MARTIN, Nolwenn,SCHÖNE, Olga,SPITZENSTÄTTER, Hans-Peter,BENITO-GARAGORRI, David
申请号：
EPEP2016/057105
公开号：
WO2016/156512A1
申请日:
2016.03.31
申请国别(地区):
WO
年份:
2016
代理人:
摘要：
A process for preparing a solid crystalline form of sofosbuvir of formula (I) having an X-ray powder diffraction pattern comprising no reflection at 2-theta angles in the range of from 2.0 to 7.8 0 and preferably comprising reflections at 2-theta values of (8.1 ± 0.2) °, (10.4 ± 0.2) °, (12.4 ± 0.2) °, (17.3 ± 0.2) °, (19.4 ± 0.2) ° when measured at a temperature in the range of from 15 to 25 °C with Cu-Kalpha1,2 radiation having a wavelength of 0.15419 nm, comprising (i) providing sofosbuvir in crystalline form, pseudo-crystalline form, amorphous form, or as a mixture of two or more of these forms (ii) preparing a mixture comprising the sofosbuvir provided in (i) and a solvent system comprising at least one ketone having from 4 to 8 carbon atoms and optionally at least one aprotic non-ketonic organic solvent (iii) subjecting the mixture obtained in (ii) to solvent-mediated transformation conditions, obtaining the solid crystalline form of sofosbuvir in its mother liquor. Further a composition comprising a solid crystalline form 7 and at least one ketone having from 4 to 8 carbon atoms as stabilizer is provided. Further a process for preparing said composition is provided. Further a process for preparing a solid crystalline form of sofosbuvir of formula having an X-ray powder diffraction pattern comprising no reflection at 2-theta angles in the range of from 2.0 to 7.8 °, and preferably comprising reflections at 2-theta values of (8.1 ± 0.2) °, (10.4 ± 0.2) °, (12.4 ± 0.2) °, (17.3 ± 0.2) °, (19.4 ± 0.2) 0 with a solvent system comprising at least one ketone having 9 carbon atoms and at least one aprotic non-ketonic organic solvent which does not comprise toluene is provided.Linvention concerne un procédé de préparation dune forme cristalline solide de sofosbuvir de formule (I) présentant un diagramme de diffraction des rayons X sur poudre ne comprenant aucune réflexion à des angles 2-thêta dans la plage allant de 2,0 à 7,80 et comprenant de préférence des réflexion
