Acetone → Pexmetinib hydrochloride

反応式

[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].CC(C)=O>>[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]

参加物

反応物 3

HCID 180Acetone

HCID 313Hydrochloric Acid

HCID 24765037Pexmetinib

生成物 1

HCID 71712232Pexmetinib hydrochloride

実験手順

In a glass vial, 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 mg, 0.090 mmol, 1 equivalent) was dissolved in 833 μL of solvent (acetonitrile, isopropyl acetate, ethyl acetate, acetone, isopropyl alcohol or ethanol) at ambient temperature. A single 94.3 μL aliquot of 1 M HCl in acetone (0.094 mmol, 1.05 equivalents) was added to the vial. The vial was shaken for at least 24 hours at ambient temperature and allowed to evaporate. The resulting crystalline solids (birefringent under cross-polarized light microscopy) were dried under vacuum at 50° C. overnight, and the crystalline solids were recovered. The solvents used provided 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 in all cases. Methods of characterizing 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 are described in Examples 2-F and 2-G.