Hydrochloric Acid → Pexmetinib hydrochloride

HRID 922340Notes

Reaction equation

HRID 922340 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]>C(O)(C)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]

Participants

4

Reactant 2

HCID 313Hydrochloric AcidHCID 24765037Pexmetinib

Product 1

HCID 71712232Pexmetinib hydrochlorideYield 92.9%

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent

Procedure

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.

Workup

  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

Sources & evidence

ORD record
ord-2bcf0bb7c7e0453b9a445c84ead8001e
Source dataset
uspto-grants-2016_03
Patent number
US09278936B2

Reaction notes

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