73920-60-2Relevant academic research and scientific papers
Efficient synthesis of 1,4-thiazepanones and 1,4-thiazepanes as 3d fragments for screening libraries
Pandey, Anil K.,Kirberger, Steven E.,Johnson, Jorden A.,Kimbrough, Jennifer R.,Partridge, Danika K. D.,Pomerantz, William C. K.
, p. 3946 - 3950 (2020/06/08)
1,4-Thiazepanes and 1,4-thiazepanones represent seven-membered ring systems with highly 3D character and are currently underrepresented in fragment screening libraries. A nuclear magnetic resonance (NMR) fragment screen identified 1,4-acylthiazepanes as new BET (bromodomain and extraterminal domain) bromodomain ligands; however, an efficient and readily diversified synthesis for library development has not been reported. Here we report a one-pot synthesis using α,β-unsaturated esters and 1,2-amino thiols to form 1,4-thiazepanones as precursors to 1,4-thiazepanes with high 3D character. This reaction proceeds in reasonable time (0.5-3 h) and in good yield and tolerates a broad scope of α,β-unsaturated esters. Several 1,4-thiazepanes were synthesized by a two-step transformation and were characterized as new BET bromodomain ligands using protein-observed 19F NMR. This synthesis should provide ready access to diverse 3D fragments for screening libraries.
Contributions to the Chlorination-Dehydrochlorination of Perhydro-1,4-thiazepin-5-ones
Wamhoff, Heinrich,Theis, Christoph H.
, p. 995 - 1009 (2007/10/02)
The synthesis of unsaturated derivatives of perhydro-1,4-thiazepin-5-ones 3 is investigated.Depending on the substitution the thiazepin-5-ones 3 thereby react with sulfuryl chloride to yield 7-and 2-chloro derivatives 6 and 7; the latter eliminate hydrogen chloride only in the presence of a base (PVP, 8) to give the Δ2-thiazepines 9a,b,d,e,g, whereas the 7-chloro derivatives in situ afford the Δ6-thiazepines 10a - f, the 1,4-thiazepinium chloride 11c being isolated as intermediate. tert-Butyl hypochlorite forms according to the substituent size and solvent polarity 2- and 7-halogenation products, as well as 1,4-thiazepin-5-one-S-oxides 22.Further halogenation of the Δ6-1,4-thiazepines 10a - c results in the formation of unsaturated halogen derivatives 24, 25, and 26.
