Method for preparing compound 2-(imidazo [1, 2-a] pyridine-3-yl) acetonitrile

Abstract

The invention discloses a method for preparing a compound 2-(imidazo [1,2-a] pyridine-3-yl) acetonitrile, which is a new method for preparing a key intermediate of minodronic acid, comprising the steps of: with a compound 3- imidazo [1, 2-a] pyridine carboxaldehyde with the formula (II) and a compound tosylmethyl isocyanide with the formula (III) as raw materials, carrying out chemical reaction in an organic solvent containing glycol dimethyl ether and an alkaline medium of potassium tert-butoxide or sodium tert-butoxide; separating and purifying to obtain the compound 2-(imidazo [1, 2-a] pyridine-3-base) acetonitrile, wherein the process of the chemical reaction is disclosed in the specification of the invention. In the invention, by means of the method for preparing the compound with the formula (I), the reaction procedure is shortened, the technical process of the whole reaction is simplified, the use of a highly toxic material sodium cyanide is avoided, the operability of the reaction is strong, the yield is high, and the obtained product has high purity, lower cost, and is easy for the application in the industrialized production.

Description

Technical field: The invention is a preparation method of a pharmaceutical intermediate, which relates to the preparation of a key intermediate of minodronic acid, specifically, a method for preparing 2-(imidazo[1,2-a]pyridin-3-yl)acetonitrile The method can be used as an intermediate for the preparation of minodronic acid. Background technique: Minodronic acid, chemical name 1-hydroxy-2-{(imidazo[1,2-a]pyridin-3-yl)}ethylidene-1,1-bisphosphonic acid, is a new type of heterocyclic Bisphosphonic acid compounds, developed by Japan Yamanouchi Co., Ltd., are used to treat osteoporosis and hypercalcemia caused by osteoporosis and malignant tumors. The results of pharmacological experiments show that the activity of this product in inhibiting bone resorption is 2, 10 and 100 times that of disodium incadronate, alendronate and disodium pamidronate, respectively. . Its chemical structure is as follows: minodronic acid The compound represented by formula (I) is an important ...

AI Technical Summary

Problems solved by technology

This process has a short number of reaction steps, but the synthesis method involves ultra-low temperature reactions, and a large amount of bromine needs to be used in the reaction steps for bromination reaction, which makes the industrialization of this route more difficult

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