反应详情

A 2 L flask was charged with 50.0 g (89.8 mmol, 1.00 eq.) of amorphous 1-(3-tert-butyl-1-p-tolyl-1H-pyrazol-5-yl)-3-(5-fluoro-2-(1-(2-hydroxyethyl)-1H-indazol-5-yloxy)benzyl)urea and 500 mL of isopropyl alcohol at ambient temperature. After 20 minutes all solids were dissolved. To the solution was added 7.7 mL of concentrated HCl (94.7 mmol, 1.05 eq.) and the solution was allowed to stir overnight at ambient temperature. Solids formed upon stirring. The resulting slurry was filtered and washed with twice with 100 mL isopropyl alcohol. The solids were dried under vacuum at 50° C. overnight yielding 49.5 g 1-(3-tert-butyl-1-p-tolyl-1H-pyrazol-5-yl)-3-(5-fluoro-2-(1-(2-hydroxyethyl)-1H-indazol-5-yloxy)benzyl)urea hydrochloride Form B (83.5 mmol, 92.9% theoretical yield). Methods used to characterize this material are described in Examples 2-F and 2-G.

1. dissolutionAfter 20 minutes all solids were dissolved
2. customSolids formed
3. stirringupon stirring
4. filtrationThe resulting slurry was filtered
5. washwashed with twice with 100 mL isopropyl alcohol
6. customThe solids were dried under vacuum at 50° C. overnight
7. customyielding