Реакция #1899047

Уравнение реакции

6-Chloro-2-methyl-9-(tetrahydro-2H-pyran-2-yl)-9H-purine

5-(1,3-dioxolan-2-yl)-2-fluoropyridin-3-ylboronic acid

potassium acetate

→

6-(5-(1,3-dioxolan-2-yl)-2-fluoropyridin-3-yl)-2-methyl-9-(tetrahydro-2H-pyran-2-yl)-9H-purine

Выход 93.4%

Растворители

EtOH

Условия реакции

Обработка

1. 1
   Другоеwater (10 mL) and nitrogen was bubbled through the suspension for about 15 seconds
2. 2
   ДругоеThen, the flask was fitted with a reflux condenser
3. 3
   Другоеplaced in a preheated oil bath
4. 4
   ТемператураThe reaction was cooled to room temperature
5. 5
   workup.ADDITIONpoured into water (125 mL)
6. 6
   Экстракцияextracted with DCM
7. 7
   Сушкаdried over sodium sulfate
8. 8
   Фильтрацияfiltered
9. 9
   Концентрированиеconcentrated
10. 10
    Другоеpurified on a silica gel
11. 11
    Фильтрацияfilter (600 mL fritted filter with about 3 inches of silica gel, 40:1 DCM/2 N ammonia in MeOH)
12. 12
    ДругоеThe fractions with product were collected
13. 13
    Концентрированиеconcentrated
14. 14
    Промывкаwashed repeatedly with hexanes
15. 15
    Другоеdried

Методика

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)+.

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