JP2005520831A5 - - Google Patents

Claims (15)

  A process for preparing the crystalline form I of cabergoline comprising producing the toluene solvate form X of cabergoline and converting it to the crystalline form I of cabergoline.   Cabergoline is dissolved in an appropriate amount of toluene, the resulting solution is cooled and stirred, the resulting gel is quenched with cold heptane or cold hexane, and then the resulting cabergoline having the XRD powder pattern shown in FIG. The toluene solvate form X is prepared by collecting the solvate form X and converted to cabergoline form I by storage and / or drying at room temperature. The method according to 1.   The method according to claim 2, wherein an appropriate amount of toluene is 2.5 to 4.0 g of toluene per 1 g of cabergoline.   The method according to claim 2, wherein an appropriate amount of toluene is 3.5 g of toluene per 1 g of cabergoline.   3. The process according to claim 2, wherein the cabergoline used as starting material is an oil, or is in crystalline form or a mixture thereof.   A process according to claim 2, wherein the solution of cabergoline dissolved in toluene is cooled to a temperature below -10 ° C and then stirred overnight.   The method according to any one of claims 2 to 6, wherein the obtained gel is quenched with cold heptane.   8. A process according to claim 7 wherein cold heptane is added to the gel in an amount of 10 to 20 g heptane per gram cabergoline.   The process of claim 2 wherein the final drying is accomplished by heating the solvate Form X solid, reducing the ambient pressure surrounding the solid, or a combination thereof.   The method according to claim 2, wherein the desolvation step and the drying step are combined.   Cabergoline solvate form X having the XRD powder pattern shown in FIG. Table I below:

A solvate form X of cabergoline having the characteristic peak of powder X-ray diffraction shown in FIG.   The cabergoline is dissolved in an appropriate amount of toluene, the resulting solution is cooled and stirred under shaking, the resulting gel is quenched with cold heptane or cold hexane, and then the resulting solvated form of cabergoline 13. A process for preparing a cabergoline solvate form X according to claim 11 or 12, comprising collecting X.   14. The method of claim 13, wherein the resulting gel is quenched with cold heptane.   15. The method of claim 14, wherein the amount of cold heptane added to quench the gel is 10-20 g / g cabergoline.