S_NAr-Based, Facile Synthesis of a Library of Benzothiaoxazepine-1,1′-dioxides

Abstract

The construction of a library of benzothiaoxazepine-1,1’-dioxides utilizing a one-pot, SNAr diversification – ODCT50 scavenging protocol is reported. This protocol combines microwave irradiation to facilitate the reaction, in conjunction with a soluble ROMP-derived scavenger (ODCT) to afford the desired products in good overall purity. Utilizing this protocol, a 78-member library was successfully synthesized and submitted for biological evaluation.

One Pot Regioselective Synthesis of a Small Library of Dibenzo[b,f][1,4]thiazepin-11(10H)-ones via Smiles Rearrangement

“…Additionally, the molecular structure of the representative product 3c was determined by X-ray crystallography analysis (Figure ). Thus, a plausible mechanism was presented in Scheme , on the basis of our results combined with the reported papers . The reaction of 1c with 2b yielded compound 7 .…”

“…Many methods have been used to synthesize benzoazepine-2-ones, such as multistep cyclization processes, denitrocyclization by intramolecular substitution of the nitro group, photoisomerization via homolytic cleavage of the S–N bond, and click-cyclization via microwave assistance . However, there are still some potential limitations including the demand for substrates which are not readily or commercially available, and inefficiency of the transformations restrain the wider utilization.…”

Accessing Stereochemically Rich Sultams via Microwave-assisted, Continuous-flow Organic Synthesis (MACOS) Scale-out

“…xv Utilizing the Anton Parr Synthos 3000® microwave platform, a collection of eight optically pure, stereoisomeric sultams ( 14 – 21 ) was produced demonstrating facile access to stereochemically-rich small-molecule collections for HTS (Scheme 2). Reactions were carried out on 100 mg scale in DMSO at 180 °C for 50 minutes, followed by dilution, filtration, and purification by column chromatography to produce the desired benzothiaoxazepine-1,1-dioxides 14 – 21 in high yield.…”

Sultams: Recent Syntheses and Applications

“…Hanson and co‐workers have reported several examples in which various sultam derivatives are accessed by means of nucleophilic aromatic substitution (S N Ar) . As one example, a library of seven‐membered benzosultams was prepared by click cyclization involving epoxide ring opening and S N Ar cyclization (Scheme ).…”