Improved Synthetic Approach to Tenatoprazole

Abstract

An improved synthetic approach to tenatoprazole 1 is described. It started from 2,3,5‐trimethyl‐4‐nitropyridine‐N‐oxide 2 with acetic anhydride via rearrangement and hydrolysis to give 3, Chlorination with SOCl₂ yielded 2‐chloromethyl‐3,5‐dimethyl‐4‐nitropyridine hydrochloride 4, then 4 condensed with 2‐mercapto‐5‐methoxy imidazole [4,5‐b]pyridine 5 to give 5‐methoxy‐2‐[(4‐nitro‐3,5‐dimethyl‐2‐pyridinyl)methylthio]imidazole[4,5‐b]pyridine 6. At last the title compound 1 was produced by two methods: 6 was oxidized with MCPBA and then methoxylated with CH₃ONa to give 1 and 6 was first methoxylated with CH₃ONa and then oxidized with MCPBA to give 1. The overall yield is around 26% for both five‐step syntheses.

Keywords:

• chlorination
• methoxylate
• oxidize
• rearrangement
• tenatoprazole

Acknowledgment

The authors thank the management of Zhejiang Shangyu Sanhe Pharmachem Co., Ltd., for financial assistance. We also thank Yuanjiang Pan for his assistance on ¹H NMR work.