Methyl iodide → HCID 56942725, compound

HRID 341450Notes

Reaction equation

HRID 341450 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([NH:9][C:10]2[N:15]=[C:14]([NH2:16])[N:13]=[C:12]([C:17]3[N:21]=[C:20]([C:22]4[CH:23]=[N:24][C:25]([O:28][CH2:29][C:30]([F:33])([F:32])[F:31])=[CH:26][CH:27]=4)[O:19][N:18]=3)[N:11]=2)[CH:5]=[CH:6][C:7]=1[F:8].[C:34](=O)([O-])[O-].[K+].[K+].IC.C(=O)([O-])[O-].[Cs+].[Cs+].[H-].[Na+]>CN(C=O)C>[Cl:1][C:2]1[CH:3]=[C:4]([N:9]([CH3:34])[C:10]2[N:15]=[C:14]([NH2:16])[N:13]=[C:12]([C:17]3[N:21]=[C:20]([C:22]4[CH:23]=[N:24][C:25]([O:28][CH2:29][C:30]([F:33])([F:31])[F:32])=[CH:26][CH:27]=4)[O:19][N:18]=3)[N:11]=2)[CH:5]=[CH:6][C:7]=1[F:8]

Participants

7

Reactant 5

HCID 6328Methyl iodide6×HCID 10796Cesium carbonate2×HCID 11430Potassium CarbonateHCID 24758Sodium hydride2×HCID 66803198HCID 66803198, compound

Product 1

HCID 56942725HCID 56942725, compoundYield 28.8%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 2-N-(3-Chloro-4-fluorophenyl)-6-{5-[6-(2,2,2-trifluoroethoxy)pyridin-3-yl]-1,2,4-oxadiazol-3-yl}-1,3,5-triazine-2,4-diamine (Example 413, 0.049 g, 0.101 mmol) in DMF (1 mL) was added potassium carbonate (0.028 g, 0.028 mmol) and iodomethane (0.021 g, 0.152 mmol). The reaction mixture was stirred at room temperature for 14 h after which time further iodomethane (0.042 g, 0.304 mmol) was added and the mixture was stirred at room temperature for 56 h. LCMS indicated incomplete conversion so further iodomethane (0.014 g, 0.105 mmol) was added and the mixture was heated to 50 C for 12 h. After this time cesium carbonate (0.032 g, 0.105 mmol) was added and the mixture was heated to 50 C for 1 h. Further iodomethane (0.021 g, 0.152 mmol) and cesium carbonate (0.064 g, 0.201 mmol) were added and the mixture was heated to 50 C for 14 h. Sodium hydride (60% dispersion in mineral oil, 0.004 g, 0.105 mmol) and further iodomethane (0.042 g, 0.304 mmol) were added and the mixture stirred for 1 h at 50 C. The mixture was quenched with water/ammonia/MeOH (1 mL) and extracted with EtOAc. The organic layer was washed with water, dried over sodium sulfate and concentrated under vacuum. The solid was dissolved in DMF (0.5 mL) and Sodium hydride (60% dispersion in mineral oil, 0.006 g, 0.152 mmol) and iodomethane (0.042 g, 0.304 mmol) were added. The reaction mixture was stirred at room temperature for 2 h. The reaction mixture was quenched with water/ammonia/MeOH (1 mL) and extracted with EtOAc. The organic layer was washed with water, dried over sodium sulfate and concentrated under vacuum. The residue was purified by HPLC Method B to afford the title compound (0.004 g, 8%).

Workup

  1. additionwas added
  2. additionwas added
  3. temperaturethe mixture was heated to 50 C for 12 h
  4. temperaturethe mixture was heated to 50 C for 1 h
  5. temperaturethe mixture was heated to 50 C for 14 h
  6. stirringthe mixture stirred for 1 h at 50 C
  7. customThe mixture was quenched with water/ammonia/MeOH (1 mL)
  8. extractionextracted with EtOAc
  9. washThe organic layer was washed with water
  10. dry with materialdried over sodium sulfate
  11. concentrationconcentrated under vacuum
  12. dissolutionThe solid was dissolved in DMF (0.5 mL)
  13. stirringThe reaction mixture was stirred at room temperature for 2 h
  14. customThe reaction mixture was quenched with water/ammonia/MeOH (1 mL)
  15. extractionextracted with EtOAc
  16. washThe organic layer was washed with water
  17. dry with materialdried over sodium sulfate
  18. concentrationconcentrated under vacuum
  19. customThe residue was purified by HPLC Method B

Sources & evidence

ORD record
ord-336bf3cf533c47dd991d117b2021efd1
Source dataset
uspto-grants-2014_11
Patent number
US08895733B2

Reaction notes

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