A New Method for Regioselective Synthesis of a Broad-Spectrum Parenteral S-3578-Related Cephalosporin Bearing an Imidazo[4,5-b]pyridinium Derivative at C-3’

Efficient Azacycle Formations Developed in Japanese Pharmaceutical Industries: Elegancy, Logistics, and Training (ELT) “Sandwich” for Process Chemists

“…A research group at Shionogi found an effective process for the synthesis of cephalosporin 222 bearing an imidazo­[4,5- b ]­pyridinium moiety at C-3′ (Scheme ). The group utilized a substitution reaction of iodomethyl cephalosporin intermediate 219 with 2,3-diaminopyridine derivative 225 , which was derived from 2,3-diaminopyridine, 3-aminopropionaldehyde derivative 223 , N , N -dimethylformamide dimethyl acetal (DMFDMA), and Boc 2 O, as a second-generation synthesis. Interestingly, the nucleophilic reaction at the pyridine nitrogen of 225 induced the subsequent cyclization to form the imidazopyridine ring to give only the target compound 222 , while the first-generation synthesis required an end-game separation from a mixture of 222 and the imidazolyl ammonium byproduct 221 ( 222 : 221 ratio of 4–5:1).…”

Oximes of five-membered heterocyclic compounds with two heteroatoms 2. Reactions and biological activity (Review)

“…Apart from these widely used preparations it is necessary to mention the very extensive range of patents and publications devoted to thiazole oximes, which feature in the composition of cephalosporin antibiotics . Apart from the thiazole oxime fragments cephalosporin antibiotics also include oxazole [220], isoxazole [221,222], isothiazole [223,224], selenazole [225], pyrazole [226][227][228][229][230][231], imidazole [232][233][234][235][236][237][238][239][240], and benzimidazole [241] fragments. High antibacterial activity has also been demonstrated by benzoxazole [242], isoxazole [243,244], thiazole [243,244], pyrazole [243,244], imidazole [243][244][245], and benzimidazole [249] oximes not containing cephalosporin fragments.…”