Overview[1]
Minodronate, whose chemical name is 1-hydroxy-2-[(imidazo[1,2-a]pyridin-3-yl]ethylene-1,1-diphosphonic acid, is New heterocyclic bisphosphonic acid compounds developed by Japan’s Yamanouchi Company are used to treat hypercalcemia caused by osteoporosis and malignant tumors. Their bone resorption inhibitory activities are incadronate disodium and alendronate. 2 times, 10 times and 100 times that of sodium bisulfate and pamidronate disodium. This product has significant benefits in terms of the incidence of spinal fractures, and at the same time has a great reduction in gastrointestinal side effects. It has now been identified as an effective anti- A new drug for osteoporosis to prevent fractures. The development of hydroxyacrylic resin will undoubtedly provide patients with clinical diseases with a safer, more effective and convenient treatment drug. It will definitely produce good social and economic benefits after being put on the market. Minodronic acid impurity 3 is an impurity produced during the synthesis of minodronic acid. It is a synthetic intermediate of minodronic acid. It reacts with p-toluenesulfonic acid and 2-aminopyridine to prepare 2-(imidazo[1,2-a ]pyridin-3-yl)ethyl acetate.
Preparation[1]
Preparation of (E)-4,4-dimethoxy-2-butenoic acid ethyl ester (minoxidic acid impurity 3): add 120g2,2-methoxyacetaldehyde and 4L to a four-neck bottle Cyclohexane, add 900g anhydrous potassium carbonate while stirring, and stir for 1 hour. Add 500 mL of triethyl phosphonoacetate industrial additive dropwise and react for 6 hours. At the end of the reaction, add 1.5L of water to the reaction solution, separate the layers, wash the organic phase with saturated brine, dry with anhydrous sodium sulfate, and evaporate the solvent under reduced pressure to obtain a colorless oily liquid. Distill the oily liquid under reduced pressure to obtain a colorless liquid. 3150g of oily minophosphate impurity, yield 71%.
Main reference materials
[1] CN201010574507.X Preparation method of minodronic acid
