4-[4-({[4-chloro-3-(trifluoromethyl)phenyl]carbamoyl}amino)-3-fluorophenoxy]-n-methylpyridine-2-carboxamide monohydrate

Abstract

The present invention relates to 4-[4-({[4-chloro-3-(trifluoromethyl)phenyl]carbamoyl}amino)-3-fluorophenoxy]-N-methylpyridine-2-carboxamide monohydrate, to processes for its preparation, to pharmaceutical compositions comprising it and to its use in the control of disorders.

1 . A compound of the formula (II) 
       
         
           
           
               
               
           
         
       
     
     
         2 . The compound of  claim 1  which shows in the X-ray diffractometry a peak maximum of the 2 Theta angel of 21.2. 
     
     
         3 . The compound of  claim 1  which shows in the FIR spectrum a peak maximum of 353 cm −1 . 
     
     
         4 . A process for the preparation of the compound of the formula (II) of  claim 1  which comprises dissolution of 4-[4-({[4-chloro-3-(trifluoromethyl)phenyl]carbamoyl}amino)-3-fluorophenoxy]-N-methylpyridine-2-carboxamide and adding water until precipitation. 
     
     
         5 . The preparation of the compound of the formula (II) of  claim 1  which comprises suspension of 4-[4-({[4-chloro-3-(trifluoromethyl)phenyl]carbamoyl}amino)-3-fluorophenoxy]-N-methylpyridine-2-carboxamide in an aqueous solvent and then stiffing or shaking until conversion to the compound of the formula (II). 
     
     
         6 . A compound of the formula (II) of  claim 1  for the treatment of hyper-proliferative disorders. 
     
     
         7 . A compound of the formula (II) of  claim 1  for the treatment of solid tumors, lymphomas, sarcomas, leukemias, cancers of the breast, respiratory tract, brain, reproductive organs, digestive tract, urinary tract, eye, liver, skin, head and neck, thyroid and/or parathyroid. 
     
     
         8 . A use of the compound of the formula (II) of  claim 1  for the preparation of a pharmaceutical composition for the treatment of hyper-proliferative disorders. 
     
     
         9 . The use of  claim 8  for the treatment of solid tumors, lymphomas, sarcomas, leukemias, cancers of the breast, respiratory tract, brain, reproductive organs, digestive tract, urinary tract, eye, liver, skin, head and neck, thyroid and/or parathyroid. 
     
     
         10 . A pharmaceutical composition comprising the compound of the formula (II) of  claim 1  mainly, no significant fractions of another form of 4-[4-({[4-chloro-3-(trifluoromethyl)phenyl]carbamoyl}amino)-3-fluorophenoxy]-N-methylpyridine-2-carboxamide and one or more inert, nontoxic, pharmaceutically suitable excipients. 
     
     
         11 . The pharmaceutical composition of  claim 10  containing more than 90 percent by weight of the compound of the formula (II) related to the total amount of the compound of the formula (II) present in the composition. 
     
     
         12 . The pharmaceutical composition of  claim 10  for the treatment of disorders. 
     
     
         13 . A method for treating hyper-proliferative disorders using an effective amount of the compound of the formula (II) of  claim 1  or of a pharmaceutical composition as defined in. 
     
     
         14 . A combination comprising the compound of the formula (II) of  claim 1  and one or more other pharmaceutical agents. 
     
     
         15 . The combination of  claim 14  wherein the one or more other pharmaceutical agents are cytotoxic agents, signal transduction inhibitors, anti-cancer agents, or antiemetics. 
     
     
         16 . The pharmaceutical composition of  claim 10  comprising one or more other pharmaceutical agents. 
     
     
         17 . The pharmaceutical composition of  claim 16  wherein the one or more other pharmaceutical agents are anti-hyper-proliferative agents, cytotoxic agents, signal transduction inhibitors, anti-cancer agents and/or antiemetics.