Synthesis of 5<i>H</i>‐[1]benzopyrano[4,3‐<i>b</i>]pyridin‐5‐ones containing an azacannabinoidal structure

Abstract

Abstract Starting from 7‐alkoxy‐4‐aminocoumarins 5,6,8,12 , and 13 as key intermediates, this paper describes two different methods for the preparation of azacannabinoidal 5 H [1]benzopyrano[4,3‐ b ]pyridin‐5‐ones 24–27, 38 , and 39 containing typical structural requirements for ZNS activity. First, Michael addition of 6 and 8 to the double bonds of alkyl vinyl ketones 14 and 15 resulted in a mixture of tetrahydropyridines 24–27 and fused pyridines 20–23 the latter of which were reduced by sodium cyanoborohydride to give the target compounds 24–27 . The second, pyridine ring closure was accomplished by a combination of Vilsmeier acetylation and formylation resulting in fused 4‐chloropyridines 31–33 followed by reduction.