A concise and optimized four-step approach toward 2-(aryl-)alkylsulfanyl-, 4(5)-aryl-, 5(4)-heteroaryl-substituted imidazoles using alkyl- or arylalkyl thiocyanates

2‐Alkylsulfanyl‐4(5)‐aryl‐5(4)‐heteroarylimidazoles: An Overview on Synthetic Strategies and Biological Activity

“…In 2003, Laufer and co‐workers reported a six‐step synthetic protocol to 2‐methylsulfanyl‐ and 2‐benzylsulfanyl‐substituted imidazoles 19 starting from 2‐halogeno‐4‐methylpyridines 13a – c (Scheme ), which was further optimized in 2006 . Analogously to the route depicted in Scheme , the formation of the imidazole ring takes place by cyclization of an α‐aminoketone with thiocyanate salt, although the preparation of the α‐aminoketones 16 was carried out in a different way.…”

“…As already mentioned, this synthetic strategy was further optimized by Laufer and Liedtke . Ethanones 14 were synthesized according to a protocol of Thompson et al, which consisted in reacting the 2‐halogeno‐4‐methylpyridines with ethyl 4‐fluorobenzoate instead of the Weinreb amide and in using sodium bis(trimethylsilyl)amide (NaHMDS) instead of lithium diisopropylamide (LDA) as a base.…”

7-[4-(4-Fluorophenyl)-2-methylsulfanyl-1H-imidazol-5-yl]tetrazolo[1,5-a]pyridine

“…For the biological relevance and the development of p38 MAP kinase inhibitors, see: see: Peifer et al (2006). For the preparation of 2-fluoro-4-[4-(4-fluorophenyl)-2-(methylthio)-1H-imidazol-5-yl]pyridine, see: Laufer & Liedtke (2006). For the preparation of tetrazolopyridines, see: Capelli et al (2008).…”

“…A mixture of 300 mg 2-fluoro-4-[4-(4-fluorophenyl)-2-(methylthio)-1H-imidazol-5-yl]pyridine (Laufer & Liedtke, 2006) in anhydrous DMF with 100 mg sodium azide was heated at 353 K for 12 h. The solvent was then removed under reduced pressure and the residue was diluted with ethylacetate. The organic phase was washed with water and concentrated under reduced pressure.…”

An optimized and versatile synthesis to pyridinylimidazole-type p38α mitogen activated protein kinase inhibitors

“…12 The introduction of the 3-methyl-2-butylamino moiety at the pyridine C 2 -position as well as the moiety at the imidazole C 2 -S-position was envisaged in the last two steps of the synthesis. The key compound for this route 4-(4-fluorophenyl)-5-(2-fluoropyridin-4-yl)-1,3-dihydroimidazole-2-thione (12) was prepared according to a protocol from Laufer and coworkers 8,13 in four steps starting from 2-fluoro-4-methylpyridine (11) in an overall yield of 57% (for details, see Scheme S1 in the ESI †). The alkylsulfanyl moiety was introduced by nucleophilic substitution of thione 12 and the appropriate alkyl halide.…”