Sodium hydride → 6-(2,4-Difluorophenoxy)-3-iodo-1-(2-trimethylsilanyl-ethoxymethyl)-1H-pyrazolo[3,4-d]pyrimidine

HRID 230155Notes

Reaction equation

HRID 230155 reaction equation
[H-].[Na+].[F:3][C:4]1[CH:9]=[C:8]([F:10])[CH:7]=[CH:6][C:5]=1[OH:11].[I:12][C:13]1[C:21]2[C:16](=[N:17][C:18](S(C)(=O)=O)=[N:19][CH:20]=2)[N:15]([CH2:26][O:27][CH2:28][CH2:29][Si:30]([CH3:33])([CH3:32])[CH3:31])[N:14]=1>CN(C=O)C>[F:3][C:4]1[CH:9]=[C:8]([F:10])[CH:7]=[CH:6][C:5]=1[O:11][C:18]1[N:17]=[C:16]2[N:15]([CH2:26][O:27][CH2:28][CH2:29][Si:30]([CH3:33])([CH3:32])[CH3:31])[N:14]=[C:13]([I:12])[C:21]2=[CH:20][N:19]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 1230512,4-DifluorophenolHCID 598342983-Iodo-6-methanesulfonyl-1-(2-trimethylsilanyl-ethoxymethyl)-1H-pyrazolo[3,4-d]pyrimidine

Product 1

HCID 598343496-(2,4-Difluorophenoxy)-3-iodo-1-(2-trimethylsilanyl-ethoxymethyl)-1H-pyrazolo[3,4-d]pyrimidineYield 47.5%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Conditions

Temperature
0 °C

Procedure

Sodium hydride (3.88 g of 60% dispersion in mineral oil, 0.097 mol) was added to 150 mL of dry DMF under nitrogen, and the reaction mixture was cooled in an ice bath. 2,4-Difluorophenol (8.85 mL, 0.092 mol) was added dropwise over 10 minutes (maintaining temperature between 5 and 10° C.), after which the reaction mixture was stirred for 15 minutes at 0° C., followed by 15 minutes of stirring at room temperature. A solution of 3-Iodo-6-methanesulfonyl-1-(2-trimethylsilanyl-ethoxymethyl)-1H-pyrazolo[3,4-d]pyrimidine (11.91 g, 0.026 mol) in 100 mL dry DMF was added, and the reaction mixture was heated to 140° C. for four hours while stirring under nitrogen. The reaction mixture was cooled to room temperature, and volatiles were removed under reduced pressure. The was added to 200 mL of 10% aqueous ammonium chloride, 50 mL water, and 250 mL EtOAc. The aqueous phase was partitioned off and extracted once with 250 mL EtOAc. The combined organic phases were washed with saturated aqueous brine, dried over MgSO4, filtered, and evaporated under reduced pressure to yield an oil. The oil was eluted through silica gel with hexanes EtOAc (20:1 to 10:1) to afford 6.23 g of 6-(2,4-Difluoro-phenoxy)-3-iodo-1-(2-trimethylsilanyl-ethoxymethyl)-1H-pyrazolo[3,4-d]pyrimidine.

Workup

  1. temperaturethe reaction mixture was cooled in an ice bath
  2. temperature(maintaining temperature between 5 and 10° C.)
  3. waitfollowed by 15 minutes
  4. stirringof stirring at room temperature
  5. temperaturethe reaction mixture was heated to 140° C. for four hours
  6. stirringwhile stirring under nitrogen
  7. temperatureThe reaction mixture was cooled to room temperature
  8. customvolatiles were removed under reduced pressure
  9. additionThe was added to 200 mL of 10% aqueous ammonium chloride, 50 mL water, and 250 mL EtOAc
  10. customThe aqueous phase was partitioned off
  11. extractionextracted once with 250 mL EtOAc
  12. washThe combined organic phases were washed with saturated aqueous brine
  13. dry with materialdried over MgSO4
  14. filtrationfiltered
  15. customevaporated under reduced pressure
  16. customto yield an oil
  17. washThe oil was eluted through silica gel with hexanes EtOAc (20:1 to 10:1)

Sources & evidence

ORD record
ord-392eb787032145f4a55d9c438fdab195
Source dataset
uspto-grants-2009_07
Patent number
US07566708B2

Reaction notes

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