反应详情

温度

0 °C

2M Trimethylaluminium in hexane (0.457 mL, 0.91 mmol) was added to 5-(methylthio)pyridin-2-amine (CAS no. 77618-99-6) (0.111 g, 0.79 mmol) in toluene (22 mL) at 0° C. under nitrogen. The resulting solution was stirred at 0° C. for 20 minutes. (2S)-methyl 2-(1-(3-chloropyridin-2-yl)-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy)-3-ethoxypropanoate (Intermediate L2) (0.300 g, 0.79 mmol) in toluene (6 mL) was added dropwise at this temperature. After the addition was complete, the solution was allowed to warm to ambient temperature and was then heated at reflux for 16 hours. The mixture was allowed to cool to ambient temperature and left standing for 2 days. The reaction mixture was concentrated, diluted with ethyl acetate (100 mL) then washed with saturated brine (50 mL). The organic layer was dried (MgSO4) and evaporated. The residue was purified by flash silica chromatography, eluting with 0 to 3% MeOH in DCM to afford the product.

1. customat 0° C.
2. additionAfter the addition
3. temperatureto warm to ambient temperature
4. temperaturewas then heated
5. temperatureat reflux for 16 hours
6. temperatureto cool to ambient temperature
7. waitleft
8. waitstanding for 2 days
9. concentrationThe reaction mixture was concentrated
10. additiondiluted with ethyl acetate (100 mL)
11. washthen washed with saturated brine (50 mL)
12. dry with materialThe organic layer was dried (MgSO4)
13. customevaporated
14. customThe residue was purified by flash silica chromatography
15. washeluting with 0 to 3% MeOH in DCM
16. customto afford the product