Process for preparing dazoline phospho acid

Abstract

A process for preparing Zuolailingsuan from imidazole includes such steps as reaction between imidazole and alpha-haloacetate or alpha-haloacetonitrile in inertial solvent under catalysis of alkali, hydrolyzing in phosphoric acid solution, reacting on phosphorus trichloride (or trioxychloride), acidic hydrolyzing, and recrystallizing in distilled water.

Description

technical field

[0001] The invention relates to a preparation method for one-step synthesis of zoledronic acid by using imidazole as a starting material. Background technique

[0002] Zoledronic acid, whose chemical name is [1-hydroxy-2-(1-imidazolyl) ethylidene] diphosphate monohydrate, is a heterocyclic third-generation bisphosphonic acid drug for the treatment of hypercalcemia. The drug can reduce the incidence of bone and soft tissue metastasis in cancer patients. It can be used as an adjuvant treatment for cancer patients with bone metastasis to relieve hypercalcemia, bone pain and the risk of fractures. It can also be used to delay the occurrence of bone metastasis. Its mechanism of action is to inhibit bone metastasis. Absorption reduces the release of bone matrix growth factors or inhibits cancer cells from adhering to the bone matrix. Clinical trials have shown that this product is the strongest bisphosphonate compound so far. In 2000, zoledronic acid was first ap...