Reaktion #1133933

Reaktionsgleichung

3-((4-Amino-3-iodo-1H-pyrazolo[3,4-d]pyrimidin-1-yl)methyl)-2-isopropyl-8-methylisoquinolin-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)-2-isopropyl-8-methylisoquinolin-1(2H)-one

Ausbeute 61.0%

Lösungsmittel

DMF EtOH—H2O

Reaktionsbedingungen

Aufarbeitung

1. 1
   workup.ADDITIONwere added sequentially
2. 2
   SonstigeThe resulting mixture was degassed
3. 3
   workup.ADDITIONback-filled with argon three times
4. 4
   Temperaturto cool to RT
5. 5
   Filtrationfiltered through silica gel (10 g)
6. 6
   Einengenconcentrated in vacuo
7. 7
   SonstigeThe residue was purified by flash column chromatography on silica gel (2-20% MeOH/DCM)

Vorschrift

To a stirred mixture of 3-((4-Amino-3-iodo-1H-pyrazolo[3,4-d]pyrimidin-1-yl)methyl)-2-isopropyl-8-methylisoquinolin-1(2H)-one (2008) (95 mg, 0.2 mmol) and 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenol (66 mg, 0.3 mmol) in DMF-EtOH—H2O (3:1:1, 20 mL), Pd(OAc)2 (16 mg, 0.075 mmol), PPh3 (39.3 mg 0.15 mmol) and Na2CO3 (132 mg, 1.25 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, 3-((4-amino-3-(3-hydroxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)methyl)-2-isopropyl-8-methylisoquinolin-1(2H)-one (2009, compound 62 in Table 4) (53 mg, 61% yield) as a slightly yellow solid.

Quelle