Xinafoate salt of n4-(2,2-difluoro-4h-benzo[1,4]oxazin-3-one)-6-yl]-5-fluoro-n2-[3-(methylaminocarbonylmethyleneoxy)phenyl]2,4-pyrimidinediamine

Abstract

The present invention relates to the xinafoate salt of N4-[(2,2-difluoro- 4 H-benzo[1,4]oxazin-3-one)-6-yl]-5-fluoro-N2-[3-(methylaminocarbonylmethyleneoxy)phenyl]-2,4-pyrimidinediamine. This compound is a suitable drug substance and is useful in the treatment of conditions including asthma.

I claim: 
     
         1 . A method, comprising administering to a mammal a therapeutically effective amount of a xinafoate salt of N4-[(2,2-difluoro-4H-benzo[1,4]oxazin-3-one)-6-yl]-5-fluoro-N2-[3-(methylaminocarbonylmethyleneoxy)phenyl]-2,4-pyrimidinediamine. 
     
     
         2 . The method of  claim 1  wherein the xinafoate salt has shifts at about −69.2, −72.4 and −164.0 ppm when characterized by fluorine solid state NMR referenced to an external sample of trifluoroacetic acid (50% by volume in H 2 O) assigned a resonance at −76.54 ppm. 
     
     
         3 . The method according to  claim 1  for treating a disease for which a Syk kinase inhibitor is indicated. 
     
     
         4 . The method according to  claim 1  wherein the xinafoate salt of N4-[(2,2-difluoro-4H-benzo [1,4]oxazin-3-one)-6-yl]-5-fluoro-N2-[3-(methylaminocarbonylmethyleneoxy)phenyl]-2,4-pyrimidinediamine is administered as a composition comprising N4-[(2,2-difluoro-4H-benzo[1,4]oxazin-3-one)-6-yl]-5-fluoro-N2-[3-(methylaminocarbonylmethyleneoxy)phenyl]-2,4-pyrimidinediamine, an excipient, a second pharmacologically active substance, or combinations thereof. 
     
     
         5 . The method according to  claim 4  for treating a disease for which a Syk kinase inhibitor is indicated. 
     
     
         6 . The method according to  claim 4  for treating asthma. 
     
     
         7 . The method according to  claim 4  wherein the second pharmacologically active substance is selected for treating a disease for which a Syk kinase inhibitor is indicated. 
     
     
         8 . The method according to  claim 4  wherein the second pharmacologically active substance is selected for treating asthma. 
     
     
         9 . The method according to  claim 1  wherein administering comprises administering using a dry powder inhaler. 
     
     
         10 . A composition, comprising:
 a xinafoate salt of N4-[(2,2-difluoro-4H-benzo[1,4]oxazin-3-one)-6-yl]-5-fluoro-N2-[3-(methylaminocarbonylmethyleneoxy)phenyl]-2,4-pyrimidinediamine; and   a second pharmacologically active substance.   
     
     
         11 . The composition according to  claim 10  formulated for treating a disease for which a Syk kinase inhibitor is indicated. 
     
     
         12 . The composition according to  claim 10  formulated for treating asthma. 
     
     
         13 . The composition according to  claim 10  wherein the second pharmacological substance is selected for treating a disease for which a Syk kinase inhibitor is indicated. 
     
     
         14 . The composition according to  claim 10  wherein the second pharmacological substance is selected for treating asthma. 
     
     
         15 . A method for making a composition, comprising:
 providing a xinafoate salt of N4-[(2,2-difluoro-4H-benzo[1,4]oxazin-3-one)-6-yl]-5-fluoro-N2-[3-(methylaminocarbonylmethyleneoxy)phenyl]-2,4-pyrimidinediamine; and   making a composition comprising the xinafoate salt of N4-[(2,2-difluoro-4H-benzo[1,4]oxazin-3-one)-6-yl]-5-fluoro-N2-[3-(methylaminocarbonylmethyleneoxy)phenyl]-2,4-pyrimidinediamine.   
     
     
         16 . The method according to  claim 15  where the composition is formulated for treating a disease for which a Syk kinase inhibitor is indicated. 
     
     
         17 . The method according to  claim 15  where the composition is formulated for treating asthma. 
     
     
         18 . The method according to  claim 15  wherein making the composition comprises mixing the xinafoate salt of N4-[(2,2-difluoro-4H-benzo[1,4]oxazin-3-one)-6-yl]-5-fluoro-N2-[3-(methylaminocarbonylmethyleneoxy)phenyl]-2,4-pyrimidinediamine with N4-[(2,2-difluoro-4H-benzo[1,4]oxazin-3-one)-6-yl]-5-fluoro-N2-[3-(methylaminocarbonylmethyleneoxy)phenyl]-2,4-pyrimidinediamine, an excipient, a second pharmacologically active substance, or combinations thereof. 
     
     
         19 . The method according to  claim 18  wherein the second pharmacologically active substance is selected for treating a disease for which a Syk kinase inhibitor is indicated 
     
     
         20 . The method according to  claim 18  wherein the second pharmacologically active substance is selected for treating asthma.