A new and efficient palladium‐catalyzed amination of imidazo[2,1‐b][1,3,4]thiadiazole at the C‐5 position under microwave irradiation is reported. The reactivity toward bromine release at the C‐5 position was investigated, and palladium‐catalyzed cross‐coupling conditions were optimized. A wide range of amines was employed to examine the scope and limitations of the method. To complete this methodological study, the influence of the nature and the positions of additional imidazo[2,1‐b][1,3,4]thiadiazole substitutions was investigated.
A selective, practical and scalable aerobic oxidation of alcohols is described using catalytic amounts of 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ) and HNO 3 , with molecular oxygen serving as the terminal oxidant. The method was successfully applied to the oxidation of a wide range of benzylic, propargylic and allylic alcohols, including two natural products, namely carveol and podophyllotoxin. The conditions are also applicable to the selective oxidative deprotection of PMB ethers.
Our efforts toward the process development of drug candidate 1 are described in a series of two papers. This manuscript focuses on the synthesis of kilogram quantities of acid precursor 2 to provide batches of material for preclinical studies and first-in-human clinical trials. Our approach relies on a chiral resolution to furnish the desired stereocenter, a cryogenic carboxylation, and N-alkylation of chloride derivative 26 prepared by a Suzuki coupling. Further efforts pursued to improve those key steps that could become issues on larger scale are also discussed.
Highly substituted imidazo[2,1-b][1,3,4]thiadiazole derivatives were synthesized through successive cyclization and Suzuki-Miyaura cross-coupling reactions. The palladiumcatalyzed coupling reaction was optimized and a wide range
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.