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

HRID 1929378노트

반응식

HRID 1929378 반응식
[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

참가 물질

5

반응물 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

생성물 1

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

시약·촉매·용매 1

HCID 6228Dimethylformamide용매

반응 조건

온도
90 °C

실험 절차

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).

후처리

  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

출처 및 근거

ORD 기록
ord-98a70ae7158b4a238f1a061566539f4d
출처 데이터셋
uspto-grants-2012_05
특허 번호
US08188071B2

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