Reaktion #303943

Reaktionsgleichung

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

2-amino-6-chloropurine

triethylamine

→

N6-((8-Methyl-2-o-tolylquinolin-3-yl)methyl)-9H-purine-2,6-diamine

Lösungsmittel

i-PrOH

Reaktionsbedingungen

Aufarbeitung

1. 1
   SonstigeThe mixture was partitioned between saturated aqueous NaHCO3 (15 mL) and EtOAc (15 mL)
2. 2
   Sonstigethe layers were separated
3. 3
   Extraktionthe aqueous layer was extracted with EtOAc (2×15 mL)
4. 4
   TrocknenThe combined organic layers were dried (MgSO4)
5. 5
   Einengenconcentrated under reduced pressure
6. 6
   workup.DISSOLUTIONThe resulting yellow oil was dissolved in CH2Cl2
7. 7
   Sonstigeevaporated onto silica gel
8. 8
   Sonstigepurified by flash chromatography (Biotage® Si 25+M)
9. 9
   Wascheneluting with MeOH/CH2Cl2 (5% to 10%)
10. 10
    Sonstigeto provide a white solid
11. 11
    SonstigeThe compound was further purified by reversed-phase HPLC (Gilson)
12. 12
    Wascheneluting with H2O/MeCN/TFA
13. 13
    Sonstigeto provide a white solid [PI3Kδ IC50=82 nM]

Vorschrift

A mixture of (8-methyl-2-o-tolylquinolin-3-yl)methanamine (40 mg, 0.15 mmol), 2-amino-6-chloropurine (52 mg, 0.30 mmol), and triethylamine (42 μL, 0.30 mmol) in i-PrOH (0.8 mL) was heated in a microwave reactor at 150° C. four times for 20 min. The mixture was partitioned between saturated aqueous NaHCO3 (15 mL) and EtOAc (15 mL), the layers were separated, and the aqueous layer was extracted with EtOAc (2×15 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, and purified by flash chromatography (Biotage® Si 25+M) eluting with MeOH/CH2Cl2 (5% to 10%) to provide a white solid. The compound was further purified by reversed-phase HPLC (Gilson) eluting with H2O/MeCN/TFA to provide a white solid [PI3Kδ IC50=82 nM]. MS (ESI+) m/z=396.2 (M+1).

Quelle