Reaktion #303940

Reaktionsgleichung

6-chloropurine

1,4-diazabicyclo[2.2.2]octane

(2-(2-chlorophenyl)-8-methylquinolin-3-yl)-methanol

sodium hydride

→

3-((9H-Purin-6-yloxy)methyl)-2-(2-chlorophenyl)-8-methylquinoline

Lösungsmittel

H2O

DMSO

DMSO

Reaktionsbedingungen

Aufarbeitung

1. 1
   SonstigePrepared
2. 2
   workup.STIRRINGhad been stirred at rt for 15 min
3. 3
   workup.ADDITIONto the addition
4. 4
   workup.STIRRINGThe mixture was stirred at rt for 3.5 h
5. 5
   Temperaturcooled to 0° C.
6. 6
   ExtraktionThe mixture was extracted with EtOAc (3×10 mL)
7. 7
   Trocknenthe combined organic layers were dried (MgSO4)
8. 8
   Einengenconcentrated under reduced pressure
9. 9
   workup.DISSOLUTIONThe resulting yellow oil was dissolved in CH2Cl2
10. 10
    Sonstigeevaporated onto silica gel (deactivated with 2M NH3 in MeOH)
11. 11
    Sonstigepurified by flash chromatography (Biotage® Si 25+M)
12. 12
    Wascheneluting with 2M NH3 in MeOH/CH2Cl2 (5%)
13. 13
    Sonstigeto provide a white solid [PI3Kδ IC50=25 nM]

Vorschrift

Prepared according to procedure L A mixture of 6-chloropurine (75 mg, 0.49 mmol) and 1,4-diazabicyclo[2.2.2]octane (109 mg, 0.97 mmol) in DMSO (0.5 mL) was stirred at rt for 5 h and was then added via cannula to a mixture of (2-(2-chlorophenyl)-8-methylquinolin-3-yl)-methanol (69 mg, 0.24 mmol) and sodium hydride, 60% dispersion in mineral oil (39 mg, 0.97 mmol) in DMSO (0.5 mL) that had been stirred at rt for 15 min prior to the addition. The mixture was stirred at rt for 3.5 h, cooled to 0° C., and H2O (5 mL) was added carefully. The mixture was extracted with EtOAc (3×10 mL), and the combined organic layers were dried (MgSO4) and concentrated under reduced pressure. The resulting yellow oil was dissolved in CH2Cl2, evaporated onto silica gel (deactivated with 2M NH3 in MeOH), and purified by flash chromatography (Biotage® Si 25+M) eluting with 2M NH3 in MeOH/CH2Cl2 (5%) to provide a white solid [PI3Kδ IC50=25 nM]. MS (ESI+) m/z=402.0 (M+1).

Quelle