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

Temperature

60 °C

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.

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

ORD record

ord-df0f9546bcfa4fccb9ff06d1fd55069f

Source dataset

uspto-grants-2009_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07514441B2