反应详情

温度

22.5 °C

N-[3-fluoro-4-({6-(methyloxy)-7-[(3-morpholin-4-ylpropyl)oxy]quinolin-4-yl}oxy)phenyl]-N′-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide free base was dissolved in acetone (46.0 L) and water (12.0 L). Phosphoric acid (85%, 1.2 L) was added at a rate such that the batch temperature did not exceed 30° C. The batch was maintained at approximately 15-30° C. with stirring for 1 h during which time the product precipitated. The solids were collected by filtration, washed with acetone and dried at approximately 60° C. under vacuum to afford N-[3-fluoro-4-({6-(methyloxy)-7-[(3-morpholin-4-ylpropyl)oxy]quinolin-4-yl}oxy)phenyl]-N′-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide bisphosphate (5.5 kg).

1. customdid not exceed 30° C
2. customprecipitated
3. filtrationThe solids were collected by filtration
4. washwashed with acetone
5. customdried at approximately 60° C. under vacuum