公开(公告)号：US08450491B2

公开(公告)日：2013-05-28

申请号：US10576971

申请日：2003-06-06

申请人： Sanjay Suri ,  Jujhar Singh ,  Gurdeep Singh Sarin ,  Madan Pal Tanwar ,  Manu Mahendru

发明人： Sanjay Suri ,  Jujhar Singh ,  Gurdeep Singh Sarin ,  Madan Pal Tanwar ,  Manu Mahendru

IPC分类号： C07D215/04 ,  A61K31/47

CPC分类号： C07D215/18

摘要： A method for the preparation of montelukast acid sodium salt thereof in amorphous form has been described. The method comprises of following steps: (a) generating the dilithium dianion of 1-(mercaptomethyl)cyclopropane acetic acid, by reacting with alkyl lithium, (b) coupling the said dianion with wet mesylate to get montelukast acid in crude form, (c) obtaining DCHA salt in crude form by adding dicyclohexylamine (DCHA) to crude acid obtained in the above step (b), (d) purifying and converting the said DCHA salt in crude form, to montelukast acid in pure form, and (e) reacting the pure montelukast acid in a polar protic solvent with a source of sodium ion followed by evaporating the solvent and triturating of the residue with non-polar water immiscible solvent.

摘要翻译： 已经描述了制备无定形形式的孟鲁司他酸钠盐的方法。 该方法包括以下步骤：（a）通过与烷基锂反应生成1-（巯基甲基）环丙烷乙酸的二锂二阴离子，（b）将所述二价阴离子与湿甲磺酸酯偶联得到粗制形式的孟鲁司特酸，（c 通过向上述步骤（b）中获得的粗酸加入二环己基胺（DCHA），（d）以粗制形式将所述DCHA盐纯化并转化成纯形式的孟鲁司特酸，得到粗制形式的DCHA盐，和（e） 使极性质子溶剂中的纯孟鲁司特酸与钠离子源反应，然后蒸发溶剂并用非极性水不混溶溶剂研磨残余物。