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

HRID 473744Notes

Reaction equation

HRID 473744 reaction equation
[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

Participants

6

Reactant 3

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

Product 1

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

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
120 °C

Procedure

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).

Workup

  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

Sources & evidence

ORD record
ord-258e3f854afa4d8d88b3379b0389552f
Source dataset
uspto-grants-2014_01
Patent number
US08637500B2

Reaction notes

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