Sodium hydride → HCID 178429092, 화합물

온도

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 dissloved 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-difluorophenoxy)-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. customtransferred to a sealed tube
10. temperatureheated to 90° C. for 90 minutes
11. temperatureThe reaction mixture was cooled
12. custompartitioned between water and ethyl acetate
13. additionmade basic by addition of aqueous sodium bicarbonate (to pH 9)
14. customThe organic phase was separated
15. extractionthe aqueous phase was extracted three times with ethyl acetate
16. washThe combined organic layers were washed with saturated brine
17. dry with materialdried over MgSO4
18. filtrationfiltered
19. customevaporated under reduced pressure
20. customThe residue was purified by preparative TLC plate

ORD 기록

ord-7f04185452fc4e97a6d48ab5a8568cbe

출처 데이터셋

uspto-grants-2008_11

DOI

10.6084/m9.figshare.5104873.v1

특허 번호

US07452880B2