Acetone → Pexmetinib hydrochloride

HRID 922339Notes

Reaction equation

HRID 922339 reaction equation
[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]

Participants

4

Reactant 3

HCID 180AcetoneHCID 313Hydrochloric AcidHCID 24765037Pexmetinib

Product 1

HCID 71712232Pexmetinib hydrochloride

Procedure

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.

Workup

  1. customto evaporate
  2. customThe resulting crystalline solids (birefringent under cross-polarized light microscopy) were dried under vacuum at 50° C. overnight
  3. customthe crystalline solids were recovered

Sources & evidence

ORD record
ord-e50be01e8d72476aa3bd5339d4607058
Source dataset
uspto-grants-2016_03
Patent number
US09278936B2

Reaction notes

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