تفاعل #317341

معادلة التفاعل

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

المردود 15.4%

المذيبات

DMF

ظروف التفاعل

المعالجة

1. 1
   أخرىthe tube was sealed
2. 2
   درجة الحرارةThe reaction mixture was cooled
3. 3
   أخرىpartitioned between water and ethyl acetate
4. 4
   أخرىThe organic phase was separated
5. 5
   غسيلthe aqueous phase was washed twice with ethyl acetate
6. 6
   تجفيفThe combined organic layers were dried over MgSO4
7. 7
   ترشيحfiltered
8. 8
   أخرىevaporated under reduced pressure
9. 9
   workup.DISSOLUTIONThe resulting residue was dissolved in 3 mL of 4 N HCl in dioxane
10. 10
    أخرىtransferred to a sealed tube
11. 11
    درجة الحرارةheated to 90° C. for 90 minutes
12. 12
    درجة الحرارةThe reaction mixture was cooled
13. 13
    أخرىpartitioned between water and ethyl acetate
14. 14
    workup.ADDITIONmade basic by addition of aqueous sodium bicarbonate (to pH 9)
15. 15
    أخرىThe organic phase was separated
16. 16
    استخلاصthe aqueous phase was extracted three times with ethyl acetate
17. 17
    غسيلThe combined organic layers were washed with saturated brine
18. 18
    تجفيفdried over MgSO4
19. 19
    ترشيحfiltered
20. 20
    أخرىevaporated under reduced pressure
21. 21
    أخرىThe residue was purified by preparative TLC plate

الإجراء التجريبي

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.

المصدر