反应详情

Tetrahydrofuran (2.0 mL) and cyclohexene (0.42 mL, 4.15 mmol) were cooled in an ice water bath under nitrogen, and borane-dimethyl sulfide complex (0.19 mL, 2.0 mmol) was added via syringe. The reaction was allowed to warm to room temperature while being stirred under nitrogen over 90 minutes, resulting in a suspension. In a separate flask, N-(6-methoxypyridin-3-yl)-3-(2-methyl-9-(tetrahydro-2H-pyran-2-yl)-9H-purin-6-yl)-5-vinylpyridin-2-amine (185.4 mg, 0.418 mmol) was dissolved in THF (6.0 mL), and to this solution was added 1.6 mL of the suspension generated in the first flask. The addition occurred via syringe dropwise, resulting in gas evolution. The reaction was stirred at room temperature under nitrogen for 40 minutes and then cooled in an ice/water bath and quenched with MeOH (4.0 mL), 2 N aqueous NaOH (4.8 mL), and 30% aqueous H2O2 (6.5 mL), all added via syringe. The reaction was stirred while being allowed to warm to room temperature. After 75 minutes, more 2 N aqueous NaOH (1.2 mL) and 30% aqueous hydrogen peroxide (3.5 mL) were added, and stirring was continued. Then, 3 hours after that, 5 N aqueous NaOH (1.60 mL) and 30% aqueous hydrogen peroxide (8.0 mL) were added, and stirring was continued for another hour. Then, the reaction was diluted with water (20 mL), DCM (20 mL), and MeOH (about 1 mL), and allowed to stand at room temperature overnight. Then, the layers were separated, and the aqueous phase was extracted with 10:1 DCM/MeOH. The organic extracts were combined, concentrated, and taken on to step 2.

1. additionborane-dimethyl sulfide complex (0.19 mL, 2.0 mmol) was added via syringe
2. customresulting in a suspension
3. additionThe addition
4. customoccurred via syringe
5. customdropwise, resulting in gas evolution
6. stirringThe reaction was stirred at room temperature under nitrogen for 40 minutes
7. temperaturecooled in an ice/water bath
8. customquenched with MeOH (4.0 mL), 2 N aqueous NaOH (4.8 mL), and 30% aqueous H2O2 (6.5 mL)
9. additionall added via syringe
10. stirringThe reaction was stirred
11. temperatureto warm to room temperature
12. waitAfter 75 minutes
13. additionmore 2 N aqueous NaOH (1.2 mL) and 30% aqueous hydrogen peroxide (3.5 mL) were added
14. stirringstirring
15. additionThen, 3 hours after that, 5 N aqueous NaOH (1.60 mL) and 30% aqueous hydrogen peroxide (8.0 mL) were added
16. stirringstirring
17. waitwas continued for another hour
18. additionThen, the reaction was diluted with water (20 mL), DCM (20 mL), and MeOH (about 1 mL)
19. waitto stand at room temperature overnight
20. customThen, the layers were separated
21. extractionthe aqueous phase was extracted with 10:1 DCM/MeOH
22. concentrationconcentrated