Tetrahydrofuran → 2-(6-(6-Methoxypyridin-3-ylamino)-5-(2-methyl-9-(tetrahydro-2H-pyran-2-YL)-9H-purin-6-YL)pyridin-3-YL)ethanol

HRID 1811863Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1811863
C1CCCCC=1.[CH3:7][O:8][C:9]1[N:14]=[CH:13][C:12]([NH:15][C:16]2[C:21]([C:22]3[N:30]=[C:29]([CH3:31])[N:28]=[C:27]4[C:23]=3[N:24]=[CH:25][N:26]4[CH:32]3[CH2:37][CH2:36][CH2:35][CH2:34][O:33]3)=[CH:20][C:19]([CH:38]=[CH2:39])=[CH:18][N:17]=2)=[CH:11][CH:10]=1.C1C[O:43]CC1>>[CH3:7][O:8][C:9]1[N:14]=[CH:13][C:12]([NH:15][C:16]2[N:17]=[CH:18][C:19]([CH2:38][CH2:39][OH:43])=[CH:20][C:21]=2[C:22]2[N:30]=[C:29]([CH3:31])[N:28]=[C:27]3[C:23]=2[N:24]=[CH:25][N:26]3[CH:32]2[CH2:37][CH2:36][CH2:35][CH2:34][O:33]2)=[CH:11][CH:10]=1

Komponenten

4

Edukt 3

HCID 8028Tetrahydrofuran2×HCID 8079CyclohexeneHCID 59548466N-(6-methoxypyridin-3-yl)-3-(2-methyl-9-(tetrahydro-2H-pyran-2-yl)-9H-purin-6-yl)-5-vinylpyridin-2-amine

Produkt 1

HCID 665999832-(6-(6-Methoxypyridin-3-ylamino)-5-(2-methyl-9-(tetrahydro-2H-pyran-2-YL)-9H-purin-6-YL)pyridin-3-YL)ethanol

Versuchsvorschrift

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.

Aufarbeitung

  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

Quellen und Nachweise

ORD-Eintrag
ord-7cfc1277354144e7bfa142114dc7a033
Quelldatensatz
uspto-grants-2013_01
Patentnummer
US08362241B2

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