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

HRID 1929378ノート

反応式

HRID 1929378 の反応式
[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

参加物

5

反応物 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

生成物 1

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

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

反応条件

温度
90 °C

実験手順

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).

後処理

  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

出典と根拠

ORDレコード
ord-98a70ae7158b4a238f1a061566539f4d
出典データセット
uspto-grants-2012_05
特許番号
US08188071B2

反応ノート

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