Salts and Polymorphs of Dexrabeprazole

Abstract

The present invention provides dexrabeprazole magnesium hydrate and a process for its preparation. The present invention also provides a magnesium, calcium or potassium salt of dexrabeprazole, optionally in amorphous form, and processes for its preparation.

What is claimed is: 
     
         1 . Dexrabeprazole magnesium hydrate. 
     
     
         2 . Dexrabeprazole magnesium hydrate according to  claim 1 , having a water content ranging from about 8% w/w to about 11% w/w. 
     
     
         3 . Dexrabeprazole magnesium hydrate according to  claim 2 , having a water content ranging from about 9.5% w/w to about 10.5% w/w. 
     
     
         4 . A process for preparing dexrabeprazole magnesium hydrate according to  claim 1 , which process comprises: reacting dexrabeprazole or a salt thereof with an alcoholic solution of magnesium chloride. 
     
     
         5 . The process according to  claim 4 , wherein the process comprises forming a reaction mass comprising the dexrabeprazole or salt thereof and alcoholic magnesium chloride; filtering the reaction mass; adding an organic solvent to the filtrate; and isolating the dexrabeprazole magnesium hydrate. 
     
     
         6 . The process according to  claim 5 , wherein the organic solvent is diisopropyl ether. 
     
     
         7 . The process according to  claim 4 , wherein the dexrabeprazole or salt thereof is prepared by: i) contacting 2-[[[4-(3-methoxypropoxy)-3-methyl-2-pyridinyl]methyl]thio]-1H-benzimidazole with a chiral reagent in an organic solvent; ii) adding water to the reaction mass followed by titanium isopropoxide; iii) adding a base to the reaction mass followed by an oxidizing agent to obtain dexrabeprazole; iv) optionally converting dexrabeprazole to a salt thereof. 
     
     
         8 . The process according to  claim 4 , wherein the dexrabeprazole is converted to a salt thereof and the dexrabeprazole salt is reacted with the alcoholic solution of magnesium chloride. 
     
     
         9 . The process according to  claim 7 , wherein the reaction mass is heated to a temperature ranging from 45° C. to 60° C. after addition of titanium isopropoxide. 
     
     
         10 . Dexrabeprazole magnesium salt. 
     
     
         11 . Dexrabeprazole hemicalcium salt. 
     
     
         12 . Dexrabeprazole potassium salt. 
     
     
         13 . A process for preparing dexrabeprazole magnesium salt according to  claim 10 , which process comprises contacting dexrabeprazole with a magnesium salt in an organic solvent in the presence of an organic or inorganic base. 
     
     
         14 . A process for preparing dexrabeprazole hemicalcium salt according to  claim 11 , which process comprises contacting dexrabeprazole with a calcium salt in an organic solvent in the presence of an organic or inorganic base. 
     
     
         15 . A process for preparing dexrabeprazole potassium salt according to  claim 12 , which process comprises contacting dexrabeprazole with a potassium salt in an organic solvent in the presence of an organic or inorganic base. 
     
     
         16 . The process according to  claim 13 , wherein the base is selected from the group consisting of monomethyl amine, triethyl amine, N,N-diisopropyl ethyl amine, pyridine, morpholine, sodium carbonate, potassium carbonate, sodium bicarbonate, potassium bicarbonate, potassium hydroxide, sodium hydroxide and lithium hydroxide. 
     
     
         17 . The process according to  claim 14 , wherein the base is selected from the group consisting of monomethyl amine, triethyl amine, N,N-diisopropyl ethyl amine, pyridine, morpholine, sodium carbonate, potassium carbonate, sodium bicarbonate, potassium bicarbonate, potassium hydroxide, sodium hydroxide and lithium hydroxide. 
     
     
         18 . The process according to  claim 15 , wherein the base is selected from the group consisting of monomethyl amine, triethyl amine, N,N-diisopropyl ethyl amine, pyridine, morpholine, sodium carbonate, potassium carbonate, sodium bicarbonate, potassium bicarbonate, potassium hydroxide, sodium hydroxide and lithium hydroxide. 
     
     
         19 . A salt according to  claim 10  in amorphous form. 
     
     
         20 . A salt according to  claim 11  in amorphous form. 
     
     
         21 . A salt according to  claim 12  in amorphous form. 
     
     
         22 . A process for preparing a magnesium, calcium or potassium salt of dexrabeprazole in amorphous form, the process comprising addition of an inorganic base or a salt of magnesium, calcium or potassium to dexrabeprazole or a salt thereof in a solvent to form a solution and isolation of the magnesium, calcium or potassium salt of dexrabeprazole in amorphous form. 
     
     
         23 . The process according to  claim 22 , wherein the solution is heated to a temperature ranging from 35° C. to 50° C., and the isolation comprises filtration and drying under vacuum at a temperature ranging from 20° C. to 30° C. 
     
     
         24 . The process according to  claim 22 , wherein the dexrabeprazole has been prepared by contacting 2-[[[4-(3-methoxypropoxy)-3-methyl-2-pyridinyl]methyl]thio]-1H-benzimidazole with a chiral titanium complex in an organic solvent followed by oxidation using an oxidizing agent and a base to obtain dexrabeprazole. 
     
     
         25 . The process according to  claim 24 , wherein the 2-[[[4-(3-methoxypropoxy)-3-methyl-2-pyridinyl]methyl]thio]-1H-benzimidazole is added at a temperature ranging from 45° C. to 75° C. 
     
     
         26 . The process according to  claim 24  wherein the base and oxidizing agent are added at a temperature ranging from 25° C. to 35° C. 
     
     
         27 . The process according to  claim 24 , wherein the oxidizing agent is selected from the group consisting of hydrogen peroxide, cumene hydroperoxide, tert. butyl hydorperoxide, peracetic acid, m-chloro perbenzoic acid, sodium hypochlorite and sodium hypobromite. 
     
     
         28 . The process according to  claim 24 , wherein the chiral titanium complex is prepared using (+) diethyl-L-tartrate.