Reaktion #303941

Reaktionsgleichung

6-chloropurine

1,4-diazabicyclo[2.2.2]octane

(8-methyl-2-o-tolylquinolin-3-yl)methanol

sodium hydride

→

3-((9H-Purin-6-yloxy)methyl)-8-methyl-2-o-tolylquinoline

Lösungsmittel

brine

DMSO

acetic acid

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
   Extraktionextracted with EtOAc (3×15 mL)
6. 6
   TrocknenThe combined organic layers were dried (MgSO4)
7. 7
   Einengenconcentrated under reduced pressure
8. 8
   workup.DISSOLUTIONThe resulting yellow oil was dissolved in CH2Cl2
9. 9
   Sonstigeevaporated onto silica gel (deactivated with 2M NH3 in MeOH)
10. 10
    Sonstigepurified by flash chromatography (Biotage® Si 25+M)
11. 11
    Wascheneluting with 2 M NH3 in MeOH/CH2Cl2 (5%)
12. 12
    Sonstigeto provide a white solid [PI3δ IC50=27 nM]

Vorschrift

Prepared according to procedure L A mixture of 6-chloropurine (110 mg, 0.71 mmol) and 1,4-diazabicyclo[2.2.2]octane (160 mg, 1.43 mmol) in DMSO (0.7 mL) was stirred at rt for 4 h and was then added via cannula to a mixture of (8-methyl-2-o-tolylquinolin-3-yl)methanol (94 mg, 0.36 mmol) and sodium hydride, 60% dispersion in mineral oil (57 mg, 1.43 mmol) in DMSO (1 mL) that had been stirred at rt for 15 min prior to the addition. The mixture was stirred at rt for 3.5 h, neutralized by the addition of glacial acetic acid, diluted with brine (15 mL), and extracted with EtOAc (3×15 mL). 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 2 M NH3 in MeOH/CH2Cl2 (5%) to provide a white solid [PI3δ IC50=27 nM]. MS (APCI+) m/z=282.3 (M+1).

Quelle