反应详情

温度

102.5 °C

Charge a 500 mL three-necked round bottom flask with 2-[(5-amino-6-chloro-2-methyl-pyrimidin-4-yl)amino]ethanol (13.0 g, 0.064 mol) and 1,4-dioxane (300 mL). Add 2-chlorobenzaldehyde (13.5 g, 0.096 mol) followed by iron (III) chloride, 5 wt % on silica gel (37.5 g) in one portion. Heat the mixture to 100-105° C. for 48 h. Cool to 20-35° C., filter and rinse the cake with 1,4-dioxane (40 mL). Combine the filtrates and concentrate under vacuum. Dissolve the residue with dichloromethane (260 mL, 20 mL/g) and cool to 0-5° C. Add 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (14.5 g, 0.064 mol) at 0° C., warm up the mixture to 10-25° C., and stir for 2 h. Filter and rinse the cake with ethanol (100 mL) and combine the filtrates. Concentrate down the filtrates under vacuum to give a dark residue. Re-dissolve the residue with dichloromethane (300 mL), wash this solution with 1 N aqueous sodium hydroxide to pH 10-11 followed by water (2×60 mL). Concentrate the organic layer to give crude material. Purify the crude over 400 g silica gel, eluting with dichloromethane/methanol (50:1) to afford a yellow solid (6.5 g). 1H NMR (dmso-d6): δ 7.73-7.56 (m, 4H); 4.83 (t, J=6 Hz, 1H); 4.12 (t, J=6 Hz, 2H); 3.61 (q, J=6 Hz, 2H); 2.73 (s, 3H).

1. temperatureCool to 20-35° C.
2. filtrationfilter
3. washrinse the cake with 1,4-dioxane (40 mL)
4. concentrationCombine the filtrates and concentrate under vacuum
5. dissolutionDissolve the residue with dichloromethane (260 mL, 20 mL/g)
6. temperaturecool to 0-5° C
7. filtrationFilter
8. washrinse the cake with ethanol (100 mL)
9. concentrationConcentrate down the filtrates under vacuum
10. customto give a dark residue
11. washRe-dissolve the residue with dichloromethane (300 mL), wash this solution with 1 N aqueous sodium hydroxide to pH 10-11
12. concentrationConcentrate the organic layer
13. customto give crude material
14. customPurify the crude over 400 g silica gel
15. washeluting with dichloromethane/methanol (50:1)