Method For Preparing Minodronic Acid

- Apr 10, 2019-

Minoxidoic acid is a novel heterocyclic diphosphate compound developed by Yamanouchi Pharmaceutical Co., Ltd. for the treatment of osteoporosis and hypercalcemia caused by osteoporosis and malignant tumors. Pharmacological experiments have shown that it inhibits bone. The absorbed activity is 2, 10 and 100 times that of disodium incadronate, alendronate, and disodium pamidronate, respectively, and can fight against myeloma and Tumor-induced osteolysis. This product has significant benefits in the incidence of spinal fractures, and has a significant reduction in gastrointestinal side effects, and has now been identified as an effective anti-osteoporosis, a new drug to prevent fractures. The research and development of this drug will undoubtedly provide a safer, more effective and effective treatment for patients with clinical diseases. It will produce good social and economic benefits after listing.


The invention belongs to the field of medicinal chemical industry, and particularly relates to a minodronic acid hydrate [1-hydroxy-2-(imidazo[l,2_a]pyridin-3-yl)ethylidene]1,1-diphosphonic acid monohydrate The method of synthesis of matter. Minodronic Acid Hydrate, chemical name [1-hydroxy-2_(imicono[1,2-a]pyridin-3-yl)ethylidene]1,1-diphosphate monohydrate .


A method for preparing minodronic acid hydrate by first ketone-protecting compound (VII) to obtain compound (VI), and then subjecting compound (VI) to 2-aminopyridine to undergo nucleophilic substitution reaction to obtain compound ( V), the compound (V) undergoes a cyclization reaction after deketone protection to obtain a compound (IV); the compound (IV) is hydrolyzed to obtain a compound (III), and the compound (III) is subjected to a double phosphorylation to obtain a compound (II). The compound (II) is recrystallized to obtain the minodronic acid hydrate (I); the starting material of the synthetic route of the invention has sufficient source, low cost, the reagent used in the reaction process is environmentally friendly, and the industrial production is safe, and the reaction conditions are Mild, easy to operate, less side reactions, simple post-treatment, no special or complicated reaction equipment, easy to industrialize production.

Ethyl trans-4-oxo-2-butenoate CAS 2960-66-9 is the main intermediate for producing Minoxidoic acid.