Vonoprazan FuMarate

Vonoprazan fumarate is white to nearly white crystals or crystalline powder which melts at 194.8°C . It can be dissolved in dimethyl sulfoxide, but has limited solubility in N,N-dimethylacetamide, N,N-dimethylformamide, methanol, and water. It is only slightly soluble in ethanol (99.5%), and has very low solubility in 2-propanol, acetone, 1-octanol, and acetonitrile.

Vonoprazan Fumarate (CAS# 881681-01-2) is a useful research chemical and a ATPase potassium-competitive acid blocker.

Compared with traditional irreversible proton pump inhibitors (such as omeprazole, esomeprazole, etc.), Vonoprazan fumarate advantages:
① The onset of action is good, and the maximum acid-suppressing effect will be achieved on the first day of administration;
② Oral administration, not affected by gastric acid damage;
③It can improve the phenomenon of acid breakthrough at night.

Vonoprazan fumarate (TAK-438) is a new oral anti-gastric acid drug jointly launched by Takeda Pharmaceutical and Otsuka Pharmaceutical. It can be used for the treatment of erosive esophagitis, gastric ulcer and duodenal ulcer.

Vonoprazan fumarate is a potassium ion (K+) competitive acid blocker (P-CAB), which is a reversible proton pump inhibitor. It can inhibit the combination of K+ and H+-K+-ATPase (proton pump), so that secretion of gastric acid is terminated. Vonoprazan fumarate has a strong and lasting inhibitory effect on gastric acid secretion.

Vonoprazan FuMarate is prepared by the reaction of vonoprazan and (2E)-but-2-enedioic acid. The steps are as follows:
Step 1: (2E)-but-2-enedioic acid With sodium hydroxide In water at 50 - 60℃.
Step 2: vonoprazan In water; toluene at 25 - 35℃; Reagent/catalyst.
Add 730g of water and 73g of fumaric acid to a 2L reaction flask at 5060, stir and disperse, control the temperature between 5060, add 25g of hydrogen hydroxide dropwise to the fumaric acid suspension The solution of sodium and 300 g of water was gradually dissolved in the system during the dropwise addition, and the aqueous solution of compound was obtained and kept for use.Between 25 and 35°C, take half of the toluene solution of compound obtained in the previous step and put it into a 5L reaction flask, and add the aqueous solution of the above compound dropwise to it. During the dropwise addition, the system has a white solid precipitation. After the dropwise addition was completed, keep stirring for 2-4 hours, filter, and dry the filter cake at 50°C to obtain 131.32 g of white solid, the HPLC purity was 99.96%, and the yield was 94%.