Study On Synthesis, Proton Pump Inhibitors - Thai Properly Omeprazole

Tenatoprazole, a new H⁺/ K⁺ -ATP inhibitors (i.e. proton pump inhibitor), is used to treat gastric ulcer, duodenal ulcer (DU), reflux esophagitis, Zollinger-Ellison syndrome and other diseases related to gastric acid disorder. In this paper, by using 2,6-dichloro-3-nitropyridine as the starting material, tenatoprazole has been synthesized via 2-amination, 6-methoxalation, catalytic hydrogenation and cyclization to obtain 5-methoxy-2-mecaptoimidazol[4,5-b]pyridine as the intermediate, replaced by a pro-nuclear reaction with 2-chloromethyl-4-methoxy-3,5-dimethyl pyridine and oxidation to afford the target product in 31.1 total yield. The main contents of the paper are as follows:2,6-dichloro-3-nitropyridine was converted to 2-amino-6-methoxy-3- nitropyridine "in one pot". By investigating the feed ration, reaction temperature and time, the following reaction conditions were confirmed: 2,6-dichloro- 3-nitropyridine, 30g; 25% NH₃·H₂O, 26.0g; MeOH, 600 mL; reaction temperature, 110℃; reaction time, 12h; yield, 65.0%; purity of the intermediate, over 98%.2,3-diamino-6-methoxy pyridine was prepared "in one pot" applying 2-amino-6-methoxy-3-nitropyridine as the substrate. In this method, the catalytic hydrogenation product 2,3-diamino-6-methoxy pyridine was cyclized straightforward without purification to synthesize 5-methoxy-2- mecaptoimidazol [4,5-b]pyridine in 60.0% yield.Etherification of 5-methoxy-2-mecaptoimidazol[4,5-b]pyridine and 2-chloromethyl-4-methoxy-3,5-dimethyl pyridine was accomplished in the presence of MeOH and KOH, with the 89.4% yield and 97.8% purity.In the final step, tenatoprazole was synthesized in 89.1% yield and 97.6% purity by using 8% NaClO as the oxidant and CHCl₃ as the solvent.The structures of the final compounds and the intermediate products were confirmed by NMR and MS, the purities of them were detected by HPLC.