Aminoazoles as Key Reagents in Multicomponent Heterocyclizations

TWO-STAGE ONE-POT INTERACTION OF ACYCLIC Β-Ketoesters, DMFDMA AND 2-Cyanomethylbenzimidazole

“…Since the interaction between 1,3-cyclohexanediones 1, DMFDMA (2) and 2-cyanomethylbenzimidazole 4 is a highly selective process, an analogous reaction applying acyclic β-ketoesters 6 as representatives of 1,3-diketocompounds was also expected to give the corresponding benzo [4,5]imidazo[1,2-a]pyridine-4-carbonitrile derivatives. For our initial experiments we chose ethyl acetoacetate (6a) as the simplest representative of acyclic β-ketoesters that on the first stage reacted with DMFDMA 2 (2.5 mmol of each reagent) to give enamine 7a (Table 1) according to the known method [8] with the reaction time prolonged up to 10 min to increase the conversion extent (reaction monitored by GC-MS).…”

“…An accelerated research in this field has been driven by the fast development of the high-throughput biological screening and combinatorial chemistry. Since the simple variations of the widely known multicomponent reactions are largely investigated the more and more complex and polyfunctional starting buildingblocks are involved in the studies of such processes [5][6][7]. A special attention here should be paid to the problem of selectivity and efficiency of such transformations, since the presence of several reaction centers in one building block often leads to an ambiguous reaction outcome.…”

“…Recently we used its reactivity within the discussed above synthetic approach using cyclic 1,3-dicarbonyl compounds of type 1 as the starting α-CH 2 -carbonyls (Scheme 1). This condensation was found to be a highly selective process leading to 4-oxo-1,2,3,4-tetrahydrobenzo [4,5]imidazo[1,2-a]quinolin-6-yl cyanides (5) [18].…”

“…General procedure for preparation of 4-cyanobenzo [4,5]imidazo[1,2-a]pyridine-2-carboxylates (8a-j). Enamines 7a-j were obtained by reaction of neat β-ketoesters 6a-j (2.5 mmol) with DMFDMA (297 mg, 2.5 mmol) heated under microwave irradiation at 100°С during 10 min (20 min for enamine 7h).…”

“…Carried out under microwave irradiation in 2-propanol in the presence of piperidine, this transformation leads to the formation of 4-cyanobenzo [4,5]imidazo [1,2-α]pyridine-2-carboxylates, whereas at room temperature in methanol in the presence of sodium methylate 1-hydroxybenzo [4,5]imidazo[1,2-α]pyridine-4-carbonitriles are formed. Intermediate enamines initially formed from β-ketoesters and DMFDMA attack methylene group of 2-cyanomethylbenzimidazole followed by heterocyclizaton.…”