反应详情

温度

50 °C

Acetone with 5% water (12.2 mL) was added to the crystalline 3-[2-{[3-(diethylamino)propyl]amino}-8-(2,6-difluorophenyl)-7-oxo-5,6,7,8-tetrahydropyrimido[4,5-d]pyrimidin-4-yl]-4-methyl-N-propylbenzamide free-base (0.608 g) and solid fumaric acid (1.0 equivalents; 124.8 mg). The resulting mixture was heated to 50° C. for one hour. The mixture was cooled to room temperature and stirred for 30 minutes. The product was filtered, washed with acetone with 5% water, and dried overnight in a vacuum oven at 50° C. with a slow nitrogen bleed. The yield was 85.4% (0.626 g) of 3-[2-{[3-(diethylamino)propyl]amino}-8-(2,6-difluorophenyl)-7-oxo-5,6,7,8-tetrahydropyrimido[4,5-d]pyrimidin-4-yl]-4-methyl-N-propylbenzamide fumarate salt. Examination by PLM showed that the batch may contain amorphous content. Acetone with 10% water (12.9 mL) was added to the fumarate salt, and the resulting mixture stirred several hours at room temperature. The product was filtered, washed with acetone with 10% water, and dried overnight in a vacuum oven at 50° C. with a slow nitrogen bleed. The yield was 51.3% (0.376 g) of 3-[2-{[3-(diethylamino)propyl]amino}-8-(2,6-difluorophenyl)-7-oxo-5,6,7,8-tetrahydropyrimido[4,5-d]pyrimidin-4-yl]-4-methyl-N-propylbenzamide fumarate salt with a melting onset at 192° C. (determined by DSC).

1. temperatureThe mixture was cooled to room temperature
2. filtrationThe product was filtered
3. washwashed with acetone with 5% water
4. customdried overnight in a vacuum oven at 50° C. with a slow nitrogen