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

Shokol, T., Gorbulenko, N., Tsapko, M., Khilya, V. (2024). Mannich Bases of Chromones Containing a 2,3-fused Heterocyclic Ring. French-Ukrainian Journal of Chemistry, 12(1), 1–16. https://doi.org/10.17721/fujcV12I1P1-16

Aminomethylation of chromones сontaining 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-7Н-сhromeno[3',2':3,4]pyrrolo[1,2-а]quinolin-7-ones and 9-alkyl-8-hydroxy-3-methyl-5-R-11H-chromeno[3’,2’:3,4]pyrrolo[2,1-b][1,3]thiazol-11-ones with bisdialkylaminomethanes was studied. The α-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-7Н-сhromeno[3',2':3,4]pyrrolo[1,2-а]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)-8/10-alkyl-9-hydroxy-12H-chromeno[3,2-a]indolizin-12-ones and 11,13-di(dialkylaminomethyl)-9-ethyl-10-hydroxy-7Н-сhromeno[3',2':3,4]pyrrolo[1,2-а]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-7Н-сhromeno[3',2':3,4]pyrrolo[1,2-а]quinolin-7-ones occurred only at the pyrrole ring, giving 10-alkoxy-13-dimethylaminomethyl derivatives. Taking into account that derivatives of 7Н-сhromeno[3',2':3,4]pyrrolo[1,2-а]quinolin-7-one system exhibited hypoglicemic and anabolic activities, the obtained Mannich bases may be of interest as potential biologically active substances.