反应详情

温度

150 °C

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 chroma-tography (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).

1. customThe mixture was partitioned between saturated aqueous NaHCO3 (15 mL) and EtOAc (15 mL)
2. customthe layers were separated
3. extractionthe aqueous layer was extracted with EtOAc (2×15 mL)
4. dry with materialThe combined organic layers were dried (MgSO4)
5. concentrationconcentrated under reduced pressure
6. dissolutionThe resulting yellow oil was dissolved in CH2Cl2
7. customevaporated onto silica gel
8. custompurified by flash chroma-tography (Biotage® Si 25+M)
9. washeluting with MeOH/CH2Cl2 (5% to 10%)
10. customto provide a white solid
11. customThe compound was further purified by reversed-phase HPLC (Gilson)
12. washeluting with H2O/MeCN/TFA
13. customto provide a white solid [PI3Kδ IC50=82 nM]