Potassium Hydroxide → 3-Methyl-2-phenyl-2,3-dihydro-1H-imidazo[1,2-b]pyrazole-7-carboxylic acid [1-ethyl-1-(4-trifluoromethyl-phenyl)-propyl]-amide

HRID 2108588Notes

Reaction equation

HRID 2108588 reaction equation
C(O[C:4]([C:6]1[CH:10]=[N:9][N:8]2[CH:11]([CH3:20])[CH:12]([C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=3)[NH:13][C:7]=12)=[O:5])C.[OH-].[K+].[CH2:23]([C:25]([NH2:38])([C:28]1[CH:33]=[CH:32][C:31]([C:34]([F:37])([F:36])[F:35])=[CH:30][CH:29]=1)[CH2:26][CH3:27])[CH3:24].CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C>CCO.CCOC(C)=O.O>[CH2:23]([C:25]([NH:38][C:4]([C:6]1[CH:10]=[N:9][N:8]2[CH:11]([CH3:20])[CH:12]([C:14]3[CH:15]=[CH:16][CH:17]=[CH:18][CH:19]=3)[NH:13][C:7]=12)=[O:5])([C:28]1[CH:33]=[CH:32][C:31]([C:34]([F:36])([F:37])[F:35])=[CH:30][CH:29]=1)[CH2:26][CH3:27])[CH3:24]

Participants

9

Reactant 5

HCID 14797Potassium HydroxideHCID 81531DiisopropylethylamineHCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 576315553-[4-(Trifluoromethyl)phenyl]pentan-3-amineHCID 136071815HCID 136071815, compound

Product 1

HCID 1360718583-Methyl-2-phenyl-2,3-dihydro-1H-imidazo[1,2-b]pyrazole-7-carboxylic acid [1-ethyl-1-(4-trifluoromethyl-phenyl)-propyl]-amideYield 12.4%

Reagents, catalysts & solvents 3

HCID 702EthanolSolventHCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
60 °C

Procedure

Compound 3 (0.085 g, 0.3 mmol) was dissolved in EtOH (3 mL). KOH (6M in water, 0.9 mL, 1.78 mmol) was added. The reaction stirred at 60° C. for 3 h. The solution was cooled, diluted with AcOEt (10 mL) and water (10 mL) and shaken vigorously. The Aqueous layer was separated and acidified to pH=3. This acidic layer was then extracted with AcOEt (3 times). The combined AcOEt layers were washed with brine, dried (Na2SO4) and concentrated. The residue was then dissolved in NMP (1 mL) and 1-ethyl-1-(4-trifluoromethyl-phenyl)-propylamine (0.087 g, 0.37 mmol), HATU (0.14 g, 0.37 mmol), and DIEA (0.14 mL, 0.78 mmol) were added. The reaction was heated to 80° C. for 2 days. The solution was then cooled, washed with water, dried (MgSO4), and concentrated. Flash chromatography (20% AcOEt/hexanes) gave 0.017 g (12% yield) of amide 5.

Workup

  1. temperatureThe solution was cooled
  2. stirringshaken vigorously
  3. customThe Aqueous layer was separated
  4. extractionThis acidic layer was then extracted with AcOEt (3 times)
  5. washThe combined AcOEt layers were washed with brine
  6. dry with materialdried (Na2SO4)
  7. concentrationconcentrated
  8. dissolutionThe residue was then dissolved in NMP (1 mL)
  9. temperatureThe reaction was heated to 80° C. for 2 days
  10. temperatureThe solution was then cooled
  11. washwashed with water
  12. dry with materialdried (MgSO4)
  13. concentrationconcentrated

Sources & evidence

ORD record
ord-df0f9546bcfa4fccb9ff06d1fd55069f
Source dataset
uspto-grants-2009_04
Patent number
US07514441B2

Reaction notes

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