Sodium hydride → HCID 178429092, Verbindung

Temperatur

85 °C

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.

1. customthe tube was sealed
2. temperatureThe reaction mixture was cooled
3. custompartitioned between water and ethyl acetate
4. customThe organic phase was separated
5. washthe aqueous phase was washed twice with ethyl acetate
6. dry with materialThe combined organic layers were dried over MgSO4
7. filtrationfiltered
8. customevaporated under reduced pressure
9. dissolutionThe resulting residue was dissolved in 3 mL of 4 N HCl in dioxane
10. customtransferred to a sealed tube
11. temperatureheated to 90° C. for 90 minutes
12. temperatureThe reaction mixture was cooled
13. custompartitioned between water and ethyl acetate
14. additionmade basic by addition of aqueous sodium bicarbonate (to pH 9)
15. customThe organic phase was separated
16. extractionthe aqueous phase was extracted three times with ethyl acetate
17. washThe combined organic layers were washed with saturated brine
18. dry with materialdried over MgSO4
19. filtrationfiltered
20. customevaporated under reduced pressure
21. customThe residue was purified by preparative TLC plate

ORD-Eintrag

ord-f2fd6bafe99d42e5aa5dff36d14640b1

Quelldatensatz

uspto-grants-2009_07

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US07566708B2