Hydrochloric Acid → Pexmetinib hydrochloride

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[C:1]([C:5]1[CH:9]=[C:8]([NH:10][C:11]([NH:13][CH2:14][C:15]2[CH:20]=[C:19]([F:21])[CH:18]=[CH:17][C:16]=2[O:22][C:23]2[CH:24]=[C:25]3[C:29](=[CH:30][CH:31]=2)[N:28]([CH2:32][CH2:33][OH:34])[N:27]=[CH:26]3)=[O:12])[N:7]([C:35]2[CH:40]=[CH:39][C:38]([CH3:41])=[CH:37][CH:36]=2)[N:6]=1)([CH3:4])([CH3:3])[CH3:2].[ClH:42].O1CCOCC1>C(OCC)(=O)C>[ClH:42].[C:1]([C:5]1[CH:9]=[C:8]([NH:10][C:11]([NH:13][CH2:14][C:15]2[CH:20]=[C:19]([F:21])[CH:18]=[CH:17][C:16]=2[O:22][C:23]2[CH:24]=[C:25]3[C:29](=[CH:30][CH:31]=2)[N:28]([CH2:32][CH2:33][OH:34])[N:27]=[CH:26]3)=[O:12])[N:7]([C:35]2[CH:40]=[CH:39][C:38]([CH3:41])=[CH:37][CH:36]=2)[N:6]=1)([CH3:4])([CH3:3])[CH3:2]

참가 물질

실험 절차

A round bottom was charged with 500 mL ethyl acetate and 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 (50.0 g, 89.8 mmol, 1.0 equivalent). After 10 minutes of stirring at ambient temperature a clear solution was obtained. 4 M HCl in 1,4-dioxane (23.6 mL, 94.3 mmol, 1.05 eq.) was added dropwise. A cloudy solution immediately resulted. The thick suspension was allowed to stir overnight at ambient temperature. The solids were isolated by vacuum filtration and washed with two 50 mL aliquots of ethyl acetate. The solids were suspended in 500 mL THF. The suspension was allowed to stir overnight and vacuum filtered. The solids were dried under vacuum at 50° C. overnight yielding 48.2 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 (81.4 mmol, 91% theoretical yield). Methods used to characterize this material are described in Examples 2-F and 2-G.