Water → N-(4-(3-Iodopyridin-2-yloxy)phenyl)pyridin-2-amine

HRID 473631Notes

Reaction equation

HRID 473631 reaction equation
Cl[C:2]1[C:7]([I:8])=[CH:6][CH:5]=[CH:4][N:3]=1.[N:9]1[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=1[NH:15][C:16]1[CH:21]=[CH:20][C:19]([OH:22])=[CH:18][CH:17]=1.C(=O)([O-])[O-].[Cs+].[Cs+].O>CS(C)=O>[I:8][C:7]1[C:2]([O:22][C:19]2[CH:18]=[CH:17][C:16]([NH:15][C:10]3[CH:11]=[CH:12][CH:13]=[CH:14][N:9]=3)=[CH:21][CH:20]=2)=[N:3][CH:4]=[CH:5][CH:6]=1

Participants

6

Reactant 4

HCID 962WaterHCID 10796Cesium carbonateHCID 27357432-Chloro-3-iodopyridineHCID 212625714-(Pyridin-2-ylamino)phenol

Product 1

HCID 59373959N-(4-(3-Iodopyridin-2-yloxy)phenyl)pyridin-2-amine

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Conditions

Temperature
80 °C

Procedure

To a 250-mL round-bottomed flask was added 2-chloro-3-iodopyridine (5.32 g, 22.22 mmol), 4-(pyridin-2-ylamino)phenol (4.96 g, 26.6 mmol) and cesium carbonate (11.27 g, 34.6 mmol) in DMSO (100 mL) and the reaction was heated at 80° C. overnight. The reaction was cooled to rt and poured into water (400 mL). The solution was extracted with EtOAc (4×100 mL) and the combined organic layers were washed with brine and dried over Na2SO4. The solution was filtered, evaporated onto silica gel and purified by flash chromatography (Isco, (330 gram)) eluting with 2M NH3 in MeOH:CH2Cl2 (0:1→1:19). The material was dissolved in MeOH, evaporated onto silica gel and further purified by flash chromatography (Isco (330 gram)) eluting with EtOAc:hexanes (0:1→3:1) to give a white amorphous solid. MS (ESI, pos. ion) m/z: 389.9. IC50 (uM)=0.2284.

Workup

  1. temperatureThe reaction was cooled to rt
  2. extractionThe solution was extracted with EtOAc (4×100 mL)
  3. washthe combined organic layers were washed with brine
  4. dry with materialdried over Na2SO4
  5. filtrationThe solution was filtered
  6. customevaporated onto silica gel
  7. custompurified by flash chromatography (Isco, (330 gram))
  8. washeluting with 2M NH3 in MeOH:CH2Cl2 (0:1→1:19)
  9. dissolutionThe material was dissolved in MeOH
  10. customevaporated onto silica gel
  11. customfurther purified by flash chromatography (Isco (330 gram))
  12. washeluting with EtOAc:hexanes (0:1→3:1)
  13. customto give a white amorphous solid

Sources & evidence

ORD record
ord-c95da350112849abba2d5baac6340481
Source dataset
uspto-grants-2014_01
Patent number
US08637500B2

Reaction notes

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