Details for Patent: 6,894,051
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Title: | Crystal modification of a N-phenyl-2-pyrimidineamine derivative, processes for its manufacture and its use |
Abstract: | The invention relates to a new crystalline form of the methanesulfonic acid addition salt of 4-(4-methylpiperazin-1-ylmethyl)-N-[4-methyl-3-(4-pyridin-3-yl)pyrimidin-2 -ylamino)phenyl]benzamide of formula 1, which may be used for example for tumor therapy. |
Inventor(s): | Zimmermann; Jurg (Basel, CH), Sutter; Bertrand (Hesingue, FR), Burger; Hans Michael (Allschwil, CH) |
Assignee: | Novartis AG (Basel, CH) |
Filing Date: | Jan 18, 2000 |
Application Number: | 09/463,097 |
Claims: | 1. A crystalline form of the monomethanesulfonic acid addition salt of a compound of formula I, ##STR3## which is non-hygroscopic in a glass climatic chamber at 25.degree. C. and relative humidities up to and including 93%. 2. A crystalline form according to claim 1 of the methanesulfonic acid addition salt of a compound of formula I, which comprises at least 95% by weight crystals of the .beta.-modification and remains dry at 93% relative humidity and 25.degree. C. 3. A crystalline form according to claim 1 of the methanesulfonic acid addition salt of a compound of formula I, which comprises at least 99% by weight crystals of the .beta.-modification and remains dry at 93% relative humidity and 25.degree. C. 4. A crystalline form according to claim 1 of the methanesulfonic acid addition salt of a compound of formula I, which comprises at least 99% by weight crystals of the .beta.-modification and has a melting point below 225.degree. C. 5. A crystalline form according to claim 1 of the methanesulfonic acid addition salt of a compound of formula I, which comprises at least 99% by weight crystals of the .beta.-modification and has a melting point of less than 217.degree. C., defined as the start of melting in the differential scanning calorimetry thermogram. 6. A crystalline form according to claim 1 of the methanesulfonic acid addition salt of a compound of formula I, which shows on X-ray diffraction a peak at an angle of refraction 2theta of 20.degree., said peak having a relative line intensity of about 65% as compared to the most intense line in the diagram. 7. A crystalline form according to claim 3 of the methanesulfonic acid addition salt of a compound of formula I, which shows in an X-ray diffraction diagram lines having a relative line intensity, as compared to the most intense line in the diagram, of about 20% or more at the following angles of refraction 2theta: 9.7.degree., 13.9.degree., 14.7.degree., 17.5.degree., 18.2.degree., 20.0.degree., 20.6.degree., 21.1.degree., 22.1.degree., 22.7.degree., 23.8.degree., 29.8.degree. and 30.8.degree.. 8. A crystalline form according to claim 5 of the methanesulfonic acid addition salt of a compound of formula I, which has a melting point of about 217.degree. C., defined as the start of melting in the differential scanning calorimetry diagram, and which shows essentially the X-ray diffraction diagram as illustrated in FIG. 2/3, wherein the angle of refraction, 2 theta, is plotted on the horizontal axis and the relative line intensity on the vertical axis. 9. A pharmaceutical composition, comprising the .beta.-crystal form according to claim 1 of the methanesulfonic acid addition salt of a compound of formula I and a pharmaceutically acceptable carrier. 10. A process for the preparation of the .beta.-crystal form of the methanesulfonic acid addition salt of a compound of formula I ##STR4## which comprises a) digesting another crystal form or an amorphous starting material of the methanesulfonic acid addition salt of a compound of formula I with a suitable polar solvent in suspension at a temperature between 20 and 50.degree. C., or b) dissolving another crystal form or an amorphous starting material of the methanesulfonic acid addition salt of a compound of formula I, in a polar solvent at a suitable temperature of 25.degree. C. up to the reflux temperature of the reaction mixture, and then initiating crystallisation by adding a small amount of the .delta.-crystal form as seed crystal at a temperature between 20 and 70.degree. C. 11. A crystalline form according to claim 1 of the methanesulfonic acid addition salt of a compound of formula I, which comprises at least 90% by weight crystals of the .beta.-modification and remains dry at 93% relative humidity and 25.degree. C. 12. A method for treating a tumor disease in a patient, which comprises administering to the patient an effective amount of the methanesulfonic acid addition salt of a compound of the formula ##STR5## in its .beta.-crystal modification. 13. A crystalline form of the methanesulfonic acid addition salt of a compound of formula ##STR6## which displays x-ray diffraction peaks at 9.7.degree. and 20.0.degree. 2 theta. 14. A crystalline form of claim 13 which displays x-ray diffraction peaks having a relative line intensity, as compared to the most intense line in the diagram, of about 20% or more at the following angles of refraction 2 theta: 9.7.degree., 13.9.degree., 14.7.degree., 17.5.degree., 18.2.degree., 20.0.degree., 20.6.degree., 21.1.degree., 22.1.degree., 22.7.degree., 23.8.degree., 29.8.degree. and 30.8.degree.. 15. A crystalline form of the monomethanesulfonic acid addition salt of a compound of formula I, ##STR7## characterized by the presence of the peak marked (1) in the x-ray diffraction pattern depicted in FIG. 1/3. 16. A crystalline form according to claim 15 which essentially shows the x-ray diffraction pattern depicted in FIG. 1/3. 17. A crystalline form according to claim 15 having needle-shaped crystals. 18. A crystalline form according to claim 15 which has a melting point of about 226.degree. C. defined as the start of melting in the differential scanning calorimetry diagram. |