Reaktion #304296

Reaktionsgleichung

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

(R)-but-3-yn-2-ol

(i-Pr)2NH

→

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

Ausbeute 70.0%

Lösungsmittel

THF

Reaktionsbedingungen

Aufarbeitung

1. 1
   SonstigeThe mixture was degassed
2. 2
   workup.ADDITIONback-filled with nitrogen three times
3. 3
   SonstigeThe resulting mixture was degassed
4. 4
   workup.ADDITIONback-filled with argon three times
5. 5
   Temperaturat reflux for 4 h
6. 6
   Filtrationfiltered through silica gel (10 g)
7. 7
   Einengenconcentrated in vacuo
8. 8
   SonstigeThe residue was purified by flash column chromatography on silica gel (2-20% MeOH/DCM)

Vorschrift

3-((4-amino-3-iodo-1H-pyrazolo[3,4-d]pyrimidin-1-yl)methyl)-8-methyl-2-o-tolylisoquinolin-1(2H)-one (1611)(522 mg, 1 mmol) and (R)-but-3-yn-2-ol (84 mg, 1.2 mmol) were dissolved in anhydrous THF (40 mL). The mixture was degassed and back-filled with nitrogen three times. Pd(PPh3)2Cl2 (12 mg, 0.1 mmol), CuI (47 mg 0.25 mmol) and (i-Pr)2NH (505 mg, 5 mmol) were added sequentially. The resulting mixture was degassed and back-filled with argon three times and then stirred at reflux for 4 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 (R)-3-((4-amino-3-(3-hydroxybut-1-ynyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)methyl)-8-methyl-2-o-tolylisoquinolin-1(2H)-one (1802) (324 mg, 70% yield) as a slightly yellow solid.

Quelle