Potassium Carbonate → 4-[6-(2,4-difluoro-phenoxy)-1-(2-trimethylsilanyl-ethoxymethyl)-1H-pyrazolo[3,4-d]pyrimidin-3-yl]-3-methyl-phenol

HRID 230157Notes

Reaction equation

HRID 230157 reaction equation
[F:1][C:2]1[CH:26]=[C:25]([F:27])[CH:24]=[CH:23][C:3]=1[O:4][C:5]1[N:10]=[C:9]2[N:11]([CH2:15][O:16][CH2:17][CH2:18][Si:19]([CH3:22])([CH3:21])[CH3:20])[N:12]=[C:13](I)[C:8]2=[CH:7][N:6]=1.[OH:28][C:29]1[CH:34]=[CH:33][C:32](B(O)O)=[C:31]([CH3:38])[CH:30]=1.C(=O)([O-])[O-].[K+].[K+]>O1CCOCC1.CCO.O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[F:1][C:2]1[CH:26]=[C:25]([F:27])[CH:24]=[CH:23][C:3]=1[O:4][C:5]1[N:10]=[C:9]2[N:11]([CH2:15][O:16][CH2:17][CH2:18][Si:19]([CH3:22])([CH3:21])[CH3:20])[N:12]=[C:13]([C:32]3[CH:33]=[CH:34][C:29]([OH:28])=[CH:30][C:31]=3[CH3:38])[C:8]2=[CH:7][N:6]=1

Participants

8

Reactant 3

HCID 11430Potassium CarbonateHCID 27734484-Hydroxy-2-methylbenzeneboronic acidHCID 598343496-(2,4-Difluorophenoxy)-3-iodo-1-(2-trimethylsilanyl-ethoxymethyl)-1H-pyrazolo[3,4-d]pyrimidine

Product 1

HCID 1360666024-[6-(2,4-difluoro-phenoxy)-1-(2-trimethylsilanyl-ethoxymethyl)-1H-pyrazolo[3,4-d]pyrimidin-3-yl]-3-methyl-phenolYield 64.6%

Reagents, catalysts & solvents 4

HCID 178418397HCID 178418397, compoundCatalystHCID 702EthanolSolventHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
90 °C

Procedure

6-(2,4-Difluoro-phenoxy)-3-iodo-1-(2-trimethylsilanyl-ethoxymethyl)-1H-pyrazolo[3,4-d]pyrimidine from Example 11 (0.5 g, 0.99 mmol) was dissolved in 10 mL of dry dioxane, and the reaction mixture was degassed by treatment with vacuum and flushed with argon. Tetrakis(triphenylphosphine)palladium(0) (0.115 g, 0.1 mmol) was added, and the reaction mixture was stirred for 10 minutes. A solution of 4-hydroxy-2-methylphenyl boronic acid (0.311 g, 2.0 mmol) in 3 mL EtOH was added, and the reaction mixture was degassed, purged with argon, and stirred for 10 minutes. AA solution of potassium carbonate (0.411 g, 3.0 mmol) in 1 mL water was then added, and the reaction mixture was again degassed and flushed with argon. The reaction mixture was heated to 90° C. with stirring for 16 hours under argon. The reaction mixture was cooled, filtered, and the filtrate was partitioned between water and ethyl acetate. The organic phase was separated, and the aqueous phase was extracted three times with EtOAc. The combined organic layers were dried over MgSO4, filtered, and evaporated under reduced pressure. The resulting residue was subject to flash chromatography (hexanes/EtOAc 1:0 to 2:1) to yield 0.308 g (0.64 mmol, 64%) of 4-[6-(2,4-difluoro-phenoxy)-1-(2-trimethylsilanyl-ethoxymethyl)-1H-pyrazolo[3,4-d]pyrimidin-3-yl]-3-methyl-phenol.

Workup

  1. customthe reaction mixture was degassed by treatment with vacuum
  2. customflushed with argon
  3. customthe reaction mixture was degassed
  4. custompurged with argon
  5. stirringstirred for 10 minutes
  6. customthe reaction mixture was again degassed
  7. customflushed with argon
  8. stirringwith stirring for 16 hours under argon
  9. temperatureThe reaction mixture was cooled
  10. filtrationfiltered
  11. customthe filtrate was partitioned between water and ethyl acetate
  12. customThe organic phase was separated
  13. extractionthe aqueous phase was extracted three times with EtOAc
  14. dry with materialThe combined organic layers were dried over MgSO4
  15. filtrationfiltered
  16. customevaporated under reduced pressure

Sources & evidence

ORD record
ord-456810584c8a4f1a9d50de1b141b1a46
Source dataset
uspto-grants-2009_07
Patent number
US07566708B2

Reaction notes

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