Cesium carbonate → N-(4-(3-bromo-5-methoxypyridin-2-yloxy)phenyl)-5-methylpyridin-2-amine

HRID 473744ノート

反応式

HRID 473744 の反応式
[Br:1][C:2]1[C:3](Cl)=[N:4][CH:5]=[C:6]([O:8][CH3:9])[CH:7]=1.[CH3:11][C:12]1[CH:13]=[CH:14][C:15]([NH:18][C:19]2[CH:24]=[CH:23][C:22]([OH:25])=[CH:21][CH:20]=2)=[N:16][CH:17]=1.C(=O)([O-])[O-].[Cs+].[Cs+]>CN1C(=O)CCC1.O>[Br:1][C:2]1[C:3]([O:25][C:22]2[CH:21]=[CH:20][C:19]([NH:18][C:15]3[CH:14]=[CH:13][C:12]([CH3:11])=[CH:17][N:16]=3)=[CH:24][CH:23]=2)=[N:4][CH:5]=[C:6]([O:8][CH3:9])[CH:7]=1

参加物

6

反応物 3

HCID 10796Cesium carbonateHCID 467388143-Bromo-2-chloro-5-methoxypyridineHCID 593739864-(5-Methylpyridin-2-ylamino)phenol

生成物 1

HCID 59374202N-(4-(3-bromo-5-methoxypyridin-2-yloxy)phenyl)-5-methylpyridin-2-amine

試薬・触媒・溶媒 2

HCID 962Water溶媒HCID 13387N-methyl-2-pyrrolidone溶媒

反応条件

温度
120 °C

実験手順

3-Bromo-2-chloro-5-methoxypyridine (0.30 g, 1.35 mmol), 4-(5-methylpyridin-2-ylamino)phenol (0.68 g, 3.37 mmol), and cesium carbonate (1.32 g, 4.05 mmol) were mixed in NMP (4 mL) under a nitrogen atmosphere. The reaction mixture was stirred at 120° C. for 16 h. The reaction mixture was cooled to room temperature, diluted with water, and extracted with EtOAc (2×). The combined organic layers were washed with sat. sodium chloride (1×), dried over magnesium sulfate, filtered, and concentrated in vacuo. The resulting crude product was purified by silica gel chromatography. The isolated product contained a significant impurity. The impurity was removed by reverse phase HPLC. The desired product was partitioned between DCM and sat. aqueous sodium bicarbonate. The organic layers were separated, dried over magnesium sulfate, filtered, and concentrated in vacuo to give N-(4-(3-bromo-5-methoxypyridin-2-yloxy)phenyl)-5-methylpyridin-2-amine. MS (ESI, pos. ion) m/z: 386.1 and 388.1 (M+1).

後処理

  1. temperatureThe reaction mixture was cooled to room temperature
  2. extractionextracted with EtOAc (2×)
  3. washThe combined organic layers were washed with sat. sodium chloride (1×)
  4. dry with materialdried over magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe resulting crude product was purified by silica gel chromatography
  8. customThe impurity was removed by reverse phase HPLC
  9. customThe desired product was partitioned between DCM and sat. aqueous sodium bicarbonate
  10. customThe organic layers were separated
  11. dry with materialdried over magnesium sulfate
  12. filtrationfiltered
  13. concentrationconcentrated in vacuo

出典と根拠

ORDレコード
ord-258e3f854afa4d8d88b3379b0389552f
出典データセット
uspto-grants-2014_01
特許番号
US08637500B2

反応ノート

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