反应详情

温度

60 °C

2-Butanone (750 mL) was added to 1-(3-(tert-butyl)-1-(p-tolyl)-1H-pyrazol-5-yl)-3-(4-((2-((6-ethylpyrazin-2-yl)amino)pyridin-4-yl)methoxy)naphthalen-1-yl)urea (7.50 g) and the mixture was stirred. The mixture was warmed to 60° C. over 20 min. A solution of maleic acid (1.39 g) in 2-butanone (12 mL) was added to the mixture over 5 min. Spontaneous crystallisation occurred after approximately half of the maleic acid solution was added. The mixture was stirred for 30 min at 60° C. then cooled to 5° C. over 6 h with an exponential ramp (exponent=2.3) then stirred for 30 min at 5° C. then heated to 65° C. over 30 min then stirred for 30 min at 65° C. then cooled to 5° C. over 6 h with an exponential ramp (exponent=2.3) then stirred for 30 min at 5° C. then heated to 65° C. over 30 min then stirred for 30 min at 65° C. then cooled to 5° C. over 6 h with an exponential ramp (exponent=2.3). The product was filtered and washed twice with 2-butanone (50 mL), subsequently dried at 45° C. in vacuo to give 1-(3-(tert-butyl)-1-(p-tolyl)-1H-pyrazol-5-yl)-3-(4-((2-((6-ethylpyrazin-2-yl)amino)pyridin-4-yl)methoxy)naphthalen-1-yl)urea maleate (Form 2) (7.0 g).

1. customSpontaneous crystallisation
2. additionwas added
3. stirringThe mixture was stirred for 30 min at 60° C.
4. temperaturethen cooled to 5° C. over 6 h with an exponential ramp (exponent=2.3)
5. stirringthen stirred for 30 min at 5° C.
6. temperaturethen heated to 65° C. over 30 min
7. stirringthen stirred for 30 min at 65° C.
8. temperaturethen cooled to 5° C. over 6 h with an exponential ramp (exponent=2.3)
9. stirringthen stirred for 30 min at 5° C.
10. temperaturethen heated to 65° C. over 30 min
11. stirringthen stirred for 30 min at 65° C.
12. temperaturethen cooled to 5° C. over 6 h with an exponential ramp (exponent=2.3)
13. filtrationThe product was filtered
14. washwashed twice with 2-butanone (50 mL)
15. customsubsequently dried at 45° C. in vacuo