A Novel Method For The Selective Functionalization Of Imidazo[1,2-a]pyridine

Imidazo[1,2-a]pyridine is a very important skeleton in drug design and nowadays it is often found in common drug molecules and chemical products. More than 1450 patents about the heterocycle have been applied for since 2000. Drugs containing this fragment have a wide variety of pharmacological activities and they are commercial available in the pharmaceutical market, such as Minodronic acid,Alpidem,Olprinone, Zolpidem, Zolimidine and so on.By comparison,there is an obvious common ground that the C-3 position of theimidazo[1,2-a]pyridine of these drugs are occupied by substituent groups. Thus,themodification on imidazo [1,2-a] pyridine C-3 has attracted much attention in the fieldof organic chemistry.The C-3 position of imidazo [1,2-a] pyridine is electron rich,which makes it capable of being attacked by an electrophilic agent or a radical. At thesame time,through the electrophilic and free radicals to achieve the C-3 position ofthe functional group also become research hot spots of the field of organic chemistry.Our modification of the imidazo [1,2-a] pyridine C-3 position mainly consists of two parts:1. A regioselective synthesis of 3-fluorinated imidazo[1,2-a]pyridines usingSelectfluor as the fluorinating reagent in aqueous condition is described. In thepresence of DMAP,the reaction mainly gave monofluorinated product viaelectrophilic fluorinated process in moderate to good yields.2. A regioselective alkoxycarbonylation of imidazoheterocycles using carbazatesas ester group sources in DMSO was developed,in which an inexpensive FeCl2·4H2Owas used as the catalyst and (NH4)2S2O8 as the oxidant. The reaction proceededsmoothly under air atmosphere to give the 3-alkoxycarbonylated products in moderateto good yields.