Forms of methyl methyl carbamate

Abstract

This present invention relates to forms of methyl {4.6-diamino-2-[1-(2-fluorobenzyl)-1H-pyrazolo[3.4-b]pyridino-3-yl]pyrimidino-5-yl}methylcarbamate comprising its Modification I. Modification II. mono-DMSO solvate. sesqui-DMSO solvate and ¼-ethyl acetate solvate.

1 . A compound of the formula (I) 
       
         
           
           
               
               
           
         
         in the form of Modification I, Modification II, as mono-DMSO solvate, as sesqui-DMSO solvate, as ¼-ethyl acetate solvate, in the amorphous form or a mixture thereof. 
       
     
     
         2 . The compound of  claim 1  characterized by one or more of the following: X-Ray powder diffractogram substantially as shown in  FIGS. 1 ,  4 ,  7 ,  10 ,  13 ,  16 ; DSC- and TGA-Thermogram substantially as shown in  FIGS. 2 ,  5 ,  8 ,  11 ,  14 ,  17 ; IR-Spectrum (ATR) substantially as shown in  FIGS. 3 ,  6 ,  9 ,  12 ,  15 ,  18 . 
     
     
         3 . The compound of  claim 1  which is methyl {4,6-diamino-2-[1-(2-fluorobenzyl)-1H-pyrazolo[3,4-b]pyridino-3-yl]pyrimidino-5-yl}methylcarbamate in the Modification I. 
     
     
         4 . The compound of  claim 3  characterized by a X-Ray powder diffractogram comprising peak maxima of the 2 Theta angle of 6.7, 9.1 and 17.8. 
     
     
         5 . The compound of  claim 1  which is methyl {4,6-diamino-2-[1-(2-fluorobenzyl)-1H-pyrazolo[3,4-b]pyridino-3-yl]pyrimidino-5-yl}methylcarbamate in the Modification II. 
     
     
         6 . The compound of  claim 5  characterized by a X-Ray powder diffractogram comprising peak maxima of the 2 Theta angle of 13.9, 17.3, 25.5. 
     
     
         7 . The compound of  claim 1  which is the mono-DMSO solvate of methyl {4,6-diamino-2-[1-(2-fluorobenzyl)-1H-pyrazolo[3,4-b]pyridino-3-yl]pyrimidino-5-yl}methylcarbamate. 
     
     
         8 . The compound of  claim 7  characterized by a X-Ray powder diffractogram comprising peak maxima of the 2 Theta angle of 10.8, 15.5, 20.7. 
     
     
         9 . The compound of  claim 1  which is the sesqui-DMSO solvate of methyl {4,6-diamino-2-[1-(2-fluorobenzyl)-1H-pyrazolo[3,4-b]pyridino-3-yl]pyrimidino-5-yl}methylcarbamate. 
     
     
         10 . The compound of  claim 9  characterized by a X-Ray powder diffractogram comprising peak maxima of the 2 Theta angle of 8.3, 13.7, 15.7. 
     
     
         11 . The compound of  claim 1  which is the ¼-ethyl acetate solvate of methyl {4,6-diamino-2-[1-(2-fluorobenzyl)-1H-pyrazolo[3,4-b]pyridino-3-yl]pyrimidino-5-yl}methylcarbamate. 
     
     
         12 . The compound of  claim 10  characterized by a X-Ray powder diffractogram comprising peak maxima of the 2 Theta angle of 8.7, 17.8, 26.7. 
     
     
         13 . The compound of  claim 1  which is methyl {4,6-diamino-2-[1-(2-fluorobenzyl)-1H-pyrazolo[3,4-b]pyridino-3-yl]pyrimidino-5-yl}methylcarbamate in the amorphous form. 
     
     
         14 . A pharmaceutical composition comprising only one of the forms selected from the group comprising Modification I, Modification II, mono-DMSO solvate, sesqui-DMSO solvate and ¼-ethyl acetate solvate of the compound of  claim 1  and a pharmaceutically acceptable carrier. 
     
     
         15 . A pharmaceutical composition of  claim 14  comprising only Modification I of the compound of the formula (I). 
     
     
         16 . A pharmaceutical composition of  claim 15  comprising only Modification I mainly and no significant fractions of another form of the compound of the formula (I). 
     
     
         17 . A pharmaceutical composition of  claim 14  comprising only Modification II of the compound of the formula (I). 
     
     
         18 . A pharmaceutical composition of  claim 17  comprising only Modification II mainly and no significant fractions of another form of the compound of the formula (I). 
     
     
         19 . A pharmaceutical composition of  claim 14  comprising only the mono-DMSO solvate of the compound of the formula (I). 
     
     
         20 . A pharmaceutical composition of  claim 19  comprising only the mono-DMSO solvate mainly and no significant fractions of another form of the compound of the formula (I). 
     
