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

HRID 1811865Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1811865
Cl[C:2]1[N:10]=[C:9]([CH3:11])[N:8]=[C:7]2[C:3]=1[N:4]=[CH:5][N:6]2[CH:12]1[CH2:17][CH2:16][CH2:15][CH2:14][O:13]1.[O:18]1[CH2:22][CH2:21][O:20][CH:19]1[C:23]1[CH:24]=[C:25](B(O)O)[C:26]([F:29])=[N:27][CH:28]=1.C([O-])(=O)C.[K+]>CCO.C(P([Pd](P(C1C=CC(N(C)C)=CC=1)(C(C)(C)C)C(C)(C)C)(Cl)Cl)(C(C)(C)C)C1C=CC(N(C)C)=CC=1)(C)(C)C>[O:18]1[CH2:22][CH2:21][O:20][CH:19]1[C:23]1[CH:24]=[C:25]([C:2]2[N:10]=[C:9]([CH3:11])[N:8]=[C:7]3[C:3]=2[N:4]=[CH:5][N:6]3[CH:12]2[CH2:17][CH2:16][CH2:15][CH2:14][O:13]2)[C:26]([F:29])=[N:27][CH:28]=1

Komponenten

6

Edukt 3

HCID 517044Potassium AcetateHCID 595482686-chloro-2-methyl-9-(tetrahydro-2H-pyran-2-yl)-9H-purineHCID 595483675-(1,3-Dioxolan-2-yl)-2-fluoropyridin-3-ylboronic acid

Produkt 1

HCID 666114866-(5-(1,3-dioxolan-2-yl)-2-fluoropyridin-3-yl)-2-methyl-9-(tetrahydro-2H-pyran-2-yl)-9H-purineAusbeute 93,4 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 178482906HCID 178482906, VerbindungKatalysatorHCID 702EthanolLösungsmittel

Reaktionsbedingungen

Temperatur
80 °C

Versuchsvorschrift

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)+.

Aufarbeitung

  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

Quellen und Nachweise

ORD-Eintrag
ord-b72815e2382b4732bbcb7bebf5efc32a
Quelldatensatz
uspto-grants-2013_01
Patentnummer
US08362241B2

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