Triphenylphosphine → HCID 10317695, compound

HRID 2113079Notes

Reaction equation

HRID 2113079 reaction equation
Cl[C:2]1[CH:11]=[CH:10][C:9]2[C:4](=[C:5]([NH:12][C:13]3[CH:18]=[C:17]([C:19]4[CH:24]=[CH:23][C:22]([C:25]([F:28])([F:27])[F:26])=[CH:21][CH:20]=4)[N:16]=[CH:15][N:14]=3)[CH:6]=[CH:7][CH:8]=2)[N:3]=1.[N-:29]=[N+]=[N-].[Na+].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>CS(C)=O.O.C1(C)C=CC=CC=1>[F:26][C:25]([F:28])([F:27])[C:22]1[CH:23]=[CH:24][C:19]([C:17]2[N:16]=[CH:15][N:14]=[C:13]([NH:12][C:5]3[CH:6]=[CH:7][CH:8]=[C:9]4[C:4]=3[N:3]=[C:2]([NH2:29])[CH:11]=[CH:10]4)[CH:18]=2)=[CH:20][CH:21]=1

Participants

7

Reactant 3

HCID 11776TriphenylphosphineHCID 33557Sodium AzideHCID 10092419HCID 10092419, compound

Product 1

HCID 10317695HCID 10317695, compound

Reagents, catalysts & solvents 3

HCID 679Dimethyl SulfoxideSolventHCID 962WaterSolventHCID 1140TolueneSolvent

Conditions

Temperature
105 °C

Procedure

To a round-bottomed flask containing (2-chloroquinolin-8-yl)-[6-(4-trifluoromethyl-phenyl)pyrimidin-4-yl]amine, Example 32(e), (0.090 g, 0.22 mmol) in DMSO (10 mL) was added NaN3 (0.53 g, 8.1 mmol, Aldrich). The reaction mixture was stirred at 105° C. for 4 days and then at 115° C. for 1 day. The reaction mixture was cooled to room temperature and then diluted with H2O and extracted with EtOAc. The combined extracts were washed with H2O (3×), brine, dried over Na2SO4, and concentrated in vacuo to afford a tan solid. The tan solid was dissolved in toluene (5 mL), triphenylphosphine (0.12 g, 0.44 mmol, Aldrich) was added with stirring at room temperature and the mixture was stirred at reflux for 8 h. After cooling to room temperature, the mixture was concentrated in vacuo to remove the toluene. To the residue was added AcOH/H2O (2:1, 7 mL) and the mixture was stirred at 55° C. for 1 day. The reaction mixture was cooled to room temperature and then diluted with satd NaHCO3 (75 mL) and extracted with EtOAc (2×75 mL). The combined extracts were washed with brine, dried over K2CO3 and concentrated in vacuo. The residue was dissolved in EtOAc and concentrated in vacuo onto silica gel. Purification by silica gel chromatography with gradient from 20% to 60% EtOAc in hexane afforded the title compound as a yellow solid. MS (ESI, pos. ion) m/z: 382 (M+1). MP: 211-213° C.

Workup

  1. waitat 115° C. for 1 day
  2. temperatureThe reaction mixture was cooled to room temperature
  3. extractionextracted with EtOAc
  4. washThe combined extracts were washed with H2O (3×), brine
  5. dry with materialdried over Na2SO4
  6. concentrationconcentrated in vacuo
  7. customto afford a tan solid
  8. stirringwith stirring at room temperature
  9. stirringthe mixture was stirred
  10. temperatureat reflux for 8 h
  11. temperatureAfter cooling to room temperature
  12. concentrationthe mixture was concentrated in vacuo
  13. customto remove the toluene
  14. additionTo the residue was added AcOH/H2O (2:1, 7 mL)
  15. stirringthe mixture was stirred at 55° C. for 1 day
  16. temperatureThe reaction mixture was cooled to room temperature
  17. additiondiluted with satd NaHCO3 (75 mL)
  18. extractionextracted with EtOAc (2×75 mL)
  19. washThe combined extracts were washed with brine
  20. dry with materialdried over K2CO3
  21. concentrationconcentrated in vacuo
  22. dissolutionThe residue was dissolved in EtOAc
  23. concentrationconcentrated in vacuo onto silica gel
  24. customPurification by silica gel chromatography with gradient from 20% to 60% EtOAc in hexane

Sources & evidence

ORD record
ord-506499651ecf43f69dfd81af69ae1e81
Source dataset
uspto-grants-2009_04
Patent number
US07524874B2

Reaction notes

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