     
         21 . A pharmaceutical composition of  claim 14  comprising only the sesqui-DMSO solvate of the compound of the formula (I). 
     
     
         22 . A pharmaceutical composition of  claim 21  comprising only the sesqui-DMSO solvate mainly and no significant fractions of another form of the compound of the formula (I). 
     
     
         23 . A pharmaceutical composition of  claim 14  comprising only the ¼-ethyl acetate solvate of the compound of the formula (I). 
     
     
         24 . A pharmaceutical composition of  claim 23  comprising only the ¼-ethyl acetate solvate mainly and no significant fractions of another form of the compound of the formula (I). 
     
     
         25 . A pharmaceutical composition comprising the compound of  claim 1  in the Modification I and the compound of formula (I) in the Modification II and optionally no other form of the compound of the formula (I). 
     
     
         26 . A pharmaceutical composition comprising the compound of  claim 1  in the Modification I and the mono-DMSO solvate of the compound of formula (I) and optionally no other form of the compound of the formula (I). 
     
     
         27 . A pharmaceutical composition comprising the compound of  claim 1  in the Modification I and the sesqui-DMSO solvate of the compound of formula (I) and optionally no other form of the compound of the formula (I). 
     
     
         28 . A pharmaceutical composition comprising the compound of  claim 1  in the Modification I and the ¼-ethyl acetate solvate of the compound of formula (I) and optionally no other form of the compound of the formula (I). 
     
     
         29 . The pharmaceutical composition of  claim 25  further comprising one or more inert, nontoxic, pharmaceutically suitable excipients. 
     
     
         30 . (canceled) 
     
     
         31 . (canceled) 
     
     
         32 . A pharmaceutical composition of  claim 15  comprising only Modification I of the compound of the formula (I) and 0.1 to 10 percent ¼-ethyl acetate solvate of the compound of the formula (I) and no significant fractions of another form of the compound of the formula (I). 
     
     
         33 . A pharmaceutical composition of  claim 32  comprising only Modification I of the compound of the formula (I) and 2.5 to 7.5 percent ¼-ethyl acetate solvate of the compound of the formula (I) and no significant fractions of another form of the compound of the formula (I). 
     
     
         34 . A pharmaceutical composition of  claim 33  comprising only Modification I of the compound of the formula (I) and 5 percent ¼-ethyl acetate solvate of the compound of the formula (I) and no significant fractions of another form of the compound of the formula (I). 
     
     
         35 . A pharmaceutical composition of  claim 15  comprising only Modification I of the compound of the formula (I) and 0.1 to 10 percent mono-DMSO solvate of the compound of the formula (I) and no significant fractions of another form of the compound of the formula (I). 
     
     
         36 . A pharmaceutical composition of  claim 35  comprising only Modification I of the compound of the formula (I) and 1.0 to 5 percent mono-DMSO solvate of the compound of the formula (I) and no significant fractions of another form of the compound of the formula (I). 
     
     
         37 . A pharmaceutical composition of  claim 36  comprising only Modification I of the compound of the formula (I) and 2.5 percent mono-DMSO solvate of the compound of the formula (I) and no significant fractions of another form of the compound of the formula (I). 
     
     
         38 . A pharmaceutical composition of  claim 15  comprising only Modification I of the compound of the formula (I) and 0.1 to 10 percent ¼-ethyl acetate solvate of the compound of the formula (I) and 0.1 to 10 percent mono-DMSO solvate of the compound of the formula (I) and optionally no other form of the compound of the formula (I). 
     
     
         39 . A pharmaceutical composition of  claim 38  comprising only Modification I of the compound of the formula (I) and 2.5 to 7.5 percent ¼-ethyl acetate solvate of the compound of the formula (I) and 1.0 to 5 percent mono-DMSO solvate of the compound of the formula (I) and optionally no other form of the compound of the formula (I). 
     
     
         40 . A pharmaceutical composition of  claim 38  comprising only Modification I of the compound of the formula (I) and 5 percent ¼-ethyl acetate solvate of the compound of the formula (I) and 2.5 percent mono-DMSO solvate of the compound of the formula (I) and optionally no other form of the compound of the formula (I). 
     
     
         41 . A pharmaceutical composition of  claim 38  comprising only Modification I of the compound of the formula (I) and 5 percent ¼-ethyl acetate solvate of the compound of the formula (I) and 2.5 percent mono-DMSO solvate of the compound of the formula (I) and optionally and no significant fractions of another form of the formula (I). 
     
     
         42 . A method for the treatment and/or prophylaxis of cardiovascular, pulmonary, thromboembolic and fibrotic diseases comprising administering a therapeutically effective amount of the compound of  claim 1  to a patient in need thereof. 
     
     
         43 . A method for the treatment and/or prophylaxis of cardiovascular, pulmonary, thromboembolic and fibrotic diseases comprising administering a therapeutically effective amount of the pharmaceutical composition of  claim 14  to a patient in need thereof.