Reaktion #304293

Reaktionsgleichung

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

3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenol

PPh3

Na2CO3

→

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

Ausbeute 69.1%

Lösungsmittel

DMF EtOH-H2O

EtOH

Reaktionsbedingungen

Aufarbeitung

1. 1
   SonstigeThe resulting mixture was degassed
2. 2
   workup.ADDITIONback-filled with argon three times
3. 3
   Temperaturto cool to RT
4. 4
   Filtrationfiltered through silica gel (10 g)
5. 5
   Einengenconcentrated in vacuo
6. 6
   SonstigeThe residue was purified by flash column chromatography on silica gel (2-20% MeOH/DCM)
7. 7
   Sonstigeto afford the product (1613) (9 g, 76% yield) as a slight yellow solid
8. 8
   Temperaturheated
9. 9
   Temperaturto reflux for 30 min
10. 10
    Temperaturto cool to RT
11. 11
    Filtrationthe solid was collected by filtration
12. 12
    workup.STIRRINGstirred overnight
13. 13
    FiltrationThe precipitate was collected by filtration
14. 14
    Sonstigefurther dried in vacuo

Vorschrift

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.

Quelle