| 摘要 |
<P>PROBLEM TO BE SOLVED: To provide a production method for the crystalline form of 4-((4-fluoro-2-methyl-1H-indol-5-yl)oxy)-6-methoxy-7-(3-(pyrrolidin-1-yl)propoxy)quinazoline, suitable for production and processing performed on the commercial scale. <P>SOLUTION: The A type crystalline form of a maleate salt of 4-((4-fluoro-2-methyl-1H-indol-5-yl)oxy)-6-methoxy-7-(3-(pyrrolidin-1-yl)propoxy)quinazoline is obtained by, for example, (i) dissolving a free base of 4-((4-fluoro-2-methyl-1H-indol-5-yl)oxy)-6-methoxy-7-(3-(pyrrolidin-1-yl)propoxy)quinazoline in an organic solvent to form a solution; (ii) adding an aqueous solution of maleic acid or adding a solution of maleic acid in an organic solvent thereto; (iii) generating natural nucleation; (iv) slurrying the mixture in the solvent till the maleic acid salt of the whole 4-((4-fluoro-2-methyl-1H-indol-5-yl)oxy)-6-methoxy-7-(3-(pyrrolidin-1-yl)propoxy)quinazoline becoming A form; and (v) isolating the so formed crystalline solid. <P>COPYRIGHT: (C)2011,JPO&INPIT |
