Preparation method and application of vilazodone hydrochloride IV crystal

Abstract

The invention discloses a preparation method and application of a 5-(4-(4-(5-cyano-3-indolyl)butyl)-1-piperazinyl)benzofuran-2-formamide hydrochloride IV crystal. The method comprises the steps of: 1) under certain temperature, dissolving 5-(4-(4-(5-cyano-3-indolyl)butyl)-1-piperazinyl)benzofuran-2-formamide in an organic solvent to obtain a solution; 2) heating the solution obtained in step 1) to a reflux temperature of 40DEG C; 3) slowly adding concentrated hydrochloric acid dropwise; 4) subjecting the system obtained in step 3) to heat preservation reaction for 0.5-12 hours; 5) conducting filtering to obtain an IV crystal form wet product; and 6) conducting vacuum drying to the wet product obtained in step 5) at 80-140DEG C to a constant weight, thus obtaining the IV crystal. By adopting the technical scheme, the process is simplified, a complex preparation process of the existing IV crystal is overcome, and a mixed crystal can be avoided. The method provided by the invention can achieve high crystal purity, stable volume production and high yield, and is easy to realize industrialized production.

Description

technical field [0001] The present invention relates to the preparation method of 5-(4-(4-(5-cyano-3-indolyl) butyl)-1-piperazinyl) benzofuran-2-carboxamide hydrochloride type IV and application. Background technique [0002] 5-(4-(4-(5-cyano-3-indolyl)butyl)-1-piperazinyl)benzofuran-2-carboxamide hydrochloride (Vilazodone Hydrochloride ), an antidepressant developed by Clinical Date, approved by the U.S. Food and Drug Administration (FDA) on January 21, 2011, for the treatment of moderate to severe depression in adults, the trade name is Viibryd , whose structure is as Figure 10 shown. [0003] Vilazodone hydrochloride is a dual-action potent and selective serotonin (5-HT) reuptake inhibitor and 5-HT1A receptor partial agonist, and it is also the first new type of indolealkylamine antidepressant , compared with the existing clinical antidepressants, it has the characteristics of rapid onset of action and no side effects of sexual dysfunction. Therefore, the research on...

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Problems solved by technology

[0022] The inventors have found through research that the common point of the above two preparation methods of IV crystal form is that other crystal forms of vilazodone hydrochloride are obtained through vacuum drying and crystallization under different temperature conditions, which is very easy to cause mixed crystal phenomenon. Occurs, and the preparation process of the related IV crystal form is complicated

In addition, among the above three preparation methods of V crystal form, method 1 is a direct preparation, but the amount of solvent used is very large, and there is no description of the temperature range that is one of the decisive factors in the preparation of the crystal form; method 2 and method 3 are respectively passed Type IV and Type XIII are obtained by crystal transformation, which has obvious disadvantages that the process is complicated and easily leads to mixed crystals. Therefore, it is very socially meaningful and economically valuable to study the direct preparation method of the new vilazodone hydrochloride IV crystal form.

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