Processes for the preparation of uracil derivatives

Abstract

The present invention relates to processes and intermediates for preparing Gonadotropin-Releasing Hormone (GnRH) receptor antagonists of structure (VI); and stereoisomers and pharmaceutically acceptable salts thereof.

1 .- 11 . (canceled) 
     
     
         12 . Amorphous 4-((R)-2-[5-(2-fluoro-3-methoxy-phenyl)-3-(2-fluoro-6-trifluoromethyl-benzyl)-4-methyl-2,6-dioxo-3,6-dihydro-2H-pyrimidin-1-yl]-1-phenyl-ethylamino)-butyric acid sodium salt (compound 5-1) having an impurity profile comprising one or more of the following substances:
 heptane,   methyl isobutyl ketone,   isopropyl acetate, and   methyl ethyl ketone.   
     
     
         13 . A pharmaceutical composition comprising amorphous 4-((R)-2-[5-(2-fluoro-3-methoxy-phenyl)-3-(2-fluoro-6-trifluoromethyl-benzyl)-4-methyl-2,6-dioxo-3,6-dihydro-2H-pyrimidin-1-yl]-1-phenyl-ethylamino)-butyric acid sodium salt (compound 5-1) having an impurity profile of  claim 12 , and a pharmaceutically acceptable carrier and/or diluent. 
     
     
         14 . 4-((R)-2-[5-(2-fluoro-3-methoxy-phenyl)-3-(2-fluoro-6-trifluoromethyl-benzyl)-4-methyl-2,6-dioxo-3,6-dihydro-2H-pyrimidin-1-yl]-1-phenyl-ethylamino)-butyric acid sodium salt (compound 5-1) having an impurity profile comprising one or more of the following substances:
 heptane,   methyl isobutyl ketone,   isopropyl acetate, and   methyl ethyl ketone.   
     
     
         15 . A pharmaceutical composition comprising 4-((R)-2-[5-(2-fluoro-3-methoxy-phenyl)-3-(2-fluoro-6-trifluoromethyl-benzyl)-4-methyl-2,6-dioxo-3,6-dihydro-2H-pyrimidin-1-yl]-1-phenyl-ethylamino)-butyric acid sodium salt (compound 5-1) having an impurity profile of  claim 14  and a pharmaceutically acceptable carrier and/or diluent. 
     
     
         16 . A method for treating a condition selected from endometriosis and uterine fibroids in a subject in need thereof, comprising administering to the subject a pharmaceutical composition of  claim 13 . 
     
     
         17 . A method for treating a condition selected from endometriosis and uterine fibroids in a subject in need thereof, comprising administering to the subject a pharmaceutical composition of  claim 15 .