反应详情

温度

62 °C

Approx. 15.2 kg of 6-(1-methyl-1H-pyrazol-4-yl)-2-{3-[5-(2-morpholin-4-yl-ethoxy)-pyrimidin-2-yl]-benzyl}-2H-pyridazin-3-one (free base) were dispersed in approx. 31 kg DI water at T<30° C. After addition of approx. 5.5 kg aqueous phosphoric acid solution (85%), the solution was slurried for 30 minutes, and subsequently filtered. The resulting filtrate was diluted at 25° C. with approx. 55.8 kg acetone, resulting in a dispersion. The dispersion was heated to 62° C., resulting in a clear solution. The solution was cooled down to 50° C. (thermostat jacket temperature) with a defined cooling rate of 0.1 K/min, and slurried for approx. 6.5 hours, until a turbid dispersion was resulting. The dispersion was further cooled down to −10° C. (thermostat jacket temperature) with a defined cooling rate of 0.1 K/min, and post-slurried for approx. 1 hour at this temperature. The dispersion was filtered, and resulting crystals were washed with acetone and dried under vacuum at 70° C.

1. filtrationsubsequently filtered
2. additionThe resulting filtrate was diluted at 25° C. with approx. 55.8 kg acetone
3. customresulting in a dispersion
4. customresulting in a clear solution
5. temperatureThe solution was cooled down to 50° C. (thermostat jacket temperature) with
6. temperaturea defined cooling rate of 0.1 K/min
7. waitslurried for approx. 6.5 hours, until a turbid dispersion
8. customwas resulting
9. temperatureThe dispersion was further cooled down to −10° C. (thermostat jacket temperature) with
10. temperaturea defined cooling rate of 0.1 K/min
11. waitpost-slurried for approx. 1 hour at this temperature
12. filtrationThe dispersion was filtered
13. customresulting crystals
14. washwere washed with acetone
15. customdried under vacuum at 70° C.