Sodium Carbonate → 3-((4-amino-3-(3-hydroxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)methyl)-8-methyl-2-o-tolylisoquinolin-1(2H)-one

HRID 217111Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 217111
[NH2:1][C:2]1[N:7]=[CH:6][N:5]=[C:4]2[N:8]([CH2:12][C:13]3[N:14]([C:25]4[CH:30]=[CH:29][CH:28]=[CH:27][C:26]=4[CH3:31])[C:15](=[O:24])[C:16]4[C:21]([CH:22]=3)=[CH:20][CH:19]=[CH:18][C:17]=4[CH3:23])[N:9]=[C:10](I)[C:3]=12.CC1(C)C(C)(C)OB([C:40]2[CH:41]=[C:42]([OH:46])[CH:43]=[CH:44][CH:45]=2)O1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C([O-])([O-])=O.[Na+].[Na+]>CN(C=O)C.C(O)C.O.CCO.CC([O-])=O.CC([O-])=O.[Pd+2]>[NH2:1][C:2]1[N:7]=[CH:6][N:5]=[C:4]2[N:8]([CH2:12][C:13]3[N:14]([C:25]4[CH:30]=[CH:29][CH:28]=[CH:27][C:26]=4[CH3:31])[C:15](=[O:24])[C:16]4[C:21]([CH:22]=3)=[CH:20][CH:19]=[CH:18][C:17]=4[CH3:23])[N:9]=[C:10]([C:40]3[CH:45]=[CH:44][CH:43]=[C:42]([OH:46])[CH:41]=3)[C:3]=12

Komponenten

8

Edukt 4

HCID 10340Sodium CarbonateHCID 11776TriphenylphosphineHCID 27346233-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)phenolHCID 580086523-((4-amino-3-iodo-1H-pyrazolo[3,4-d]pyrimidin-1-yl)methyl)-8-methyl-2-o-tolylisoquinolin-1(2H)-one

Produkt 1

HCID 580087113-((4-amino-3-(3-hydroxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)methyl)-8-methyl-2-o-tolylisoquinolin-1(2H)-oneAusbeute 69,1 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 167845palladium(II) acetateKatalysatorHCID 702EthanolLösungsmittelHCID 86633292ethanol water DMFLösungsmittel

Reaktionsbedingungen

Temperatur
100 °C

Versuchsvorschrift

3-((4-amino-3-iodo-1H-pyrazolo[3,4-d]pyrimidin-1-yl)methyl)-8-methyl-2-o-tolylisoquinolin-1(2H)-one (1611) (13 g, 24.9 mmol) and 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenol (1612)(6.6 g, 30 mmol) were dissolved in DMF-EtOH-H2O (120 mL, 40 mL, 40 mL). Pd(OAc)2 (1.684 g, 7.5 mmol), PPh3 (3.935 g 15 mmol) and Na2CO3 (13.25 g 125 mmol) were added sequentially. The resulting mixture was degassed and back-filled with argon three times and then stirred at 100° C. for 1 h. The mixture was allowed to cool to RT, filtered through silica gel (10 g) and concentrated in vacuo. The residue was purified by flash column chromatography on silica gel (2-20% MeOH/DCM) to afford the product (1613) (9 g, 76% yield) as a slight yellow solid. Then above product was suspended in EtOH (100 mL) and heated to reflux for 30 min. The mixture was allowed to cool to RT, and the solid was collected by filtration. The solid was then suspended in EA (100 mL) and stirred overnight. The precipitate was collected by filtration and further dried in vacuo to afford the desired product, 3-((4-amino-3-(3-hydroxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)methyl)-8-methyl-2-o-tolylisoquinolin-1(2H)-one (1613)(8.4 g, 69% yield) as a white solid.

Aufarbeitung

  1. customThe resulting mixture was degassed
  2. additionback-filled with argon three times
  3. temperatureto cool to RT
  4. filtrationfiltered through silica gel (10 g)
  5. concentrationconcentrated in vacuo
  6. customThe residue was purified by flash column chromatography on silica gel (2-20% MeOH/DCM)
  7. customto afford the product (1613) (9 g, 76% yield) as a slight yellow solid
  8. temperatureheated
  9. temperatureto reflux for 30 min
  10. temperatureto cool to RT
  11. filtrationthe solid was collected by filtration
  12. stirringstirred overnight
  13. filtrationThe precipitate was collected by filtration
  14. customfurther dried in vacuo

Quellen und Nachweise

ORD-Eintrag
ord-3e2e0e57bfed4e998e784f1ab6e5b5a2
Quelldatensatz
uspto-grants-2012_06
Patentnummer
US08193182B2

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