| A new synthesis route of 2-mercapto-5-methoxyimidazo[4,5-b]pyridine was discussed. The route was:2,6-dichloropyridine as the starting material was reacted with sodium methoxide,after nitration,amination,reduction and cyclization to give 2-mercapto-5-methoxyimidazo[4,5-b]pyridine.The effects of the ratio of materials,reaction time and reaction temperature on elementary reaction were studied.Synthetic technologies were optimized.Optimum conditions of target compound were gained through studying single factor experiments and orthogonal experiment.Total yields of the synthesis route was 38.4%.Optimal conditions of methoxylation were obtained as follows:2,6-dichloropyridine 2.96g,sodium methoxide 1.51g,reaction temperature 65℃,reaction time 5h.Optimal conditions of nitration were obtained as follows:2-chloro-6-methoxypyridine 2.87g, fuming nitric acid 12.5mL,concentrated sulfuric acid 25mL,reaction temperature20℃, reaction time 4h.Optimal conditions of amination were obtained as follows: 2-chloro-3-nitro-6-methoxypyridine 3.7g,ammonia 70mL,reaction temperature75℃, reaction time7h.Meanwhile,2-mercapto-5-methoxyimidazo[4,5-b]pyridine was prepared "in one pot": 2,3-diamino-6-methoxypyridine was reduced by hydrazine hydrate with Raney Nickel in normal pressure.Finally cyclization was cyclized straightforward without purification to give 2-mercapto-5-methoxyimidazo[4,5-b]pyridine.Optimum conditions of reduction and cyclization were gained through studying orthogonal experiment:2-amino-3-nitro-6-methoxypyridine 3.38g,hydrazine hydrate 1.36g,Raney Ni 0.38g,NaOH1.2g, CS21.57mL.In addition,the advantages and diadvantages of new synthesis route and reported route were discussed through comparing reaction conditions and yields of single factor experiments.The structures of the final compounds and the intermediate produets were confirmed by melting point,MS and NMR. |
