反应详情

温度

23 °C

To a suspension of crude 4-(1-(1-ethoxyethyl)-1H-pyrazol-4-yl)-7-((2-(trimethylsilyl)ethoxy)methyl)-7H-pyrrolo[2,3-d]pyrimidine (15) made as described above in tetrahydrofuran (THF, 4.2 L) in the reactor was charged water (H2O, 20.8 L), and a 10% aqueous HCl solution (16.2, 45.89 mol, 3.44 equiv) at room temperature. The resulting reaction mixture was stirred at 16-30° C. for 2-5 h. When the reaction was deemed complete by HPLC analysis, the reaction mixture was treated with a 30% aqueous sodium hydroxide (NaOH) solution (4 L, 50.42 mol, 3.78 equiv) at room temperature. The resulting reaction mixture was stirred at room temperature for 1-2 h. The solids were collected by filtration and washed with water (2×5 L). The wet cake was charged back to the reactor with acetonitrile (21.6 L), and resulting suspension was heated to gentle reflux for 1-2 h. The clear solution was then gradually cooled to room temperature with stirring, and solids were precipitated out from the solution with cooling. The mixture was stirred at room temperature for an additional 1-2 h. The solids were collected by filtration, washed with acetonitrile (2×3.5 L), and dried in oven under reduced pressure at 45-55° C. to constant weight to afford 4-(1H-pyrazol-4-yl)-7-(2-trimethylsilanyl-ethoxymethyl)-7H-pyrrolo[2,3-d]pyrimidine (5, 3281.7 g, 3996.8 g theoretical, 82.1% yield) as white crystalline solids (99.5 area % by HPLC), which was found to be identical in every comparable aspect to the material made from Method A and B.

1. customat room temperature
2. customThe resulting reaction mixture
3. customThe resulting reaction mixture
4. stirringwas stirred at room temperature for 1-2 h
5. filtrationThe solids were collected by filtration
6. washwashed with water (2×5 L)
7. additionThe wet cake was charged back to the reactor with acetonitrile (21.6 L)
8. customresulting suspension
9. temperaturewas heated
10. temperatureto gentle reflux for 1-2 h
11. temperatureThe clear solution was then gradually cooled to room temperature
12. stirringwith stirring
13. customsolids were precipitated out from the solution
14. temperaturewith cooling
15. stirringThe mixture was stirred at room temperature for an additional 1-2 h
16. filtrationThe solids were collected by filtration
17. washwashed with acetonitrile (2×3.5 L)
18. customdried in oven under reduced pressure at 45-55° C. to constant weight