HCID 178460521, compound → HCID 178523894, compound

HRID 1776998Notes

Reaction equation

HRID 1776998 reaction equation
CC(C)=O.[Cl:5][C:6]1[CH:7]=[C:8]([CH:32]=[CH:33][CH:34]=1)[C:9]([N:11]=[C:12]([NH:23][C:24]1[CH:29]=[C:28]([F:30])[CH:27]=[C:26]([Cl:31])[CH:25]=1)[NH:13][C:14]1[CH:18]=[C:17]([C:19]([F:22])([F:21])[F:20])[NH:16][N:15]=1)=[O:10]>CCO>[Cl:5][C:6]1[CH:7]=[C:8]([CH:32]=[CH:33][CH:34]=1)[C:9]([N:11]=[C:12]([NH:23][C:24]1[CH:29]=[C:28]([F:30])[CH:27]=[C:26]([Cl:31])[CH:25]=1)[NH:13][C:14]1[CH:18]=[C:17]([C:19]([F:22])([F:20])[F:21])[NH:16][N:15]=1)=[O:10]

Participants

3

Reactant 1

HCID 178460521HCID 178460521, compound

Product 1

HCID 178523894HCID 178523894, compoundYield 83.2%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
40 °C

Procedure

3-Chloro-N-(((3-chloro-5-fluorophenyl)amino)((5-(trifluoromethyl)-1H-pyrazol-3-yl)amino)methylene)benzamide acetone solvate (176 g) was dissolved in EtOH (875 mL) and warmed to 40° C. The mixture was clarified by filtration through celite and then diluted with EtOH/water (1/1 mixture by volume, 175 mL) at 40° C. Form II crystals of 3-chloro-N-(((3-chloro-5-fluorophenyl)amino)((5-(trifluoromethyl)-1H-pyrazol-3-yl)amino)methylene)benzamide (437 mg) were added to the mixture. Next, the suspension was further diluted with EtOH/water (1/1 mixture by volume, 700 mL) at 40° C. over 40 minutes, and then the mixture was allowed to cool to room temperature and stirring was continued overnight. Finally, the resulting suspension was filtered, the isolated residue was rinsed with EtOH/water (1/1 mixture by volume, 500 mL) and dried (60° C./10 Torr) to afford 130 g (74% recovery) of 3-chloro-N-(((3-chloro-5-fluorophenyl)amino)((5-(trifluoromethyl)-1H-pyrazol-3-yl)amino)methylene)benzamide as crystalline solid Form II. Analytical analysis did not identify solvate molecules in the crystalline solid.

Workup

  1. filtrationThe mixture was clarified by filtration through celite
  2. additiondiluted with EtOH/water (1/1 mixture by volume, 175 mL) at 40° C
  3. additionForm II crystals of 3-chloro-N-(((3-chloro-5-fluorophenyl)amino)((5-(trifluoromethyl)-1H-pyrazol-3-yl)amino)methylene)benzamide (437 mg) were added to the mixture
  4. additionNext, the suspension was further diluted with EtOH/water (1/1 mixture by volume, 700 mL) at 40° C. over 40 minutes
  5. temperatureto cool to room temperature
  6. filtrationFinally, the resulting suspension was filtered
  7. washthe isolated residue was rinsed with EtOH/water (1/1 mixture by volume, 500 mL)
  8. customdried (60° C./10 Torr)

Sources & evidence

ORD record
ord-8d5c9bd769384c718ffe17c6b900ac45
Source dataset
uspto-grants-2016_02
Patent number
US09266839B2

Reaction notes

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