Sodium hydride → (R)-1-[6-(2,4-Difluoro-phenoxy)-1-(2-trimethylsilanyl-ethoxymethyl)-1H-pyrazolo[3,4-d]pyrimidin-4-ylamino]-propan-2-ol

HRID 230184Notes

Reaction equation

HRID 230184 reaction equation
[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[OH:9].[H-].[Na+].CS([C:16]1[N:21]=[C:20]2[N:22]([CH2:25][O:26][CH2:27][CH2:28][Si:29]([CH3:32])([CH3:31])[CH3:30])[N:23]=[CH:24][C:19]2=[C:18]([NH:33][CH2:34][C@H:35]([OH:37])[CH3:36])[N:17]=1)(=O)=O>CN(C=O)C>[F:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[O:9][C:16]1[N:21]=[C:20]2[N:22]([CH2:25][O:26][CH2:27][CH2:28][Si:29]([CH3:32])([CH3:30])[CH3:31])[N:23]=[CH:24][C:19]2=[C:18]([NH:33][CH2:34][C@H:35]([OH:37])[CH3:36])[N:17]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 1230512,4-DifluorophenolHCID 68878421(R)-1-[6-Methanesulfonyl-1-(2-trimethylsilanyl-ethoxymethyl)-1H-pyrazolo[3,4-d]pyrimidin-4-ylamino]-propan-2-ol

Product 1

HCID 68879179(R)-1-[6-(2,4-Difluoro-phenoxy)-1-(2-trimethylsilanyl-ethoxymethyl)-1H-pyrazolo[3,4-d]pyrimidin-4-ylamino]-propan-2-olYield 43.7%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
100 °C

Procedure

2,4-Difluorophenol (510 mg, 3.922 mmol) was dissolved in 5 mL dry DMF, and sodium hydride (152 mg of 60% suspension in mineral oil, 3.791 mmol) was added. The reaction mixture was stirred for 25 minutes, and then (R)-1-[6-Methanesulfonyl-1-(2-trimethylsilanyl-ethoxymethyl)-1H-pyrazolo[3,4-d]pyrimidin-4-ylamino]-propan-2-ol (525 mg, 1.307 mmol) was added. The reaction mixture was heated to 100° C. for four hours with stirring, then was stirred for 16 hours at room temperature. The reaction mixture was quenched by addition to water, and was partitioned between water and ethyl acetate. The organic layer was separated, dried over MgSO4, filtered, and evaporated under reduced pressure. The residue was purified by flash chromatography (8% MeOH in methylene chloride) to give 258 mg of (R)-1-[6-(2,4-Difluoro-phenoxy)-1-(2-trimethylsilanyl-ethoxymethyl)-1H-pyrazolo[3,4-d]pyrimidin-4-ylamino]-propan-2-ol. Mass Spec. M+H=452.

Workup

  1. stirringwith stirring
  2. stirringwas stirred for 16 hours at room temperature
  3. customThe reaction mixture was quenched by addition to water
  4. customwas partitioned between water and ethyl acetate
  5. customThe organic layer was separated
  6. dry with materialdried over MgSO4
  7. filtrationfiltered
  8. customevaporated under reduced pressure
  9. customThe residue was purified by flash chromatography (8% MeOH in methylene chloride)

Sources & evidence

ORD record
ord-b10206f5efb246238b5ccce51c7ff26f
Source dataset
uspto-grants-2009_07
Patent number
US07566708B2

Reaction notes

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