Synthetic study of vonoprazan fumarate / 国际药学研究杂志

ABSTRACT

Objective To develop a practical synthetic process of vonoprazan fumarate with high-yield and lower impurities to meet the quality requirements. Methods By using 5-(2-fluorophenyl)pyrrole-3-carboxaldehyde as the starting material,the qualified vonoprazan fumarate was synthesized via the following steps:①N-sulfonylation and the chloride impurity was removed by recrystalli-zation from MeOH;②the aldehyde was converted to amine by reductive amination,followed by forming the vonoprazan chloride to re-move the dimethylamino impurity;③vonoprazan free base was obtained by neutralization and then converted to fumarate at room tem-perature and finally recrystallized from MeOH/H2O(11). Results An impurity controllable synthetic process was developed with a 4％total yield improving. The final product was confirmed by ESI-MS and 1H NMR. Conclusion The synthetic process with single im-purity less than 0.1％and purity above 99.5％was obtained and suitable for scale production of vonoprazan fumarate.