反应详情

温度

80 °C

6-Chloro-2-methyl-9-(tetrahydro-2H-pyran-2-yl)-9H-purine (3.200 g, 12.66 mmol), 5-(1,3-dioxolan-2-yl)-2-fluoropyridin-3-ylboronic acid (3.165 g, 14.86 mmol), bis(di-tert-butyl(4-dimethylaminophenyl)phosphino)dichloropalladium (514.9 mg, 0.7272 mmol), and potassium acetate (4.180 g, 42.59 mmol) were suspended in EtOH (50 mL) and water (10 mL) and nitrogen was bubbled through the suspension for about 15 seconds. Then, the flask was fitted with a reflux condenser and placed in a preheated oil bath (80° C.), and stirred under nitrogen for 1 hour. The reaction was cooled to room temperature, poured into water (125 mL), and extracted with DCM. The organic extracts were combined, dried over sodium sulfate, filtered, concentrated, and purified on a silica gel filter (600 mL fritted filter with about 3 inches of silica gel, 40:1 DCM/2 N ammonia in MeOH). The fractions with product were collected, concentrated, and washed repeatedly with hexanes and dried to give 6-(5-(1,3-dioxolan-2-yl)-2-fluoropyridin-3-yl)-2-methyl-9-(tetrahydro-2H-pyran-2-yl)-9H-purine (4.557 g), which was used for the next step. MS (ESI pos. ion) m/z 386 (M+H)+.

1. customwater (10 mL) and nitrogen was bubbled through the suspension for about 15 seconds
2. customThen, the flask was fitted with a reflux condenser
3. customplaced in a preheated oil bath
4. temperatureThe reaction was cooled to room temperature
5. additionpoured into water (125 mL)
6. extractionextracted with DCM
7. dry with materialdried over sodium sulfate
8. filtrationfiltered
9. concentrationconcentrated
10. custompurified on a silica gel
11. filtrationfilter (600 mL fritted filter with about 3 inches of silica gel, 40:1 DCM/2 N ammonia in MeOH)
12. customThe fractions with product were collected
13. concentrationconcentrated
14. washwashed repeatedly with hexanes
15. customdried