Stable crystal of 4-oxoquinoline compound

Abstract

Provision of a stabilized crystal of 6-(3-chloro-2-fluorobenzyl)-1-[(S)-1-hydroxymethyl-2-methylpropyl]-7-methoxy-4-oxo-1,4-dihydroquinoline-3-carboxylic acid (compound A). A crystal of compound A, which shows a particular X-ray powder diffraction pattern of a characteristic diffraction peaks at diffraction angles 2θ(°) as measured by X-ray powder diffractometry.

1 - 14 . (canceled) 
     
     
         15 . A method of producing a crystal of 6-(3-chloro-2-fluorobenzyl)-1-[(S)-1-hydroxymethyl-2-methylpropyl]-7-methoxy-4-oxo-1,4-dihydroquinoline-3-carboxylic add, having an X-ray powder diffraction pattern having characteristic diffraction peaks at diffraction angles 2θ of 8.54°, 14.02°, 15.68°, 17.06°, 17.24°, 24.16°, 25.74° as measured by X-ray powder diffractometer, comprising
 dissolving 6-(3-chloro-2-fluorobenzyl)-1-[(S)-1-hydroxymethyl-2-methylpropyl]-7-methoxy-4-oxo-1,4-dihydroquinoline-3-carboxylic add, having an X-ray powder diffraction pattern having characteristic diffraction peaks at diffraction angles 2θ of 6.56°, 13.20°, 19.86°, 20.84°, 21.22°, 25.22° as measured by X-ray powder diffractometer in a solvent; and 
 adding a seed crystal of 6-(3-chloro-2-fluorobenzyl)-1-[(S)-1-hydroxymethyl-2-methylpropyl]-7-methoxy-4-oxo-1,4-dihydroquinoline-3-carboxylic add, having an X-ray powder diffraction pattern having characteristic diffraction peaks at diffraction angles 2θ of 8.54°, 14.02°, 15.68°, 17.06°, 17.24°, 24.16°, 25.74° as measured by X-ray powder diffractometer to the solution. 
 
     
     
         16 . The method of  claim 15 , wherein the solvent is chosen from
 isobutyl acetate;   isopropanol; or   aqueous ethanol.   
     
     
         17 . The method of  claim 15 , additionally comprising heating the solution. 
     
     
         18 . The method of  claim 17 , additionally comprising heating the solution at the reflux temperature of the solution.