Potassium Carbonate → (S)-(2-aminopyridin-3-yl)(6-(3-isobutylpiperazin-1-yl)-3-(trifluoromethyl)pyridin-2-yl)methanone

HRID 401489Notes

Reaction equation

HRID 401489 reaction equation
[NH2:1][C:2]1[C:7]([C:8]([C:10]2[C:15]([C:16]([F:19])([F:18])[F:17])=[CH:14][CH:13]=[C:12](Cl)[N:11]=2)=[O:9])=[CH:6][CH:5]=[CH:4][N:3]=1.C(=O)([O-])[O-].[K+].[K+].[CH2:27]([C@H:31]1[CH2:36][NH:35][CH2:34][CH2:33][N:32]1C(OC(C)(C)C)=O)[CH:28]([CH3:30])[CH3:29]>CN(C)C=O>[NH2:1][C:2]1[C:7]([C:8]([C:10]2[C:15]([C:16]([F:19])([F:18])[F:17])=[CH:14][CH:13]=[C:12]([N:35]3[CH2:34][CH2:33][NH:32][C@@H:31]([CH2:27][CH:28]([CH3:30])[CH3:29])[CH2:36]3)[N:11]=2)=[O:9])=[CH:6][CH:5]=[CH:4][N:3]=1

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 17750437tert-Butyl (2S)-2-(2-methylpropyl)piperazine-1-carboxylateHCID 57690845(2-Aminopyridin-3-yl)(6-chloro-3-(trifluoromethyl)pyridin-2-yl)methanone

Product 1

HCID 24995659(S)-(2-aminopyridin-3-yl)(6-(3-isobutylpiperazin-1-yl)-3-(trifluoromethyl)pyridin-2-yl)methanoneYield 77%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
90 °C

Procedure

A microwave vial was charged with (2-aminopyridin-3-yl)(6-chloro-3-(trifluoromethyl)pyridin-2-yl)methanone (2.12 g, 7.028 mmol), potassium carbonate (1.166 g, 8.434 mmol), (S)-tert-butyl 2-isobutylpiperazine-1-carboxylate (1.874 g, 7.731 mmol) and dimethylformamide (4 mL). The reaction mixture was heated under microwave irradiation at 90° C. for 50 minutes. The reaction mixture was cooled down to room temperature and partitioned between a saturated solution of sodium bicarbonate and ethyl acetate. The organic extract was washed with brine, dried over magnesium sulfate, filtered and concentrated in vacuo. The residue was taken up in dichloromethane (50 ml) and trifluoroacetic acid (8 ml) was added. The reaction mixture was stirred at room temperature for 3 hours. The reaction mixture was concentrated to dryness and partitioned between dichloromethane and a saturated solution of sodium carbonate. The organic extract was dried over magnesium sulfate, filtered and concentrated in vacuo. The residue was purified on silica gel by flash column chromatography to afford the title compound as a pale yellow oil (2.203 g, 77% yield).

Workup

  1. temperatureThe reaction mixture was cooled down to room temperature
  2. custompartitioned between a saturated solution of sodium bicarbonate and ethyl acetate
  3. extractionThe organic extract
  4. washwas washed with brine
  5. dry with materialdried over magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. additiontrifluoroacetic acid (8 ml) was added
  9. concentrationThe reaction mixture was concentrated to dryness
  10. custompartitioned between dichloromethane
  11. extractionThe organic extract
  12. dry with materialwas dried over magnesium sulfate
  13. filtrationfiltered
  14. concentrationconcentrated in vacuo
  15. customThe residue was purified on silica gel by flash column chromatography

Sources & evidence

ORD record
ord-98dd51303bc54c7bb8d9e27b7c2a95df
Source dataset
uspto-grants-2014_06
Patent number
US08741931B2

Reaction notes

Loading…