Potassium Hydroxide → (S)-3-(2-Chloro-phenyl)-6-(2,4-difluoro-phenoxy)-4-(2,2-dimethyl-[1,3]dioxolan-4-ylmethoxy)-1H-pyrazolo[3,4-d]pyrimidine

HRID 2114570Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 2114570
[OH-].[K+].[Cl:3][C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=1[C:10]1[C:18]2[C:13](=[N:14][C:15](S(C)(=O)=O)=[N:16][C:17]=2[O:19][CH2:20][C@H:21]2[CH2:25][O:24][C:23]([CH3:27])([CH3:26])[O:22]2)[NH:12][N:11]=1.[F:32][C:33]1[CH:38]=[C:37]([F:39])[CH:36]=[CH:35][C:34]=1[OH:40]>>[Cl:3][C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=1[C:10]1[C:18]2[C:13](=[N:14][C:15]([O:40][C:34]3[CH:35]=[CH:36][C:37]([F:39])=[CH:38][C:33]=3[F:32])=[N:16][C:17]=2[O:19][CH2:20][C@H:21]2[CH2:25][O:24][C:23]([CH3:27])([CH3:26])[O:22]2)[NH:12][N:11]=1

Komponenten

4

Edukt 3

HCID 14797Potassium HydroxideHCID 1230512,4-DifluorophenolHCID 178431483HCID 178431483, Verbindung

Produkt 1

HCID 178431482(S)-3-(2-Chloro-phenyl)-6-(2,4-difluoro-phenoxy)-4-(2,2-dimethyl-[1,3]dioxolan-4-ylmethoxy)-1H-pyrazolo[3,4-d]pyrimidine

Reaktionsbedingungen

Temperatur
120 °C

Versuchsvorschrift

Powdered KOH (1.0 g) was taken up in 4 mL of 2,4-difluorophenol, and the resulting mixture was heated at 120° C. for 15 minutes. (S)-3-(2-Chloro-phenyl)-4-(2,2-dimethyl-[1,3]dioxolan-4-ylmethoxy)-6-methylsulfonyl-1H-pyrazolo[3,4-d]pyrimidine (1.34 g, 0.305 mmol) was added, and the reaction mixture was stirred for one hour at 120° C. The reaction mixture was cooled to room temperature, partitioned between water (100 mL) and EtOAc (300 ML0, and the layers were separated. The organic layer was washed three times with 2N aqueous NaOH, once with brine, dried over MgSO4, filtered, and concentrated under reduced pressure. The residue was purified by preparative scale TLC (50% MeOH in methylene chloride to provide 1.395 mg of (S)-3-(2-Chloro-phenyl)-6-(2,4-difluoro-phenoxy)-4-(2,2-dimethyl-[1,3]dioxolan-4-ylmethoxy)-1H-pyrazolo[3,4-d]pyrimidine. Mass Spec. M+H=489. Mp.=70.1-75.9° C.

Aufarbeitung

  1. temperatureThe reaction mixture was cooled to room temperature
  2. custompartitioned between water (100 mL) and EtOAc (300 ML0
  3. customthe layers were separated
  4. washThe organic layer was washed three times with 2N aqueous NaOH
  5. dry with materialonce with brine, dried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customThe residue was purified by preparative scale TLC (50% MeOH in methylene chloride

Quellen und Nachweise

ORD-Eintrag
ord-cc80d4766877403ba5844aa4f6d93866
Quelldatensatz
uspto-grants-2008_10
Patentnummer
US07435731B2

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