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

HRID 473744노트

반응식

HRID 473744 반응식
[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

참가 물질

6

반응물 3

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

생성물 1

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

시약·촉매·용매 2

HCID 962Water용매HCID 13387N-methyl-2-pyrrolidone용매

반응 조건

온도
120 °C

실험 절차

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).

후처리

  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

출처 및 근거

ORD 기록
ord-258e3f854afa4d8d88b3379b0389552f
출처 데이터셋
uspto-grants-2014_01
특허 번호
US08637500B2

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