Mannich Bases of Chromones Containing a 2,3-fused Heterocyclic Ring

Aminomethylation of chromones & scy;ontaining a 2,3-fused heterocyclic ring, such as indolizine, pyrroloquinoline and pyrrolothiazole, namely 9-hydroxy-6/8-alkyl-12H-chromeno[3,2-a]indolizin- 12-ones, 10-(alk)oxy-9-R-7 & Ncy;-& scy;hromeno[3',2':3,4]pyrrolo[1,2-& acy;]quinolin-7-ones and 9-alkyl-8hydroxy-3-methyl-5-R-11H-chromeno[3',2':3,4]pyrrolo[2,1-b][1,3]thiazol-11-ones with bis dialkylaminomethanes was studied. The alpha-position of the pyrrole ring and the ortho-positions to the hydroxyl group in the benzene ring in the above mentioned systems are active sites and the Mannich reaction can occur at these three positions as shown for 10-hydroxy-7 & Ncy;- & scy;hromeno[3',2':3,4]pyrrolo[1,2-& acy;]quinolin-7-one yielding 9,11,13-tri(dialkylaminomethyl) derivative. Using the strategy of introducing substituents into the active centers, as well as replacing the OH group with OAlk, it was possible to obtain mono- and diaminomethylation products. The above systems substituted at positions 6 or 8 of the chromone ring afforded di(dialkylaminomethyl) products, respectively 5,7-di(dimethylaminomethyl)-9-alkyl-8-hydroxy-3-methyl-11H- chromeno[3',2':3,4]pyrrolo[2,1-b][1,3]thiazol-11-ones, 6,8- or 6,10-di(dimethylaminomethyl)-8/10alkyl-9-hydroxy-12H-chromeno[3,2-a]indolizin-12-ones and 11,13-di(dialkylaminomethyl)-9ethyl-10-hydroxy-7 & Ncy;-& scy;hromeno[3',2':3,4]pyrrolo[1,2-& acy;]quinolin-7-ones. Monoaminomethylated products were prepared for 5-acyl-8-hydroxy-3-methyl-11H-chromeno[3',2':3,4]pyrrolo[2,1- b ][1,3]thiazol-11-ones. Aminomethylation of 10-alkoxy-7 & Ncy;-& scy;hromeno[3',2':3,4]pyrrolo[1,2- & acy; ]quinolin-7-ones occurred only at the pyrrole ring, giving 10-alkoxy-13-dimethylaminomethyl derivatives. Taking into account that derivatives of 7 & Ncy;-& scy;hromeno[3',2':3,4]pyrrolo[1,2-& acy;]quinolin-7- one system exhibited hypoglicemic and anabolic activities, the obtained Mannich bases may be of interest as potential biologically active substances.