Reacción #317341

Ecuación de reacción

2,2-Dimethyl-1,3-dioxolan-4-ylmethyl p-toluene sulfonate

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

sodium hydride

→

3-{4-[6-(2,4-difluoro-phenoxy)-1H-pyrazolo[3,4-d]pyrimidin-3-yl]-3-methyl-phenoxy}-propane-1,2-diol

Rendimiento 15.4%

Disolventes

DMF

Condiciones de reacción

Tratamiento posterior

1. 1
   Otrothe tube was sealed
2. 2
   TemperaturaThe reaction mixture was cooled
3. 3
   Otropartitioned between water and ethyl acetate
4. 4
   OtroThe organic phase was separated
5. 5
   Lavadothe aqueous phase was washed twice with ethyl acetate
6. 6
   SecadoThe combined organic layers were dried over MgSO4
7. 7
   Filtraciónfiltered
8. 8
   Otroevaporated under reduced pressure
9. 9
   workup.DISSOLUTIONThe resulting residue was dissolved in 3 mL of 4 N HCl in dioxane
10. 10
    Otrotransferred to a sealed tube
11. 11
    Temperaturaheated to 90° C. for 90 minutes
12. 12
    TemperaturaThe reaction mixture was cooled
13. 13
    Otropartitioned between water and ethyl acetate
14. 14
    workup.ADDITIONmade basic by addition of aqueous sodium bicarbonate (to pH 9)
15. 15
    OtroThe organic phase was separated
16. 16
    Extracciónthe aqueous phase was extracted three times with ethyl acetate
17. 17
    LavadoThe combined organic layers were washed with saturated brine
18. 18
    Secadodried over MgSO4
19. 19
    Filtraciónfiltered
20. 20
    Otroevaporated under reduced pressure
21. 21
    OtroThe residue was purified by preparative TLC plate

Procedimiento

4-[6-(2,4-Difluoro-phenoxy)-1-(2-trimethylsilanyl-ethoxymethyl)-1H-pyrazolo[3,4-d]pyrimidin-3-yl]-3-methyl-phenol ( 0.125 g, 0.26 mmol) from Example 12 was placed in a microwave tube together with dry DMF (3.0 mL) and sodium hydride ( 0.021 g of 60% suspension in mineral oil, 0.31 mmol). 2,2-Dimethyl-1,3-dioxolan-4-ylmethyl p-toluene sulfonate (0.91 g, 0.31 mmol) was added, and the tube was sealed and heated to 85° C. for five minutes via microwave. The reaction mixture was cooled and partitioned between water and ethyl acetate. The organic phase was separated, and the aqueous phase was washed twice with ethyl acetate. The combined organic layers were dried over MgSO4, filtered, and evaporated under reduced pressure. The resulting residue was dissolved in 3 mL of 4 N HCl in dioxane, transferred to a sealed tube, and heated to 90° C. for 90 minutes. The reaction mixture was cooled, partitioned between water and ethyl acetate, and made basic by addition of aqueous sodium bicarbonate (to pH 9). The organic phase was separated, and the aqueous phase was extracted three times with ethyl acetate. The combined organic layers were washed with saturated brine, dried over MgSO4, filtered, and evaporated under reduced pressure. The residue was purified by preparative TLC plate using methylene chloride/MeOH 93:7 to yield 0.016 g (0.04 mmol, 14.5%) of 3-{4-[6-(2,4-difluoro-phenoxy)-1H-pyrazolo[3,4-d]pyrimidin-3-yl]-3-methyl-phenoxy}-propane-1,2-diol. Mass Spec. M+H=429.

Fuente