(2′‐pyridyl)‐2<i>H</i>‐1,4‐benzodiazepin‐2‐one

Abstract

Abstract A new synthesis of 7‐bromo‐1,3‐dihydro‐3‐hydroxy‐5‐(2′‐pyridyl)‐2 H ‐1,4‐benzodiazepin‐2‐one ( 5 ) is described. Starting from bromazepam ( 3 ), C(3) acylation with lead tetraacetate/potassium iodide in acetic acid affords 4 , while its mild hydrolysis according to our recently described method (5) gives 5 . Improved hexamine cyclization of 1 into 3 , via quaternary hexaminium salt 2 , is discussed, and identification of the intermediates 7 and 8 is performed. Compound 5 undergoes on melting, or on brief heating in glacial acetic acid, the thermal rearrangement into quinazolin‐2‐aldehyde ( 13 ), the structure of which is confirmed by oxidation into the ester 14 , which in turn was hydrolyzed to the acid 15 . The same compound ( 5 ) rearranges on heating with manganese(III) acetate in acetic acid into the 3‐amino‐2‐quinolone derivative 6 . On heating in glacial acetic acid in the presence of lead tetraacetate/potassium iodide (or iodine), compound 4 , in addition to giving the aldehyde 13 , ester 14 and acid 15 rearrangement products, affords 1,2‐dihydroquinazolin‐2‐carboxylic acid 16 .